Synthesis of Partially Saturated Nitrogen Heterocycles Through Stereo- And Regioselective Dearomatization of Heteroarenes

通过杂芳烃的立体和区域选择性脱芳构化合成部分饱和氮杂环

基本信息

批准号：
10672398
负责人：
Rashad Karimov
金额：
$ 37.41万
依托单位：
AUBURN UNIVERSITY AT AUBURN
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-15 至 2027-06-30
项目状态：
未结题

项目摘要

Synthesis of partially saturated nitrogen heterocycles through stereo- and regioselective dearomatization of heteroarenes. Nitrogen-containing heterocycles are important in multiple areas of chemistry including pharmaceutical, agrochemical and materials science due to their chemical properties and biological significance. These heterocycles are often grouped as aromatic and non-aromatic heterocycles. Aromatic heterocycles are widely available and recent advances in various cross coupling and C-H activation chemistry have further improved the access to these heterocycles. On the other hand, methods for the synthesis of non-aromatic heterocycles which often contain stereogenic centers at sp3 hybridized carbon centers are less developed. Our long-term goal is to develop new chemical transformations that will regio-, and stereoselectively introduce functionality into the heteroarenes to enable synthesis of partially saturated nitrogen heterocycles. Partially saturated heterocycles are excellent precursors to both aromatic and non-aromatic azaheterocycles. For example, dihydropyridines can be functionalization or reduced to yield tetrahydropyridines and piperidines and they can be oxidized to yield pyridines. The current proposal addresses the regioselective, stereoselective and catalytic addition of nucleophiles and electrophiles to the heteroarenes for the synthesis of partially saturated six- membered azaheterocycles. Specifically, we propose methodologies supported by significant preliminary results and literature precedents for the transition metal catalyzed dearomatization reactions of heteroarenes focusing on the regioselective dearomatization of six-membered heteroarenes containing one or two nitrogen atoms. Dearomatization approaches proposed by us include Rh, Pd, Ni and Cu catalyzed addition of boron nucleophiles as well as addition of organometallic nucleophiles to activated N-alkyl and N-acyl heteroarenes. In addition to coupling of nucleophiles, we propose dearomative coupling of heteroarenium salts with electrophiles using Ni-photoredox system. Catalyst design approaches for controlling the regio- and stereoselectivity of the addition reactions will also be explored. Methods described by us are innovative as they involve previously unexplored approaches, coupling partners and catalysts. The results obtained from these studies will be significant as the saturated and partially saturated heterocycles are common structural motifs in bioactive natural products and pharmaceuticals.

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rhodium-Catalyzed Asymmetric Functionalization of Quinoxalinium Salts.

铑催化的喹喔啉盐的不对称官能化。

DOI：
10.1021/acs.orglett.3c03555
发表时间：
2023-12-07
期刊：
Organic letters
影响因子：
5.2
作者：
Kacey G. Ortiz;Jensen S. Hammons;Rashad R. Karimov
通讯作者：
Rashad R. Karimov

Catalyst-Controlled Enantioselective and Regiodivergent Addition of Aryl Boron Nucleophiles to N-Alkyl Nicotinate Salts.

芳基硼亲核试剂与 N-烷基烟酸盐的催化剂控制对映选择性和区域发散加成。

DOI：
10.1021/jacs.3c03048
发表时间：
2023-05-19
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Kacey G. Ortiz;Jordan J. Dotson;Donovan J Robinson;M. Sigman;Rashad R. Karimov
通讯作者：
Rashad R. Karimov