Novel Stable Chiral Ligation for Asymmetric Organoborane Conversions via 10-Substituted-9-borabicyclo[3.3.2]decanes

由稳定的重氮甲烷与B-甲氧基-9-硼双环[3.3.1]正庚烷(B-MeO-9-BBN)反应，合成了新型的10-(取代)-9-硼双环[3.3.2]正十一烷体系(BBDS)。这些试剂很容易按顺序分解，产生两种形式的试剂，它们都是对映体纯的。这些络合物与格氏试剂反应，直接提供B-烯丙基、烯丙基或炔丙基-10R-BBDS，定量地作为稳定的、可分离的化合物，以对映体纯的形式存在。相应的B-巴豆基(E和Z)和Z-伽马-或-烯丙基试剂也很容易从对映体纯的B-MeO-10R-9-BBDS中制备。10-TMS和10-Ph试剂分别专为醛和酮的极不对称加成反应量身定做。这个项目的具体目标是开发这些强健的手性硼烷的新化学，包括1)与新的2-硼基-1，3-二烯的不对称“烯丙基硼”反应，可能导致手性β-烯丙基甲醇，2)酮的不对称伽马-甲氧基烯丙基硼化反应，3)不对称Suzuki-Miyaura偶联和烯基化反应，3)不对称Suzuki-Miyaura偶联和烯基化反应，具有高的非对映和对映选择性，4)B-炔基-BBD与酮和N-酰亚胺的不对称加成反应，5)酮的不对称丙醛基硼加成反应，5)酮的不对称丙醛基硼加成反应，和6)1，1-二取代烯烃的不对称氢硼化反应，得到适合不对称Suzuki-Miyaura烷基偶联的非外消旋产物。有了这个续展奖，有机化学和高分子化学计划支持波多黎各大学化学系的John A.Soderquist博士的研究。索德奎斯特教授和他的学生将学习含有碳和硼之间键的化合物的合成和反应化学。这些新的“有机硼烷”试剂有望达到或超过其他已知试剂或方法的选择性，同时提供极大的通用性以及易于制备、处理和回收。这些研究利用有机硼烷的刚性、健壮的双环性质来创造一个稳定的、类似酶的环境，以协调高度选择性和受控的反应。这种方法为研究以及制药和化学工业中的各种合成应用提供了希望。

Novel 10-(substituted)-9-borabicyclo[3.3.2]decane systems (BBDs) are readily prepared from the reaction of stable diazomethanes with B-methoxy-9- borabicyclo[3.3.1]nonane (B-MeO-9-BBN). These reagents are easily resolved in a sequential manner producing both enantiomerically pure forms of the reagents. Reaction of these complexes with Grignard reagents directly provides B-allyl-, allenyl-, or propargyl-10R-BBDs, quantitatively, as stable, isolable compounds in enantiomerically pure form. The corresponding B-crotyl (E and Z) and Z-gamma-OR-allyl reagents are also readily prepared from the enantiomerically pure B-MeO-10R-9-BBDs. The 10-TMS and 10-Ph reagents are specifically tailored for extremely enantioselective additions to aldehydes and ketones, respectively. The specific goals of this project are to develop new chemistry with these robust chiral boranes, including 1) asymmetric "allylboration" with novel 2-boryl-1,3-dienes potentially leading to chiral beta-allenyl carbinols, 2) asymmetric gamma-methoxyallylboration of ketones with a fostriecin application, 3) asymmetric Suzuki-Miyaura coupling and allenylation potentially giving chiral allenes and beta-TMS homopropargylic alcohols with high diastereo- and enantioselectivity, 4) conjugate additions of B-alkynyl-BBDs to enones and N-acylimines, 5) asymmetric propargylboration of ketones, and 6) asymmetric hydroboration of 1,1-disubstituted alkenes to give non-racemic products which are suitable for asymmetric Suzuki-Miyaura alkyl coupling.With this renewal award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. John A. Soderquist of the Department of Chemistry at the University of Puerto Rico. Professor Soderquist and his students will study the synthesis and reaction chemistry of compounds containing bonds between carbon and boron. These new "organoborane" reagents are expected to equal or exceed the selectivities reported for other known reagents or processes while offering great versatility as well as ease of preparation, handling and recycling. These studies utilize the rigid, robust bicyclic nature of the organoboranes to create a stable, "enzyme-like" environment for orchestrating highly selective and controlled reactions. This methodology offers promise for a variety of synthetic applications in research and in the pharmaceutical and chemical industries.