Mannich Reaction

C. Mannich, W. Krosche, Arch. Pharm. 250, 647 (1912).

Reaction of compounds having an active hydrogen with non-enolizable aldehydes and ammonia or primary or secondary amines to give aminomethylated products (Mannich bases):

Early reviews: F. F. Blicke, Org. React. 1, 303 (1942); H. O. House, Modern Synthetic Reactions (W. A. Benjamin, Menlo Park, California, 2nd ed., 1972) pp 654-660. p-Substituted phenols as substrates: D. A. Leigh, P. Linnane, Tetrahedron Letters 34, 5639 (1993). In synthesis of vinylphosphonates: H. Krawezyk, Synth. Commun. 24, 2263 (1994). Diastereoselectivity: P. C. B. Page et al., J. Org. Chem. 58, 6902 (1993); enantioselectivity: H. Ishitani et al., J. Am. Chem. Soc. 119, 7153 (1997); eidem, Tetrahedron Letters 40, 2161 (1999); K. Yamada, Angew. Chem. Int. Ed. 38, 3504 (1999). Reviews: M. Tramontini, et al., Tetrahedron 46, 1791-1837 (1990); E. F. Kleinman, Comp. Org. Syn. 2, 893-951 (1991); H. Heane, ibid. 953-973; L. E. Overman, D. J. Ricca, ibid. 1007-1046; M. Arend et al., Angew. Chem. Int. Ed. 37, 1044-1070 (1998). Cf. Betti Reaction; Robinson-Schöpf Reaction.