Catalytic Asymmetric Synthesis of Allenes Bearing Axial Chirality

具有轴向手性的光学活性联烯是合成各种天然生物活性化合物的重要中间体。这类化合物的不对称合成受到了广泛的关注。光学活性联烯的制备方法有外消旋联烯的光学拆分和光学活性前体的手性转移反应。本项目主要探索了利用手性催化剂合成光学活性联烯的方法.使用带有光学活性双膦配体的钯络合物催化剂进行外消旋炔丙基磷酸酯的羰基化，并进行动力学光学拆分，得到轴向手性丙二烯羧酸酯沿着回收的光学活性炔丙基磷酸酯。这是使用催化量的手性化合物不对称合成联烯的第一个实例。对映选择性取决于所用的CO压力，在CO高压下的反应和在CO常压下的反应得到相反绝对构型的联烯.使用带有光学活性双膦配体的钯配合物催化剂，用各种亲核试剂对外消旋2，3-二烯基磷酸盐进行亲核取代，得到光学活性的取代联烯。机理研究揭示了1，3-烷二烯基钯作为不对称诱导的关键中间体的中间性。

Optically active allenes bearing an axial chirality are important synthetic intermediates for various naturally occurring biologically active compounds. Much attention has been paid to the asymmetric synthesis of this class of compounds. Optically active allenes have been prepared by either optical resolution of racemic allenes or chirality transfer reactions of optically active precursors. In this project, some attractive methods for preparation of optically active allenes using a chiral catalyst were explored.1. Carbonylation of racemic propargylic phosphates using a palladium complex catalyst bearing an optically active bisphosphine ligand proceeds with kinetic optical resolution to give axially chiral allenecarboxylic acid esters along with recovered optically active propargylic phosphates. This is the first example of asymmetric synthesis of allenes using a catalytic amount of chiral compound. The enantioselectivity depends on CO pressure employed, and the reaction under high pressure of CO and that under atmospheric pressure of CO give allenes of oposite absolute configurations.2. Nucleophilic substitution of racemic 2,3-alkadienyl phosphates with a variety of nucleophiles using a palladium complex catalyst bearing an optically active bisphosphine ligand gives optically active substituted allenes. Mechanistis studies reveal the intermediacy of 1,3-alkadienylpalladium as a key intermediate for asymmetric induction.