Cyclopropanation - Carbohydrates: Tools for Stereoselective Synthesis - page 107

of exo - and endo -diastereoisomers. The endo isomer was a major product in all
cases, and the mixtures were easily separated by chromatography.
In the case of bulky residues R 1 cyclopropanation of 9 occurred predominantly
on the back face of the alkene, affording cyclopropane derivative 10 (Table 5.2).
Mild acid hydrolysis of 10 followed by reduction provided the hydroxymethyl-
cyclopropane 11 in a modest 65-85 ee in the case of endo -acetals and in lower ee
for exo- acetals [9].

Table 5.2

Effect of the alkyl chain R 1 at C3 of 9 (R 2 = Ph, in Scheme 5.3) in cyclopropanation.

Entry Starting

material 9
(R 2 = Ph)

R 1 Cyclopropanated

product, 10

Yield
(%)

Hydrolysis-reduction
11 (R 2 = Ph) Yield
(%)

ee (%)

1 9a Bn 10a 85 88 71

2 9b CH 3 10b 88 88 46

3 9c o- MeC 6 H 4 CH 2 10d 72 86 68

4 9d m- MeC 6 H 4 CH 2 10d 87 89 72

5 9e p- MeC 6 H 4 CH 2 10e 43 90 82

6 9f p- MeOC 6 H 4 CH 2 10f 87 85 66

7 9g p-t BuC 6 H 4 CH 2 10g 89 91 69

8 9h p- PhC 6 H 4 CH 2 10h 85 93 77

9 9i 2-NpCH 2 10i 85 90 64

An exhaustive study of the Simmons-Smith cyclopropanation of five-
and six-membered alkenylidene acetals derived from carbohydrates has
recently been carried out by Vega-Pérez and Iglesias-Guerra (Scheme 5.4). The
stereoselective cyclopropanation of unsaturated acetals 12a-f derived from
methyl l-rhamnopyranoside, 1,2- O- isopropylidene-d-glucofuranose, methyl d-
glucopyranoside, and dodecyl N -acetyl-2-amino-2-deoxy-d-glucopyranoside have
been studied using Charette's initial conditions. Even when the problem of endo-,
exo -adducts was solved, the cyclopropanated products 13a-f were obtained only
with modest diastereoselectivities (Scheme 5.4) [10].
Utilization of 1,2- O- isopropylidene-d-xylofuranoside as chiral auxiliary afforded
better results (Table 5.3). Indeed, the cyclopropanation of alkenylidene acetals
derived from 1,2- O- isopropylidene-d-xylofuranoside 14a-h in 1,2-dicloroethane
leads to cyclopropanated products 15a-h in good yields and good diastereoselectivi-
ties. The absolute configuration has been determined by chemical correlation with
known hydroxymethyl cyclopropanes 16 obtained by acid hydrolysis of the acetals
followed by reduction of the obtained aldehyde [11].
Beside Simmons-Smith cyclopropanation reactions, transition-metal-catalyzed
decomposition of diazo compounds using carbohydrates as chiral auxiliaries has
also been examined for the diastereoselective synthesis of cyclopropanes. In this
regard, the Ferreira group studied the stereoselectivity in the cyclopropanation
with several sugars tethered diazoacetates 17a-e, using achiral Rh 2 (OAc) 4 as