Organocatalytic site- and stereoselective 1,6-additions of N-aryl-3-oxobutanamides to propargylic aza-p-quinone methides

Abstract

A chiral phosphoric acid catalyzed site-selective 1,6-conjugate addition of N-aryl-3-oxobutanamides to in situ formed propargylic aza-p-quinone methides from propargylic alcohols have been established and represents the first report on organocatalytic...

Recent Advances in Organocatalytic Enantioselective Synthesis of Axially Chiral Allenes

“… [29] The steric hindrance of 1,3‐dicarbonyl compounds had an essential effect on the reaction. When acyclic 1,3‐dicarbonyl compounds were employed as reaction partners, 1,6‐adducts were obtained from the chiral phosphoric acid mediated reaction of in situ formed propargylic aza‐ p ‐QMs from propargylic alcohols [30] …”

“…When acyclic 1,3-dicarbonyl compounds were employed as reaction partners, 1,6-adducts were obtained from the chiral phosphoric acid mediated reaction of in situ formed propargylic aza-p-QMs from propargylic alcohols. [30] Continuing their previous progress in the field of chiral phosphoric acid catalysis, Sun et al elegantly realized asymmetric construction of axially chiral tetrasubstituted allenes from the reactions of α-(2indolyl) propargylic alcohols 68 (Scheme 20). [31] In the presence of chiral phosphoric acid C23, alkynyl indole imine methides were formed in situ from α-(3-indolyl) propargylic alcohols 64 to react with 3-substituted indoles 69 to afford allenes 70 bearing two indole units in 52-97% yields with 43-99% ee.…”

β‐Keto Amides: A Jack‐of‐All‐Trades Building Block in Organic Chemistry

“…In the presence of silica gel‐supported NaHSO 4 [138] and Hf(OTf) 4 , [139] β ‐keto amides were α ‐alkylated with benzyl alcohols to give 300 and 301 respectively. In 2020, Li and co‐workers [140] reported a chiral phosphoric acid 304 catalyzed site‐selective 1,6‐conjugate addition of 302 to the in situ formed propargylic aza ‐ p ‐quinone methides from 303 , leading to 305 in 83–95 % ee's and >20/1 dr's (Scheme 57).…”

Brønsted Acid-Catalyzed Formal (3+3)-Annulation of Propargylic (Aza)-para-Quinone Methides with 4-Hydroxycoumarins and 1,3-Dicarbonyl Compounds

“…Owing to the intrinsic electrophilicity, p -QMs as excellent Michael acceptors have attracted great attention from synthetic chemists . Compared with the fact that numerous methodologies for 1,6-conjugate additions of p -QMs have been developed, − however, less attention has been devoted to 1,8-conjugate additions of (aza)- para -quinone methides ((aza)- p -QMs). In 2017, Sun’s group first reported the challenging asymmetric 1,8-conjugate addition of in situ generated propargylic p -QMs for the synthesis of chiral tetrasubstituted allene compounds (Scheme a).…”