Ketene Recognizes 1,3-Dienes in Their s-Cis Forms through [4 + 2] (Diels−Alder) and [2 + 2] (Staudinger) Reactions. An Innovation of Ketene Chemistry

Abstract

The mechanism of ketene-diene reactions has been studied both experimentally and theoretically. Careful experiments of the reactions of diphenylketene (1) with cyclic (s-cis) 1,3-dienes [cyclopentadiene (2) and cyclohexa-1,3-diene (3)] lead to the first direct detection of the Diels-Alder cycloadducts (10 and 11) by low-temperature NMR spectroscopy. The initially formed cycloadducts are converted to the final Staudinger products, cyclobutanones (6 and 7), by [3,3] sigmatropic (Claisen) rearrangements. In contrast, ketene 1 reacts with open-chain 1,3-dienes [2,3-dimethyl-1,3-butadiene (4) and 1-methoxy-1,3-butadiene ( 5)] to afford initially both the Staudinger-type (8, 9) and Diels-Alder-type cycloadducts (12, 13). The Staudinger cycloadducts (8, 9) are converted eventually to Diels-Alder products (12, 13) by the retro-Claisen rearrangement. Thus, ketene recognizes dienes in cycloadditions as ketenophiles different from olefins. [4 + 2] and [2 + 2] cycloadducts are generated and can be intermediates or products flexibly according to diene structures.

Pericyclic Reaction of Ketenes with Cascade Reaction Products of Pyridine N-Oxides and Dipolarophiles. X-Ray Structures of the Adducts and Formation Mechanism

“…Path A is a cascade-type reaction (see also Chart 2). 2,5) The barrier for Path A is 18.9 kcal/mol higher than that for the stepwise [2ϩ2] cycloaddition and 12.5 kcal/mol higher than the barrier for the corresponding cyclohexadiene model.…”

“…5) However, this reaction mechanism may not be applicable to the reaction of 1-azadienes. The molecular orbital (MO) calculation of the reaction pathway suggests that the reaction proceeds via a stepwise [2ϩ2] cycloadditiion that is initiated by the imine nucleophile attacking the ketene, followed by cyclization of the 2-azadiene intermediate (5) (Path B). Isolation of two stereoisomeric 2 : 1 cycloadducts from the reaction of 3,3-dimethyl-3H-indole with 2 strongly supports the presence of a zwitterionic reaction intermediate.…”

Chemical Reactivity of Dihydropyrazine Derivatives. Cycloaddition Behavior toward Ketenes

“…This finding has caused a revolution in ketene chemistry. 14) In this connection, we previously reported another cycloaddition mechanism for the reaction of dihydropyridines with ketenes on the basis of MO calculations, 15) in which the lactam ring formation does not proceed via a sequential pericyclic reaction mechanism but takes place by a stepwise reaction mechanism (Chart 3, entry c). Based on the results for dihydropyridines, we considered that the reaction of a ketene with an a,b-unsaturated cyclic imine does not fall into the new category but involves initial nucleophilic attack of the imine nitrogen on the ketene sp-hybridized carbon, followed by 4p electrocyclic ring closure to give the [2ϩ2] cycloaddition product.…”

Pericyclic Cascade with Chirality Transfer: Reaction Pathway and Origin of Enantioselectivity of the Hetero‐Claisen Approach to Oxindoles

“…Nevertheless, the interplay between theory and experiment continues to uncover novel cascade mechanisms with new or underexplored reactivity patterns. Indeed, for the 2+2 cycloadditions of ketenes with 1,3-dienes [3] and imines, [4] the pericyclic mechanisms once formulated have recently been revised to cascades of more than one elementary mechanistic step. Other more elaborate pericyclic cascades of synthetic interest have also been elucidated by computations.…”