Reactions of alkoxyaryloxycarbenes with tethered triple bonds: a new synthesis of substituted benzofurans

Abstract

Cyclic 3-alkoxy-3-aryloxyvinylcarbenes can be generated by a highly exo-selective intramolecular cyclization of a dioxycarbene onto a tethered triple bond. Like their dialkoxy counterparts, the 3-alkoxy-3-aryloxyvinylcarbene intermediates are capable of interesting reactions. In contrast to 3,3-dialkoxyvinylcarbenes, which undergo a formal [3 + 2] cycloaddition with highly electron-deficient olefins such as benzylidenemalononitrile, 3-alkoxy-3-aryloxyvinylcarbenes undergo a highly diastereoselective [1 + 2] cycloaddition with benzylidenemalononitrile to give cyclopropylketene acetals. At high temperatures, those cyclopropylketene acetals undergo a clean vinylcyclopropane rearrangement in which the stereochemical integrity of the cyclopropane is retained. Keywords: carbene, alkoxyaryloxy, [1 + 2] cycloaddition, ketene acetal, vinylcyclopropane rearrangement, oxadiazoline.

Thermal Rearrangements of Vinylcyclopropanes to Cyclopentenes

“…Specific recent examples suggest that the rearrangement can be effected successfully even with reasonably complex polyfunctional systems, as in the isomerization of 64 to 65, 173 and in a variety of heteroatomrich analogues, as in 66 to 67. [174][175][176][177][178] Additional examples attest to the synthetic utility of various transition-metal-catalyzed vinylcyclopropane rearrangements, 179 as well as conversions of alkynyl and allenylcyclopropanes to cyclopentene structures!…”

“…Efficient preparations of novel complex structures anticipated to have pharmacological interest can be achieved through vinylcyclopropane rearrangements. Specific recent examples suggest that the rearrangement can be effected successfully even with reasonably complex polyfunctional systems, as in the isomerization of 64 to 65 , and in a variety of heteroatom-rich analogues, as in 66 to 67 . −

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Homolysis of Carbenes. Free Radicals from Dialkoxycarbenes

“…2-Methoxy-2-allyloxy-5,5-dimethyl-Δ 3 -1,3,4-oxadiazolines ( 2a , 2b ) were prepared by the acid-catalyzed exchange reaction − of the 2-acetoxy-2-methoxy analogue ( 1 ) with 1-phenyl-2-propen-1-ol and with cinnamyl alcohol, respectively, Scheme . Thermolysis of 2 in benzene (sealed tube) at 110 °C afforded the esters ( 6 ), Scheme .…”

Heterocycles Derived from Heteroatom-Substituted Carbenes

“…A hydrogen or methyl substituent led to formation of the endocyclic vinylcarbene, while an ester substituent preferred exocyclic carbene formation. The 3,3-dialkoxyvinylcarbene 252 and 254 can be trapped by an alcohol, which afforded pyrans 253 or furans 255 (Scheme ). , 3,3-Dialkoxyvinylcarbenes behave as highly efficient 1,3-dipoles in their reactions with electron-deficient olefins . Thermolysis of the oxadiazoline precursors 249c and 249d in the presence of benzylidenemalononitrile or DMAD led to exocyclic vinylcarbenes which underwent [3 + 2]-cycloaddition with benzylidenemalononitrile or DMAD to form bicyclic heterocycles 256 − 260 in good yields (Scheme ) …”

“…67 The cyclization of (alkynyl-1-oxy)-alkoxycarbenes has been extensively studied by Warkentin's group. [68][69][70] The (alkynyl-1-oxy)methoxycarbenes 250, generated by thermolysis of the corresponding oxadiazoline precursors 249, cyclized by carbene attack of the C-C triple bond, leading to a new carbene. The endocyclic or exocyclic 3,3-dialkoxyvinylcarbenes 252 or 254 apparently form by way of the highly strained dialkoxycyclopropene 251.…”