Parallel synthesis of homochiral β-amino acids

Article abstract of DOI:10.1016/j.tetasy.2007.06.008

The parallel asymmetric synthesis of an array of 30 β-amino acids of high enantiomeric purity using the conjugate addition of homochiral lithium N-benzyl-N-(α-methylbenzyl)amide as the key step is accomplished. The experimental simplicity and highly practical nature of the protocol is demonstrated by the efficient parallel conversion of 15 α,β-unsaturated esters to both enantiomeric series of the corresponding β-amino acids in high overall yields and selectivities with minimal purification involved in each step of the reaction protocol.

Full text of DOI:10.1016/j.tetasy.2007.06.008

Tetrahedron: Asymmetry 18 (2007) 1554–1566
Parallel synthesis of homochiral b-amino acids
Stephen G. Davies,* Andrew W. Mulvaney, Angela J. Russell and Andrew D. Smith
The Department of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
Received 29 May 2007; accepted 7 June 2007
Abstract—The parallel asymmetric synthesis of an array of 30 b-amino acids of high enantiomeric purity using the conjugate addition of
homochiral lithium N-benzyl-N-(a-methylbenzyl)amide as the key step is accomplished. The experimental simplicity and highly practical
nature of the protocol is demonstrated by the efficient parallel conversion of 15 a,b-unsaturated esters to both enantiomeric series of the
corresponding b-amino acids in high overall yields and selectivities with minimal purification involved in each step of the reaction
protocol.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
esters,10 the addition of N-benzylhydroxylamines to imi-
des,11 the catalytic reduction of b-amino crotonates12 or
b-acylamino acrylates13 and the dipolar cycloaddition of
homochiral nitrones14 among others.15 We have previously
shown that the conjugate addition of homochiral lithium
amides derived from a-methylbenzylamine to a,b-unsatu-
rated esters may be used as a general route to allow the
asymmetric synthesis of b-amino acid derivatives.16,17
Rapid progress has been made in recent years in the prac-
tice of a high throughput screening of compounds for bio-
logical testing. This procedure has ensured that synthetic
chemists are constantly striving to develop new and effi-
cient protocols for the production of arrays of compounds
in a rapid and efficient way. Although the syntheses of
numerous libraries of compounds using parallel synthesis
have been reported, the vast majority of these arrays have
been concerned with the preparation of achiral com-
pounds, with limited characterisation data reported.1
Herein, the highly practical nature of this protocol is dem-
onstrated by the parallel generation of an array of homo-
chiral b-amino acids. These b-amino acids and the
corresponding intermediate b-amino esters may be subse-
quently elaborated to generate libraries of b-amino acid
derivatives and evaluated as organocatalysts in a variety
of reaction manifolds.18 To demonstrate both the experi-
mental simplicity and synthetic versatility of this methodol-
ogy, all reactions in this series were performed using a
Radleys CarouselTM reaction station,19 enabling the simul-
taneous completion of twelve reactions at once, with min-
imal purification involved in each step of the reaction
protocol.
The pharmacological activities of a variety of b-amino
acids and their derivatives have been well documented.2
For example, the a-hydroxy-b-phenylalanine component
of Taxolꢁ, a potent anti-cancer agent, was found to be
essential to its anti-tumour activity3 and (S)-b-tyrosine
was found to be a key component of the antibiotic edeine
A.4 In addition, the pharmacological and conformational
properties of synthetic peptides derived from b-amino acids
have been receiving increasing attention.5 The development
of generally applicable, robust methodologies towards the
asymmetric synthesis of b-amino acids and derivatives is
of widespread interest to the synthetic community with
numerous routes described in the literature.6 These include
Arndt-Eistert homologation of a-amino acids,7 enzymatic
resolutions,8 stereoselective Mannich reactions,9 the conju-
gate addition of amines to homochiral a,b-unsaturated
2. Results and discussion
2.1. Parallel synthesis of a,b-unsaturated esters; application
of Horner–Wadsworth–Emmons methodology
In order to generate the desired array of b-amino acids
from readily available starting materials, our synthetic
strategy required a range of (E)-a,b-unsaturated ester
substrates to undergo conjugate addition, which it was
*
Corresponding author. E-mail: steve.davies@chem.ox.ac.uk
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.06.008

S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
1555
unsaturated acceptors,14 relative to the known configura-
tion of the a-methylbenzyl stereocentre. Subsequent chro-
matographic purification using a BAKERBOND speTM
manifold21 gave each antipode of b-amino esters 18–32 in
excellent yield (79–98%) and in high de (>95%) in each case
(Scheme 2).
O
P
t
CO2 Bu
EtO
EtO
Li
(i)
H
t
CO2 Bu
R
O
R
2-16
2.3. Parallel synthesis of b-amino acids
R
Yield (%) d.e.20 (%) Purity* (%)
2
3
4
5
6
7
8
9
Me
93
89
93
89
93
88
94
95
78
96
87
93
93
96
93
>95
>96
>97
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>99
With an array of b-amino esters 18–32 available in each
enantiomeric series, deprotection to the corresponding b-
amino acids was investigated. We have previously demon-
strated that N-debenzylation of N-benzyl-N-a-methyl-
benzyl protected tertiary b-amino esters by catalytic
hydrogenolysis is an efficient method for N-deprotection
in these systems. Although this deprotection is typically
achieved under 5 atm of hydrogen, this protocol is unsuit-
able for parallel synthesis using the Radleys CarouselTM
reaction station, which necessitated the cleavage of the N-
benzyl protecting groups of b-amino esters 18–32 under a
hydrogen pressure of 1 atm. As the addition of acid is
known to promote N-debenzylation,16 the deprotection
of b-amino esters 18–32 to their corresponding primary
b-amino esters was carried out in a methanol/acetic acid/
water mixture (40:4:1 v/v/v) using Pd(OH)2 on C under a
hydrogen balloon. After filtration through Celite to remove
the heterogenous catalyst and concentration of the result-
ing reaction mixture, the crude product was subjected to
chromatographic purification, giving the desired b-amino
esters 33–47 in 73–93% yield (Scheme 3).
(CH3)2CHCH2
CH3(CH2)6
94.8
>99
>99
4-(MeO)C6H4
3-(MeO)C6H4
2-(MeO)C6H4
3,5-(MeO)2C6H3
3,4-(MeO)2C6H3
>99
99.0
>99
99.3
98.6
>99
98.7
>99
>99
98.8
>99
10 2,4-(MeO)2C6H3
11
12
13
14
15
Ph
4-PhC6H4
Piperon-3-yl
3-(BnO)C6H4
4-(BnO)C6H4
16 3,4-(BnO)2C6H3
t
Scheme 1. Reagents and conditions: (i) (EtO)2POCH(Li)CO2 Bu 1, THF,
ꢀ78 ꢂC to rt; *Purity determined by HPLC analysis.
Subsequent ester hydrolysis of b-amino esters 33–47 by
treatment with TFA, conversion to the corresponding
hydrochloride salts and ion exchange chromatography
yielded the free b-amino acids 48–61 in uniformly excellent
yields (92–99%). The only exceptions to this protocol in-
volved the isolation of (R)- and (S)-58 as their hydrochloride
salts due to the limited solubility of the free amino acids, and
(R)- and (S)-62 as their hydrochloride salts due to decompo-
sition upon ion exchange chromatography (Scheme 4).
envisaged could be readily prepared using Horner–Wads-
worth–Emmons methodology from the corresponding
aldehydes. In this manner, a range of commercially avail-
able alkyl and aryl aldehydes were treated with the lithium
anion of tert-butyl diethylphosphonoacetate 1, furnishing
tert-butyl (E)-a,b-unsaturated esters 2–16 with a high dia-
stereoselectivity (generally >98% de).20 Purification of the
desired a,b-unsaturated esters was carried out by chroma-
tography on silica gel in an SPE tube on a Baker SPE man-
ifold, which enabled simultaneous purification of all
samples, giving the desired range of tert-butyl (E)-b-alkyl-
and (E)-b-aryl-a,b-unsaturated esters 2–16 in high yields
(78–96%) and in high de (>98% de) and in >94% purity
as shown by HPLC analysis (Scheme 1).
In conclusion, the generality and practicality of the highly
diastereoselective conjugate addition reaction of homochi-
ral lithium amides derived from a-methylbenzylamine with
an array of b-alkyl and b-aryl a,b-unsaturated esters have
been demonstrated. The resulting array of tertiary b-amino
esters were readily deprotected by N-debenzylation via
hydrogenolysis and subsequent ester hydrolysis afforded
the corresponding b-amino acids in high yield and ee.
The further functionalisation and elaboration of the inter-
mediate b-amino esters to generate libraries of b-amino
acid derivatives and the assessment of the corresponding
b-amino acids as organocatalysts are currently underway
in our laboratory.
2.2. Parallel synthesis of b-amino esters; conjugate addition
of lithium (R)- or (S)-N-benzyl-N-(a-methylbenzyl)amide 17
With a range of a,b-unsaturated esters 2–16 in hand,
conjugate addition of homochiral lithium (R)- and (S)-N-
benzyl-N-(a-methylbenzyl)amide 17 (>98% ee) to each
conjugate acceptor was followed. Following our standard
protocol, addition of each of the a,b-unsaturated esters
2–16 to a THF solution of either lithium (R)- or (S)-amides
17 at ꢀ78 ꢂC in THF proceeded to high conversion, giving
each antipode of the b-amino esters 18–32 in uniformly
high de (>95%). The absolute configuration at C(3) within
b-amino esters 18–32 was assigned by analogy with pre-
vious models developed to explain the stereoselectivity
observed during the addition of lithium amide 17 to a,b-
3. Experimental
3.1. General experimental
All reactions involving organometallic or other moisture
sensitive reagents were performed under an atmosphere

