Howard Hughes Medical Institute, Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 61801, USA.
J Am Chem Soc. 2011 Sep 7;133(35):13774-7. doi: 10.1021/ja205912y. Epub 2011 Aug 10.
Efficient access to chiral C(sp(3)) boronates in stereochemically pure form is critical for realizing the substantial potential of such building blocks in complex-molecule synthesis. We herein report that a pinene-derived iminodiacetic acid (PIDA) ligand enables the highly diastereoselective synthesis of a wide range of oxiranyl C(sp(3)) boronates from the corresponding olefins. These oxiranyl PIDA boronates, in turn, can be readily transformed into unprecedented stable α-boryl aldehydes via a novel 1,2-migration of the boronate group that proceeds with complete maintenance of stereochemical purity. B-Protected haloboronic acids containing dual sp(3)-hybridized C centers are readily accessible via this platform, and the herein demonstrated capacity for stereocontrolled iterative C(sp(3)) cross-coupling with this novel type of bifunctional reagent to access a medicinally important chiral small-molecule target in highly enantioenriched form represents a substantial advance for the building-block-based approach to synthesis.
高效获得手性 C(sp(3))硼酸酯以纯立体化学形式对于实现在复杂分子合成中此类构建块的巨大潜力至关重要。我们在此报告称，一种来源于蒎烯的亚氨基二乙酸（PIDA）配体能够高非对映选择性地合成各种环氧化合物 C(sp(3))硼酸酯，原料为相应的烯烃。这些环氧化合物 PIDA 硼酸酯，反过来，通过硼酸盐基团的新型 1,2-迁移，很容易转化为前所未有的稳定α-硼基醛，同时完全保持立体化学纯度。通过这个平台可以轻松获得含有双 sp(3)-杂化 C 中心的 B-保护卤代硼酸，并且在此展示的能力是通过这种新型双官能试剂进行立体控制迭代 C(sp(3))交叉偶联，以高度富集的对映体形式获得一种具有医学重要性的手性小分子靶标，这代表了基于构建块的合成方法的重大进展。
