Control of diastereoselectivity in the aldolization of methyl phenylacetate

Article abstract of DOI:10.1016/S0040-4039(00)00582-7

The aldolization of methyl phenylacetate with benzaldehyde in several conditions was studied. While the use of LDA in THF-HMPA gave the anti-aldol, the dibutylboron triflate furnished the syn-aldol in high diastereoselectivity (syn:anti=97:3). (C) 2000 El

Full text of DOI:10.1016/S0040-4039(00)00582-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 4033–4034
Control of diastereoselectivity in the aldolization of methyl
phenylacetate
Sergio Pinheiro,∗ Marcelo B. Lima, Clara B. S. S. Gonçalves, Sérgio F. Pedraza and
Florence M. C. de Farias
Instituto de Química, GQO, Universidade Federal Fluminense, CEG, Niterói, 24210-150, RJ, Brazil
Received 15 February 2000; revised 4 April 2000; accepted 5 April 2000
Abstract
The aldolization of methyl phenylacetate with benzaldehyde in several conditions was studied. While the use of
LDA in THF–HMPA gave the anti-aldol, the dibutylboron triflate furnished the syn-aldol in high diastereoselectiv-
ity (syn:anti=97:3). © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: phenylacetate; aldol; diastereoselection; dibutylboron triflate.
In contrast to the importance of the asymmetric α-alkylation of arylacetic derivatives to prepare
biologically active compounds,1 the aldol reaction from arylacetic esters has been scarcely used in
organic synthesis due to the modest diastereoselections observed.2,3 It can be due, in many cases, to
the formation of mixtures of E and Z-lithium enolates4,5 upon deprotonation of this class of esters. Some
time ago was reported6 the aldol reaction of benzaldehyde with the E-boron enolate produced from ethyl
phenylacetate and c-Hex2BI to give the anti-aldol (anti:syn=97:3) and recently the c-Hex2BOTf and the
widely used Bu2BOTf were employed7 for the aldolization of propionate esters with aldehydes.
As part of our interest in the aldol reaction of arylacetic esters for the synthesis of isoflavans, we
describe herein the aldolization of methyl phenylacetate with benzaldehyde employing different metal
enolates and the use of Bu2BOTf as a highly stereoselective reagent for this purpose (Table 1).
In spite of the E-enolate being predominant (E:Z=81:19),4a the aldolization in LDA at −78°C led a
mixture of isomers (entry 1),8 with the product of anti-aldol being favored at 0°C (entry 2). The reaction
under Mukaiyama’s conditions did not show high preference for the anti-aldol (entry 3). This selectivity
was dramatically increased by the enolization in the presence of THF–HMPA (entry 4),8 a condition that
leads to the Z-enolate (E:Z=9:91).4a While the zirconium9 and titanium10 enolates were not selectives
(entries 5 and 6), the use of Bu2BOTf in i-Pr2NEt in the deprotonation11 gave the syn-aldol in excellent
diastereoselectivity (entry 7) perhaps due to the formation of a Z-boron enolate.6
∗
Corresponding author. E-mail: spinuff@hotmail.com (S. Pinheiro)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00582-7
tetl 16861

4034
Table 1
Stereoselectivities in the aldolization of methyl phenylacetate
While the formation of syn-aldol (entry 7) from a Z-boron enolate is attributed to a widespread accepted
Zimmerman–Traxler chelate transition state,8 in the presence of HMPA (entry 4) the Z-lithium enolate
could lead to the anti-aldol by means of a acyclic transition state.12
In conclusion, while the use of LDA in THF-23% HMPA is an attractive alternative to reach the isomer
anti-aldol from methyl phenylacetate, the commercially available Bu2BOTf was proved to be an excellent
and complementary organoboron reagent to the use of c-Hex2BI to access syn-aldols.
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