1556
S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
Ph
Ph
Ph
Ph
Ph
N
Li
Ph
N
Li
Ph
Ph
N
Ph
N
t
t
t
(S
)-17
(
R
)-17
CO2 Bu
CO2 Bu
CO2 Bu
R
R
R
(ii)
(i)
2-16
(α
S
)-18-32
(α
R
)-18-32
Ph
Ph
Ph
Ph
Ph
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
Me
Me
Me
Me
(3S,αS)-18, 87%, 96% d.e. (3S,αS)-19, 92%, 96% d.e. (3S,αS)-20, 95%, 96% d.e.
(3R,αR)-18, 89%, 96% d.e. (3R,αR)-19, 95%, 96% d.e. (3R,αR)-20, 96%, 97% d.e.
Ph
Ph
Ph
Ph
Ph
Ph
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
OMe
(3S,αR)-21, 91%, 96% d.e. (3S,αR)-22, 94%, 95% d.e. (3S,αR)-23, 88%, 95% d.e.
MeO
(3R,αS)-21, 89%, 96% d.e. (3R,αS)-22, 94%, 96%
OMe
MeO
OMe
OMe
(3R,αS)-23, 86%, 97% d.e.
d.e.
Ph
Ph
Ph Ph
Ph
Ph
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
MeO
CO2tBu
CO2tBu
MeO
CO2tBu
CO2tBu
CO2tBu
CO2tBu
MeO
MeO
MeO
OMe
MeO
OMe
OMe
(3R,αS)-24, 98%, 96% d.e. (3R,αS)-25, 88%, 96% d.e. (3R,αS)-26, 84%, 97% d.e.
Ph
OMe
OMe
(3S,αR)-24, 96%, 95% d.e. (3S,αR)-25, 95%, 96% d.e. (3S,αR)-26, 79%, 96% d.e.
Ph
OMe
Ph
Ph
Ph
Ph
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
O
O
O
O
Ph
Ph
(3R,αS)-27, 96%, 96% d.e. (3R,αS)-28, 91%, 96% d.e. (3R,αS)-29, 93%, 96% d.e.
Ph Ph
(3S,αR)-27, 88%, 98% d.e. (3S,αR)-28, 89%, 96% d.e. (3S,αR)-29, 91%, 97% d.e.
Ph Ph
Ph
Ph
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
BnO
BnO
BnO
BnO
OBn
OBn
OBn
OBn
(3R,αS)-30, 90%, 96% d.e. (3R,αS)-31, 93%, 96% d.e. (3R,αS)-32, 94%, 96% d.e.
(3S,αR)-30, 87%, 96% d.e. (3S,αR)-31, 90%, 96% d.e. (3S,αR)-32, 89%, 96% d.e.
Scheme 2. Reagents and conditions: (i) (S)-17, THF, ꢀ78 ꢂC, 2 h; (ii) (R)-17, THF, ꢀ78 ꢂC, 2 h.
of nitrogen via standard vacuum line techniques. All glass-
ware were flame-dried and allowed to cool under vacuum.
THF was distilled under an atmosphere of dry nitrogen from
sodium benzophenone ketyl. Water was distilled. n-Butylli-
thium was used as a solution in hexanes at the molarity sta-
ted. All other solvents and reagents were used as supplied
(Analytical or HPLC grade), without prior purification.
The reactions were dried with MgSO4. Thin-layer chroma-
tography (TLC) was performed on aluminium sheets coated
with 60 F254 silica. Sheets were visualised using iodine, UV
light or 1% aqueous KMnO4 solution. Flash chromatogra-
phy was performed on Kieselgel 60 silica. Nuclear magnetic
resonance (NMR) spectra were recorded on Bruker DPX
400 (1H: 400 MHz and 13C: 100.6 MHz), AMX 500 (1H:
500 MHz and 13C: 125.3 MHz), Bruker W-H 300 (1H:
300 MHz) or Varian 200 (1H: 200 MHz) spectrometers in
the deuterated solvent stated. All chemical shifts (d) are
quoted in parts per million and coupling constants (J) in
hertz. Coupling constants are quoted twice, each being
recorded as observed in the spectrum without averaging.
Residual signals from the solvents were used as an internal
reference. 13C multiplicities were assigned using a DEPT
sequence. In all cases, the reactions diastereoselectivity
was assessed by peak integration of the 1H NMR spectrum
of the crude reaction mixture. Infrared spectra were
recorded on a Perkin–Elmer 1750 IR Fourier Transform
spectrophotometer using either thin films on NaCl plates
(film) or KBr discs (KBr) as stated. Only the characteristic
peaks are quoted. Low resolution mass spectra (m/z) were
recorded on B.G. micromass ZAB 2F instrument, VG Mas-
sLab 20-250 or Micromass Platform 1 spectrometers and
high resolution mass spectra (HRMS) on a Micromass
Autospec 500 OAT spectrometer or on a Waters 2790
Micromass LCT Exact Mass Electrospray Ionisation Mass
Spectrometer. The techniques used were chemical ionisation
(CI, NH3), atmospheric pressure chemical ionisation
(APCI) or electrospray ionisation (ESI) using partial purifi-
cation by HPLC with methanol/acetonitrile/water
(40:40:20 v/v/v) as eluent. Optical rotations were recorded
on a Perkin–Elmer 241 polarimeter with a water-jacketed
10 cm cell and specific rotations are given in units of
10ꢀ1 deg cm2 gꢀ1. Concentrations are quoted in g/100 mL.
Melting points were recorded on a Leica VMTG Galen III
apparatus and are uncorrected. High-performance liquid
chromatography (HPLC) was performed on a Gilson instru-
ment equipped with Gilson 306 pumps, a Gilson 811C
dynamic mixer, a Gilson 806 manometric module with an
automated sample injection on a Gilson 215 Liquid
Handler, configured with a Gilson 819 valve actuator.
Separations were performed on a Varian Omnisphere 5
C18 (analytical) column (5 lm particle size, 150.0 mm ·
4.6 mm). All experiments were performed under gradient
elution with a flow rate of 1.0 mL/min: solvent A (H2O con-
taining 0.1% (v/v) TFA) and solvent B (CH3CN), starting

S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
1557
Ph
Ph
NH2
NH2
(i)
(i)
Ph
N
Ph
N
t
t
CO2 Bu
CO2 Bu
R
R
t
t
CO2 Bu
CO2 Bu
R
R
33-57
33-57
18-32
18-32
NH2
NH2
NH2
NH2
NH2
NH2
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
Me
Me
Me
Me
(S)-33, 73%
(S)-34, 90%
(S)-35, 83%
(R)-33, 84%
(R)-34, 91%
(R)-35, 87%
NH2
NH2
NH2
NH2
NH2
NH2
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
MeO
MeO
OMe
MeO
MeO
OMe
OMe
OMe
(R)-36, 90%
(R)-37, 86%
(R)-38, 90%
(S)-36, 93%
(S)-37, 87%
(S)-38, 88%
NH2
NH2
NH2
NH2
NH2
NH2
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
MeO
MeO
MeO
OMe
MeO
OMe
OMe
OMe
OMe
OMe
(R)-39, 88%
(R)-40, 87%
(R)-41, 82%
(S)-39, 88%
(S)-40, 85%
(S)-41, 85%
NH2
NH2
NH2
NH2
NH2
NH2
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
O
O
O
O
Ph
Ph
(R)-42, 89%
(R)-43, 81%
(R)-44, 83%
(S)-42, 91%
(S)-43, 76%
(S)-44, 87%
NH2
NH2
NH2
NH2
NH2
NH2
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
CO2tBu
HO
HO
HO
HO
OH
(R)-45, 77%
OH
OH
(S)-45, 77%
OH
(R)-46, 81%
(R)-47, 82%
(S)-46, 82%
(S)-47, 85%
Scheme 3. Reagents and conditions: (i) H2 (1 atm), Pd(OH)2/C, MeOH, H2O, AcOH, rt, 15 h.
from 95% A, 5% B to 5% A, 95% B over 8 min then isocratic
for 4 min. Absorption was measured at wavelengths of 220,
254 and 290 nm using a Gilson 170 Diode Array Detector.
added n-BuLi (3.5 mL, 2.5 M in hexanes, 8.8 mmol) with
cooling to ꢀ78 ꢂC. After 30 min, a solution of a,b-unsatu-
rated ester (5.5 mmol) also at ꢀ78 ꢂC was transferred via a
cannula. The resulting solution was stirred at ꢀ78 ꢂC for
3h before quenching with saturated aqueous NH4Cl
(5 mL). Upon warming to room temperature, the product
was extracted with DCM. The organic fractions were com-
bined, dried (Na2SO4) and the solvent was removed in
vacuo. The residue was taken up in DCM and the excess
auxiliary extracted with 10% aq citric acid. The organic
layer was washed with saturated aqueous sodium bicarbon-
ate, dried (Na2SO4) and the solvent removed in vacuo to
yield the crude product, which was used without further
purification.
3.2. Representative procedure 1
To a stirred solution of tert-butyl diethylphosphonoacetate
(4.40 g, 17.4 mmol) in THF (15 mL) was slowly added n-
BuLi (7.0 mL, 2.5 M in hexanes, 17.4 mmol) with cooling
to ꢀ78 ꢂC. After stirring for 30 min at ꢀ78 ꢂC, a solution
of the aldehyde (16.0 mmol) also cooled to ꢀ78 ꢂC was
transferred via a cannula. The resulting solution was stirred
at ꢀ78 ꢂC for 30 min before being allowed to warm to rt.
The solution was subsequently cooled back to ꢀ78 ꢂC
and quenched with satd aq NH4Cl (10 mL). The product
was extracted with dichloromethane (3 · 20 mL) and the
combined organic extracts were dried (Na2SO4), and the
solvent was removed in vacuo to yield the crude product.
The excess phosphonate was removed by passing through
a plug of silica (DCM eluent) to yield the products which
were used without further purification.
3.4. Representative procedure 3
A stirred solution of lithium amide adduct (4.5 mmol) in
methanol (20 mL), distilled water (2 mL) and acetic acid
(0.5 mL) was degassed before palladium hydroxide on car-
bon (0.5 g) was added. A hydrogen balloon was attached
and the resulting suspension stirred for 24 h under 1 atm
of hydrogen. The reaction mixture was filtered through
Celiteꢁ and the solvent removed in vacuo. The residue
was partitioned between dichloromethane (20 mL) and sat-
urated aqueous NaHCO3 (10 mL). The organic phase was
3.3. Representative procedure 2
To a stirred solution of (R)- or (S)-N-benzyl-N-a-methyl-
benzylamine (1.86 g, 8.8 mmol) in THF (10 mL) was slowly

1558
S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
NH2
38-47
NH2
NH2
NH2
NH2
(i)
(i)
t
t
CO2 Bu
CO2H
CO2 Bu
CO2H
R
R
R
R
48-62
38-47
48-62
NH2
NH2
NH2
NH2
NH2
CO2H
CO2H
CO2H
CO2H
CO2H
CO2H
Me
Me
Me
Me
(R
)-50, 94%
(S
)-49, 92%
(S
)-50, 96%
(R
)-49, 97%
(S
)-48, 92%
(
R
)-48, 97%
NH2
NH2
NH2
NH2
NH2
NH2
CO2H
CO2H
CO2H
CO2H
CO2H
CO2H
OMe
OMe
MeO
MeO
MeO
MeO
OMe
OMe
(
(
S
)-53, 98%
(R
)-52, 99%
(
R
R
)-53, 95%
(S
)-52, 94%
(
R
R
)-51, 99%
(
S
S
)-51, 99%
NH2
NH2
NH2
NH2
NH2
NH2
CO2H
CO2H
CO2H
CO2H
CO2H
CO2H
MeO
MeO
MeO
OMe
MeO
OMe
OMe
OMe
OMe
OMe
S
)-56, 99%
(R
)-55, 97%
(
)-56, 99%
(S
)-55, 97%
(
)-54, 95%
(
)-54, 97%
NH2
NH2
NH2
NH2
NH2
NH2
CO2H
CO2H
CO2H
CO2H
O
O
CO2H
CO2H
O
O
Ph
Ph
(
S)-59, 96%
(R
)-58, 99%
(R
)-59, 96%
(S
)-58, 99%
(R
)-57, 96%
(S
)-57, 96%
NH2.HCl
CO2H
NH2.HCl
CO2H
NH2
NH2
NH2
NH2
CO2H
CO2H
CO2H
CO2H
HO
HO
HO
HO
OH
OH
)-62.HCl, 94%
OH
)-60, 99%
OH
)-60, 99%
(S)-62.HCl, 94%
(R
)-61, 94%
(R
(S)-61, 98%
(R
(S
Scheme 4. Reagents and conditions: (i) TFA, DCM, rt, 15 h.
separated and the aqueous phase was extracted with
dichloromethane (2 · 20 mL). The combined organic layers
were dried (Na2SO4) and the solvent removed in vacuo.
The residue was purified by passing through a short plug
of silica (doped 1% Et3N; wash 1:1 Et2O/pentane; elute
9:1 Et2O/MeOH) to yield the product which was used with-
out further purification.
6.9, 1.4, Me), 5.75 (1H, dq, J 15.5, 1.4, CHCO2), 6.85
(1H, dq, J 15.5, 6.9, CH@CHCO2).
3.6.1. tert-Butyl (E)-5-methyl-hex-2-enoate 3. Yield:
2.62 g, 89%; HPLC (MeCN/H2O) 94.8%; dH (400 MHz,
CDCl3) 0.92 (6H, d, J 6.7, CHMe2), 1.48 (9H, s, CMe3),
1.69–1.79 (1H, m, CHMe2), 2.03–2.08 (2H, m,
CH2CHMe2), 5.73 (1H, dt, J 15.6, 1.2, CHCO2), 6.83
(1H, dt, J 15.6, 7.6, CH@CHCO2).
3.5. Representative procedure 4
Trifluoroacetic acid (1 mL) was added dropwise to a stirred
solution of b-amino ester (200 lmol) in dichloromethane
(1 mL) under an atmosphere of argon, at room tempera-
ture. The solution was stirred for 15 h at room tempera-
ture. The solvents were removed in vacuo and co-
evaporated with ethereal HCl. The residue was subjected
to ion exchange chromatography (Dowex 80W-X8, elute
1 M NH4OH) to yield the free amino acid.
3.6.2. tert-Butyl (E)-dec-2-enoate 4. Yield: 3.36 g, 93%;
HPLC (MeCN/H2O) >99%; dH (400 MHz, CDCl3) 0.87
(3H, t, J 6.8, Me), 1.21–1.35 (8H, m, CH2), 1.40–1.47
(2H, m, CH2CH2CH@CH), 1.47 (9H, s, CMe3), 2.11–
2.19 (2H, m, CH2CH@CH), 5.72 (1H, dt, J 15.6, 1.5,
CHCO2), 6.85 (1H, dt, J 15.6, 7.0, CH@CHCO2).
3.6.3.
tert-Butyl
(E)-3-(4-methoxyphenyl)propenoate
5. Yield: 3.33 g, 89%; mp 40–41 ꢂC (lit.22 mp 41–44 ꢂC);
HPLC (MeCN/H2O) >99%; dH (400 MHz, CDCl3) 1.53
(9H, s, CMe3), 3.83 (3H, s, OMe), 6.25 (1H, d, J 15.6,
CHCO2), 6.89 (2H, d, J 9.2, Ar), 7.46 (2H, d, J 9.2, Ar),
7.55 (1H, d, J 15.6, CH@CHCO2).
3.6. tert-Butyl (E)-but-2-enoate 2
Yield: 2.11 g, 93%; HPLC (MeCN/H2O) >99%; dH
(400 MHz, CDCl3) 1.46 (9H, s, CMe3), 1.83 (3H, dd, J

