Enantioselectivity carbonyl ylide 1,3-dipolar cycloadditions

Good yields of the bridged tetrahydropyran-3-one 38 are obtained when the a-diazoketones 37 are decomposed by chiral Rh(II)-catalysts in the presence of DMAD. It is proposed that an enantioselective intermolecular 13-dipolar cycloaddition follows the generation of a carbonyl ylide which is bound to the rhodium (Scheme 21) <99JA1417>. 

Hashimoto and co-workers have shown the enantioselective 1,3-dipolar cycloaddition of the ester-derived carbonyl ylides using chiral dirhodium(II) carboxylates [110]. The ester-derived carbonyl ylide from the a-diazo ketone 98 in the presence (1 mol%) of Rh2(S-PTTL)4 99 as the catalyst afforded the cycloadduct 100 with 93% ee (Scheme 30). 

Another successful catalytic enantioselective 1,3-dipolar cycloaddition of Qf-diazocarbonyl compounds using phthaloyl-derived chiral rhodium(II) catalysts has been demonstrated [ill]. Six-membered ring carbonyl ylide formation from the a-diazo ketone 80 and subsequent 1,3-cycloaddition with DMAD under the influence of 1 mol % of dirhodium(II) tetrakis[M-benzene-fused-phthaloyl-(S)-phenylvaline], Rh2(S-BPTV)4 101 [112], has been explored to obtain the cycloadduct 102 in up to 92% ee (Scheme 31). 

Hashimoto and coworkers [69] have recently begun to explore the use of chiral rhodium catalysts in the intramolecular dipolar cycloadditirai reactions of indoles, and have applied their methodology to the synthesis of the Aspidosperma ring system. Thus, the cycloaddition of the cyclopropyl carbonyl ylides derived from cyclopropyl diazo-5-imido-3-ketoesters 135 upon treatment with dirhodium (11) tetrakis[Af-tetrachlorophthaloyl-(5)-ferf-leucinate] gave cycloadducts 136 along with the spiro[2.3]hexanes 137 in only moderate yields (Scheme 34). Although the reaction proceeds with exclusive endo diastereoselectivity, only moderate enantioselectivities of up to 66% enantiomeric excess (ee) could be obtained. 

Muthusamy S, Gunanathan C et al (2004) Regioselective synthesis of mono- and bis-decahy-drobenzocarbazoles via tandem reactions of a-diazo ketones. Tetrahedron 60 7885-7897 Nambu H, Hikime M et al (2009) Asymmetric approach to the pentacyclic skeleton of aspidosperma alkaloids via enantioselective intramolecular 1,3-dipolar cycloaddition of carbonyl ylides catalyzed by chiral dirhodium(II) carboxylates. Tetrahedron Lett 50 3675-3678... 

The asymmetric induction on the 1,3-dipolar cycloaddition reaction of carbonyl ylides has also been studied using chiral dipolarophile. The Rh2(OAc)4-catalyzed reactions of o-(methoxycarbonyl)diazoacetophenone 89 with enantiomerically pure vinyl sulfoxides 103 afforded 4,10-epoxybenzo-[4,5]cyclohepta[l,2-c]furan-3,9-dione 105, in good or moderate yield with complete regioselectivity [113]. The endo stereoisomer 105a is favored with respect to the exo isomer 105b and interestingly, high diastereoselectivity and complete enantioselectivity have been achieved (Scheme 32). 

An enantioselective version of the above reactions has been reported. Lewis acids such as Yb(OTf)3 can profoundly affect the stereochemical outcome of the carbonyl ylide 1,3-dipolar cycloadditions [137]. This provided an indication to effect asymmetric carbonyl ylide cycloaddition using a chiral Lewis acid. The first example of such asymmetric induction using the chiral lanthanide catalysts has been reported [138,139]. For example, the reaction of diazoacetophenone 89 with benzyloxyacetaldehyde, benzyl pyruvate and 3-acryloyl-2-oxazoHdinone in the presence of chiral 2,6-bis(oxazolinyl)pyridine ligands and scandium or ytterbium complexes furnished the corresponding cycloadducts 165-167 with high enantioselectivity (Scheme 53). 

Somfai has described three-component 1,3-dipolar cycloadditions of in situ generated carbonyl ylides to aldimines induced by chiral Rh(II) carboxylate catalysts 202 [65]. The reaction of ethyl diazoacetate 164, benzaldehyde (92a), and benzylidene benzylamine (203) gave rise to the corresponding syn- -amino alcohol 206 in 62% yield and 88% dr with 24% ee. In spite of its low enantioselectivities, this process provided interesting building blocks for the synthesis of natural products and other biologically important products that are syn- -amino alcohols (Scheme 11.44). 

In 2010, Suga et al. reported high enantioselectivities of up to 97% ee for the inverse electron-demand 1,3-dipolar cycloaddition between cyclohe)yl or bulyl vinyl ethers and carbonyl ylides in situ generated via rhodium-catalysed... 

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