Unusual Reagent Control of Diastereoselectivity in the 1,2-Addition of Hard Carbon Nucleophiles to C₆-Heteroatom Substituted Cyclohexenones

Abstract

[reaction: see text] A surprising and synthetically useful counterion-dependent reversal of diastereoselectivity was found in 1,2-additions of hard carbon nucleophiles to C(6)-heterosubstituted cyclohexenones. In general, Grignard reagents added syn to the C(6)-substituent and Li reagents added anti, although some exceptions were found. Selectivities could be increased in some cases by appropriate choice of solvent and/or cosolvent.

Zn-Catalyzed Multicomponent KA2 Coupling: One-Pot Assembly of Propargylamines Bearing Tetrasubstituted Carbon Centers

“…Even though the abovementioned differences bare intrinsic informational value, the exact identity of the diastereoisomers was not uncovered in neither case and, therefore, unambiguous conclusions regarding stereocontrol cannot be drawn. It is important to note that the exact nature of the metal acetylide, as well as other factors contributing to π-face selection render the reasons for these differences far from obvious. , High yields and remarkably high diastereoselectivities were obtained when norbornanone was used in combination with pyrrolidine and piperidine, leading to single diastereoisomers of tetrasubstituted propargylamines 4g and 4h , respectively. Benzylamine was also successfully coupled with norbornanone and phenylacetylene, albeit leading to a substantially lower yield of propargylamine 4k , a fact which is attributed to the increased stability of the intermediate imine.…”

Approach to the Synthesis of Cladiell-11-ene-3,6,7-triol

“…Treatment of ester 2 (available in three steps from ( S )-(+)-carvone) with KHMDS and TIPSOTf afforded a single stereoisomeric product 3 possessing the Z -alkene and the ( S )-stereochemistry at C7 (Scheme ). The Ireland−Claisen rearrangement presumably proceeded via a chairlike transition state analogous to conformer i , with the larger C11 substituent occupying the pseudoequatorial position.…”

Synthesis of the bis(cyclohexenone) core of (−)-lomaiviticin A

“…29 We envisioned 1,2-addition of a two-carbon nucleophile to the ketone within 7 to construct the tertiary alcohol of the target. However, consistent with the studies by McIntosh and co-workers, 41 signicant optimization was required to obtain the cis-1,2-addition product in high yield and stereoselectivity. Aer much empirical experimentation, we found that the addition of ethylmagnesium bromide to solutions of the ketone 7 in toluene at À78 C provided the tertiary alcohol 11 in 70% yield and with 4 : 1 diastereoselectivity in favor of the desired product 11.…”