S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
1559
3.6.4. tert-Butyl (E)-3-(3-methoxyphenyl)propenoate 6.
3.6.11. tert-Butyl (E)-3-piperon-3-ylpropenoate 13. Yield:
3.70 g, 93%; mp 79–80 ꢂC; HPLC (MeCN/H2O) >99%;
Yield: 3.48 g, 93%; HPLC (MeCN/H2O) >99%; mmax
/
cmꢀ1 (film) 1707, 1638; dH (400 MHz, CDCl3) 1.54 (9H,
s, CMe3), 3.82 (3H, s, OMe), 6.36 (1H, d, J 16.0, CHCO2),
6.89–7.31 (4H, m, Ar), 7.56 (1H, d, J 16.0, CH@CHCO2);
dC (100 MHz, CDCl3) 28.2, 55.2, 80.5, 112.7, 115.8, 120.4,
120.7, 129.8, 136.0, 143.4, 159.8, 166.2; m/z (APCI+) 179
(100%), 161 (100); HRMS (CI+) 235.1326 (C14H19O3
requires 235.1334).
m
max/cmꢀ1 (CHCl3) 1698, 1633; dH (400 MHz, CDCl3)
1.53 (9H, s, CMe3), 5.99 (2H, s, OCH2O), 6.20 (1H, d, J
16.2, CHCO2), 6.79 (1H, d, J 8.0, Ar(5)H), 6.97 (1H, dd,
J 8.0, 1.6, Ar(6)H), 7.02 (1H, d, J 1.6, Ar(2)H), 7.49 (1H,
d, J 16.2, CH@CHCO2); dC (100 MHz, CDCl3) 28.2
(CMe3), 80.3, 101.4, 106.4, 108.5, 118.1, 124.1, 129.0,
143.2, 148.2, 149.3, 166.5; m/z (APCI+) 193 (65%), 175
(100); HRMS (ESI+) 249.1138 (C14H17O4 requires
249.1127).
3.6.5. tert-Butyl (E)-3-(2-methoxyphenyl)propenoate 7.
Yield: 3.60 g, 88%; HPLC (MeCN/H2O) 99.0%; mmax
/
cmꢀ1 (film) 1706, 1631; dH (400 MHz, CDCl3) 1.54 (9H,
s, CMe3), 3.89 (3H, s, OMe), 6.45 (1H, d, J 16.0, CHCO2),
6.88–7.51 (4H, m, Ar), 7.92 (1H, d, J 16.0, CH@CHCO2);
dC (100 MHz, CDCl3) 28.2, 55.4, 80.2, 111.0, 120.6, 120.6,
123.6, 128.7, 131.1, 138.9, 158.2, 166.8; m/z (APCI+) 179
(100%), 161 (100); HRMS (ESI+) 235.1339 (C14H19O3
requires 235.1334).
3.6.12. tert-Butyl (E)-3-(3-benzyloxyphenyl)propenoate
14. Yield: 4.60 g, 93%; mp 66–67 ꢂC; HPLC (MeCN/
H2O) >99%;
m
max/cmꢀ1 (CHCl3) 1702, 1638; dH
(400 MHz, CDCl3) 1.56 (9H, s, CMe3), 5.09 (2H, s,
PhCH2O), 6.37 (1H, d, J 16.0, CHCO2), 6.98–7.48 (10H,
m, Ar), 7.57 (1H, d, J 16.0, CH@CHCO2); dC (100 MHz,
CDCl3) 28.2, 70.0, 80.5, 113.8, 116.7, 120.5, 120.9, 127.5,
128.1, 128.6, 129.8, 136.1, 136.7, 143.4 (C(3)H), 159.0,
166.2; m/z (APCI+) 255 (100%); HRMS (CI+) 310.1570
(C20H22O3 requires 310.1569).
3.6.6. tert-Butyl (E)-3-(3,5-dimethoxyphenyl)propenoate 8.
Yield: 3.99 g, 94%; mp 45–46 ꢂC; HPLC (MeCN/H2O)
>99%; mmax/cmꢀ1 (CHCl3) 1702, 1640; dH (400 MHz,
CDCl3) 1.54 (9H, s, CMe3), 3.80 (6H, s, OMe), 6.34 (1H,
d, J 15.8, CHCO2), 6.48 (1H, t, J 2.3, Ar(4)H), 6.65 (2H,
d, J 2.3, Ar(4)H and Ar(6)H), 7.50 (1H, d, J 15.8,
CH@CHCO2); dC (100 MHz, CDCl3) 28.6, 55.8, 81.0,
102.8, 106.3, 121.1, 137.0, 144.0, 161.4, 166.6; m/z (APCI+)
209 (100%), 191 (83); HRMS (CI+) 264.1261 (C15H20O4 re-
quires 264.1362).
3.6.13. tert-Butyl (E)-3-(4-benzyloxyphenyl)propenoate 15.
Yield: 4.72 g, 96%; mp 74–75 ꢂC; HPLC (MeCN/H2O)
98.8%; mmax/cmꢀ1 (CHCl3) 1698, 1634; dH (400 MHz,
CDCl3) 1.56 (9H, s, CMe3), 5.10 (2H, s, PhCH2O), 6.26
(1H, d, J 15.8, CHCO2), 6.98 (2H, d, J 8.8, Ar(3)H and
Ar(5)H), 7.33–7.50 (7H, m, Ar), 7.57 (1H, d, J 15.8,
CH@CHCO2); dC (100 MHz, CDCl3) 28.2, 70.0, 80.2,
115.1, 117.8, 127.5, 127.6, 128.1, 128.6, 129.6, 136.5,
143.1, 160.3, 166.7; m/z (APCI+) 255 (100%), 237 (45);
HRMS (CI+) 310.1559 (C20H22O3 requires 310.1569).
3.6.7. tert-Butyl (E)-3-(3,4-dimethoxyphenyl)propenoate 9.
Yield: 4.00 g, 95%; HPLC (MeCN, H2O) 99.3%; dH
(400 MHz, CDCl3) 1.54 (9H, s, CMe3), 3.90 (3H, s,
OMe), 3.91 (3H, s, OMe), 6.25 (1H, d, J 15.8, CHCO2),
6.83–7.10 (3H, m, Ar), 7.53 (1H, d, J 15.8, CH@CHCO2).
3.6.14. tert-Butyl (E)-3-(3,4-dibenzyloxyphenyl)propenoate
16. Yield: 6.18 g, 93%; mp 85–87 ꢂC; HPLC (MeCN/
H2O) >99%;
m
max/cmꢀ1 (CHCl3) 1698, 1634; dH
3.6.8. tert-Butyl (E)-3-(2,4-dimethoxyphenyl)propenoate 10.
Yield: 3.66 g, 78%; HPLC (MeCN/H2O) 98.6%; mmax/cmꢀ1
(CHCl3) 1701, 1626; dH (400 MHz, CDCl3) 1.53 (9H, s,
CMe3), 3.83 (3H, s, OMe), 3.86 (3H, s, OMe), 6.36 (1H,
d, J 16.0, CHCO2), 6.42–6.53 (2H, m, Ar), 7.43 (1H, d, J
8.6, Ar(6)H), 7.83 (1H, d, J 16.0, CH@CHCO2); dC
(100 MHz, CDCl3) 28.2, 55.4, 55.4, 79.9, 98.3, 105.1,
116.7, 118.0, 130.1, 138.8, 159.6, 162.4, 167.3; m/z (APCI+)
209 (100%), 191 (100); HRMS (CI+) 265.1443 (C15H21O4
requires 265.1440).
(400 MHz, CDCl3) 1.54 (9H, s, CMe3), 5.18 (2H, s,
PhCH2O), 5.20 (2H, s, PhCH2O), 6.20 (1H, d, J 15.8,
CHCO2), 6.92 (1H, d, J 8.3, Ar(2)H), 7.04–7.52 (12H, m,
Ar), 7.49 (1H, d, J 15.8, CH@CHCO2); dC (100 MHz,
CDCl3) 28.2, 70.9, 71.3, 80.3, 113.6, 114.2, 118.1, 122.7,
127.2, 127.3, 127.9, 128.1, 128.5, 136.8, 136.9, 143.3,
148.9, 150.7, 166.5; m/z (APCI+) 361 (100%), 343
(38); HRMS (CI+) 416.1994 (C27H28O4 requires 416.1988).
3.6.15. tert-Butyl (3S,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)butanoate (3S,aS)-18. Yield: 1.69 g, 87%; 96% de;
3.6.9. tert-Butyl (E)-3-phenylpropenoate 11. Yield: 3.47 g,
96%; HPLC (MeCN/H2O) >99%; dH (400 MHz, CDCl3)
1.55 (9H, s, CMe3), 6.38 (1H, d, J 16.2, CHCO2), 7.35–
7.56 (5H, m, Ar), 7.60 (1H, d, J 16.2, CH@CHCO2).
25
20
½aꢁD ¼ þ5:1 (c 1.1, CHCl3) {lit.16 for (3R,aR)-18 ½aꢁD
¼
ꢀ3:4 (c 1.2, CH2Cl2)}; dH (500 MHz, CDCl3) 1.12 (3H,
d, J 7.0, Me), 1.34 (3H, d, J 7.0, C(a)Me), 1.39 (9H, s,
CMe3), 2.02 (1H, dd, J 14.3, 9.3, C(2)H2), 2.26 (1H, dd,
J 14.3, 4.8, C(2)H2), 3.40–3.48 (1H, m, C(3)H), 3.61 (1H,
d, J 15.0, PhCH2), 3.76 (1H, d, J 15.0, PhCH2), 3.90 (1H,
q, J 7.0, C(a)H), 7.20–7.46 (10H, m, Ar).
3.6.10. tert-Butyl (E)-3-(4-biphenyl)propenoate 12. Yield:
3.90 g, 87%; mp 110–111 ꢂC; HPLC (MeCN/H2O) 98.7%;
m
max/cmꢀ1 (CHCl3) 1701, 1636; dH (400 MHz, CDCl3)
1.58 (9H, s, CMe3), 6.43 (1H, d, J 15.8, CHCO2), 7.23–
7.64 (9H, m, Ar), 7.65 (1H, d, J 15.8, CH@CHCO2); dC
(100 MHz, CDCl3) 28.2, 80.5, 120.0, 127.0, 127.5, 127.8,
128.4, 128.9, 133.6, 140.2, 142.7, 143.1, 166.4; m/z (APCI+)
225 (52%), 207 (100); HRMS (CI+) 280.1469 (C19H20O2 re-
quires 280.1463).
3.6.16. tert-Butyl (3R,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-butanoate (3R,aR)-18. Yield: 1.73 g, 89%; 96%
25
de; ½aꢁD ¼ ꢀ5:2 (c 1.1, CHCl3); other physical and
spectroscopic properties identical with those described
above.

