Domino Reactions Including SN2-Type Alkylations

Taking advantage of the usually high enantioselectivity of the addition of diphe-nylprolinol silyl enamines to nitroolefins the Enders group developed a large palette of domino sequences [7], including Michael/5 2 tandems in the presence of aliphatic aldehydes and the (o-iodonitroalkenes [5f]. Cyclopentanes were obtained, albeit in a low chemical yield and diastereoselectivity (20%, 70 30 dr) but with excellent enantioselectivity [irans 94% ee, ds 95% ee). The presence of benzoic acid co-catalyst increased both chemical yield and enantioselectivity 

The reaction is general for various acrylates having or not substituents at the y-position (R = Aryl, C02Me) and aldehydes (R = alkyl, alkenyl, carbamate, acetal, ester), ()rield 50-87%, ee 87-98%, syn anti 80 20-94 6). By using chiral aldehydes such as (S) itronellal, the reaction presented high diastereoselectivity (97 3 dr) for the matched pair. 

SN2-type organocatalytic alkylations have been developed under intramolecular conditions, leading to chiral cyclopropanes and cyclopentane derivatives under intramolecular conditions and were used in domino transformations as the final step. SN2-type alkylations with phase-transfer alkylations (Chapter 14), SNl-type reactions (Chapter 26), and free radical and electron-transfer SOMO-alkylations (Chapter 39) are gaining increasing importance in the organocatalytic arsenal. 

3 For selected general reviews on aminocatalysis see (a) Nielsen, M., Worgull, D Zweifel, T Gschwend, B., Bertelsen, S and Jorgensen, K.A. (2011) Chem. Commun., 632-649 (b) Bertelsen, 

and Shi, Z.H. (2010) Adv. Synth. Catal., 352, 243-279. For a manual see List, B. (ed.) (2012) Asymmetric Organocatalysis 1. Lewis Base and Acid Catalysts, Thieme, Stuttgart (1) For a further manual see Maruoka, K. (ed.) (2012) Asymmetric Organocatalysis 2. Erpnsted Base and Acid Catalysts, and Additional Topics, Thieme, Stuttgart. 

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