1217263-86-9Relevant academic research and scientific papers
Mechanistic Insights into the Origin of Stereoselectivity in an Asymmetric Chlorolactonization Catalyzed by (DHQD)2PHAL
Ashtekar, Kumar Dilip,Borhan, Babak,Holmes, Daniel,Jackson, James E.,Kakeshpour, Tayeb,Reed, Paul,Sarkar, Aritra,Whitehead, Daniel C.,Yousefi, Roozbeh
, p. 7179 - 7189 (2020/05/14)
Electrophilic halofunctionalization reactions have undergone a resurgence sparked by recent discoveries in the field of catalytic asymmetric halocyclizations. To build mechanistic understanding of these asymmetric transformations, a toolbox of analytical methods has been deployed, addressing the roles of catalyst, electrophile (halenium donor), and nucleophile in determining rates and stereopreferences. The test reaction, (DHQD)2PHAL-catalyzed chlorocyclization of 4-arylpent-4-enoic acid with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH), is revealed to be first order in catalyst and chlorenium ion donor and zero order in alkenoic acid substrate under synthetically relevant conditions. The simplest interpretation is that rapid substrate-catalyst binding precedes rate-limiting chlorenium attack, controlling the face selectivity of both chlorine attack and lactone closure. ROESY and DFT studies, aided by crystal structures of carboxylic acids bound by the catalyst, point to a plausible resting state of the catalyst-substrate complex predisposed for asymmetric chlorolactonization. As revealed by our earlier labeling studies, these findings suggest modes of binding in the (DHQD)2PHAL chiral pocket that explain the system's remarkable control over rate- A nd enantioselection-determining events. Though a comprehensive modeling analysis is beyond the scope of the present work, quantum chemical analysis of the fragments' interactions and candidate reaction paths point to a one-step concerted process, with the nucleophile playing a critical role in activating the olefin for concomitant electrophilic attack.
Monomeric Cinchona Alkaloid-Based Catalysts for Highly Enantioselective Bromolactonisation of Alkynes
Wilking, Michael,Daniliuc, Constantin G.,Hennecke, Ulrich
supporting information, p. 18601 - 18607 (2016/12/16)
The cinchona alkaloid dimer (DHQD)2PHAL has been shown to be a broadly applicable catalyst for asymmetric halogenations. However, this catalyst does not have to be dimeric and a class of monomeric quinidine and quinine-derived catalysts was prepared, often showing superior selectivity in bromolactonisations of terminal alkynoic acids. Mechanistic investigations show that these organocatalysts act as host molecules that can bind carboxylic acid-based substrates as guests with substantial binding constants. Based on these findings, it is proposed that this class of catalysts is bifunctional in nature activating the halogenating agent as well as the nucleophile in electrophilic halogenation reactions.
Catalytic enantioselective halolactonization of enynes and Alkenes
Zhang, Wei,Liu, Na,Schienebeck, Casi M.,Decloux, Kyle,Zheng, Suqing,Werness, Jenny B.,Tang, Weiping
experimental part, p. 7296 - 7305 (2012/07/03)
New organocatalysts have been developed for the enantioselective halolactonization of (Z)-1,3-enynes and 1,1-disubstituted alkenes. In the case of 1,3-enynes, the carboxylate nucleophile and halogen electrophile were added to the conjugated π-system from the same face. Up to 99%ee was achieved for the 1,4-syn-bromolactonization of conjugated (Z)-1,3-enynes. Based on the results from the enyne halolactonization, a second generation of catalysts was designed for simple olefins. Up to 91%ee was observed for chlorolactonization of 1,1-disubstituted alkenes. The catalysts developed for the enantioselective halolactonization of both enynes and alkenes are composed of a cinchona alkaloid skeleton tethered to a urea group.
