Mannich reaction review

After the initial two reports of Rh- and Co-catalyzed reductive aldol couplings, further studies did not appear in the literature until the late 1990s. Beyond 1998, several stereoselective and enantioselective reductive aldol reactions were developed, which are catalyzed by a remarkably diverse range of metal complexes, including those based upon Pd, Cu, Ir, and In. In this chapter, transition metal-catalyzed aldol, Michael, and Mannich reactions that proceed via transition metal hydride-promoted conjugate reduction are reviewed. 

The procedure described is an example of a general reaction,1-2 the Mannich reaction, a review of which, from the experimental point of view, has recently been published. ... 

The amine-catalyzed Mannich reaction has also been a subject of special reviews [243, 244]. In general, yields and enantioselectivities of proline-catalyzed Mannich reactions are very high. Initially, the reactions were restricted to imines bearing an aromatic A-substituent, such as the p-methoxyphenyl (PMP) group. This restriction considerably limited the usefulness of the protocol, because relatively... 

Other direct asymmetric Mannich reactions that use preformed imines and unmodified ketones, aldehydes, malonates, and /i-kctocstcrs have been described by the groups of Shibasaki [12], Trost [13], Barbas [11, 14], and Jorgensen [15]. As two-component reactions, these processes are not included here but have been reviewed elsewhere [16]. 

For reviews about the asymmetric Mannich reaction, see (a) M. Arend,... 

The aldol reaction is one of the most fundamental tools in organic chemistry, and it still remains an open field for new ideas and developments504-509. Among the many reviews dedicated to this subject, the reader should refer, for a more referenced survey, to Heathcock7,11 and more recently to Braun s articles510 devoted specifically to the preformed metal enolates of group I—II. The Mannich reaction (the aza-equivalent of the aldol reaction) is a subject on its own and will be only partially treated here. 

For a brief review on the aza-Cope-Mannich reaction sequence, see L. Overman, Acc. Chem. Res., 1992,25, 352. 

More recently, some review artieles have appeared in which several applications of Mannich bases in the pharmaceutical field - and in other industries,such as those connected with maeromolccular chemistry, arc described. However, no general, complete overview of the widespread practical applications of Mannich bases has been published so far, despite their connections with important branches of industrial organic chemistry. Although the most relevant contribution of the Mannich reaction is still in pharmaceutical research (over 30% of the scientific papers published on this subject are found in journals dealing with pharmaceutical chemistry), Mannich bases have been found to have important uses in the manufacture of polymeric materials (resins and, in particular, surface coatings) and in the production of various additives and auxiliaries (for lubricants, textiles, paper, etc.) as well as, for example, in the production of water-treatment agents. 

The vast and steadily increasing volume of research into Mannich reactions makes it impossible to exhaustively review here the papers published on the topic with the same thoroughness that characterized previous publications that dealt with the literature up to the 1970s. Hence, we limit ourselves to a synthetical survey of the type of substrates employed in Mannich synthesis, with particular emphasis on the applications of the reaction. Updated references, however, enable the reader to search the literature to retrieve more comprehensive information on individual topics. 

The methylene group of methyl ethyl ketone is active in the condensation to give, upon pyrolysis, only methyl isopropenyl ketone (92%). Olefinic aldehydes, acids, esters, and nitro compounds have been prepared in a similar manner. The literature of the Mannich reaction has been reviewed. ... 

The examples outlined in this chapter show that carbohydrates are efficient stereodifferentiating auxiliaries, which offer possibilities for stereochemical discrimination in a wide variety of chemical reactions. Interesting chiral products are accessible, including chiral carbo- and heterocycles, a- and 3-amino acid derivatives, 3-lactams, branched carbonyl compounds and amines. Owing to the immense material published since the time of the earlier review articles on carbohydrates in asymmetric synthesis [9,10], the examples discussed in this chapter necessarily focused on the use of carbohydrates as auxiliaries covalently linked to and cleavable from the substrate. Given the scope of this chapter, a discussion of other interesting asymmetric reactions has not been permitted — for example, reactions in which carbohydrate-derived Lewis acids, such as cyclopentadienyl titanium carbohydrate complexes, exhibit stereocontrol in aldol reactions [180]. Similarly, processes in which in situ glycosylation induces reactivity and stereodifferentiation — for example, in Mannich reactions of imines [181] — have also been excluded from this discussion. 

Habata, Y., Akabori, S., Bradshaw, J. S., Izatt, R. M. Synthesis of Armed and Double-Armed Macrocyclic Ligands by the Mannich Reaction A Short Review. Ind. Eng. Chem. Res. 2000, 39, 3465-3470. 

The Mannich reaction is an aldol reaction with an imine. It has been the subject of many excellent reviews. For example, see Arend, M. Westerman, B. Risch, N. Angew. Chem. Int. Ed. 1998, 37, 1044-1070. Asymmetric variants have also been reported see, for example, Notz, W. Tanaka, E Barbas, C. E, III Acc. Chem. Res. 2004, 37, 580-591. 

In this review we will attempt to highlight the most important contributions toward the realization of a catalytic, enantioselective, vinylogous Mannich reaction and show the current state of the art. This chapter is organized in such a way that vinylogous Mannich reactions of preformed silyl dienolates in Mukaiyama type reactions will be discussed first followed by direct vinylogous Mannich reactions of unmodified substrates. 

The Mannich reaction has been reviewed comprehensively by Blicke (1942), Reichert (1959), Hell-mann and Opitz (1960), and Tramontini (1973). These reviews also include synthetic applications of Mannich bases. Mechanistic studies of the Mannich reaction have been reviewed by Thompson (1968). Some variants of the Mannich reaction have been covered as subtopics in other reviews for example. Layer (1963) and Harada (1970) have reviewed general additions of stabilized carbanions to imines, while Bdhme and Haake (1976) have reviewed similar additions to methyleneiminium salts. In more specific reviews, Pai and coworkers (1984) have summarized stabilized carbanion additions to 3,4-dihy-droisoquinolines and 3,4-dihydroisoquinolinium salts in connection with the total synthesis of protober-berines and phthalide isoquinolines, and Evans et al. (1982) " have analyzed the stereochemical aspects of ester enolate and silyl ketene acetal additions to imines. 

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