First Tandem Asymmetric Conjugate Addition of Alkenyl Nucleophiles and Silyl Trapping of the Intermediate Enolates

Abstract

The tandem asymmetric conjugate addition of alkyl or aryl groups to enones and subsequent silyl trapping has already been achieved and yields valuable silyl enol ethers. Herein, the first method for the respective addition of alkenyl groups is reported, which is based on a rhodium(I)‐catalyzed addition of readily available alkenylzirconocenes. As prerequisite for silyl trapping, the initially formed enolates have to be transmetalated from zirconium to lithium by treatment with methyllithium prior to addition of the silyl chloride. Starting from 5‐ to 7‐membered cycloalkenones, the respective silyl enol ethers were obtained in excellent yields and ≥93% ee; an acyclic substrate furnished a moderate enantioselectivity. Besides trimethylsilyl chloride, the silylation was also performed with tert‐butyldimethylsilyl chloride, and the synthetic scope was evaluated by employing five different alkenyl groups. Moreover, the mechanism of this sequence was elucidated by 1H NMR studies, and the efficiency of catalyst control was exemplified by synthesis of a cis‐3,5‐disubstituted cyclohexanone which, due to strong substrate control, cannot be obtained by copper‐catalyzed conjugate addition.magnified image

Asymmetric Catalysis with Ethylene. Synthesis of Functionalized Chiral Enolates

“…The closest precedent for a catalytic reaction that results in the regio- and stereoselective synthesis of a silyl enol ether involves a Rh(L*)-catalyzed enantioselective conjugate addition (Scheme 1) of an alkenylorganozirconium reagent to a cycloalkenone ( 1 ) followed by a difficult (large excess of 4 reagents, long reaction times) in situ silylation of the weakly reactive zirconium-enolate 2 (see step 2). 3a The reaction shows poor selectivity for the preparation of acyclic derivatives (e. g., 4 ). 3b While similar catalytic asymmetric conjugate alkenylation of enones using alkenyl boronates 4a,b and alkenyl aluminum reagents 4c,d are known, no such reaction has been reported for simple vinyl (H 2 C=CH-) additions.…”

“…3a The reaction shows poor selectivity for the preparation of acyclic derivatives (e. g., 4 ). 3b While similar catalytic asymmetric conjugate alkenylation of enones using alkenyl boronates 4a,b and alkenyl aluminum reagents 4c,d are known, no such reaction has been reported for simple vinyl (H 2 C=CH-) additions. In all these cases, the products of addition are almost invariably the ketones, and not the more synthetically useful, regioselectively trapped enolates.…”

Asymmetric Conjugate Additions and Allylic Alkylations Using Nucleophiles Generated by Hydro‐ or Carbometallation

“…Hoveyda's allylic alkylation. [57] Treatment of the zirconium enolatei nitially produced in the reaction with an excesso fM eLi at À78 8Cg ives al ithiume nolate which can be trapped as as ilane. [56] More recently,Z ezschwitz et al reported addition of alkenylzirconocenes followed by silyl trapping to give silylenol ethers (Scheme 20).…”

ChemInform Abstract: Asymmetric Conjugate Additions and Allylic Alkylations Using Nucleophiles Generated by Hydro‐ or Carbometalation

“…[56] More recently,Z ezschwitz et al reported addition of alkenylzirconocenes followed by silyl trapping to give silylenol ethers (Scheme 20). [57] Treatment of the zirconium enolatei nitially produced in the reaction with an excesso fM eLi at À78 8Cg ives al ithiume nolate which can be trapped as as ilane. The reactioni s quenched with au rea-hydrogen peroxide adduct, which allows isolation of the enol-silane.…”