Tetrazoles Mannich reaction

Odedra A, Seeberger PH (2009) 5-(Pyrrolidin-2yl)tetrazole-catalyzed aldol and Mannich reactions acceleration and lower catalyst loading in a continuous-flow reactor. Angew Chem Int Edit 48(15) 2699-2702... 

Fig. 9.18 Mannich reaction for the synthesis of trinitroethyl-tetrazole-1,5-diamine (TTD), bis(trinitroethyl)-tetrazole-1,5-diamine (BTTD) and bis(trinitroethyl)-l,2,4,5-tetrazine-3,6-diamine (BTAT).

Three-component Mannich reactions involving other imines also worked well in [bmim][BF4]/ but even more efficient protocols involve solvent-less conditions, in the presence of water again we deal with aqueous biphasic systems. Catalyst 15a (Table 1.1) is suitable for such an application, as well as siloxytetrazole 18a, derived from a combination of the structural features of 3 (Table 1.1) and tetrazole derivative 18b.Interestingly, while neither 3 nor 18b were suitable for such transformation, the hybrid catalyst 18a gave the excellent results shown in Scheme 1.8. 

As the intermediate enamine reacts faster with imines than aldehydes, a one-pot three component coupling of the donor ketone, aldehyde and amine is possible. List and coworkers have achieved high ees in this reaction utilising L-proline (7.66) and some aliphatic aldehydes and aromatic aldehydes such as (7.136) in combination with p-anisidene (7.137). This catalyst system is also effective for the coupling of a-hydroxyketones. Use of the tetrazole-substituted proline (7.80) allows the reaction to be performed in dichloromethane rather than DMSO and high ees in the Mannich reaction between aliphatic ketones and imines derived from ethyl glyoxalate have been obtained imder these reaction conditions. 

Barbas et al. demonstrated the first direct asymmetric three-component Mannich reaction that involved using pyrrolidine-based tetrazole 5a. The reaction of azido ketones and phthalimido ketones with aldehydes and p-anisidine afforded 1,2-diamines and 1,4-diamines, respectively. This method is an example of the synthesis of 1,2-diamines and 1,4-diamines with high to excellent levels of diastereo- and enantioselectivity (up to 99% ee) (Scheme 9.40). 

Scheme 9.39 Tetrazole 5a-catalysed enantioselective Mannich reaction.

In 2005, the first one-pot three-component Mannich reaction catalyzed by simple acyclic primary amino acids and their derivatives (e.g., tetrazole derivatives) was disclosed (Scheme 4.5) [28]. It was realized by the prior findings that natural acychc... 

In 2008, Barbas et al. reported the first primary amine-containing amino acid-catalysed indirect a n -Mannich reactions of dihydroxyacetone and acyclic protected dihydroxyacetone derivatives with a variety of imines derived from both aliphatic and aromatic aldehydes.In spite of moderate diastereoselec-tivities, good to high yields and enantioselectivities were obtained by using an L-threonine derivative as the organocatalyst in A -methylpyrrolidinone as the solvent and 5-methyl-l-7/-tetrazole as an additive, as shown in Scheme 3.14. 

Type A enamine catalysts include simple amino acids, such as proline 6, and most of their derivatives (such as the tetrazole 44 and various sulfonamides, e.g. 45). They are typically used for aldol, Mannich, a-amination and a-oxygenation reactions - these are all reactions where the electrophile can readily be activated by hydrogen bonding (Scheme 12) [8, 9, 12, 46],... 

Proline derivatives, such as (2S,4R)-4-hydroxyproline (2), (2S,4R)-4-tert-butoxy-proline, (2S,3S)-3-hydroxyproline [71b] and tetrazole-containing pyrrolidine 9 [75] also catalyzed the Mannich-type reactions using aldehydes as nucleophiles via enamine intermediates, and afforded the syn-isomer as the major diaster-eomer with high enantioselectivity at room temperature. On the other hand,... 

In 2004, Yamamoto and Arvidsson independently reported the catalytic activity of the L-proline tetrazole catalyst 30 in asymmetric aldol reactions of ketones with aldehydes [161-163]. At the same time. Ley and coworkers reached similar conclusions by applying this system to asymmetric Mannich and Michael addition reactions (Scheme 1.8) [164]. Since then, the scope of this chemistry has been expanded by several research groups [165-174]. 

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