Lewis Acid-Activated Chiral Leaving Group:  Enantioselective Electrophilic Addition to Prochiral Olefins

Abstract

A new strategy using a BINOL derivative as a chiral leaving group and Lewis acid has been developed for enantioselective alkylation of prochiral olefins. (R)-2,2'-Bis[2-(trimethylsilyl)ethoxymethyl]-1,1'-binaphthol is demonstrated to be an effective reagent for enantioselective hydroxymethylation of silyl enol ethers and trisubstituted alkenes. Electrophilic addition to prochiral olefins is accompanied by cleavage of an acetal that is dual activated by SnCl4 and the delta-effect of silicon through the S(N)2 substitution process. Enantioselective synthesis of cyclic terpenes is also described using this strategy.

Tris(pentafluorophenyl)borane

“…Thus, the trimethylsilylethyl group was removed in a site-selective reductive cleavage of ether 5 (eq 27). 44 Alkyl ethers possessing at least one tertiary alkyl group did not react under the described conditions. 43 Aryl alkyl ethers were readily cleaved to give silyl protected phenols in quantitative yield (eq 28).…”

Recent Advances in Heterolytic Nucleofugal Leaving Groups

“…Thus neryl-BINOL derivative 37 was converted to (+)-limonene (38) and α-terpinyl chloride (39) in 91% yield as a 4:5 mixture. 40 The transformation was highly enantioselective (93% ee) in chlorinated solvents such as CH 2 Cl 2 and propyl chloride. Heating the mixture of 38 and 39 in 2,4,6-collidine under reflux conditions converted chloride 38 to limonene in 71% yield (scheme 15).…”

“…40 In this strategy, a Lewis acidactivated C-O bond (as in 29) is cleaved at the moment of electrophilic addition releasing the BINOL leaving group (scheme 11). Lewis acid/LG complex 29 can be thought of as a cationic synthon possessing a chiral environment analogous to Lewis acid-assisted chiral Brønsted acid (LBA) used in enantioselective protonation reactions.…”

“…43 NMR studies indicate that the BINOL leaving group in 31 coordinates with SnCl 4 at the aryl ether oxygens (scheme 13). 40 The introduction of silyl enol ether 30 is thought to give transition state 33 which can be represented using a Newman-type diagram (scheme 13). As indicated in the scheme, transition state 33 is stabilized by a π-π attractive interaction between phenyl group of 30 and one of the napthyl groups of BINOL 31.…”

Recent advances in heterolytic nucleofugal leaving groups

“…A method for face-selective alkylation of prochiral olefins using BINOL derivatives as chiral leaving groups under acidic conditions has been developed. 40 In this strategy, a Lewis acidactivated C-O bond (as in 29) is cleaved at the moment of electrophilic addition releasing the BINOL leaving group (scheme 11). Lewis acid/LG complex 29 can be thought of as a cationic synthon possessing a chiral environment analogous to Lewis acid-assisted chiral Brønsted acid (LBA) used in enantioselective protonation reactions.…”