A Rh-catalyzed procedure for the cyclopropanation of alkenes with α-alkyl-α-diazoesters is described. With dirhodium tetraoctanoate, the predominant pathway is β-hydride elimination. While a number of sterically demanding carboxylate ligands serve to avoid β-hydride elimination, it was found that triphenylacetate (TPA) also imparts high diastereoselectivity.Rhodium carbenoids are reactive intermediates that effect a range of transformations, and both the nature of the carbenoid and the auxiliary ligands on rhodium have a dramatic impact on the selectivity of these reactions. 1 While α-alkyl-α-diazoesters (1) are readily available and attractive precursors to Rh-carbenoids, such carbenoids had only limited applicability in intermolecular reactions due to their propensity to undergo β-hydride elimination. 2 Recently, our group described several intermolecular Rhcatalyzed transformations of α-alkyl diazoesters that tolerate β-hydrogens, including reactions that produce cyclopropenes (2) 3 and dioxolanes via putative carbonyl ylides of structure 3 (Scheme 1). 4 Low reaction temperatures (−78 °C) 5 and the use of sterically demanding carboxylate ligands 6 [e.g. dirhodium tetrapivalate (Rh 2 Piv 4 )] were key to the success of these reactions and to the dramatic suppression of β-hydride elimination. In prior studies on the effects of ligand structure 6 and temperature 5 on suppressing β-hydride elimination, only modest effects had been noted.
NIH-PA Author ManuscriptNIH-PA Author Manuscript
NIH-PA Author ManuscriptThe rhodium catalyzed cyclopropanation of alkenes has broad applicability in organic syntheses. 1,7 However, examples of intermolecular cyclopropanation by diazoalkanes are rare. 8-10 With Rh-catalysis, we are aware of only three reports that describe intermolecular cyclopropanation in preference to β-hydride elimination. 8 These transformations involved a limited range of alkenes (diketene,8a methylenespiropentane 8b or furans 8c ) with ethyl α-diazopropionate. Rh-catalyzed cyclopropanation of α-alkyldiazo compounds with more reactive β-hydrogens had not been described previously.Unlike the reactions displayed in Scheme 1, cyclopropanation reactions have the additional challenge of diastereocontrol. Diastereocontrol in cyclopropanation chemistry can be highly dependent on the structure of the carbenoid, 1 and it was unclear if the reactions of α-alkyl diazoesters would be selective. As shown in Table 1, a range of catalysts were surveyed for their effectiveness in the reaction of ethyl α -diazobutanoate with styrene. These reactions were screened using the diazoalkane as the limiting reagent, so that the relative amounts of cyclopropanation and β-hydride elimination could be measured.Consistent with earlier observations on the reactions of alkynes with α-alkyl-α-diazoesters, 3 dirhodium tetraoctanoate (Rh 2 Oct 4 ) gave only small amounts of cyclopropane products: cisethyl crotonate 6 and azine 7 4 dominated. While dirhodium tetrapivalate (Rh 2 Piv 4 ) is the most useful catalyst for cyclopropenati...
Described here is a diastereoselective Rh-catalyzed method for the preparation of dioxolanes from alpha-alkyl-alpha-diazoesters. This represents the first general method for generating carbonyl ylides from alpha-diazoesters that possess beta-hydrogens, as such diazo compounds typically give rise to alkenes via beta-hydride elimination. Subsequent cycloaddition with aromatic aldehydes gives tetrasubstituted dioxolanes with unusually high diastereoselectivity. A model is set forth to explain the diastereoselectivity of the cycloaddition.
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