1,4-Addition of Nucleophiles to -Unsaturated Carbonyl Compounds - Carbohydrates: Tools for Stereoselective Synthesis - page 26

2

1,4-Addition of Nucleophiles to α , β -Unsaturated
Carbonyl Compounds
Kiichiro Totani and Kin-ichi Tadano

2.1
Introduction

In this chapter we describe the 1,4-additions of various nucleophiles to -

unsaturated carbonyl groups on carbohydrate templates. Many examples have
revealed that carbohydrates serve as effective chiral auxiliaries for realizing useful
levels of diastereoselectivity [1-8]. As acyclic 1,4-addition acceptors, acrylic amides
or acrylic esters on a carbohydrate template are described. Then, as cyclic accep-
tors, 2- and 4-pyridones are also exemplified.

α , β

2.2
1,4-Additions to Acrylic Amides and Acrylic Esters

As an early example concerning the utility of carbohydrate-based auxiliaries for
stereoselective carbon-carbon bond formation, Kunz and Pees reported in 1989
the stereoselective 1,4-addition of the carbon nucleophile generated from diethyla-
luminum chloride to a d-xylose-derived N -cinnamoyl 2-oxazinone 2 [9, 10]. The
substrate 2 was synthesized by N -cinnamoylation of 3,5- O,N -oxazin-2-one deriva-
tive 1, which in turn was synthesized from d-xylose (Scheme 2.1) [9]. The 1,4-
addition of diethylaluminum chloride to 2 at -80 °C proceeded with remarkable
π -facial selectivity to provide (S) -3-phenylpentanoyl derivative 3 in high yield with

74% diastereomeric excess (de). Hydrolysis of 3 with HCl provided enantioen-
riched (3 S )-phenylpentanoic acid 4, the absolute stereochemistry of which was
confirmed by comparison of its optical rotation to the reported [ α ] d (the yield and

ee of 4 were not reported).
Later, the Kunz group demonstrated other stereoselective syntheses of chiral

β -branched carboxylic acids using the 1,4-addition of organometallic species to

carbohydrate-derived N -acyloxazolidinones [10-12]. Thus, oxazolidinone 5 as the
auxiliary for the 1,4-addition was synthesized from d-galactose via azidonitration