Cycloaddition, tetrahydrofuran cyclopropane-aldehyde

The Lewis acid-catalysed 3 + 2-cycloaddition of cyclopropanes with aldehydes yields tetrahydrofurans with high diastereoselectivity.22 The enantiospecific Sn(II)-and Sn(IV)-catalysed formal 3 + 2-cycloadditions of aldehydes with donor-acceptor (g) cyclopropanes produce optically active tetrahydrofurans23 The bulky phosphites and phosphoramidites are excellent ligands which promote the Pd-catalysed 3 + 2-intramolecular cycloaddition between alkylidenecyclopropanes and alkynes24 The... 

Cycloaddition of cyclopropanes to aldehydes leads to the formation of tetrahydrofurans derivatives, whose enantiomeric form can be obtained either by using enantioenriched cyclopropane substrates or by a dynamic kinetic asymmetric transformation. In this regard, Johnson et al. reported a dynamic kinetic asymmetric [3 -I- 2] cycloaddition of racemic cyclopropanes 63 for the enantioselective synthesis of tetrahydrofurans 64. In this study, the magnesium catalyst can promote the ring opening of the racemic cyclopropane and catalyses the reaction of one of the ring-opened enantiomers with the aldehydes (Scheme 3.19). 

Cycloaddition Reaction. A one-step diastereoselective synthesis of cis-2,5-disubstituted tetrahydrofurans via Hf(OTf)4-catalyzed [3 + 2] cycloadditions of donor-acceptor (D-A) cyclopropanes and aldehydes has been reported (eq 13). ... 

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. 

Yang and coworkers have also examined cyclopropane [3+2]-cycloadditions to give highly substituted tetrahydrofurans (Scheme 19) [19]. Interestingly, the AICI3-mediated cycloaddition of trans-cyclopropane 65 with electronically neutral or electron-deficient aryl aldehydes led to a predominance of cfr-tetrahydrofuran 64, while the use of electron-rich aryl aldehydes resulted in the generation of the corresponding trans-tetrahydrofurans 67. The authors demonstrated that the reaction was reversible and that the trans isomer resulted from the equilibration of the cis isomer. 

Waser and coworkers have reported the first use of amino cyclopropanes in [3+2]-cycloadditions with aldehydes to give amino tetrahydrofurans with high levels of diastereoselectivity (Scheme 22) [22]. A wide range of activators could be used in these reactions including normally inert Lewis acids like FeCL on AI2O3. In contrast to the Johnson et al. work mentioned above, racemic tetrahydrofurans resulted from the use of enantiomerically eiuiched aminocyclopropanes implying that the reaction proceeds through a zwitterionic intermediate. 

The cobalt complexed cyclopropane diester 4 was then reacted with a variety of aldehydes in the presence of boron trifluoride etherate in dichloromethane to afford the desired tetrahydrofurans 5 in high yields with poor diastereoselective control (Scheme 10.6). The cycloaddition reaction was limited to electron deflcient aromatic, aliphatic, and functionalized aldehydes, where no reaction was observed with electron rich aromatic aldehydes. The tetrahydrofurans were obtained as a 1 1 mixture of cis- and fran -isomers, where the best diastereomeric ratio obtained was 2 1 (5d) in favor of the fran -isomer. Modifying the temperature of the reaction had little effect on the diastereoselectivity. Confirmation of the stereochemistry was achieved by X-ray and NMR analysis of the separated diastereoisomers, including... 

In 2009, Parsons and Johnson reported the synthesis of enantio-enriched tetrahydrofurans via a dynamic kinetic asymmetric cycloaddition of racemic cyclopropanes with aldehydes under the influence of a chiral Lewis acid as illustrated in Scheme 10.40 and Table 10.13 [38]. 

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