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

通过 10-取代-9-硼双环[3.3.2]癸烷实现不对称有机硼烷转化的新型稳定手性连接

• 批准号: 0517194
• 负责人: John Soderquist
• 金额: $ 34.3万
• 依托单位: University of Puerto Rico
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0517194&HistoricalAwards=false
• 关键词: Novel; Stable; Chiral; Ligation; Asymmetric

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.

由稳定的重氮甲烷与B-甲氧基-9-硼双环[3.3.1]壬烷（B-MeO-9-BBN）反应，合成了新型的10-（取代）-9-硼双环[3.3.2]癸烷体系（BBD）。这些试剂容易以顺序方式拆分，产生试剂的两种对映体纯形式。这些络合物与格氏试剂的反应直接提供B-烯丙基-、丙二烯基-或炔丙基-10 R-BBD，定量地，作为稳定的、可分离的对映体纯形式的化合物。相应的B-巴豆基（E和Z）和Z-γ-OR-烯丙基试剂也容易从对映体纯的B-MeO-10 R-9-BBD制备。10-TMS和10-Ph试剂分别专为醛和酮的极高对映选择性加成而定制。该项目的具体目标是用这些稳健的手性硼烷开发新的化学，包括1）用新的2-硼基-1，3-二烯的不对称“烯丙基硼化”，可能导致手性β-联烯基甲醇，2）酮的不对称γ-甲氧基烯丙基硼化，具有fostriecin应用，3）不对称的Suzuki-Miyaura偶联和联烯化，潜在地得到手性联烯和具有高非对映异构体的β-TMS高炔丙醇。和对映选择性，4）B-炔基-BBD与烯酮和N-酰基亚胺的共轭加成，5）酮的不对称炔丙基硼化，和6）1，1-二取代烯烃的不对称硼氢化，得到适合于不对称Suzuki-Miyaura烷基偶联的非外消旋产物。有机和高分子化学计划是支持博士约翰A。波多黎各大学化学系的Soderquist说。 Soderquist教授和他的学生将研究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”试剂预期等于或超过其它已知试剂或方法报道的选择性，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、稳健的双环性质来创建稳定的“酶样”环境，用于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。