Stereospecific synthesis of 1,6-dioxadecalins and 2,2′-linked ditetrahydrofurans by rearrangement of steroidal spiroacetals

The reduction of steroidal spiroacetal methanesulfonate derivatives, containing the 1,6-dioxaspiro-[4.5]decan-10-yl ring system, with DIBALH promotes a new rearrangement to give steroidal 1,6-dioxadecalin (octahydropyrano[3,2-b]pyran) or 2,2'-linked ditetrahydrofuran (octahydro[2,2']bifuranyl) derivatives. To study the scope and selectivity of the reaction, several steroidal spiroacetals such as (23R,25R)-3 beta-methoxy-5 alpha-spirostan-23-yl methanesulfonate (2) and its 23S-isomer (5) and (22R,23R,25R)-3 beta-acetoxy-16 beta,23:23,26-diepoxycholest-5-en-22-yl methanesulfonate (15) and its 22S-isomer (19) have been synthesized. Compound 2 was rearranged with absolute regio- and stereoselectivity to give (22S,23S,25R)-3 beta-methoxy-16 beta,23:22,26-diepoxy-5 alpha-cholestane (3) which possesses a cis-fused 1,6-dioxadecalin ring system. The reaction of compound 5 gave exclusively (22S,23R,25R)-3 beta-methoxy-23,26-epoxy-5 alpha-furastane (6) in which the spiroacetal was converted into a ditetrahydrofuran subunit. The two other isomeric spiroacetals 15 and 19 were also mainly transformed into (22S,23S,25R)-3 beta-acetoxy-16 beta,23:22,26-diepoxycholest-5-ene (16) and (22R,23R,25R)-3 beta-acetoxy-23,26-epoxyfurost-5-ene (20), respectively. A mechanism is proposed to explain the regio- and sterospecificity observed in the rearrangement.