Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland.
Org Biomol Chem. 2010 Feb 7;8(3):539-45. doi: 10.1039/b916506a. Epub 2009 Nov 30.
The addition of 3,4-dimethoxybenzyl thiol 8, as a benzyl thiol surrogate, to racemic 4-hydroxycyclopent-2-enone 2 and 4-hydroxycyclohex-2-enone 15 gave the corresponding cis-adducts (+/-)-3-(3,4-dimethoxybenzylthio)-4-hydroxycyclopentanone 4b and (+/-)-3-(3,4-dimethoxybenzylthio)-4-hydroxycyclohexanone 16 with good diastereocontrol. In both cases, subsequent treatment with vinyl acetate, in the presence of a lipase enabled enantiomer resolution. Thus, (+)-16 and the acetate of its enantiomer, (-)-(1R,2S)-2-(3,4-dimethoxybenzylthio)-4-oxocyclohexyl acetate, (-)-17 were isolated in 98% enantiomeric excess. Based on the 1,4-dioxygenation pattern, (-)-17 can be used to prepare both enantiomers of 4-(tert-butyldimethylsilyloxy)cyclohex-2-enone 19. Firstly, saponification, with a sub-stoichiometric amount of NaOMe, followed by a one-pot silyl ether formation-sulfide elimination sequence gave (+)-19. Then using the same starting material a 6-step sequence, featuring a diastereoselective NaBH4 reduction and a Cope-type sulfoxide elimination, gave (-)-19.
3,4-二甲氧基苄硫醇 8 作为苄硫醇的替代物，与外消旋的 4-羟基环戊-2-烯酮 2 和 4-羟基环己-2-烯酮 15 反应，得到相应的顺式加成产物（±）-3-(3,4-二甲氧基苄硫基)-4-羟基环戊酮 4b 和（±）-3-(3,4-二甲氧基苄硫基)-4-羟基环己酮 16，具有良好的非对映选择性控制。在两种情况下，随后用醋酸乙烯酯处理，并在脂肪酶的存在下，实现了对映体的拆分。因此，（+）-16 和其对映体的醋酸酯（-）-1R,2S-2-(3,4-二甲氧基苄硫基)-4-氧代环己基醋酸酯（-）-17 以 98%的对映体过量被分离出来。根据 1,4-双加氧模式，（-）-17 可用于制备 4-（叔丁基二甲基甲硅烷基氧基）环己-2-烯酮 19 的两种对映体。首先，用亚化学计量的 NaOMe 进行皂化，然后进行一锅法硅醚形成-硫醚消除反应，得到（+）-19。然后使用相同的起始原料，通过六步反应序列，其中包括一个非对映选择性的 NaBH4 还原和 Cope 型亚砜消除反应，得到（-）-19。
