Organocatalytic and Regiodivergent Mannich Reaction of Ketones with Benzoxazinones

Abstract

In this study, we have developed solvent‐controlled regioselective Mannich reaction of cyclicimines (benzoxazinones) with various ketones by using ʟ‐proline as catalyst to afford Mannich products in high yields with excellent enantio‐ and diastereoselectivity. The unsymmetrical ketones produced the linear isomer as the major product in chloroform solvent. On contrary, using the DMSO solvent favoured the formation of branch isomer product with excellent enantio‐ and diastereoselectivity. The aromatic auxiliary was successfully removed and afforded N‐protected chiral amino acid derivative.magnified image

Reagent-free intramolecular hydrofunctionalization: a regioselective 6-endo-dig cyclization of o-alkynoylphenols

“…[27][28][29][30] To the best of our knowledge, there have been no reports of intramolecular hydrofunctionalization under reagent-free conditions so far. As part of our continuous effort and interest in developing metal-free and eco-friendly synthetic methodologies for heterocyclic compound synthesis, [31][32][33][34][35][36] we hypothesized that the presence of self-acidic H-bonds in o-alkynoylphenols 1 might assist intramolecular hydrofunctionalization under reagent-free conditions, resulting in 6-endo-dig and/or 5exo-dig cyclization (compound 2), as outlined in Scheme 1D. The notable benefits of our current approach are: (a) it is reagent free and regioselective and works under mild reaction conditions, (b) it has high atom economy, atom efficiency, carbon efficiency, and reaction mass efficiency, and (c) it has a broad substrate scope with high functional group tolerance.…”

Total Synthesis of Isohericerinol A and Its Analogues to Access Their Potential Neurotrophic Effects

“…Although the Pd-catalyzed approach (Scheme ) was satisfactory in terms of overall yield and number of reaction steps involved, we further intended to develop a metal-free approach as an alternative way to isohericerinol A. As a part of our continuous interests and efforts in the search of metal-free strategy in organic small molecules synthesis, − Scheme was proposed as an alternative method for isohericerinol A ( 1 ). The method involves a sequential Mannich reaction and lactamization to synthesize isoindolinone core 7b followed by allylation (for compound 14 ) and Claisen rearrangement (for compound 6 ).…”

Recent advances in the synthesis of fluorinated amino acids and peptides

“…In 2018, the Jung group developed a regioselective l -proline-catalyzed Mannich reaction of cyclic imines with various ketones to afford the protected α-CF 3 , α-AAs with high yields and excellent enantio- and diastereo-selectivities (Scheme 7c). 22 In the same year, a new strategy for enantioselective synthesis of aza-Baylis-Hillman type products was developed by the Alemán group (Scheme 7d). 23 In this transformation, the chiral thiourea catalyst exhibited excellent Z / E - and enantio-selectivities.…”