1560
S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
3.6.17. tert-Butyl (3S,aS)-3-(N-benzyl-N-a-methylbenzyl-
PhCH2), 3.83 (3H, s, OMe), 4.02 (1H, q, J 6.8, C(a)H),
4.40 (1H, dd, J 9.9, 5.4, C(3)H), 6.77–4.48 (14H, m, Ar);
dC (100 MHz, CDCl3) 16.7, 27.9, 38.6, 51.0, 55.2, 57.3,
59.7, 80.2, 112.5, 114.3, 120.6, 126.6, 126.9, 127.9, 128.1,
128.1, 128.2, 129.1, 141.8, 143.7, 144.3, 159.6, 171.2;
m/z (APCI+) 446 (100%); HRMS (ESI+) 446.2696
(C29H36NO3 requires 446.2695).
amino)-5-methylhexanoate (3S,aS)-19. Yield: 2.02 g, 92%;
25
96% de; ½aꢁD ¼ ꢀ3:0 (c 1.4, CHCl3); mmax/cmꢀ1 (CHCl3)
1712; dH (400 MHz, CDCl3) 0.77 (3H, d, J 6.5, C(5)Me2),
0.89 (3H, d, J 6.7, C(5)Me2), 0.95–1.03 (1H, m, C(4)H2),
1.34 (3H, d, J 6.9, C(a)Me), 1.43 (9H, s, CMe3), 1.43–1.50
(1H, m, C(4)H2), 1.88 (1H, dd, J 14.1, 9.9, C(2)H2), 1.93–
2.02 (1H, m, C(5)H), 2.08 (1H, dd, J 14.1, 3.0, C(2)H2),
3.32–3.40 (1H, m, C(3)H), 3.50 (1H, d, J 15.2, PhCH2),
3.80–3.86 (2H, m, C(a)H and PhCH2), 7.23–7.47 (10H,
m, Ar); dC (100 MHz, CDCl3) 21.0, 21.9, 23.8, 24.4,
28.1, 37.6, 43.1, 50.1, 52.3, 58.9, 79.9, 126.5, 126.9, 128.0,
128.0, 128.1, 128.2, 142.4, 143.4, 172.2; m/z (ESI+) 396
(100%); HRMS (ESI+) 396.2895 (C26H38NO2 requires
396.2903).
3.6.24. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3-methoxyphenyl)propanoate (3S,aR)-22. Yield:
25
2.30 g, 94%; 95% de; ½aꢁD ¼ þ3:3 (c 1.4, CHCl3); other phys-
ical and spectroscopic properties identical with those
described above.
3.6.25. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(2-methoxyphenyl)propanoate (3R,aS)-23. Yield:
25
2.16 g, 86%; 97% de; ½aꢁD ¼ ꢀ13:7 (c 2.0, CHCl3) {lit.16
3.6.18. tert-Butyl (3R,aR)-3-(N-benzyl-N-a-methylbenzyl-
20
amino)-5-methylhexanoate (3R,aR)-19. Yield: 2.08 g, 95%;
for (3S,aR)-23, ½aꢁD ¼ þ15:0 (c 0.9, CHCl3); dH (500
25
96% de; ½aꢁD ¼ þ3:2 (c 1.6, CHCl3); other physical and
MHz, CDCl3) 1.18 (9H, s, CMe3), 1.25 (3H, d, J 6.4,
C(a)Me), 2.59 (1H, dd, J 13.5, 9.8, C(2)H2), 2.63 (1H, dd,
J 13.5, 6.3, C(2)H2), 3.73 (2H, AB q, J 15.0, PhCH2), 3.85
(3H, s, OMe), 4.08 (1H, q, J 6.4, C(a)H), 4.86 (1H, dd, J
9.8, 6.3, C(3)H), 6.85–7.44 (14H, m, Ar).
spectroscopic properties identical with those described
above.
3.6.19. tert-Butyl (3S,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)decanoate (3S,aS)-20. Yield: 2.29 g, 95%; 96% de;
25
22
½aꢁD ¼ ꢀ6:4 (c 2.9, CHCl3) {lit.23 for (3R,aR)-20, ½aꢁD
¼
3.6.26. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(2-methoxyphenyl)propanoate (3S,aR)-23. Yield:
þ5:3 (c 1.03, CHCl3)}; dH (400 MHz, CDCl3) 0.90 (3H, t,
J 7.8, Me), 1.19–1.35 (10H, m, CH2), 1.33 (3H, d, J 7.1,
C(a)Me), 1.41 (9H, s, CMe3), 1.42–1.65 (2H, m, C(4)H2),
1.87 (1H, dd, J 14.6, 9.4, C(2)H2), 1.96 (1H, dd, J 14.6,
3.4, C(2)H2), 3.25–3.34 (1H, m, C(3)H), 3.49 (1H, d, J
15.2, PhCH2), 3.66 (1H, d, J 15.2, PhCH2), 3.82 (1H, q, J
7.1, C(a)H), 7.22–7.47 (10H, m, Ar).
25
2.16 g, 88%; 95% de; ½aꢁD ¼ þ13:6 (c 2.6, CHCl3);
other physical and spectroscopic properties identical with
those described above.
3.6.27. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3,5-dimethoxyphenyl)propanoate
(3R,aS)-24.
Yield: 2.57 g, 98%; 96% de; ½aꢁD ¼ ꢀ1:6 (c 1.1, CHCl3);
max/cmꢀ1 (CHCl3) 1717; dH (500 MHz, CDCl3) 1.29
25
m
3.6.20. tert-Butyl (3R,aR)-3-(N-benzyl-N-a-methylbenzyl-
(9H, s, CMe3), 1.30 (3H, d, J 6.5 Hz, C(a)Me), 2.46 (1H,
dd, J 14.6, 10.0, C(2)H2), 2.53 (1H, dd, J 14.6, 5.1,
C(2)H2), 3.70 (2H, AB doublet, J 15.0, PhCH2), 3.80
(6H, s, OMe), 4.03 (1H, q, J 6.5, C(a)H), 4.36 (1H, dd, J
10.0, 5.1, C(3)H), 6.35–6.37 (1H, m, Ar(4)H), 6.60 (2H,
d, J 2.0, Ar(2)H and Ar(6)H), 7.20–7.49 (10H, m, Ar); dC
(100 MHz, CDCl3) 16.8, 28.0, 38.5, 51.0, 55.3, 57.4, 59.7,
80.3, 99.0, 106.5, 126.6, 126.9, 127.9, 128.1, 128.2, 128.2,
141.7, 144.3, 144.6, 160.6, 171.2; m/z (APCI+) 476
(100%); HRMS (ESI+) 476.2804 (C30H38NO4 requires
476.2801).
amino)decanoate (3R,aR)-20. Yield: 2.30 g, 96%; 97%
25
de; ½aꢁD ¼ þ6:4 (c 2.1, CHCl3); other physical and spectro-
scopic properties identical with those described above.
3.6.21. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(4-methoxyphenyl)propanoate (3R,aS)-21. Yield:
25
2.19 g, 89%; 96% de; ½aꢁD ¼ ꢀ1:8 (c 3.2, CHCl3) {lit.16
20
for (3S,aR)-21, ½aꢁD ¼ þ2:2 (c 1.0, CHCl3)}; dH
(400 MHz, CDCl3) 1.24 (9H, s, CMe3), 1.27 (3H, d, J 6.8,
C(a)Me), 2.47 (1H, dd, J 14.5, 10.1, C(2)H2), 2.55 (1H,
dd, J 14.5, 5.2, C(2)H2), 3.67 (2H, s, PhCH2), 3.81 (3H, s,
OMe), 4.01 (1H, J 6.8, C(a)H), 4.36 (1H, dd, J 10.1, 5.2,
C(3)H), 6.88 (2H, J 8.7, Ar(3)H and Ar(5)H), 7.13–7.43
(13H, m, Ar).
3.6.28. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3,5-dimethoxyphenyl)propanoate
(3S,aR)-24.
25
Yield: 2.51 g, 96%; 95% de; ½aꢁD ¼ þ1:8 (c 1.0, CHCl3);
other physical and spectroscopic properties identical with
those described above.
3.6.22. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(4-methoxyphenyl)propanoate (3S,aR)-21. Yield:
25
2.22 g, 91%; 96% de; ½aꢁD ¼ þ2:0 (c 2.1, CHCl3); other phys-
ical and spectroscopic properties identical with those
described above.
3.6.29. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3,4-dimethoxyphenyl)propanoate
(3R,aS)-25.
25
Yield: 2.29 g, 88%; 96% de; ½aꢁD ¼ ꢀ1:0 (c 1.0, CHCl3);
dH (500 MHz, CDCl3) 1.26 (9H, s, CMe3), 1.28 (3H, d, J
7.0, C(a)Me), 2.48 (1H, dd, J 14.6, 10.0, C(2)H2), 2.55
(1H, dd, J 14.6, 5.0, C(2)H2), 3.68 (2H, AB q, J 14.8,
PhCH2), 3.87 (3H, s, OMe), 3.91 (3H, s, OMe), 3.99 (1H,
q, J 7.0, C(a)H), 4.36 (1H, dd, J 10.0, 5.0, C(3)H), 6.79–
7.48 (13H, m, Ar).
3.6.23. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3-methoxyphenyl)propanoate (3R,aS)-22. Yield:
25
2.31 g, 94%; 96% de; ½aꢁD ¼ ꢀ3:2 (c 2.8, CHCl3); mmax/cmꢀ1
(CHCl3) 1716; dH (400 MHz, CDCl3) 1.27 (9H, s, CMe3),
1.29 (3H, d, J 6.8, C(a)Me), 2.49 (1H, dd, J 14.5, 9.9,
C(2)H2), 2.55 (1H, dd, J 14.5, 5.4, C(2)H2), 3.70 (2H, s,

