A halide-initiated aza-Baylis–Hillman reaction: generation of unnatural amino acids

A general protocol for stereoselective construction of enaminyl sulfonyl fluorides

“…A putative mechanism of this reaction was proposed based on previous examples from the literature 18–20 and our investigation, as presented in Scheme 5. With the promotion of base, CESF 2 could be converted to propa-1,2-diene-1-sulfonyl fluoride A through β-elimination, and subsequently the amine would undergo a nucleophilic attack on the β-position of the electron-deficient allene via a Michael addition type of reaction to achieve the thermodynamically more stable E -configuration of vinyl product 3 .…”

Highlighting the Rich Chemistry of the Allenone Moiety

“…[255] Treatment of allenones 2 with MgBr 2 in the presence of the electrophilic tosylimino acetates 602 results in a formal aza-Morita-Bailys-Hillman reaction affording mixtures of two adducts 603 and 604 (Scheme 102b). [256,257] The formation of allenone-decorated aminoesters 603 can be explained from the attack of C2 carbon atom in intermediate 605 through path a, while compounds 604 are probably obtained through the attack of the terminal carbon atom following path b from the same reaction intermediate (Scheme 102b). [256,257] An alternative chemical behaviour has been recently reported from in situ generated β-allenones towards the synthesis of dienones.…”

“…[256,257] The formation of allenone-decorated aminoesters 603 can be explained from the attack of C2 carbon atom in intermediate 605 through path a, while compounds 604 are probably obtained through the attack of the terminal carbon atom following path b from the same reaction intermediate (Scheme 102b). [256,257] An alternative chemical behaviour has been recently reported from in situ generated β-allenones towards the synthesis of dienones. Alkynols 606 react with acids generating allene carbocations 611, which can be trapped by oxonium ylides (formed in situ from alcohols and diazoketones 607) providing the observed conjugate dienones 610, which are generated from the tautomerization of intermediate allenones 609 (Scheme 103).…”

“…Initial deprotonation of 2 and S N reaction with α‐bromoketones 599 lead to allenyl diketones 600 , which in situ undergo TBAF‐assisted hydration to yield the experimentally observed tricarbonyl compounds 601 (Scheme 102a) [255] . Treatment of allenones 2 with MgBr 2 in the presence of the electrophilic tosylimino acetates 602 results in a formal aza‐Morita‐Bailys‐Hillman reaction affording mixtures of two adducts 603 and 604 (Scheme 102b) [256,257] . The formation of allenone‐decorated aminoesters 603 can be explained from the attack of C2 carbon atom in intermediate 605 through path a , while compounds 604 are probably obtained through the attack of the terminal carbon atom following path b from the same reaction intermediate (Scheme 102b) [256,257] …”