982
T. Chanda et al. / Tetrahedron Letters 56 (2015) 981–985
Previous reports:
Metal catalytic
OH
R1
OH
O
or
X
R2
Br/Cl
R1
Enzymetic
Pd
R2
R
+
Oxidative
desymmetryzation
R3O
HO
OH
OH
O
OH
O
Ref. 2a
Ref. 3
OTBS
OH
OTBS
O
OH
O
CHO
CHO
CHO
O
O
OH
X
Ref. 2b
R1
COR
OH
O
This work:
O
O
R
HO
R
X
X
H2N
X
O
NH
H
NH
R
Pb(OAc)4
THF, rt
N
C
R1
OH
R1
R1
EtOH, reflux
O
OH
A
2
R1
1
O
B
D
Scheme 1. Comparison between reported methods and this work.
Table 1
developed [3+2] annulation of ortho-trimethylsilyl substituted
chromium benzaldehyde complexes with lithium ester enolates
for the synthesis of spirocyclic indanone ring systems.4
Optimization studies for the intramolecular aldolization of 1a
O
HO
H
Br
Br
Directed toward construction of useful synthetic building
blocks, recent efforts have been made to replace transition-metal
catalysts with bio-compatible counterparts.5 Natural amino acids
and their derivatives have been serving as organocatalyst in intra-
molecular-aldolization reactions for the construction of C–C bonds
since the first report of proline-catalyzed Hajos–Parrish–Eder–
Sauer–Wiechert reaction in the early 1970.6 Recent interest has
been developed in the catalytic application of environmentally
accepted metal salts of naturally abundant amino acids that may
show dual behavior as organo-base as well as Brønsted acid in
aldol reactions.7 Despite having superior catalytic functionality
application of alkali metal salt of amino acids can rarely be found
in the literature.
H
H
Catalyst
solvent (3 mL), rt
Me
Me
O
O
2a
1a
(1 mmol)
Entry
Catalyst
mmol
Solvent
Time (h)
Yield (%)
trans/cis
1
2
3
4
5
6
7
8
E
F
G
H
I
I
J
K
L
L
L
L
0.30
0.30
0.30
0.30
0.30
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
0.10
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
3.5
12
24
48
2.5
4.0
3
2
2
6
6
12
3
3
12
12
12
95
92
85
90
94
82
88
96
97
69
78
nr
82
55
nr
nr
nr
9:10
4:1
4:1
8:1
4:1
4:1
6:1
9:1
9:1
6:1
6:1
—
4:1
4:1
—
—
—
9
Herein, we disclose
a straightforward approach for the
10
11
12
13
14
15
16
17
DME
H2O
construction of alkyl/aryl/hetaryl substituted and spirocyclic 3-
hydroxyindanone frameworks via an amino acid salt catalyzed
trans-selective intramolecular-aldolization of ortho-diacylbenz-
enes, synthesized from corresponding ortho-hydroxyacylbenzenes
by the modified method described by Kotali et al. (Scheme 1, for
details see Supporting information).8 However, most of the avail-
able protocols to generate 3-hydroxyindanone frameworks make
use of either metal catalyst or preformed indane nucleus. In
addition to that the initial substrates used in most of the reported
reactions are also hardly available. Whereas, in our protocol car-
boxylic acid derivatives and substituted ortho-acyl phenols are
the initial substrates, which are the most primitive feedstock to
be used to generate libraries of new molecules.
K2CO3
NaOH
InCl3
BF3ꢀOEt2
DMSO
DMSO
DMSO
DMSO
DMSO
CH3CO2H
nr = no reaction.
Ph
CO2Et
CO2Bu-tert
CO2H
N
N
Ph
N
H
F
N
H
G
H
OH
H
E
H
CO2K
CO2K
Ph
Ph
CO2K
Results and discussion
N
H
I
N
H
J
NH2
NH2
K
L
Initially, we started our investigation with 1.0 mmol of 5-
bromo-2-propionylbenzaldehyde 1a as model substrate, DMSO as
a solvent (3 mL), and (S)-proline E (0.3 mmol) as a catalyst at room
temperature (Table 1, entry 1).9 The reaction proceeded smoothly
and completed within 4 h to afford the desired product 2a in 95%
yield (ee = 0), but the ratio of trans- to cis-diastereomer of 2a was
found to be 9:10. As proline was found to be inefficient to generate
stereoselectivity in the above intramolecular aldolization, we
hypothesized that modification of the carboxylic acid group of
(S)-proline into ester might unlock new reactivity (see Scheme 2).10
Therefore, ethyl and tert-butyl esters of (S)-proline F and G, respec-
tively, were separately used as catalyst in the model reaction.
Interestingly, a high trans-selectivity (trans/cis = 4:1) was achieved.
However, enantioselectivity remained absent in both the cases
(Table 1, entries 2 and 3). Next, (S)-diphenyl(pyrrolidin-2-yl)
Scheme 2. List of organo-bases used in intramolecular aldolization of 1a.
methanol H was used as catalyst. Though, an improvement in
trans-selectivity (trans/cis = 8:1) was observed, but still follows
the same course of enantioselectivity (ee = 0) and the rate of the
reaction is too sluggish (Table 1, entry 4). The result remained
almost same when pyrrolidine I (0.3 mmol) was used as catalyst
in the above reaction (Table 1, entry 5).
The above disappointing results regarding the lack of enantiose-
lectivity and low trans-selectivity in the intramolecular aldoliza-
tion reaction prompted us to switch over new alternative
catalysts (Scheme 2). In this regard, we prepared potassium salt
of (S)-proline J and 10 mol % of it was used as catalyst in the model