S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
1561
3.6.30. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3,4-dimethoxyphenyl)propanoate (3S,aR)-25.
Yield: 2.48 g, 95%; 96% de; ½aꢁD ¼ þ1:0 (c 1.1, CHCl3);
other physical and spectroscopic properties identical with
those described above.
3.6.37. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(piperon-3-yl)propanoate (3R,aS)-29. Yield:
25
25
2.34 g, 93%; 96% de; ½aꢁD ¼ ꢀ6:3 (c 1.5, CHCl3); dH
(500 MHz, CDCl3) 1.27 (9H, s, CMe3), 1.29 (3H, d, J
6.9, C(a)Me), 2.41 (1H, dd, J 14.5, 10.4, C(2)H2), 2.51
(1H, dd, J 14.5, 4.5, C(2)H2), 3.67 (2H, s, PhCH2), 4.00
(1H, q, J 6.9, C(a)H), 4.31 (1H, dd, J 10.4, 4.5, C(3)H),
5.96 (2H, s, OCH2O), 6.76 (1H, d, J 8.0, Ar(5)H), 6.84
(1H, dd, J 8.0, 1.5, Ar(6)H), 7.97 (1H, d, J 1.5, Ar(2)H),
7.16–7.46 (10H, m, Ar).
3.6.31. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(2,4-dimethoxyphenyl)propanoate
(3R,aS)-26.
Yield: 2.20 g, 84%; 97% de; ½aꢁD ¼ ꢀ8:4 (c 0.8, CHCl3);
max/cmꢀ1 (CHCl3) 1718; dH (500 MHz, CDCl3) 1.19
25
m
(9H, s, CMe3), 1.24 (3H, d, J 6.5, C(a)Me), 2.57 (1H, dd,
J 14.0, 9.8, C(2)H2), 2.61 (1H, dd, J 14.0, 6.3, C(2)H2),
3.70 (2H, AB q, J 14.8, PhCH2), 3.81 (6H, s, OMe,
OMe), 4.06 (1H, q, J 6.5, C(a)H), 4.60 (1H, dd, J 9.8,
6.3, C(3)H), 6.46 (1H, s, Ar(3)H), 7.14–7.47 (12H, m,
Ar); dC (100 MHz, CDCl3) 14.6, 27.7, 40.0, 50.8, 53.7,
55.1, 55.3, 56.5, 79.7, 98.4, 103.8, 122.2, 126.2, 126.4,
127.7, 127.9, 128.0, 128.0, 129.7, 142.3, 144.7, 158.9,
159.8, 171.1; m/z (APCI+) 265 (100%); HRMS (ESI+)
476.2800 (C30H38NO4 requires 476.2801).
3.6.38. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(piperon-3-yl)propanoate
(3S,aR)-29. Yield:
25
2.29 g, 91%; 97% de; ½aꢁD ¼ þ5:9 (c 1.2, CHCl3);
other physical and spectroscopic properties identical with
those described above.
3.6.39. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3-benzyloxyphenyl)propanoate
(3R,aS)-30.
25
Yield: 2.58 g, 90%; 96% de; ½aꢁD ¼ ꢀ2:5 (c 1.5,
CHCl3); mmax/cmꢀ1 (CHCl3) 1717; dH (500 MHz, CDCl3)
1.26 (3H, d, J 6.8, C(a)Me), 1.27 (9H, s, CMe3), 2.49
(1H, dd, J 12.7, 9.7, C(2)H2), 2.55 (1H, dd, J 12.7, J 5.3,
C(2)H2), 3.68 (2H, s, PhCH2N), 4.00 (1H, q, J 6.8,
C(a)H), 4.39 (1H, dd, J 9.7, 5.3, C(3)H), 5.10 (2H, s,
PhCH2O), 6.90–7.54 (19H, m, Ar); dC (100 MHz, CDCl3)
16.6, 28.0, 38.6, 51.0, 57.2, 59.7, 70.0, 80.3, 113.7, 115.1,
120.9, 126.6, 126.9, 127.5, 128.0, 128.1, 128.2, 128.7,
129.2, 137.3, 141.8, 143.7, 144.2, 158.8, 171.2; m/z (APCI+)
522 (100%); HRMS (ESI+) 522.3002 (C35H40NO3 requires
522.3008).
3.6.32. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(2,4-dimethoxyphenyl)propanoate
(3S,aR)-26.
25
Yield: 2.07 g, 79%; 96% de; ½aꢁD ¼ þ8:6 (c 1.0, CHCl3);
other physical and spectroscopic properties identical with
those described above.
3.6.33. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-phenylpropanoate (3R,aS)-27. Yield: 3.47 g, 96%;
25
96% de; ½aꢁD ¼ ꢀ7:2 (c 1.0, CHCl3) {lit.16 for (3S,aR)-27,
20
½aꢁD ¼ þ3:9 (c 0.7, CHCl3)}; dH (500 MHz, CDCl3) 1.24
(9H, s, CMe3), 1.28 (3H, d, J 6.8, C(a)Me), 2.51 (1H, dd, J
13.4, 9.8, C(2)H2), 2.57 (1H, dd, J 13.4, 5.3, C(2)H2), 3.69
(2H, AB doublet, J 14.3, PhCH2), 4.01 (1H, q, J 6.8,
C(a)H), 4.42 (1H, dd, J 9.8, 5.3, C(3)H), 7.12–7.45 (15H,
m, Ar).
3.6.40. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3-benzyloxyphenyl)propanoate
(3S,aR)-30.
25
Yield: 2.50 g, 87%; 96% de; ½aꢁD ¼ þ2:7 (c 1.1, CHCl3);
other physical and spectroscopic properties identical with
those described above.
3.6.34. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
3.6.41. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-phenylpropanoate (3S,aR)-27. Yield: 3.60 g, 88%;
amino)-3-(4-benzyloxyphenyl)propanoate
(3R,aS)-31.
25
25
98% de; ½aꢁD ¼ þ7:3 (c 0.8, CHCl3); other physical and
Yield: 2.66 g, 93%; 96% de; ½aꢁD ¼ ꢀ2:1 (c 1.4,
CHCl3); mmax/cmꢀ1 (CHCl3) 1714; dH (500 MHz, CDCl3)
1.23 (9H, s, CMe3), 1.27 (3H, d, J 7.0, C(a)Me), 2.46
(1H, dd, J 14.5, 10.4, C(2)H2), 2.54 (1H, dd, J 14.5, 4.5,
C(2)H2), 3.67 (2H, s, PhCH2N), 4.00 (1H, q, J 7.0,
C(a)H), 4.36 (1H, dd, J 10.4, 4.5, C(3)H), 5.07 (2H, s,
PhCH2O), 6.95 (2H, d, J 8.5, Ar(3)H and Ar(5)H), 7.22–
7.52 (17H, m, Ar); dC (100 MHz, CDCl3) 16.5, 27.9, 38.8,
50.9, 57.2, 59.3, 70.0, 80.2, 114.5, 126.6, 126.9, 127.6,
127.9, 128.0, 128.2, 128.6, 129.4, 134.3, 137.2, 142.0,
144.4, 157.9, 171.3; m/z (APCI+) 522 (21%), 311 (100);
HRMS (ESI+) 522.3007 (C35H40NO3 requires 522.3008).
spectroscopic properties identical with those described
above.
3.6.35. tert-Butyl (3R,aS)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(4-biphenyl)propanoate (3R,aS)-28. Yield: 2.47 g,
25
91%; 96% de; ½aꢁD ¼ þ1:7 (c 1.2, CHCl3); mmax/cmꢀ1
(CHCl3) 1717; dH (500 MHz, CDCl3) 1.26 (9H, s, CMe3),
1.32 (3H, d, J 6.8, C(a)Me), 2.54 (1H, dd, J 15.0, 9.7,
C(2)H2), 2.58 (1H, dd, J 15.0, 5.0, C(2)H2), 3.73 (2H, s,
PhCH2), 4.05 (1H, q, J 6.8, C(a)H), 4.46 (1H, dd, J 9.7,
5.0, C(3)H), 7.22–7.71 (19H, m, Ar); dC (100 MHz, CDCl3)
16.6, 27.9, 38.6, 51.1, 57.3, 59.5, 80.3, 126.7, 126.9, 127.0,
127.1, 127.3, 128.0, 128.1, 128.3, 128.8, 128.8, 139.9, 141.0,
141.1, 141.8, 144.2, 171.3; m/z (APCI+) 492 (100%); HRMS
(ESI+) 492.2917 (C34H38NO2 requires 492.2903).
3.6.42. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(4-benzyloxyphenyl)propanoate
(3S,aR)-31.
25
Yield: 2.61 g, 90%; 96% de; ½aꢁD ¼ þ2:0 (c 1.0,
CHCl3); other physical and spectroscopic properties identi-
cal with those described above.
3.6.36. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(4-biphenyl)propanoate (3S,aR)-28. Yield: 2.40 g,
25
89%; 96% de; ½aꢁD ¼ ꢀ1:6 (c 1.1, CHCl3); other physical
and spectroscopic properties identical with those described
above.

