696
J . Org. Chem. 1999, 64, 696-697
Ta ble 1. Va r ia tion of Ca ta lyst a n d Solven t in Ad d ition s
of Allen ylin d iu m Rea gen ts Der ived F r om Mesyla te (R)-1
to Cycloh exa n eca r boxa ld eh yd e
F or m a tion of Tr a n sien t Ch ir a l Allen ylin d iu m
Rea gen ts fr om En a n tioen r ich ed P r op a r gylic
Mesyla tes th r ou gh Oxid a tive
Tr a n sm eta la tion . Ap p lica tion s to th e
Syn th esis of En a n tioen r ich ed
Hom op r op a r gylic Alcoh ols
J ames A. Marshall* and Charsetta M. Grant
Department of Chemistry, University of Virginia,
Charlottesville, Virginia 22901
catalyst
none
Pd(dppf)Cl2
Pd(dppf)Cl2
Pd(dppf)Cl2
Pd(dppf)Cl2
yield, %
anti:syna
ee, %a
66
76
63
80
66
75
96:4
95:5
87:13
91:9
93:7
95:5
0
95
87
90
91
91
Received November 12, 1998
b
c
d
Reactions of allenylmetal compounds with aldehydes and
ketones have been the subject of a number of investigations
over the past half-century.1 Early work addressed the issues
of regiochemistry (propargyl vs allenyl) and relative stereo-
chemistry (syn and anti). In recent years attention has been
directed to the synthesis and utility of chiral nonracemic
allenylmetal compounds as reagents for enantioselective
synthesis.2,3 We have described a simple, direct route to
chiral allenylstannanes through SN2′ displacement of enan-
tioenriched secondary propargylic mesylates with Bu3SnCu
reagents.2 Lewis-acid promoted additions of these reagents
to aldehydes lead to syn homopropargylic alcohols whereas
anti adducts are obtained through transmetalation of the
chiral allenic Bu3Sn intermediates with SnCl4, BuSnCl3, or
InX3 compounds, followed by addition of the aldehyde (eq
1).4 These reactions are capable of outstanding levels of
enantio- and diastereoselectivity, especially in additions
involving R-branched aliphatic aldehydes. However, the
inevitable formation of toxic Bu3SnX byproducts presents a
significant obstacle to their widespread usage.
Pd(OAc)2‚PPh3
a
b
Ratios and ee values were determined by GC analysis. 3:1
THF-DMPU as the solvent. c 1:1 THF-DMPU as the solvent.d 20:
1 THF-HMPA as the solvent.
stirred suspension of indium powder in various solvents
afforded the homopropargylic alcohol 4a . Of the solvents
examined (EtOH, EtOH-H2O, THF, THF-H2O, DMF,
DMF-H2O, DMA, DMA-H2O), the combination of DMA and
5-10% H2O gave the best overall results.7 However, while
the yield and diastereoselectivity of the addition were
excellent, the enantioselectivity was poor (eq 2). This result
could reflect partial racemization during metalation and/or
the configurational lability of the intermediate allenylindium
reagent.3
Attempted formation of an allenylindium intermediate
from the propargyl mesylate (R)-1 and indium powder in
the presence of aldehyde was not successful. The aldehyde
was recovered. However, when InI was employed, metalation
of the mesylate took place, and the adduct 4a was produced
in 66% yield as a 95:5 mixture of anti and syn isomers (Table
1). Unfortunately, the adduct was racemic. We then explored
the possible transmetalation of an allenylpalladium inter-
mediate with InI, a process that we perceived to be concep-
tually related to a Pd-Zn metathesis of recent interest for
the in situ formation of chiral allenylzinc reagents.8,9 In fact,
the reaction proceeded as planned. Adduct 4a (95:5 anti:
syn) of 95% ee was obtained in 76% yield from mesylate (R)-1
and InI in the presence of 5 mol % Pd(dppf)Cl2 as the catalyst
The low toxicity of organoindium compounds stimulated
our interest in the use of allenylindium reagents for these
additions.5 As noted above, the indium reagents have pre-
viously been prepared in nonracemic form from allenyltin
intermediates. We now describe alternative routes that do
not involve tin compounds.
Propargylic mesylates have been shown to undergo ef-
ficient anti SN2′ displacement with LiX/CuX reagents to
afford allenic halides.6 We envisioned an in situ preparation
of chiral allenylindium reagents from these halides by
reaction with indium metal. As a test of concept we prepared
the known allenyl iodide 26 from mesylate (R)-1 of >95%
ee. Sequential addition of the iodide and aldehyde to a
(1) Yamamoto, H. Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon Press: Oxford, 1991; Vol. 2, Chapter 1.3.
(2) Marshall, J . A. Chem. Rev. 1996, 96, 31.
(3) Marshall, J . A.; Palovich, M. R. J . Org. Chem. 1997, 62, 6001.
Marshall, J . A.; Lu, Z.-H.; J ohns, B. A. J . Org. Chem. 1998, 63, 817.
Marshall, J . A.; J ohns, B. A.; J . Org. Chem. 1998, 63,
(4) Cf. Marshall, J . A.; Perkins, J . F.; Wolf, M. A.; J . Org. Chem. 1995,
60, 5556.
(7) DMA ) N,N-dimethylacetamide, DMPU ) N,N-dimethylpropylene-
urea, DPS ) diphenyl-tert-butylsilyl.
(8) Marshall, J . A.; Adams, N. D. J . Org. Chem. 1998, 63, 3812. Tamaru,
Y.; Goto, S.; Tanaka, A.; Shimizu, M.; Kimura, M. Angew Chem., Int. Ed.
Engl. 1996, 35, 878.
(9) A reviewer called our attention to a report of Trost and co-workers
who found that 10 mol % of In(acac)3 in the presence of 5 mol % Pd(OAc)2
and various phosphine ligands causes the reagent TMSCH2(CdCH2)CH2-
OAc to undergo 1,2- as opposed to 1,4-additions to conjugated aldehydes
and ketones. Trost, B. M.; Sharma, S.; Schmidt, T. J . Am. Chem. Soc. 1992,
114, 7903.
(5) Marshall, J . A.; Chemtracts - Organic Chemistry 1997, 10, 481.
(6) Elsevier: C. J .; Vermeer, P.; Gedanken, A.; Runge, W. J . Org. Chem.
1985, 50, 364.
10.1021/jo982255p CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/09/1999