Tetrazole catalysts

The conjugate addition of tetrahydrothiopyran-4-one to l-nitro-2-(3-nitrophenyl)ethene is promoted by the enantiomers of 5-pyrrolidin-2-yl-17/-tetrazole and gives the adducts in acceptable yields and with ca. 70% ee as determined by chiral HPLC (Equation 27) <20050BC84>. An enantiomeric excess of 90% was achieved using a homoproline tetrazole catalyst (Equation 28) <2005SL611>. 

A number of organocatalysts such as derivatives of proline and morpholine were screened by Barbas group and the tetrazole catalyst 26 gave the best result, with 95 % yield and 80 % ee. The enantiomerically enriched mixture could be recrystallized to yield 71 % of aminoaldehyde 27 in >99 % ee. 

Two different models were proposed by Ley for the 2b-catalyzed reaction which should also be of application for the cases of proline 1 and proline-tetrazole catalysts 2a, both of them in good agreement with the observed absolute configuration of the final Michael adducts (Figure 2.2). One proposal involved the possibility of the tetrazole moiety acting as a bulky substituent which directed the income of the electrophile by the less hindered face of the enamine intermediate in the most stable pseudo-rrarw conformation. Alternatively, the formation of a hydrogen-bonded transition state was also proposed, in this case with the participation of the pseudo-cj5 enamine conformer. This second pathway was afterwards estimated to be the energetically most favored one by DFT calculations. ... 

Yamamoto and co-workers developed a Class 111 process, whereby tetrazole catalyst 70 was utilized in an a-amino-hydroxylation. The resulting nitrogen anion then undergoes 1,4-addition to generate bicyclic species 197 (Scheme 1.44) [62], which although formally a [4+2] product gives the opposite regiochemistry to normal nitroso-Diels-Alder reaction (Fig. 1.10). 

Torii H, Nakadai M, Ishihara K, Saito S, Yamamoto H (2004) Asymmetric Direct Aldol Reaction Assisted by Water and a Proline-Derived Tetrazole Catalyst. Angew Chem Int Ed 43 1983... 

Ley et al. have demonstrated that the pyrrolidinyl tetrazole catalyst, depicted in Scheme 1.13, could be used to efficiently induce the enantioselective Michael addition of malonates to oi,p-unsaturated enones. Cyclic, acyclic and aromatic enones could be involved in this process, and the reaction with the most efficient ethyl malonate provided, in the presence of piperidine as an additive, the corresponding Michael products in high yields with good to excellent enantioselectivities, as shown in Scheme 1.13. 

Torii, H., Nakadai, M., Ishihara, K., Saito, S. and Yamamoto, H., Asymmetric direct aldol reaction assisted by water and a proline-derived tetrazole catalyst, Angew. Chem. Int. Ed., 2004,43,1983 1986. 

Pro line tetrazole catalysts (category C in Figure 1.1) are readily accessible from L-proline (1) [158]. They are remarkably useful in asymmetric synthesis [159]. As shown in Figure 1.2, the pfCj of tetrazole is very similar to that of carboxyUc acid. Moreover, the advantage of tetrazole catalysts is their robust and lipophihc nature compared to L-proline (1) itself, which allows them to escape parasitic bicyclo-oxazolidinone formation [160]. 

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]. 

Knudsen KR, Mitchell GET, Ley SV. Asymmetric organo-catalytic conjugate addition of malonates to enones using a proline tetrazole catalyst. Chem. Commun. 2006 1 66-68. 

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