Carbocyclisation of zinc enolates onto unactivated double bonds: a mechanistic point of view

Abstract

The recent results concerning the carbocyclisation reaction of zinc enolates onto an unactivated double bond are summarized, particularly on the stereochemical point of view. The implications of the observed stereochemistries on the mechanism of the reaction (O-centred zinc enolate vs C-centred zinc enolate) are discussed. Some new results leading stereoselectively to 1-amino-1-carbomethoxy-2-methyl cyclopentanes are reported, as well as the consequences of the observed stereochemistry as a strong evidence for a C-centred zinc enolate intermediate.

Radical‐Polar Crossover Domino Reactions Involving Organozinc and Mixed Organocopper/Organozinc Reagents

“…We have recently shown (Scheme ) that zinc enolates derived from β‐ N ‐allyl amino esters undergo smooth and diastereoselective carbocyclization to trans 3‐carboxymethyl‐4‐methylzinc compounds 1 , which can be further functionalized to substituted trans ‐pyrrolidines 2 1. The diastereoselectivity was explained2 by a transition state involving C‐centered3 zinc enolate 3 .…”

Asymmetric Synthesis of 3-Substituted Proline Chimeras Bearing Polar Side Chains of Proteinogenic Amino Acids

“…In a typical procedure, olefin 1 (methyl ester or benzyl ester) was treated with LDA in THF at −78 °C, and the lithium enolate was transmetalated with zinc bromide. Warming the reaction mixture to room temperature led to organozinc derivative 2 , with a cis relative stereochemistry and 2 S absolute configuration as previously demonstrated 1 …”

“…Several methods for the synthesis of 3-substituted prolines have been reported, but there is still a need for a general stereoselective route to these compounds . We have already reported the amino−zinc−ene−enolate cyclization as a versatile strategy for the asymmetric synthesis of cis -3-alkylprolines . We report here the extension of this methodology for the synthesis of proline chimeras bearing polar side chains of natural amino acids and suitably protected for peptide synthesis.…”

Carbometalation of unactivated alkenes by zinc enolate derivatives

“…The stereochemical outcome observed with b-(N-allyl)aminoesters bearing additional substituents a to the nitrogen was also in agreement with this model. 46 The high stereoselectivities obtained in the carbocyclisation of b-(N-allyl)aminoesters 53 prompted us to develop an enantioselective version. 47 Here again, we were glad to see that the 1-phenylethylamino group proved to be a stereodirecting group of choice (Scheme 28).…”

“…To shed some light on this issue we studied the carbocyclisation of amino enolates derived from 68 (Scheme 32). 46 We reasoned that if carbozincation involved an O-metalated species, metalated cyclopentane trans-70 would be favored over cis-70, and on the other hand if a C-metalated intermediate was involved, cyclopentane cis-70 should be predominant. Deprotonation of 68 followed by transmetalation with ZnBr 2 resulted in a smooth carbocyclisation leading to cis-1-amino-1-carbomethoxy-2-methyl cyclopentanes 69 as major compounds.…”