Ring synthesis Brook rearrangement

Nucleophilic substitution of a,/3-epoxysilanes followed by the Peterson elimination is valuable for the stereoselective synthesis of alkenes.3 The reactions with lithium phenylsulfide and diphenylphosphide form alkenyl sulfides and alkenylphosphines, respectively, in a stereospecific manner. 7-Metallo-a,/ -epoxysilanes are isomerized to a-siloxyallylmetals by anionic ring opening and subsequent Brook rearrangement (Equation... 

Radical cyclization reactions have proven to be a very efficient approach for polycyclic natural product synthesis. In many cases, the last step involves a reduction of a cyclic radical with formation of a new stereogenic center. Very good stereochemical control has been achieved with such polycyclic radicals. For example, Beckwith has reported a highly stereoselective formation of a quinolizidine ring (Scheme 19, Eq. 19.1) [41b]. This process is the key reaction in a four-step synthesis of epilupinine and the stereochemical outcome results from a stereoselective axial reduction by tin hydride of a bicyclic radical. In a related process, Tsai has prepared silylated hydroxyquinolizidine by radical cyclization to an acylsilane followed by a radical-Brook rearrangement (Scheme 19, Eq. 19.2) [42]. 

The third section of the chapter describes recently developed anion relay chemistry (ARC) involving threefold domino Sj -Brook rearrangement/ reactions, discovered by Tietze and extensively explored by Amos Smith 111 and his group. These reactions are also initiated by nucleophihc ring opening of epoxides, usually by silyl-substituted dithiane anions, and find useful apphcation in natural product synthesis. 

Scheme 4.28 Synthesis of enantiopure 1,5-diols via domino epoxide ring opening/1,4-Brook rearrangement/S, reaction.

Another instance of successful homo-Brook rearrangement occurred in a total synthesis of the antitumor agent FR66979. Here the tendency for Peterson elimination from -hydroxysilane 99 was overcome by the countervailing aziridine-opening pathway, providing the ring-expanded product 100. "... 

The Brook 1,4-rearrangement is useful in cyclopentanol synthesis. For example, Schaumann and co-workers demonstrated that lithiated or-silyl dithiane 112 was useful for construction of cyclopentanol 115. Addition to epoxytosylate 113 followed by 1,4-silyl migration provided lithiodithiane 114 for closure of the five-membered ring. ... 

---