A Novel Enantioselective Catalytic Tandem Oxa‐Michael–Henry Reaction: One‐Pot Organocatalytic Asymmetric Synthesis of 3‐Nitro‐2H‐chromenes

Abstract

An enantioselective oxa-Michael-Henry reaction of substituted salicylaldehydes with nitroolefins that proceeds though an aromatic iminium activation (AIA) has been developed by using a chiral secondary amine organocatalyst and salicylic acid as a co-catalyst. The corresponding 3-nitro-2H-chromenes were obtained in moderate-to-good yields with up to 91% ee under mild conditions. Based on the experimental results and ESI-mass spectrometric detection of the intermediates, a plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.

Simultaneous Synthesis of Both Rings of Chromenes via a Benzannulation/o-Quinone Methide Formation/Electrocyclization Cascade

“…2 Nearly all of the methods for the synthesis of chromenes involve the closure of the pyran ring on a substrate containing a pre-formed phenol unit of the type 2 . Recent representative methods include Claisen rearrangement 3 or electrophile induced cyclization of aryl propargyl ethers, 4 palladium-catalyzed 5 and selenium-mediated 2a cyclization of 2-butenylphenols, ring closing metathesis, 6 cyclization of salicylaldehydes with enamines, 7 Wittig olefination, 8 Petasis reaction of salicylaldehydes 9 and the reaction of salicylaldehydes with vinyltrifluoroborates, 10 palladium catalyzed oxidative cyclization of aryl-3-butenyl ethers, 11 ene 12 and Baylis-Hillman 13 reactions of salicylaldehydes, ylide induced annulation, 14 enolization of vinylquinones, 15 cyclization onto 3,4-epoxy alcohols, 16 the reactions of phenols with α, β-unsaturated aldehydes, 17 the oxa-Michael-aldol/Henry reaction of salicylaldehydes 18 and the dehydrative cyclizations of 2-(1-hydroxy-2-propenyl)phenols. 19 Of all the methods of the myriad, to the best of our knowledge, there is not a single one in which both rings of the chromene core are constructed at the same time.…”

Organocatalytic Enantioselective Henry Reactions

“…In order to synthesize interesting chromene derivatives, Xu et al applied this tandem methodology using the chiral secondary amine organocatalyst 17 with salicylaldehydes and β-nitrostyrenes via a domino oxa-Michael/Henry reaction (Scheme 14) [55]. The mechanism proposed by the authors explains the isolated final adducts.…”

A reaction mode of carbene-catalysed aryl aldehyde activation and induced phenol OH functionalization

“…Organic catalyst-enabled activation of aromatic or benzylic carbon as reactive centre has been much less developed. Representative examples in this direction include photoredox/organocatalytic radical reactions from MacMillan and colleagues4 and Melchiorre and colleagues5, and amine-mediated reactions via an enamine or iminium intermediate from Melchiorre and colleagues6, Jørgensen and colleagues7, Chen and colleagues8 and Xu et al 9…”