定义Definition
夏普莱斯不对称双羟基化是用催化量四氧化锇和金鸡纳碱衍生的手性配体，在共氧化剂（如 K₃Fe(CN)₆）存在下把烯烃顺式转化为光学活性的邻二醇的反应。
The Sharpless asymmetric dihydroxylation converts alkenes into optically active syn-1,2-diols using catalytic osmium tetroxide, a cinchona-alkaloid-derived chiral ligand and a co-oxidant such as K₃Fe(CN)₆.
试剂与选择性Reagents and selectivity
商品化的 AD-mix-α（含 (DHQ)₂PHAL）和 AD-mix-β（含 (DHQD)₂PHAL）分别给出相反的对映体。手性配体与 OsO₄ 配位，形成一个“结合口袋”，决定烯烃哪一面受到进攻；配体同时加速反应（配体加速催化）。
Commercial AD-mix-α ((DHQ)₂PHAL) and AD-mix-β ((DHQD)₂PHAL) give opposite enantiomers. The ligand binds OsO₄, forming a pocket that selects the alkene face and also accelerates the reaction (ligand-accelerated catalysis).
机理Mechanism
OsO₄–配体配合物与烯烃发生 [3+2] 环加成生成锇酸酯，水解释放顺式二醇和 Os(VI)；共氧化剂把 Os(VI) 重新氧化为 Os(VIII)，使锇只需催化量（< 1 mol%）。加入甲磺酰胺可加速水解。
The OsO₄–ligand complex undergoes [3+2] cycloaddition with the alkene to an osmate ester, whose hydrolysis releases the syn-diol and Os(VI); the co-oxidant regenerates Os(VIII), so osmium is catalytic (< 1 mol %). Methanesulfonamide speeds hydrolysis.
由来Origin
夏普莱斯课题组于 1988 年报道，1992 年推出 PHAL 配体与 AD-mix。它几乎适用于各类烯烃，是 2001 年诺贝尔化学奖成果之一。
Reported by Sharpless’s group in 1988, with PHAL ligands and AD-mix introduced in 1992. Applicable to almost all alkene classes, it is part of the work recognised by the 2001 Nobel Prize.
反应Reactions
AD-mix（K₂OsO₂(OH)₄、手性配体、K₃Fe(CN)₆、K₂CO₃），t-BuOH/H₂O 1:1，0 °C
AD-mix (K₂OsO₂(OH)₄, chiral ligand, K₃Fe(CN)₆, K₂CO₃) in 1:1 t-BuOH/H₂O at 0 °C
OsO₄ 与手性配体配位。
OsO₄ coordinates the chiral ligand.
与烯烃 [3+2] 环加成生成锇酸酯。
[3+2] cycloaddition gives the osmate ester.
水解释放二醇；共氧化剂再生 Os(VIII)。
Hydrolysis releases the diol; the co-oxidant regenerates Os(VIII).
极高选择性的例子。
An example with very high selectivity.
年表Timeline
- 1936
克里吉发现 OsO₄ 双羟化及吡啶加速效应
Criegee discovers OsO₄ dihydroxylation and pyridine acceleration
- 1988
夏普莱斯报道催化不对称双羟化
Sharpless reports catalytic asymmetric dihydroxylation
- 1992
PHAL 配体与 AD-mix 问世
PHAL ligands and AD-mix introduced