1562
S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
22
CHCl3) {lit.16 for (3S,aR)-32, ½aꢁD ¼ ꢀ2:0 (c 1.4, CHCl3)};
dH (500 MHz, CDCl3) 1.18 (3H, d, J 6.8, C(a)Me), 1.24
(9H, s, CMe3), 2.43 (1H, dd, J 14.5, 10.1, C(2)H2), 2.51
(1H, dd, J 14.5, 5.0, C(2)H2), 3.62 (2H, s, PhCH2N), 3.93
(1H, q, J 6.8, C(a)H), 4.29 (1H, dd, J 10.1, 5.0, C(3)H),
5.18 (2H, s, PhCH2O), 5.21 (2H, s, PhCH2O), 6.97–7.61
(23H, m, Ar).
3.6.52. tert-Butyl (S)-3-amino-3-(4-methoxyphenyl)propan-
25
oate (S)-36. Yield: 1.05 g, 93%; ½aꢁD ¼ þ16:5 (c 1.4,
CHCl3); other physical and spectroscopic properties identi-
cal with those described above.
3.6.53. tert-Butyl (R)-3-amino-3-(3-methoxyphenyl)propan-
25
oate (R)-37. Yield: 0.97 g, 86%; ½aꢁD ¼ þ15:4 (c 1.5,
CHCl3); mmax/cmꢀ1 (film) 3381, 1724; dH (400 MHz,
CDCl3) 1.43 (9H, s, CMe3), 1.75 (2H, br s, NH2), 2.52–
2.62 (2H, m, C(2)H2), 3.80 (3H, s, OMe), 4.35 (1H, app
t, J 6.8, C(3)H), 6.78–6.82 (1H, m, Ar(4)H), 6.90–6.95
(1H, m, Ar(6)H), 6.93 (1H, s, Ar(2)H), 7.21–7.26 (1H, m,
Ar(5)H); dC (100 MHz, CDCl3) 28.1, 45.3, 52.7, 55.2,
80.7, 111.7, 112.8, 118.6, 129.5, 146.5, 159.8, 171.3; m/z
(APCI+) 252 (8%), 196 (100); HRMS (ESI+) 252.1594
(C14H22NO3 requires 252.1600).
3.6.44. tert-Butyl (3S,aR)-3-(N-benzyl-N-a-methylbenzyl-
amino)-3-(3,4-dibenzyloxyphenyl)propanoate
(3S,aR)-32.
25
Yield: 3.08 g, 89%; 96% de; ½aꢁD ¼ ꢀ2:0 (c 2.2, CHCl3);
other physical and spectroscopic properties identical with
those described above.
3.6.45. tert-Butyl (S)-3-aminobutanoate (S)-33. Yield:
25
0.52 g, 73%; ½aꢁD ¼ þ21:4 (c 0.6, CHCl3); dH
(200 MHz, CDCl3) 1.12 (3H, d, J 6.5, Me), 1.42 (9H, s,
CMe3), 2.28 (1H, dd, J 15.7, 8.0, C(2)H2), 2.32 (1H, dd,
J 15.7, 5.4, C(2)H2), 3.21–3.39 (1H, m, C(3)H).
3.6.54. tert-Butyl (S)-3-amino-3-(3-methoxyphenyl)propan-
25
oate (S)-37. Yield: 0.98 g, 87%; ½aꢁD ¼ ꢀ15:5 (c 1.4,
CHCl3); other physical and spectroscopic properties identi-
cal with those described above.
3.6.46. tert-Butyl (R)-3-aminobutanoate (R)-33. Yield:
25
0.60 g, 84%; ½aꢁD ¼ ꢀ22:2 (c 0.5, CHCl3); other
physical and spectroscopic properties identical with those
described above.
3.6.55. tert-Butyl (R)-3-amino-3-(2-methoxyphenyl)propan-
25
oate (R)-38. Yield: 1.02 g, 90%; ½aꢁD ¼ þ22:4 (c 2.4,
20
CHCl3) {lit.16 for (S)-38, ½aꢁD ¼ ꢀ20:0 (c 0.7, CHCl3)};
dH (400 MHz, CDCl3) 1.42 (9H, s, CMe3), 1.82 (2H, br s,
NH2), 2.61 (1H, dd, J 15.6, 9.0, C(2)H2), 2.71 (1H, dd, J
15.6, 4.9, C(2)H2), 3.86 (3H, s, OMe), 4.58 (1H, dd, J
9.0, 4.9, C(3)H), 6.85–6.96 (2H, m, Ar), 7.20–7.34 (2H,
m, Ar).
3.6.47. tert-Butyl (S)-3-amino-5-methylhexanoate (S)-34.
25
Yield: 0.81 g, 90%; ½aꢁD ¼ þ21:2 (c 2.9, CHCl3); mmax
/
cmꢀ1 (CHCl3) 3385, 1726; dH (200 MHz, CDCl3) 0.83
(3H, d, J 6.6, C(5)Me2), 0.85 (3H, d, J 6.6, C(5)Me2),
1.22–1.42 (2H, m, C(4)H2), 1.43 (9H, s, CMe3), 1.55–1.77
(1H, m, C(5)H), 2.34–2.55 (2H, m, C(2)H2), 3.28–3.41
(1H, m, C(3)H); dC (100 MHz, CDCl3) 22.0, 22.2,
24.6, 28.1, 44.3, 46.2, 46.7, 80.4, 172.0; m/z (ESI+) 202
(100%); HRMS (ESI+) 202.1813 (C11H24NO2 requires
202.1807).
3.6.56. tert-Butyl (S)-3-amino-3-(2-methoxyphenyl)propan-
25
oate (S)-38. Yield: 1.00 g, 88%; ½aꢁD ¼ ꢀ22:0 (c 2.4,
CHCl3); other physical and spectroscopic properties identi-
cal with those described above.
3.6.48. tert-Butyl (R)-3-amino-5-methylhexanoate (R)-34.
3.6.57. tert-Butyl (R)-3-amino-3-(3,5-dimethoxyphenyl)pro-
25
25
Yield: 0.82 g, 91%; ½aꢁD ¼ ꢀ21:1 (c 2.5, CHCl3); other
panoate (R)-39. Yield: 1.11 g, 88%; ½aꢁD ¼ þ12:3 (c 2.2,
CHCl3); mmax/cmꢀ1 (film) 3377, 1723; dH (400 MHz,
CDCl3) 1.42 (9H, s, CMe3), 1.71 (2H, br s, NH2), 2.48–
2.57 (2H, m, C(2)H2), 3.76 (6H, s, OMe), 4.29 (1H, dd, J
7.9, 5.8, C(3)H), 6.34 (1H, t, J 2.3, Ar(4)H), 6.51 (2H, d,
J 2.3, Ar(2)H and Ar(6)H); dC (100 MHz, CDCl3) 28.1,
45.3, 52.9, 55.3, 80.7, 99.3, 104.2, 147.4, 160.9, 171.3; m/z
(APCI+) 282 (19%), 226 (81), 209 (100); HRMS (ESI+)
282.1715 (C15H24NO4 requires 282.1705).
physical and spectroscopic properties identical with those
described above.
3.6.49. tert-Butyl (S)-3-aminodecanoate (S)-35. Yield:
25
0.91 g, 83%; ½aꢁD ¼ þ11:2 (c 1.4, CHCl3) {lit.23 for
25
(R)-35, ½aꢁD ¼ ꢀ6:5 (c 0.8, CHCl3)}; dH (200 MHz, CDCl3)
0.82 (3H, t. J 6.1, Me), 1.18–1.37 (12H, m, CH2), 1.40 (9H,
s, CMe3), 1.55 (2H, br s, NH2), 2.10 (1H, dd, J 16.0, 8.8,
C(2)H2), 2.30 (1H, dd, J 16.0, 4.1, C(2)H2), 3.04–3.18
(1H, m, C(3)H).
3.6.58. tert-Butyl (S)-3-amino-3-(3,5-dimethoxyphenyl)-
25
propanoate (S)-39. Yield: 1.12 g, 88%; ½aꢁD ¼ ꢀ11:7 (c
2.7, CHCl3); other physical and spectroscopic properties
identical with those described above.
3.6.50. tert-Butyl (R)-3-aminodecanoate (R)-35. Yield:
25
0.95 g, 87%; ½aꢁD ¼ ꢀ11:3 (c 1.3, CHCl3); other physical
and spectroscopic properties identical with those described
above.
3.6.59. tert-Butyl (R)-3-amino-3-(3,4-dimethoxyphenyl)pro-
25
panoate (R)-40. Yield: 1.10 g, 87%; ½aꢁD ¼ þ11:1 (c 2.5,
3.6.51. tert-Butyl (R)-3-amino-3-(4-methoxyphenyl)propan-
CHCl3); mmax/cmꢀ1 (film) 3374, 1723; dH (400 MHz,
CDCl3) 1.41 (9H, s, CMe3), 1.73 (2H, br s, NH2), 2.49–
2.59 (2H, m, C(2)H2), 3.84 (3H, s, OMe), 3.87 (3H, s,
OMe), 4.32 (1H, app t, J 6.8, C(3)H), 6.80 (1H, d, J 8.3,
Ar(6)H), 6.87 (1H, dd, J 8.3, 2.0, Ar(5)H), 6.91 (1H, d, J
2.0, Ar(2)H); dC (100 MHz, CDCl3) 28.0, 45.5, 52.4, 55.8,
55.9, 80.7, 109.4, 111.0, 118.3, 137.4, 148.1, 149.0, 171.4;
25
oate (R)-36. Yield: 1.02 g, 90%; ½aꢁD ¼ ꢀ16:4 (c 1.5,
20
CHCl3) {lit.16 ½aꢁD ¼ ꢀ14:1 (c 0.8, CHCl3)}; dH
(400 MHz, CDCl3) 1.42 (9H, s, CMe3), 1.73 (2H, br s,
NH2), 2.50–2.60 (2H, m, C(2)H2), 3.80 (3H, s, OMe),
4.34 (1H, dd, J 7.8, 6.0, C(3)H), 6.87 (2H, d, J 8.7,
Ar(3)H, Ar(5)H), 7.28 (2H, d, J 8.7, Ar(2)H, Ar(6)H).

S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
1563
m/z (APCI+) 265 (86%), 209 (100); HRMS (ESI+) 282.1711
(C15H24NO4 requires 282.1705).
(28), 193 (100); HRMS (ESI+) 266.1395 (C14H20NO4 re-
quires 266.1392).
3.6.60. tert-Butyl (S)-3-amino-3-(3,4-dimethoxyphenyl)pro-
3.6.68. tert-Butyl (S)-3-amino-3-(piperon-3-yl)propanoate
25
25
panoate (S)-40. Yield: 1.07 g, 85%; ½aꢁD ¼ ꢀ11:0 (c 2.5,
(S)-44. Yield: 1.04 g, 87%; ½aꢁD ¼ ꢀ13:0 (c 2.2, CHCl3);
CHCl3); other physical and spectroscopic properties identi-
cal with those described above.
other physical and spectroscopic properties identical with
those described above.
3.6.61. tert-Butyl (R)-3-amino-3-(2,4-dimethoxyphenyl)pro-
panoate (R)-41. Yield: 1.04 g, 82%; mp 83–84 ꢂC;
3.6.69. tert-Butyl (R)-3-amino-3-(3-hydroxyphenyl)propano-
ate (R)-45. Yield: 0.82 g, 77%; mp 111–113 ꢂC;
25
½aꢁD ¼ þ17:0 (c 2.2, CHCl3); mmax/cmꢀ1 (KBr) 2981,
25
½aꢁD ¼ þ7:8 (c 1.2, CHCl3); mmax/cmꢀ1 (KBr) 3278, 2973,
1732; dH (400 MHz, CDCl3) 1.41 (9H, s, CMe3), 1.88
(2H, br s, NH2), 2.58 (1H, dd, J 15.5, 8.7, C(2)H2), 2.66
(1H, dd, J 15.5, 5.0, C(2)H2), 3.78 (3H, s, OMe), 3.81
(3H, s, OMe), 4.49 (1H, dd, J 8.7, 5.0, C(3)H), 6.40–6.46
(2H, m, Ar), 7.18–7.22 (1H, m, Ar); dC (100 MHz, CDCl3)
28.1, 43.4, 48.0, 55.2, 55.3, 80.3, 98.7, 103.8, 125.3, 127.5,
157.8, 159.8, 171.8; m/z (APCI+) 282 (22%), 265 (100);
HRMS (ESI+) 282.1702 (C15H24NO4 requires 282.1705).
1726; dH (400 MHz, CDCl3) 1.42 (9H, s, CMe3), 2.54–
2.66 (2H, m, C(2)H2), 4.29 (1H, dd, J 8.3, 5.5, C(3)H),
6.68–6.81 (3H, m, Ar), 7.15 (1H, app t, J 7.8, Ar(5)H);
dC (100 MHz, CDCl3) 28.0, 44.2, 52.5, 81.1, 113.5, 115.1,
118.0, 129.8, 144.9, 157.1, 171.4; m/z (APCI+) 238 (4%),
182 (100); HRMS (ESI+) 238.1445 (C13H20NO3 requires
238.1443).
3.6.62. tert-Butyl (S)-3-amino-3-(2,4-dimethoxyphenyl)pro-
3.6.70. tert-Butyl (S)-3-amino-3-(3-hydroxyphenyl)propano-
25
25
panoate (S)-41. Yield: 1.07 g, 85%; ½aꢁD ¼ ꢀ16:9 (c 1.6,
ate (S)-45. Yield: 0.82 g, 77%; ½aꢁD ¼ ꢀ7:8 (c 1.3,
CHCl3); other physical and spectroscopic properties identi-
cal with those described above.
CHCl3); other physical and spectroscopic properties identi-
cal with those described above.
3.6.63. tert-Butyl (R)-3-amino-3-phenylpropanoate (R)-
3.6.71. tert-Butyl (R)-3-amino-3-(4-hydroxyphenyl)propano-
25
42. Yield: 0.89 g, 89%; ½aꢁD ¼ þ18:3 (c 2.5, CHCl3)
25
ate (R)-46. Yield: 0.87 g, 81%; mp 91–92 ꢂC; ½aꢁD
¼
20
{lit.16 for (S)-42 ½aꢁD ¼ ꢀ21:0 (c 1.0, CHCl3)}; dH
þ9:0 (c 1.1, CHCl3); mmax/cmꢀ1 (KBr) 3300, 2980, 1715;
dH (400 MHz, CDCl3) 1.42 (9H, s, CMe3), 2.58 (1H, dd,
J 15.9, 5.0, C(2)H2), 2.65 (1H, dd, J 15.9, 8.9, C(2)H2),
4.25 (1H, br s, OH), 4.31 (1H, dd, J 8.9, 5.0, C(3)H),
6.70 (2H, d, J 8.5, Ar(3)H and Ar(5)H), 7.16 (2H, d, J
8.5, Ar(2)H and Ar(6)H); dC (100 MHz, CDCl3) 28.0,
44.5, 52.1, 81.1, 115.8, 127.6, 134.6, 156.1, 171.6; m/z
(APCI+) 221 (14%), 165 (100); HRMS (ESI+) 238.1450
(C13H20NO3 requires 238.1443).
(400 MHz, CDCl3) 1.42 (9H, s, CMe3), 1.74 (2H, br s,
NH2), 2.58 (2H, app d, J 6.9, C(2)H2), 4.37 (1H, app t, J
6.9, C(3)H), 7.21–7.37 (5H, m, Ar).
3.6.64. tert-Butyl (S)-3-amino-3-phenylpropanoate (S)-
25
42. Yield: 0.91 g, 91%; ½aꢁD ¼ ꢀ17:9 (c 1.4, CHCl3); other
physical and spectroscopic properties identical with those
described above.
3.6.65.
tert-Butyl
(R)-3-amino-3-(4-biphenyl)propan-
3.6.72. tert-Butyl (S)-3-amino-3-(4-hydroxyphenyl)propano-
oate (R)-43. Yield: 1.09 g, 81%; mp 59–60 ꢂC;
25
25
½aꢁD ¼ þ11:8 (c 1.4, CHCl3); mmax/cmꢀ1 (KBr) 3326,
ate (S)-46. Yield: 0.88 g, 82%; ½aꢁD ¼ ꢀ8:5 (c 1.1,
CHCl3); other physical and spectroscopic properties identi-
cal with those described above.
1723; dH (400 MHz, CDCl3) 1.44 (9H, s, CMe3), 1.77
(2H, br s, NH2), 2.64 (2H, app d, J 6.9, C(2)H2), 4.44
(1H, app t, J 6.9, C(3)H), 7.31–7.52 (9H, m, Ar); dC
(100 MHz, CDCl3) 28.1, 45.3, 52.5, 80.8, 126.8, 127.2,
127.3, 127.3, 128.8, 140.2, 140.8, 143.8, 171.3; m/z (APCI+)
298 (3%), 281 (6), 225 (100); HRMS (ESI+) 298.1822
(C19H24NO2 requires 298.1807).
3.6.73. tert-Butyl (R)-3-amino-3-(3,4-dihydroxyphenyl)pro-
25
panoate (R)-47. Yield: 0.93 g, 82%; ½aꢁD ¼ ꢀ7:9 (c 0.3,
MeOH); dH (400 MHz, CD3OD) 1.38 (9H, s, CMe3), 1.32
(4H, br s, NH2, OH), 2.80 (1H, dd, J 16.0, 7.7, C(2)H2),
2.93 (1H, dd, J 16.0, 7.1, C(2)H2), 4.36–4.43 (1H, m,
C(3)H), 6.76 (1H, dd, J 8.2, 2.0, Ar(6)H), 6.81 (1H, dd, J
8.2, Ar(5)H), 6.88 (1H, d, J 2.0, Ar(2)H).
3.6.66. tert-Butyl (S)-3-amino-3-(4-biphenyl)propanoate (S)-
25
43. Yield: 1.02 g, 76%; ½aꢁD ¼ ꢀ11:3 (c 1.1, CHCl3); other
physical and spectroscopic properties identical with those
described above.
3.6.74. tert-Butyl (S)-3-amino-3-(3,4-dihydroxyphenyl)pro-
25
panoate (S)-47. Yield: 0.97 g, 85%; ½aꢁD ¼ þ8:0 (c 0.4,
3.6.67. tert-Butyl (R)-3-amino-3-(piperon-3-yl)propanoate
25
MeOH); other physical and spectroscopic properties iden-
tical with those described above.
(R)-44. Yield: 0.99 g, 83%; ½aꢁ ¼ þ13:2 (c 2.2, CHCl3);
m
max/cmꢀ1 (film) 3379, 1724; dHD (400 MHz, CDCl3) 1.41
(9H, s, CMe3), 1.68 (2H, br s, NH2), 2.51 (2H, app d, J
6.9, C(2)H2), 4.28 (1H, app t, J 6.9, C(3)H), 5.92 (2H, s,
OCH2O), 6.73 (1H, d, J 8.0, Ar(5)H), 6.79 (1H, dd, J 8.0,
1.7, Ar(6)H), 6.86 (1H, d, J 1.7, Ar(2)H); dC (100 MHz,
CDCl3) 28.1, 45.5, 52.6, 80.8, 101.0, 106.8, 108.1, 119.5,
138.9, 146.6, 147.7, 171.3; m/z (APCI+) 266 (4%), 249
3.6.75. (S)-3-Aminobutanoic acid (S)-48. Yield: 19 mg,
25
92%; mp 207–208 ꢂC (lit.24 mp 210 ꢂC); ½aꢁD ¼ þ32:0 (c
20
0.6, H2O) {lit.24 ½aꢁD ¼ þ34 (c 0.6, H2O)}; dH (400 MHz,
D2O) 1.18 (3H, d, J 6.5, Me), 2.25–2.40 (2H, m, C(2)H2),
3.39–3.50 (1H, m, C(3)H).

