Forming all-carbon quaternary stereogenic centres in acyclic systems from alkynes

Abstract

The formation of all-carbon quaternary stereocentres in acyclic systems is one of the most difficult contemporary challenges in modern synthetic organic chemistry. Particularly challenging is the preparation of all-carbon quaternary stereocentres in aldol adducts; this difficulty is problematic because the aldol reaction represents one of the most valuable chemical transformations in organic synthesis. The main problem that limits the formation of these stereocentres is the absence of an efficient method of preparing stereodefined trisubstituted enolates in acyclic systems. Here we describe a different approach that involves the formation of two new stereogenic centres--including the all-carbon quaternary one--via a combined carbometalation-oxidation reaction of an organocuprate to give a stereodefined trisubstituted enolate. We use this method to generate a series of aldol and Mannich products from ynamides with excellent diastereomeric and enantiomeric ratios and moderate yields.

Stereodefined acyclic trisubstituted metal enolates towards the asymmetric formation of quaternary carbon stereocentres

“…65 Despite this reaction provided the expected enolate intermediate in an efficient manner, a simple modification of the carbocupration step using Gilman-type organocuprates 74,75 R 2 CuLiÁLiX instead of organocopper reagents RCuÁMX n allowed the authors to perform the direct and selective oxidation by commercially available t-BuOOH (Scheme 25). 65,76 Thus, it was Scheme 24 Stereoselective construction of the quaternary stereocentre of (R)-puraquinonic acid using Gleason auxiliary. found that the oxidation reaction proceeds with a complete retention of configuration initially obtained during the carbocupration reaction, as determined by X-ray crystallographic analysis of the stereochemistry of the silylenol ether obtained by reaction of the copper enolate with triethylchlorosilane.…”

At the Forefront of the Suzuki–Miyaura Reaction: Advances in Stereoselective Cross-Couplings

“…Cross-coupling of aliphatic substrates, in spite of recent developments, is still in its infancy in terms of its applications to organic synthesis. Most catalytic systems in cross-coupling reactions of alkyl substrates still require a high catalyst loading, and the current state of the art is still not applicable towards the coupling of tertiary alkyl substrates for the formation of quaternary stereogenic centres [99][100][101]. Better mechanistic understanding coupled with improved reaction conditions will be essential for future achievements in these areas.…”

1.04 Regio-, Diastereo-, and Enantioselective Addition of Organocopper Reagents onto CO and CN Bonds

“…The stereospecific oxidation, through a 1,2-metallate rearrangement, of the vinylcopper derivatives allows the access to a stereodefined copper enolate which is mandatory for a selective addition of an electrophile. 41 Starting from a chiral ynamide, Marek, and collaborators have described the enantioselective one-pot construction of all-carbon quaternary centers in aldol-type reactions. Thanks to highly the organized six-membered transition states, aldol and Mannich products are obtained from the corresponding aryl aldehydes and imines in good yields and excellent dr (Scheme 26).…”