Efficient Syntheses of Secondary and Tertiary 2-Aryl- and 2-Heteroaryl-allyl Alcohols

Abstract

Reactions of α-aryl-, α-heteroaryl-, and α-heteroatom-substituted masked alkenyllithiums with aldehydes and ketones provide a general method for the synthesis of allylic alcohols substituted with an aryl or heteroaryl in the β position and aryl, heteroaryl or alkyl substituents in the α position via a [1,4]-C→O silicon rearrangement. In the case of reactions with enolizable aldehydes and ketones, anhydrous CeCl3 was used as an additive. High diastereoselectivities are observed for allyl alcohols produced from α-substituted aldehydes.

The Preparation of Mono-, 1,1-Di-, trans-1,2-Di- and Trisubstituted Ethylenes by Benzotriazole Methodology

“…The preliminary formation of a Ce(III) reagent by transmetallation with 1 equiv anhydrous CeCl 3 prevents enolization, and addition to the carbonyl group is successfully accomplished to give the corresponding allyl ethers in good yields. 18 Homoallylic alcohols can be obtained from oxiranes. Thus, phenyloxirane reacts with the carbanion 2 (where X = Ar) to give the intermediate 31 which did not rearrange to the corresponding homoallylic alcohol 33 by a [1,5]-Brook rearrangement on refluxing in THF but, instead, gave 32 in 72% yield upon aqueous work-up of 31 (Scheme 10).…”

“…Upon warming from -78°C to r.t., most lithium alkoxides 27a-g undergo a [1,4]-C®O Brook rearrangement [15][16][17] with benzotriazole as the leaving group (Scheme 9, path A) to give the trimethylsilyl ethers 28. 18 The process 27®28 is probably intramolecular since the stereochemistry of the intermediate alkoxides Reactions involving enolizable aldehydes and ketones pose additional challenges due to the possibility of proton abstraction by the hard alkenyl anion. The preliminary formation of a Ce(III) reagent by transmetallation with 1 equiv anhydrous CeCl 3 prevents enolization, and addition to the carbonyl group is successfully accomplished to give the corresponding allyl ethers in good yields.…”

“…The preliminary formation of a Ce(III) reagent by transmetallation with 1 equiv anhydrous CeCl 3 prevents enolization, and addition to the carbonyl group is successfully accomplished to give the corresponding allyl ethers in good yields. 18 Homoallylic alcohols can be obtained from oxiranes. corresponding alkoxide and then treated with TBAF to afford the desired elimination product 33 in 81% yield (Scheme 10).…”

“…Upon warming from -78°C to r.t., most lithium alkoxides 27a-g undergo a [1,4]-C®O Brook rearrangement [15][16][17] with benzotriazole as the leaving group (Scheme 9, path A) to give the trimethylsilyl ethers 28. 18 The process 27®28 is probably intramolecular since the stereochemistry of the intermediate alkoxides 27 dramatically influences the reaction conditions required. When a phenyl group, either of the substrate or of the aromatic aldehyde, possesses an ortho-substituent, the rearrangement of the alkoxide 27 requires stronger reaction conditions, i.e.…”

1,2,3-Triazoles

“…Consecutive α-lithiation followed by addition to a carbonyl group of an aldehyde leads to alkoxide 405 . During heating, anions 405 undergo an intramolecular rearrangement with elimination of benzotriazole to produce silylated allyl alcohols 406 ( Scheme 66 ) <1998JOC9978> . This approach provides a general method for the synthesis of allyl alcohols substituted with an aryl or heteroaryl group in the β position.…”