Thermally Induced Cyclobutenone Rearrangements and Domino Reactions

Abstract

The thermal rearrangement of vinylcyclobutenones has become established as a reliable method of preparing hydroquinones owing, in large part, to the pioneering work of the research groups of Moore and Liebeskind. [1][2][3] The basic reaction, 1!2, extends to various aryl-and heteroaryl cyclobutenones, [3][4][5] and has been incorporated into a number of more-elaborate domino sequences. [1,6] From a synthetic perspective, the rearrangement has been used primarily to access quinones by the oxidation of 2 into 3 and in that capacity has featured in several natural-products total syntheses. [1,5] Mindful of this, we conceived a simple extension to facilitate the direct conversion of vinylcyclobutenones into quinones. Our plan was to incorporate a leaving group on the vinyl appendage in the hope that thermolysis would induce a domino reaction comprising electrocyclic ring opening to 4, electrocyclization to 5, and elimination of HX to quinone 3 (Scheme 1). Herein we describe our realization of that objective and the discovery of four new thermal rearrangements of cyclobutenones.Our study began with the thermolysis of enol ether 6. Unexpectedly, heating a THF solution of 6 at 120 8C for 30 min by microwave irradiation failed to yield the anticipated quinone and gave instead a complex product mixture from which two diastereoisomers of spirocycle 7 and dione 8 were isolated in yields ranging from 20 to 27 %. Further experimentation showed dione 8 to be an artifact derived by aerial oxidation of 7, and that it could be produced in 73 % yield by oxidation of the crude product mixture with the Dess-Martin periodinane reagent (Scheme 2). [7] Our discovery of a new vinylcyclobutenone rearrangement raised questions as to the mechanistic course of the reaction and the factors responsible for promoting this pathway over the classical sequence depicted in Scheme 1. Scheme 1. The Moore rearrangement and our planned approach to quinones.Scheme 2. Thermal rearrangements of (alkoxyvinyl)cyclobutenones that lead to spirocycles. DCM = dichloromethane.

Enabling the Development of N-Heterocyclic Carbene (NHC) Catalyzed Reactions: Practical Methods for the Preparation of 1-Acyl-2-Alkylcycloalkenes from Cycloalkanones

“…The aqueous phase was extracted with CH 2 Cl 2 (3 Â 50 mL) and the combined organic layers washed with NaHCO 3 (2 Â 20 mL of a saturated aqueous solution), dried (MgSO 4 ) and the volatiles evaporated. The resulting residue was purified by flash column chromatography to afford, after concentration of the appropriate fractions, compounds 10a, [14] 10o [15] and 10p, [16] which matched previously reported data.…”

Photoassisted Diversity-Oriented Synthesis: Accessing 2,6-Epoxyazocane (Oxamorphan) Cores

“…Further diversification of photoprecursors was achieved by making use of vinyl carboxaldehydes 20 – 22 as starting materials. These aldehydes are readily obtained via a variation of the Vilsmeier–Haack reaction 28 from commercially available cyclic ketones on a multigram scale, using DMF and PBr 3 . In these cases, the developed synthetic sequence of Suzuki coupling, followed by aldol condensation and conjugate addition to chalcone, gives the photoprecursors 29 – 31 in good yields (Scheme 4 ).…”

Cycloaddition and Electrocyclic Reactions of Vinylketenes, Allenylketenes, and Alkynylketenes

“…107 The reaction is proposed to involve a carbonyl ene reaction of the initially formed vinylketene. Activation of the hydrogens allylic to the enol ether is proposed to be important to the course of the reaction, as dienylketenes from less activated substrates, such as the vinyl-substituted system in Scheme 74, afford cyclohexene-1,4-diones by the more typical electrocyclization of the dienylketene.…”