Regioselective Aliphatic Retro‐[1,4]‐Brook Rearrangements

Abstract

The migration of silicon is a ubiquitous process in reactions, and the Brook rearrangement is an intramolecular migration of a silicon atom from a carbon to an oxygen atom.[1] The reverse process-migration of a silicon atom from an oxygen to a carbon atom-is referred to as the retro-or reverseBrook rearrangement and is a common occurrence.[2] Studies on retro-[1,2]-Brook rearrangements have revealed that the rearrangement is highly stereospecific with regard to the configuration at the carbon atom and proceeds with retention of configuration in the a-silyloxy carbanions generated from aliphatic substrates, whereas inversion is observed for benzylic and allylic carbanions.[3] As the retro-Brook rearrangement requires excess base, the driving force for the reaction may be the formation of a lithium alkoxide that is more stable than the starting organolithium compound. Higher-order retro-[1,3]-, -[1,4]-, -[1,5]-, and -[1,6]-Brook rearrangements have also been the subject of numerous investigations, and have been utilized for the preparation of functionalized organosilane derivatives. [4][5][6][7][8] The general trend of the ease of silyl migration has been reported to be] based on the logic that the shorter transfer distance is more favored, [9] and this order of migration has long been accepted without question.[5a, 6c] It has recently been reported that the regioselectivity of the retro-[1,2]-and [1,4]-Brook rearrangements in an allyllithium system depends upon the reaction conditions, and that the addition of hexamethylphosphoramide (HMPA) as a cosolvent improves the [1,4] selectivity.[5l] However, there has been no study of competitive silyl migration occurring in aliphatic retro-Brook rearrangements. We decided to investigate the relative ease of otherwise comparable [1,2] and [1,4] migrations. We report here the first documented example of the preference of retro-[1,4]-migration over retro-[1,2] migration in an a,g-disilyloxy organolithium system.To evaluate the regioselectivity of the retro-Brook rearrangement, we examined 1,3-disilyloxy-1-tributylstannylbutane derivatives 1, which can form [1,2] and [1,4] products 2 and 3, respectively, after transmetalation and rearrangement (Scheme 1). The optically active stannanes 4 and 5 were synthesized in a pure form by the reaction of tributylstannyllithium [10] and an aldehyde prepared from methyl (R)-3-hydroxybutylate (98 % ee) followed by silylation and separation by flash chromatography (Scheme 2). The configurations of 4 and 5 were determined to be syn and anti, respectively, by formation of the acetonide [11] and by 13 C NMR analysis using the Rychnovsky method.

Unexpected Propargylic Retro-Brook Rearrangements in Alkynes

“…The Brook rearrangement, which involves an intramolecular migration of silyl group from a carbon to an oxygen, was first recognized in the late 1950s and reflects the migratory tendency of silyl groups that results in the conversion of an oxyanion to a carbanion . The reverse reaction, where the silyl group undergoes intramolecular migration from oxygen to carbon, is known as a retro-Brook rearrangement …”