1564
S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
20
3.6.76. (R)-3-Aminobutanoic acid (R)-48. Yield: 20 mg,
½aꢁD ¼ þ15:5 (c 1.0, H2O)}; dH (400 MHz, D2O) 2.66
(1H, dd, J 16.2, 6.5, C(2)H2), 2.82 (1H, dd, J 16.2, 8.5,
C(2)H2), 3.78 (3H, s, OMe), 4.62 (1H, dd, J 8.5, 6.5,
C(3)H), 6.88–6.99 (2H, m, Ar), 7.15–7.32 (2H, m, Ar).
25
97%; ½aꢁD ¼ ꢀ32:4 (c 0.6, H2O); other physical and spec-
troscopic properties identical with those described above.
3.6.77. (S)-3-Amino-5-methylhexanoic acid (S)-49. Yield:
19 mg, 92%; mp 222–224 ꢂC (lit.25 mp 227 ꢂC);
3.6.86. (S)-3-Amino-3-(2-methoxyphenyl)propanoic acid (S)-
25
24
½aꢁD ¼ þ27:8 (c 0.6, H2O) {lit.25 ½aꢁD þ 27 (c 1, H2O)};
dH (400 MHz, D2O) 0.78 (3H, d, J 6.4, C(5)Me2), 0.80
(3H, d, J 6.4, C(5)Me2), 1.32–1.47 (2H, m, C(4)H2), 1.50–
1.64 (1H, m, C(5)H), 2.28 (1H, dd, J 16.6, 8.1, C(2)H2),
2.44 (1H, dd, J 16.6, 4.8, C(2)H2), 3.40–3.48 (1H, m,
C(3)H).
25
53. Yield: 38 mg, 98%; ½aꢁD ¼ þ18:8 (c 0.6, H2O); other
physical and spectroscopic properties identical with those
described above.
3.6.87. (R)-3-Amino-3-(3,5-dimethoxyphenyl)propanoic acid
25
(R)-54. Yield: 38 mg, 95%; mp 202–203 ꢂC; ½aꢁD ¼ ꢀ0:8
(c 0.7, H2O);
m
max/cmꢀ1 (KBr) 3129br, 1638; dH
3.6.78. (R)-3-Amino-5-methylhexanoic acid (R)-49. Yield:
(400 MHz, D2O) 2.62 (1H, dd, J 16.4, 6.1, C(2)H2), 2.72
(1H, dd, J 16.4, 8.4, C(2)H2), 3.67 (6H, s, OMe), 4.42
(1H, dd, J 8.4, 6.1, C(3)H), 6.42 (1H, t, J 2.2, Ar(4)H),
6.51 (1H, d, J 2.2, Ar(2)H and Ar(6)H); dC (100 MHz,
D2O) 40.6, 53.0, 55.8, 101.1, 105.7, 139.0, 161.0, 177.3;
m/z (APCI+) 226 (5%), 209 (100); HRMS (ESIꢀ)
224.0917 (C11H14NO4 requires 224.0923).
25
20 mg, 97%; ½aꢁD ¼ ꢀ27:9 (c 0.7, H2O); other physical
and spectroscopic properties identical with those described
above.
3.6.79. (S)-3-Aminodecanoic acid (S)-50. Yield: 37 mg,
25
96%; mp 215–216 ꢂC (lit.23 mp 202–204 ꢂC); ½aꢁD ¼ þ2:5
(c 0.1, H2O); dH (400 MHz, D2O) 0.73 (3H, t, J 7.0, Me),
1.08–1.29 (10H, m, CH2), 1.46–1.53 (2H, m, C(4)H2),
2.30 (1H, dd, J 16.7, 8.3, C(2)H2), 2.44 (1H, dd, J 16.7,
4.9, C(2)H2), 3.30–3.39 (1H, m, C(3)H).
3.6.88. (S)-3-Amino-3-(3,5-dimethoxyphenyl)propanoic acid
25
(S)-54. Yield: 39 mg, 97%; ½aꢁD ¼ þ0:7 (c 0.8, H2O);
other physical and spectroscopic properties identical with
those described above.
3.6.80. (R)-3-Aminodecanoic acid (R)-50. Yield: 36 mg,
25
94%; ½aꢁD ¼ ꢀ2:4 (c 0.2, H2O); other physical and spectro-
scopic properties identical with those described above.
3.6.89. (R)-3-Amino-3-(3,4-dimethoxyphenyl)propanoic acid
25
(R)-55. Yield: 39 mg, 97%; mp 216–218 ꢂC; ½aꢁD ¼ ꢀ0:9
3.6.81. (R)-3-Amino-3-(4-methoxyphenyl)propanoic acid
(R)-51. Yield: 41 mg, 99%; mp 229–230 ꢂC (lit.8 238–
(c 0.7, H2O); dH (400 MHz, D2O) 2.64 (1H, dd, J 16.3,
6.5, C(2)H2), 2.76 (1H, dd, J 16.3, 8.2, C(2)H2), 3.68 (3H,
s, OMe), 3.72 (3H, s, OMe), 4.44 (1H, dd, J 8.2, 6.5,
C(3)H), 6.87–9.97 (3H, m, Ar).
25
340 ꢂC); ½aꢁD ¼ þ0:6 (c 0.1, H2O) {lit.16 for (S)-51,
20
½aꢁD ¼ ꢀ1:4 (c 0.2, H2O); dH (400 MHz, D2O) 2.71 (1H,
dd, J 16.2, 6.8, C(2)H2), 2.82 (1H, dd, J 16.2, 8.0,
C(2)H2), 3.75 (3H, s, OMe), 4.53 (1H, dd, J 8.0, 6.8,
C(3)H), 6.97 (2H, d, J 8.8, Ar(3)H, Ar(5)H), 7.32 (2H, d,
J 8.8, Ar(2)H, Ar(6)H).
3.6.90. (S)-3-Amino-3-(3,4-dimethoxyphenyl)propanoic acid
25
(S)-55. Yield: 39 mg, 97%; ½aꢁD ¼ þ0:9 (c 0.7, H2O);
other physical and spectroscopic properties identical with
those described above.
3.6.82. (S)-3-Amino-3-(4-methoxyphenyl)propanoic acid (S)-
25
51. Yield: 41 mg, 99%; ½aꢁD ¼ ꢀ0:8 (c 0.2, H2O); other
3.6.91. (R)-3-Amino-3-(2,4-dimethoxyphenyl)propanoic acid
physical and spectroscopic properties identical with those
described above.
25
(R)-56. Yield: 40 mg, 99%; mp 215–217 ꢂC; ½aꢁD ¼ ꢀ5:1
(c 0.8, H2O); mmax/cmꢀ1 (KBr) 2947, 1616; dH (400 MHz,
D2O) 2.66 (1H, dd, J 16.3, 6.4, C(2)H2), 2.84 (1H, dd, J
16.3, 8.5, C(2)H2), 3.71 (3H, s, OMe), 3.77 (3H, s, OMe),
4.59 (1H, dd, J 8.5, 6.4, C(3)H), 6.49 (1H, dd, J 8.5, 2.4,
Ar(5)H), 6.54 (1H, d, J 2.4, Ar(2)H), 7.13 (1H, d, J 8.5,
Ar(6)H); dC (100 MHz, D2O) 38.9, 49.7, 55.8, 99.2, 105.6,
116.4, 129.7, 158.6, 161.4, 178.0; m/z (ESIꢀ) 224 (100%);
HRMS (ESIꢀ) 224.0922 (C11H14NO4 requires 224.0923).
3.6.83. (R)-3-Amino-3-(3-methoxyphenyl)propanoic acid
25
(R)-52. Yield: 41 mg, 99%; mp 215–216 ꢂC; ½aꢁD ¼ þ3:8
(c 0.9, H2O); mmax/cmꢀ1 (KBr) 2981, 1606; dH (400 MHz,
D2O) 2.70 (1H, dd, J 16.3. 6.4, C(2)H2), 2.80 (1H, dd, J
16.3, 8.2, C(2)H2), 3.75 (3H, s, OMe), 4.53 (1H, dd, J
8.2, 6.4, C(3)H), 6.92–7.00 (3H, m, Ar), 7.29–7.37 (1H,
m, Ar(5)H); dC (100 MHz, D2O) 53.0, 55.8, 55.8, 113.0,
115.1, 119.8, 131.0, 138.1, 159.7, 177.5; m/z (ESIꢀ) 194
(100%); HRMS (ESIꢀ) 194.0814 (C10H12NO3 requires
194.0817).
3.6.92. (S)-3-Amino-3-(2,4-dimethoxyphenyl)propanoic acid
25
(S)-56. Yield: 41 mg, 99%; ½aꢁD ¼ þ5:3 (c 0.6, H2O);
other physical and spectroscopic properties identical with
those described above.
3.6.84. (S)-3-Amino-3-(3-methoxyphenyl)propanoic acid (S)-
25
52. Yield: 38 mg, 94%; ½aꢁD ¼ ꢀ3:9 (c 1.0, H2O); other
physical and spectroscopic properties identical with those
described above.
3.6.93. (R)-3-Amino-3-phenylpropanoic acid (R)-57. Yield:
36 mg, 96%; mp 227–229 ꢂC (lit.16 mp 227–229 ꢂC);
25
22
½aꢁD ¼ þ6:8 (c 0.9, H2O) {lit.26 for (S)-57, ½aꢁD ¼ ꢀ6:3 (c
0.8, H2O)}; dH (200 MHz, D2O) 2.70 (1H, dd, J 15.9, 7.0,
C(2)H2), 2.86 (1H, dd, J 15.9, 7.5, C(2)H2), 4.48–4.57
(1H, m, C(3)H), 7.28–7.43 (5H, m, Ar).
3.6.85. (R)-3-Amino-3-(2-methoxyphenyl)propanoic acid
(R)-53. Yield: 37 mg, 95%; mp 208–210 ꢂC (lit.16 mp
25
208–210 ꢂC); ½aꢁD ¼ ꢀ18:5 (c 0.5, H2O) {lit.16 for (S)-53,

