The first example of enantioselective intermolecular cycloaddition of carbonyl ylides with indoles is described. The cycloaddition of five- and six-membered carbonyl ylides derived from diazodiketoesters with N-methylindoles under catalysis by dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], Rh(2)(S-TCPTTL)(4), gave cycloadducts in high yields and with high levels of enantioselectivity (up to 99% ee) as well as excellent exo diastereoselectivity.

This paper describes asymmetric tandem carbonyl ylide formation-intramolecular 1,3-dipolar cycloaddition reaction of diazo imides containing a tethered indole catalyzed by chiral dirhodium(II) carboxylates as an approach to the pentacyclic skeleton of Aspidosperma alkaloids. The cycloaddition of carbonyl ylides derived from indolyl-substituted 2-diazo-5-imido-3-ketoesters under the influence of dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], Rh 2 (S-TCPTTL) 4 , provides cycloadducts in moderate yields and enantioselectivities of up to 66% ee as well as with perfect endo diastereoselectivity. This is the first example of asymmetric induction in an intramolecular cycloaddition of a carbonyl ylide across an indolyl -bond. --------------------------------Over the past four decades, Aspidosperma alkaloids have been a source of structurally intriguing target molecules that continue to challenge the capabilities of contemporary organic synthesis. Efficient and elegant strategies for the total synthesis of various members of this alkaloid family have been reported. 1,2Padwa and co-workers demonstrated that the tandem cyclic carbonyl ylide formation-1,3-dipolar cycloaddition reaction 3 of diazo imides catalyzed by Rh 2 (OAc) 4 is one of the most powerful methods for the rapid construction of the pentacyclic ABCDE framework of (−)-vindoline (1) 4,5 and (−)-vindorosine (2) 6,7 (eq. 1). 8The same group has Corresponding author. Tel.: +81 11 706 3236; fax: +81 11 706 4981. E-mail address: hsmt@pharm.hokudai.ac.jp (S. Hashimoto).2 accomplished the total synthesis of (±)-aspidophytine 9 employing an intramolecular 1,3-dipolar cycloaddition of carbonyl ylide across the indole -bond. 10((Please Insert Eq. 1 here:))The synthetic utility of the carbonyl ylide cycloaddition strategy has also been demonstrated in its application to the synthesis of a variety of natural products. 11Over the past decade, considerable effort has been directed to the development of an enantioselective version of carbonyl ylide formation-1,3-dipolar cycloaddition catalyzed by chiral dirhodium(II) complexes. [12][13][14][15] In this process, the chiral dirhodium(II) catalyst must be capable of associating with carbonyl ylide intermediates in the cycloaddition step, because catalyst-free carbonyl ylides are achiral. Hodgson and co-workers were the first to demonstrate high levels of asymmetric induction (up to 90% ee) in intramolecular cycloadditions of carbonyl ylides derived from unsaturated -diazo--ketoesters using binaphtholphosphate catalyst Rh 2 (R-DDBNP) 4 (4) ( Figure 1).Recently, we reported catalytic enantioselective intermolecular cycloadditions of 2-diazo-3,6-diketoesters-derived carbonyl ylides with arylacetylene, alkoxyacetylene, and styrene dipolarophiles using Rh 2 (S-TCPTTL) 4 (3a), Gratifyingly, the use of benzyl ester 7c greatly improved the enantioselectivity to provide cycloadduct 6c in 50% yield with 63% ee (entry 3), whereas a low level of asymmetric induction was obtained in the reaction of 2-pheny...

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The first catalytic asymmetric hetero-Diels-Alder reaction between 2-aza-3-silyloxy-1,3-butadienes and aldehydes is described. With dirhodium(II) tetrakis[N-benzene-fused-phthaloyl-(S)-piperidinonate], Rh(2)(S-BPTPI)(4), the cycloaddition reaction proceeded exclusively in an endo mode to give all-cis-substituted 1,3-oxazinan-4-ones in high yields with up to 98% ee.

The reverse regio- and diastereoselectivities are observed between the reactions involving 5- and 6-membered-ring cyclic carbonyl ylide dipoles with alpha-methylene ketones. A mild catalytic route to synthesize spirocyclic systems with high regio-, chemo- and diastereoselectivities is described.