Recent advances in carbocupration of α-heterosubstituted alkynes

Abstract

SummaryCarbocupration of α-heterosubstituted alkynes leads to the formation of stereodefined functionalized vinyl copper species as single isomer. Recent advances in the field show that a simple pre-association of the organometallic derivative with an additional polar functional group in the vicinity of the reaction center may completely change the stereochemical outcome of the reaction. Representative examples are given in this mini-review.

Axial Preferences in Allylation Reactions via the Zimmerman–Traxler Transition State

“…5 For instance, the transformation of alkynyl sulfoxide 1 into enantiomerically pure homoallylic alcohols 5 was performed in a single-pot operation starting with a regio- and stereoselective carbometalation reaction of alkynyl sulfoxide 1 6 that provide the corresponding metalated β,β-dialkylated ethylenic sulfoxide 2 in quantitative yields (scheme 2). 7 The defined stereochemistry of the two alkyl groups on the double bond that will be subsequently translated into the γ,γ-disubstituted allylzinc species results from this regio- and stereoselective carbocupration reaction. Subsequently, the in-situ homologation reaction was performed by the successive addition of aldehyde, Et 2 Zn and CH 2 I 2 .…”

“…This very interesting aspect of stereochemistry, never explored to the best of our knowledge, led us to envisage a detailed study on the diastereoselectivity of γ,γ-disubstituted allylzinc species with carbonyl compounds. To this end, we initially tested the allylation reaction by in-situ transforming vinyl iodides 12 , easily obtained by carbocupration of alkynes, 7 into γ,γ-disubstituted allylzinc species. The successive treatment of vinyl iodide 12 with t -BuLi followed by the subsequent addition of soluble copper salt solution, Et 2 Zn, CH 2 I 2 and aldehydes at −80 °C leads to the expected homoallylic alcohols 13 in very high diastereomeric ratios (Scheme 10).…”

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

“…In this context, an efficient strategy to control these selectivity issues is the incorporation of a heteroatom directly attached to the triple bond, which can dramatically affect both the regio- and stereochemical outcomes due to the polarization of the triple bond and/or the formation of chelation-stabilized vinylmetal species. The carbometallation of O-, N-, P-, S-, and Si-substituted alkynes has indeed been quite extensively studied and shown to provide most efficient entries to polysubstituted, stereodefined heteroatom-substituted alkenes and has been implemented in remarkably elegant processes [6]. Intramolecular versions are especially attractive and provide most useful entries to highly substituted carbo- and heterocycles.…”

Axial Preferences in Allylations via the Zimmerman–Traxler Transition State

“…[2] In the last few years, we have been involved in the development of synthetic strategies that have led to the formation of these desired fragments, but we have focused on the concomitant creation of several carbon–carbon bonds in a one-pot operation. [3] Our method consists of a carbometalation reaction of various α-hetero-substituted functionalized alkynes [4] followed by a zinc homologation reaction [5] through the use of a zinc carbenoid, formed in situ, [6] and then an allylation reaction of carbonyl compounds (Scheme 1). …”

“…[8] After extensive experimentation, we found that the successive treatment of vinyl iodides 3 , prepared by carbometalation of alkynes [4] with t BuLi followed by the addition of a soluble solution of copper salt led to the formation of vinyl copper 5 . Then, at −80°C, the addition of aldehydes, Et 2 Zn, and CH 2 I 2 to this vinyl copper compound gave the expected homoallylic alcohols 7 through the formation of 3,3-disubstituted allylzinc species 6 (Scheme 4).…”