S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
1565
3.6.94. (S)-3-Amino-3-phenylpropanoic acid (S)-57. Yield:
3.6.103. (R)-3-Amino-3-(3,4-hydroxyphenyl)propanoic acid
25
25
36 mg, 96%; ½aꢁD ¼ ꢀ6:3 (c 0.6, H2O); other physical and
hydrochloride (R)-62ÆHCl. Yield: 37 mg, 94%; ½aꢁD ¼
spectroscopic properties identical with those described
above.
ꢀ4:6 (c 0.5, MeOH); dH (400 MHz, CD3OD) 2.93 (1H,
dd, J 17.1, 6.2, C(2)H2), 3.02 (1H, dd, J 17.1, 8.9,
C(2)H2), 4.43–4.52 (1H, m, C(3)H), 6.76–6.92 (3H, m, Ar).
3.6.95. (R)-3-Amino-3-(4-biphenyl)propanoic acid hydro-
chloride (R)-58ÆHCl. Yield: 41 mg, 99%; mp 239–240 ꢂC;
3.6.104. (S)-3-Amino-3-(3,4-hydroxyphenyl)propanoic acid
25
25
½aꢁD ¼ ꢀ3:3 (c 0.8, MeOH); mmax/cmꢀ1 (KBr) 3011 br,
hydrochloride (S)-62ÆHCl. Yield: 37 mg, 94%; ½aꢁD ¼ þ4:8
(c 0.2, MeOH); other physical and spectroscopic properties
1728; dH (400 MHz, CD3OD) 3.05 (1H, dd, J 17.1, 6.4,
C(2)H2), 3.17 (1H, dd, J 17.1, 7.6, C(2)H2), 4.77 (1H, dd,
J 7.6, 6.4, C(3)H), 7.34–7.75 (9H, m, Ar); dC (100 MHz,
CD3OD) 38.1, 51.9, 127.0, 127.8, 127.9, 127.9, 129.0,
135.4, 140.3, 142.6, 177.5; m/z (ESIꢀ) 240 (100%); HRMS
(ESIꢀ) 240.1020 (C15H14NO2 requires 240.1025).
identical with those described above.
Acknowledgements
The authors would like to thank the BBSRC and Yama-
nouchi, UK, for an industrial CASE studentship
(A.J.R.), and New College, Oxford, for a Junior Research
Fellowship (A.D.S.).
3.6.96. (S)-3-Amino-3-(4-biphenyl)propanoic acid hydrochlo-
25
ride (S)-58ÆHCl. Yield: 41 mg, 99%; ½aꢁD ¼ þ3:3 (c 0.8,
MeOH); other physical and spectroscopic properties iden-
tical with those described above.
References
3.6.97. (R)-3-Amino-3-(piperon-3-yl)propanoic acid (R)-
25
59. Yield: 38 mg, 96%; mp 219–220 ꢂC; ½aꢁD ¼ ꢀ42:0 (c
1. For selected examples of asymmetric parallel synthesis, see:
Paterson, I.; Donghi, M.; Gerlach, K. Angew. Chem., Int. Ed.
2000, 39, 3315; Stavenger, R. A.; Schreiber, S. L. Angew.
Chem., Int. Ed. 2001, 40, 3417; Myers, A. G.; Lanman, B. A.
J. Am. Chem. Soc. 2002, 124, 12969; Kubota, H.; Lim, J.;
Depew, K. M.; Schreiber, S. L. Chem. Biol. 2002, 9, 265;
Volonterio, A.; Chiva, G.; Fustero, S.; Piera, J.; Sanchez
Rosello, M.; Sani, M.; Zanda, M. Tetrahedron Lett. 2003, 44,
7019; Lo, M. M. C.; Neumann, C. S.; Nagayama, S.;
Perlstein, E. O.; Schreiber, S. L. J. Am. Chem. Soc. 2004,
126, 16077; Hutchinson, P. C.; Heightman, T. D.; Proctor, D.
0.3, H2O); mmax/cmꢀ1 (KBr) 2890 br, 1653; dH (400 MHz,
D2O) 2.65 (1H, dd, J 16.2, 6.9, C(2)H2), 2.76 (1H, dd, J
16.2, 8.2, C(2)H2), 4.44 (1H, dd, J 8.2, 6.9, C(3)H), 5.86
(2H, s, OCH2O), 6.78–6.89 (3H, m, Ar); dC (100 MHz,
D2O) 40.7, 52.9, 101.8, 107.6, 109.2, 121.5, 130.0, 148.1,
148.1, 177.4; m/z (ESI+) 208 (100%); HRMS (ESIꢀ)
208.0613 (C10H10NO4 requires 208.0610).
3.6.98. (S)-3-Amino-3-(piperon-3-yl)propanoic acid (S)-
25
59. Yield: 38 mg, 96%; ½aꢁD ¼ þ42:4 (c 0.3, H2O); other
J. J. Org. Chem. 2004, 69, 790; Bulow, A.; Sinning, S.;
Wiborg, O.; Bols, M. J. Comb. Chem. 2004, 6, 509; Krishnan,
S.; Schreiber, S. L. Org. Lett. 2004, 6, 4021; Delpiccolo, C. M.
¨
physical and spectroscopic properties identical with those
described above.
´
L.; Mendez, L.; Fraga, M. A.; Mata, E. G. J. Comb. Chem.
2005, 7, 331; Lei, X.; Zaarur, N.; Sherman, M. Y.; Porco, J.
A., Jr. J. Org. Chem. 2005, 70, 6474; Timmer, M. S. M.;
Risseeuw, M. D. P.; Verdoes, M.; Filippov, D. V.; Plaisier, J.
R.; van der Marel, G. A.; Overcleeft, H. S.; van Boom, J. H.
Tetrahedron: Asymmetry 2005, 16, 177; Hotha, S.; Tripathi,
A. J. Comb. Chem. 2005, 7, 968; Bauer, J.; Brandenburg, K.;
Za¨ringer, U.; Rademann, J. Chem. Eur. J. 2006, 12, 7116;
Dorbec, M.; Florent, J. C.; Monneret, C.; Rager, M. N.;
Bertounesque, E. Tetrahedron 2006, 62, 11766; Miao, H.;
3.6.99. (R)-3-Amino-3-(3-hydroxyphenyl)propanoic acid
25
(R)-60. Yield: 38 mg, 99%; 233–234 ꢂC; ½aꢁD ¼ þ7:2
(c 0.5, H2O); mmax/cmꢀ1 (KBr) 3021, 1568; dH (200 MHz,
D2O) 2.68 (1H, dd, J 16.3, 6.5, C(2)H2), 2.77 (1H, dd, J
16.3, 8.1, C(2)H2), 4.47 (1H, dd, J 8.1, 6.5, C(3)H), 6.81–
6.98 (3H, m, Ar), 7.21–7.34 (1H, m, Ar(5)H); dC
(100 MHz, D2O) 40.7, 52.9, 114.2, 116.5, 119.2, 131.1,
138.2, 156.3, 177.5; m/z (ESIꢀ) 180 (100%); HRMS (ESIꢀ)
180.0658 (C9H10NO3 requires 180.0661).
Tallarico, J. A.; Hayakawa, H.; Munger, K.; Duffner, J. L.;
¨
Koehler, A. N.; Schreiber, S. L.; Lewis, T. A. J. Comb. Chem.
2007, 9, 245; Franz, A. K.; Dreyfuss, P. D.; Schreiber, S. L. J.
Am. Chem. Soc. 2007, 129, 1020.
3.6.100. (S)-3-Amino-3-(3-hydroxyphenyl)propanoic acid
25
(S)-60. Yield: 39 mg, 99%; ½aꢁD ¼ ꢀ7:2 (c 0.3,
2. Tamariz, J. In Enantioselective Synthesis of b-Amino Acids;
Juaristi, E., Ed.; Wiley: New York, 1996; p 45.
3. Wani, M. C.; Taylor, H. L.; Wall, M. E.; Coggon, P.;
McPhail, A. T. J. Am. Chem. Soc. 1971, 93, 2325.
H2O); other physical and spectroscopic properties identical
with those described above.
3.6.101. (R)-3-Amino-3-(4-hydroxyphenyl)propanoic acid
4. Roncari, G.; Kurylo-Borowska, Z.; Craig, L. C. Biochemistry
1966, 5, 2153; Hettinger, T. P.; Craig, C. C. Biochemistry
1968, 7, 4147; Parry, R. J.; Kurylo-Borowska, Z. J. Am.
Chem. Soc. 1980, 102, 836; Gould, S. J.; Thiruvengadam, T.
K. J. Am. Chem. Soc. 1981, 103, 6752.
5. For reviews see: Seebach, D.; Matthews, J. L. Chem.
Commun. 1997, 2015; Gellman, S. H. Acc. Chem. Res. 1998,
31, 173; For selected other papers see: Dado, G. P.; Gellman,
S. H. J. Am. Chem. Soc. 1994, 116, 1054; Appella, D. H.;
Christianson, L. A.; Klein, D. A.; Powell, D. R.; Huang, X.;
Barchi, J. J.; Gellman, S. H. Nature 1997, 387, 381; Seebach,
D.; Abele, S.; Gademann, K.; Guichard, G.; Hintermann, T.;
25
(R)-61. Yield: 36 mg, 94%; mp 220–221 ꢂC; ½aꢁD ¼ ꢀ6:0
(c 0.6, H2O); dH (400 MHz, D2O) 2.66 (1H, dd, J 16.2,
6.6, C(2)H2), 2.78 (1H, dd, J 16.2, 8.2, C(2)H2), 4.41–4.48
(1H, m, C(3)H), 6.81 (2H, d, J 8.7, Ar(3)H and Ar(5)H),
7.22 (2H, d, J 8.7, Ar(2)H and Ar(6)H).
3.6.102. (S)-3-Amino-3-(4-hydroxyphenyl)propanoic acid
25
(S)-61. Yield: 37 mg, 98%; ½aꢁD ¼ þ5:9 (c 0.5,
H2O); other physical and spectroscopic properties identical
with those described above.

1566
S. G. Davies et al. / Tetrahedron: Asymmetry 18 (2007) 1554–1566
Jaun, B.; Matthews, J. L.; Schrieber, J.; Oberer, L.; Hommel,
U.; Widmer, H. Helv. Chim. Acta 1998, 81, 932.
1999, 335; Juaristi, E.; Balderas, M.; Ramirez-Quiros, X.
Tetrahedron: Asymmetry 1998, 9, 3881.
6. For a review see: Liu, M.; Sibi, M. P. Tetrahedron 2002, 58,
7991.
7. Plucinska, K.; Liberek, B. Tetrahedron 1987, 43, 3509;
Grieco, P. A.; Hon, Y. S.; Pedrez-Medrano, A. J. Am. Chem.
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