Abstract
Controlling the sequence of the three consecutive reactive carbon centres of Cu-allenylidene remains a challenge. One of the impressive achievements in this area is the Cu-catalyzed annulation of 4-ethynyl benzoxazinanones, which are transformed into zwitterionic Cu-stabilized allenylidenes that are trapped by interceptors to provide the annulation products. In principle, the reaction proceeds via a preferential γ-attack, while annulation reactions via an α- or β-attack are infrequent. Herein, we describe a method for controlling the annulation mode, by the manipulation of a CF3 or CH3 substituent, to make it proceed via either a γ-attack or an α- or β-attack. The annulation of CF3-substituted substrates with sulfamate-imines furnished densely functionalized N-heterocycles with excellent enantioselectivity via a cascade of an internal β-attack and an external α-attack. CH3-variants were transformed into different heterocycles that possess a spiral skeleton, via a cascade of an internal β-attack and a hydride α-migration followed by a Diels−Alder reaction.
Highlights
Controlling the sequence of the three consecutive reactive carbon centres of Cu-allenylidene remains a challenge
We commenced our investigation with an annulation reaction of 4-ethynyl CF3-benzoxazinanone 1a and sulfamate-derived cyclic imine 2a at room temperature in the presence of CuOTf·1/2 C6H6 (10 mol%), a methyl-substituted Pybox ligand (L1, 20 mol%), and iPr2NEt (2.4 equiv) in toluene (Table 1, entry 1)
Based on the experimental results and our own hypotheses, we propose a feasible reaction mechanism to rationalize the formation of polycyclic merged indolines 3 from the reaction of 4-ethynyl 4-CF3-benzoxazinanones 1 with cyclic sulfamate imines 2 (Fig. 7a)
Summary
Controlling the sequence of the three consecutive reactive carbon centres of Cu-allenylidene remains a challenge. Efficient methods for the construction of alkaloid-like polycyclic indole scaffolds that contain a CF3 group at a stereogenic carbon centre would be a great advantage for the production of chemically novel drugs[17,18,19,20,21,22] To this end, we are interested in cascade annulation reactions using 4-ethynyl benzoxazinanone[23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41]. Substantial transformations of 3 into more complex molecules are demonstrated
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