Synthesis of the rarely obtained syn-adducts in the reaction of organocopper compounds with 2,3-O-isopropylideneglyceraldehyde. Preparation of optically active epoxy alcohols

Abstract

Organocopper compounds, prepared from Grignard reagents and copper(1) iodide in tetrahydrofuran-dimethyl sulphide, react with 2,3-U-isopropyIideneglyceraldehyde highly stereoselectively ( > l o : 1 ) affording the rarely obtained syn-addition products which can be readily converted into optically active epoxy alcohols, useful intermediates in organic synthesis. 2,3-O-Isopropylideneglyceraldehyde(1), readily available in the (S)-l as well as the (R)-form,2 is a synthetically useful chiral starting material for the construction of optically active organic molecules.3 There has been much recent interest in the steric course of organometallic additions to (l), since if the stereochemical features of this reaction could be controlled,(1) would be extremely useful synthetically. Usually, organometallic compounds (R-M) such as Grignard, organolithium, or organozinc reagents afford anti-addition products (3) selectively [equation (l)] .4 The degree of diastereoselectivity is dependent on R-M, but, with a few exceptions,4bh it is not satisfactory from a synthetic point of view.

The Synthesis of Boronolide

“…2). Such stereoselectivity is characteristic of acrolein dimer [7] [8] and has also been observed for structurally similar aldehydes such as 2,3-0 -isopropylideneglyceraldehyde [9] and 2,3-0 -dibenzylglyceraldehyde [ 171.…”

Total Synthesis of the Putative Structure of Asperipin-2a and Stereochemical Reassignment

“…Accordingly, (R)-glyceraldehyde acetonide 8 was treated with phenylmagnesium bromide in the presence of CuI to give the alcohol 9 in 99:1 d.r. 15,16 Analysis of 9 by X-ray crystallography confirmed the (R,R)-configuration ( Figure 3). The Mitsunobu reaction of alcohol 9 with tyrosine derivative 11 under sonication and at high concentration (3 M) successfully generated ether adduct 12.…”

Organocopper Reagents

“…Et 2 0, -78°C 2h 75%õ (17) Most of the early work in this area was done by House 46 in the course of developing a model for cuprate conjugate additions to a,J3-unsaturated ketones based on measured (polarographic) reduction potentials. 47 Products of 1,2-addition or reductive elimination (in the case of e.g.…”