Cyclopropanation - Carbohydrates: Tools for Stereoselective Synthesis - page 104

5

Cyclopropanation
Noureddine Khiar, Inmaculada Fernández, Ana Alcudia, Maria Victoria García and
Rocío Recio

5.1
Introduction

The asymmetric synthesis of chiral non-racemic cyclopropane subunits has been
of great interest in recent decades as several natural [1] and synthetic [2] products
contain a cyclopropane ring in their structure. Analysis of the literature shows
that three main approaches have been used in the catalytic and stoichiometric
stereoselective construction of the cyclopropane framework: (i) halomethyl-
metal-mediated cyclopropanation reactions, (ii) transition-metal-catalyzed decom-
position of diazo compounds, and (iii) nucleophilic addition ring closure

sequence [3]. Of these approaches the Simmons-Smith reaction [4], the paradig-
matic example of halomethyl-metal-mediated cyclopropanations, is one of the
successful and general approaches for the synthesis of enantiopure cyclopropanes
[3]. Particularly powerful are diastereoselective cyclopropanation reactions of sub-
stituted allylic alcohol or

−

-unsaturated carbonyl compounds linked to a chiral
auxiliary. In this regard Charette et al. has developed one of the most efficient
diastereoselective cyclopropanation approaches using glucose as chiral platform
(Table 5.1).
The Simmons-Smith cyclopropanation of allylic d-glucopyranose 1 affords the
products 2, usually with a diastereomeric ratio larger than 50 : 1 [5]. The different
2-hydroxyglucopyranisides 1a-g were readily accessible using Danishefsky's glyco-
sylation method with commercially available tri- O -benzyl-d-glucal and several
allylic alcohols. Structure-diastereoselectivity relationships of the starting allyl-
glycosides show that the free hydroxyl group at C2 plays a key role in the dias-
tereofacial differentiation in 1. This group reacts with diethylzinc and forms a
coordinate anchor for the Simmons-Smith intermediate with the iodomethyl-zinc
unit. Indeed, allyl glycopyranosides in which the 2-position is protected showed
only a modest asymmetric induction in cyclopropanation under standard condi-
tions. The scope of the reaction is very broad, as illustrated by the high level of
asymmetric induction observed with several differently substituted allylic alcohols
(Table 5.1).

α , β