Formation of optically active chromanes by catalytic asymmetric tandem oxa-Michael addition–Friedel–Crafts alkylation reactions

Abstract

A novel tandem reaction involving an oxa-Michael addition, followed by a Friedel-Crafts alkylation has been developed. This catalytic tandem reaction, which provides facile and efficient access to optically active functionalised chromanes, proceeds under the influence of bisoxazoline-based catalysts to give diastereomerically pure products in enantioselectivities up to 81% and excellent yields. The optimisation studies, the scope of the reaction, and a model that on the basis of PM3 calculations predicts the outcome of the reaction will be detailed.

The Asymmetric Formal Hetero‐Diels–Alder Reaction of Methyl (E)‐4‐Aryl‐2‐oxo‐3‐butenoates Catalyzed by [Sc(OTf)3/pybox] Complexes

“…Amongst them, (E)-4-aryl-2-oxo-3-butenoates 1 have a specific advantage due to the presence of a further carbonyl group in the αЈ-position, because the 1,2dicarbonyl system may coordinate to a Lewis acid (Figure 1). Although certain reactions have been only occasionally investigated (e.g., alkylation, [1] hydrogenation, [2] and the aldol reaction [3] ), the classical Michael reaction has been extensively studied, [4,5] as has its oxa-, thio-, and Henry variants, [6][7][8] and tandem Michael-cyclization processes. ray crystal analysis.…”

Catalytic Asymmetric Syntheses of 2‐Aryl Chromenes

“…The asymmetric intermolecular cyclization for synthesis of chiral chromanes often involved modified phenols as substrates . As to chiral flavanes, the first example was published by Jørgenson's group in 2003 . There they developed a novel enantioselective catalytic tandem reaction involving an oxa‐Michael addition and subsequent Friedel‐Crafts alkylation between electron‐rich phenol 52 b‐c and β,γ‐unsaturated α‐ketoesters 74 catalyzed by bisoxazoline‐based catalysts, providing optically active functionalized flavanes 76 with up to 81% enantiomeric excess and excellent yields (Scheme ).…”

Domino Reactions Involving Catalytic Enantioselective Conjugate Additions

“…In this way, functionalized chromanes may become accessible through a methodology introduced by the group of Jørgensen, utilizing a Mg-Box-species 80 as catalyst (Scheme 8.18) [30]. This complex, which is formed in situ from Mg(OTf ) 2 and 80, is able to catalyze the domino transformation of phenols 77 containing a methoxy group in the meta-position and the β,γ-unsaturated α-ketoesters 78 to give the corresponding chromanes 79, with excellent diastereo-and enantioselectivity of up to 80%.…”