Herein, we present a novel [3 + 2] cycloaddition reaction of β-keto esters with nitrile oxides, which were generated in situ from copper carbene and tert-butyl nitrite. This three-component reaction provides new methodology for the direct synthesis of fully substituted isoxazole derivatives, featuring mild reaction conditions, readily accessible starting materials and simple operation. The experimental studies and DFT calculations suggest that the reaction starts with the generation of the key intermediate nitrile oxides, followed by a [3 + 2] cycloaddition reaction of β-keto esters to give the final isoxazole products.
Computational
studies were carried out to provide mechanistic insights
into the Rh(I)-catalyzed activation of cyclopropenes and the detailed
mechanistic pathways of [3+2+1] carbonylative carbocyclization of
tethered ene- and yne-cyclopropenes. Computational results suggest
that it is more favorable for the cyclopropene moiety of tethered
ene-cyclopropenes to initially undergo heterolytic cleavage of a C–C
σ-bond to form a vinyl Rh(I) carbenoid intermediate than to
proceed through homolytic C–C σ-bond cleavage to generate
a rhodacyclobutene intermediate. The yielded vinyl Rh(I) carbenoid
intermediate could undergo cyclization to generate a Rh(III) metallacyclobutene
intermediate, which could further lead to a thermodynamically more
stable six-coordinated Rh(III) metallacycle intermediate in the presence
of additional CO. Afterward, it is more feasible for the yielded six-coordinated
Rh(III) metallacycle to sequentially undergo CO migratory insertion,
cyclization, and reductive elimination to furnish the final cyclohexenone
product. The origin of stereoselectivity of the product was also discussed.
The proposed mechanistic pathway can also be applied to the Rh(I)-catalyzed
carbonylative carbocyclization of tethered yne-cyclopropenes and vinyl
cyclopropenes to produce phenol derivatives. The main mechanistic
difference for the vinyl cyclopropene substrate is that the conversion
of Rh(I) carbenoid intermediate to the Rh(III) metallacycle proceeds
via intramolecular 6π electrocyclization.
The detailed mechanisms of gold(i)-catalyzed annulations of propiolates with substituted and unsubstituted isoxazoles were investigated by DFT calculations.
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