Chiral phosphoric acid-catalyzed regio- and enantioselective reactions of functionalized propargylic alcohols

Abstract

Propargylic alcohols have been known as useful substrates in a wide range of asymmetric reactions. Particularly, the chiral phosphoric acids (CPAs) catalyzed reactions of functionalized propargylic alcohols opened a robust...

Chiral Brønsted Acid Catalyzed Enantioselective Synthesis of Spiro-Isoindolinone-Indolines via Formal [3 + 2] Cycloaddition

“…This probably suggests that the substitute at 3-position of indole is essential for obtaining the formal [3 + 2] adduct. As reported by Li et al, we also performed the reaction of propargylic alcohol 2a with catalyst VI but in a deuterated dichloromethane; however, we did not observe the hemiaminal functionality peak (i.e., 79.5 ppm) in the 13 C NMR spectra . Further, we have conducted the nonlinear effect experiments study, which revealed that only one catalyst molecule is involved in enantio-controlling transition states…”

“…In continuation of our earlier efforts to organocatalytic enantioselective syntheses of 3-substituted isoindolinones, here we report a chiral Brønsted acid catalyzed enantioselective formal [3 + 2] cycloaddition of β,γ-alkynyl-α-ketimines with 3-substituted 1H-indoles to give spiro-isoindolinone-indolines. During the preparation of our paper, Li et al reported very similar findings on enantioselective synthesis of spiro-isoindolidinone-derived containing N (acyl), N -acetals; however, in contrast to their optimized reaction conditions, our reaction works without molecular sieves and at ambient temperature in the presence of the same chiral phosphoric acid catalyst but in a different solvent.…”

“…Unfortunately, skatole having highly electron withdrawing substituent 3l (4-CN) and 3m (5-NO 2 ) did not produce the corresponding spiro compounds. The absolute configuration of compound 4a was determined as ( S ) by comparing the optical rotation with its literature value and the configuration of other spiro-isoindolinones ( 4 and 5 ) within this series were assigned by analogy.…”

Catalyst-Controlled Divergent Reactions of 2,3-Disubstituted Indoles with Propargylic Alcohols: Synthesis of 3H-Benzo[b]azepines and Axially Chiral Tetrasubstituted Allenes

“…13,14 Recently, we have developed a CPAcatalyzed regio-and enantioselective addition of alkynyl ketimides formed in situ from 3-alkynyl-3-hydroxyisoindolinones with indoles (Scheme 1B). 15 In continuation of our efforts in the field of CPA-catalyzed reactions of propargylic alcohols, here we report a catalyst-controlled divergent reactions between 3-alkynyl-3-hydroxyisoindolinones and 2,3disubstituted indoles (Scheme 1C). With strong acid as the catalyst, an allenylation/annulation cascade reaction occurred to afford [5 + 2] ring-expansion products, which is in sharp contrast to the discovery by Swamy et al Furthermore, the configuration of the annulation products depended on the substrates.…”

“…Recently, significant progress has been made in the field of chiral phosphoric acid (CPA) catalyzed reactions of propargylic alcohols via in situ formed quinone methides, aza-quinone methides, and indole imine methides . However, the reactions between propargylic alcohols and 2,3-disubstituted indoles failed to construct axially chiral tetrasubstituted allenes with high stereoselectivity. , Recently, we have developed a CPA-catalyzed regio- and enantioselective addition of alkynyl ketimides formed in situ from 3-alkynyl-3-hydroxyisoindolinones with indoles (Scheme B) . In continuation of our efforts in the field of CPA-catalyzed reactions of propargylic alcohols, here we report a catalyst-controlled divergent reactions between 3-alkynyl-3-hydroxyisoindolinones and 2,3-disubstituted indoles (Scheme C).…”