Dipolar cycloadditions tetrahydrofurans from

The present preparation illustrates a general and convenient irethod for ring contraction of cyclic ketones. The first step is the usual procedure for the preparation of enamines. The second step involves 1,3-dipolar cycloaddition of diphenyl phosphorazidate to an enamine followed by ring contraction with evolution of nitrogen. Ethyl acetate and tetrahydrofuran can be used as a solvent in place of toluene. Pyrrolidine enamines from various cyclic ketones smoothly undergo the reaction under similar reaction conditions. Diphenyl (cycloalkyl-1-pyrrolidinylmethylene)phosphoramidates with 5,6,7, and 15 members in the ring have been prepared in yields of 68-76%. 

The application of 1,3-dipolar cycloaddition processes to the synthesis of substituted tetrahydrofurans has been investigated, starting from epoxides and alkenes under microwave irradiation. The epoxide 85 was rapidly converted into carbonyl ylide 86 that behaved as a 1,3-dipole toward various alkenes, leading to quantitative yields of tetrahydrofuran derivatives 87 (Scheme 30). The reactions were performed in toluene within 40 min instead of 40 h under classical conditions, without significantly altering the selectivi-ties [64]. 

For the first time, DFT theory has been applied to a study of diastereofacial selectivity in 1,3-dipolar cycloadditions of nitrones to di-3,4-dimethylcyclobutene. ° The stereochemical outcome of the INAC reactions of nitrones (49) and (52) derived from 3-(9-allyl-D-hexoses is dependent only on the relative configuration at C(2,3), and thus 3-(9-allyl-D-glucose (48) and -o-altrose (threo configuration) afford oxepanes (50) selectively whereas 3-O-allyl-D-allose (51) and -D-mannose (erythro configuration) give tetrahydrofurans (53) and (54) selectively (Scheme 18). frani-2-Methylene-... 

An approach to 2,5-disubstituted tetrahydrofurans is outlined in Scheme 29. Solid-phase-bound 2-nitroethanol 108 was synthesized in two steps from Merrifield resin. TMS protection and reaction with phenyl isocyanate in the presence of 1,5-hexadiene gave the dihydroisoxazole 109 in a 1,3-dipolar cycloaddition of the nitrile oxide formed by dehydration of the nitroalkane. Treatment with ICl at -78 °C initiated a ring-closing-ring-opening sequence (electrophilic cyclization), which resulted in cleavage from the resin with the formation of tetrahydrofuran 110 in 40% yield as a mixture of diastereomers [44, 45]. 

Cycloadditions have become a valuable means of generating tetrahydrofurans. They typically involve the condensation of an aldehyde with a 1,3-dipole in an overall [3+2]-cycloaddition process. With one exception, the focus of this section is on tetrahydrofuran formation from dipolar cycloadditions of either push-pull cyclopropanes or allylsilanes with aldehydes. 

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