Formal [4 + 1]- and [5 + 1]-Annulation by an S_N2–Conjugate Addition Sequence: Stereoselective Synthesis of Highly Substituted Carbocycles

Abstract

K(2)CO(3)-mediated reactions of 6-bromo-2-hexenoates and 7-bromo-2-heptenoate with active methylene compounds deliver highly substituted cyclopentane and cyclohexane derivatives, respectively via a sequence of S(N)2-conjugate addition reactions (formal [4 + 1]- and [5 + 1]-annulation) in a diastereoselective manner.

Sulfone–Metal Exchange and Alkylation of Sulfonylnitriles

“…[7] Conspicuously absent from the types of exchangeable functionality are sulfones such as 8. [10] Fors ubstituted sulfonyl acetonitriles such as 9,anadditional advantage lies in using mild base for the alkylation of commercially available sulfonyl acetonitrile [11] (9!10,S cheme 2). [10] Fors ubstituted sulfonyl acetonitriles such as 9,anadditional advantage lies in using mild base for the alkylation of commercially available sulfonyl acetonitrile [11] (9!10,S cheme 2).…”

“…[8] Conceptually,as ulfone-metal exchange would combine the exceptionally rich chemistry of sulfones [9] with the diverse alkylation potential of organometallics while providing aversatile alternative to reductive desulfonylation. [2] Developing as ulfone-metal exchange requires overcoming the excellent directing group ability of sulfones, [12] and guiding organometallics to attack at the tetrasubstituted sulfur center (12)r ather than complex-directed ortho deprotonation [13] (11). The sequence obviates the need for two equivalents of as trong base,w hich is typically required in nitrile alkylations.…”

“…[10] Fors ubstituted sulfonyl acetonitriles such as 9,anadditional advantage lies in using mild base for the alkylation of commercially available sulfonyl acetonitrile [11] (9!10,S cheme 2). Indeed, attempted sulfone-metal exchange with BuLi and the phenylsulfone 10 afforded the imine 13,p resumably by complexation, ortho-deprotonation (11), and attack of the resultant aryllithium on the nitrile. [2] Developing as ulfone-metal exchange requires overcoming the excellent directing group ability of sulfones, [12] and guiding organometallics to attack at the tetrasubstituted sulfur center (12)r ather than complex-directed ortho deprotonation [13] (11).…”

“…[8] Conceptually,as ulfone-metal exchange would combine the exceptionally rich chemistry of sulfones [9] with the diverse alkylation potential of organometallics while providing aversatile alternative to reductive desulfonylation. [10] Fors ubstituted sulfonyl acetonitriles such as 9,anadditional advantage lies in using mild base for the alkylation of commercially available sulfonyl acetonitrile [11] (9!10,S cheme 2). The sequence obviates the need for two equivalents of as trong base,w hich is typically required in nitrile alkylations.…”

“…The sequence obviates the need for two equivalents of as trong base,w hich is typically required in nitrile alkylations. [2] Developing as ulfone-metal exchange requires overcoming the excellent directing group ability of sulfones, [12] and guiding organometallics to attack at the tetrasubstituted sulfur center (12)r ather than complex-directed ortho deprotonation [13] (11). Indeed, attempted sulfone-metal exchange with BuLi and the phenylsulfone 10 afforded the imine 13,p resumably by complexation, ortho-deprotonation (11), and attack of the resultant aryllithium on the nitrile.…”