Synthesis of 2,2‐Disubstituted 2H‐Chromenes through Carbon‐Carbon Bond Formation Utilizing a [1,2]‐Phospha‐Brook Rearrangement under Brønsted Base Catalysis

Abstract

A new methodology for the synthesis of 2,2‐disubstituted 2H‐chromenes was developed by utilizing the [1,2]‐phospha‐Brook rearrangement under Brønsted base catalysis. Phosphazene P2‐tBu efficiently catalyzed the addition reaction of 4H‐chromen‐4‐ols containing a diethoxyphosphoryl group with α,β‐unsaturated ketones, which involved the catalytic generation of a carbanion through the [1,2]‐phospha‐Brook rearrangement and subsequent conjugate addition at the 2‐position to afford adducts possessing an alkenylphosphate moiety in a highly diastereoselective manner. Further transformation of the adducts based on a nickel‐catalyzed cross‐coupling reaction with arylzinc reagents provided densely functionalized 2,2‐disubstituted 2H‐chromenes.

Organophosphates as Versatile Substrates in Organic Synthesis

“…The initially formed phosphonate 29 – 1 undergoes rearrangement to produce an alkyl phosphate 29 – 2 , which is then amenable to a further reaction with an electrophile. Terada’s group has extensively used the [1,2]-phospha-Brook rearrangement for the synthesis of substituted furans [ 123 , 124 ], pyrroles [ 125 ], phenantherenes [ 126 ], indolizine [ 127 ], piperidines [ 128 ], oxindoles [ 129 ], chromenes [ 130 ], and many others [ 131 , 132 , 133 , 134 , 135 , 136 , 137 ]. The [1,2]-Phospha-Brook rearrangement has also attracted significant attention from other research groups, leading to numerous studies [ 138 , 139 , 140 , 141 , 142 ] and comprehensive reviews [ 143 , 144 ].…”

Asymmetric Organocatalytic 1,6-Conjugate Addition of para-Quinone Methides Using [1,2]-Phospha-Brook Rearrangement

“…This rearrangement generates reactive α-phosphonyloxy enolates for further transformations. A number of excellent studies were reported by using this method such as aldolization, Mannich addition, conjugate addition, protonation, and substitution, but most of them were established in racemic versions. Ooi’s and Johnson’s groups − reported the asymmetric Pudovik addition/phospha-Brook rearrangement/aldolization/phosphate migration cascade reaction catalyzed by iminophosphorane or triaryliminophosphorane catalysts (Scheme b).…”

Stereoselective Reductive Coupling Reactions Utilizing [1,2]-Phospha-Brook Rearrangement: A Powerful Umpolung Approach

“…In subsequent years, the authors also successfully trapped allyl anion intermediates realized through phosphazene base-catalyzed [1,2]-phospha-Brook rearrangement of phosphoryl group containing 4 H -chromen-4-ols 59 and subsequent addition to many electrophiles such as α,β- unsaturated ketones 60 , vinyl sulfones, aldehydes, and imines (Scheme ). This approach allowed generation of a collection of 2,2-disubstituted 2 H -chromenes 61 in good yields and high diastereomeric excess. The applicability of this protocol was also exemplified by various scalable transformations.…”