Tetrazoles pyrrolidinyl

Ley developed an efficient tandem organocatalytic synthesis of chiral dialkyl 3-alkyl-l,2,3,6-tetrahydropyridazine-1,2-dicarboxylates 272 from /3-oxohydrazines 271. Compound 271 was obtained from commercially available achiral aldehydes and dialkyl azodicarboxylates using (6)-pyrrolidinyl tetrazole as the chiral catalyst. This synthesis proceeds with good to excellent yields (58-89%) and enantioselectivities (69-99% ee). The highest ee values are obtained for the most bulky di-/-butyl azodicarboxylate and the shortest branched aldehydes (Scheme 67) <2006SL2548>. 

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. 

Scheme 1.13 Pyrrolidinyl tetrazole-catalysed Michael additions of ethyl malonate to a,P-unsaturated enones.

Other methodologies can be appUed for the direct enantioselective organocata-lytic a-oxidation of carbonyl compounds [146]. Thus, proline (21), pyrrolidinyl tetrazole (36), or its a-methyl derivative (30mol%) catalyzed the oxidation of several aldehydes and cyclohexanone using tron.s-2-(p-methoxyphenylsulfonyl)-3-phenyloxaziridine as oxidant [147], with the use of a-methyl substituted derivatives affording the a-oxidized aldehydes with moderate results (23-67% yield, 12-45% ee). 

R) -a-pyrrolidinyl tetrazole 1119 pyrroline-1-carbonyl group 1249 pyrrolo-indole core 1104 -tricyclic 1104 pyrroloindoline 750... 

In 2006, Ley et al. successfully employed pyrrolidinyl tetrazole as catalyst in the asymmetric Michael addition of malonate to a wide range of enones (Table 9.7). This organocatalysis applies the electrophilic iminium ion mechanism. In the presence of pyrrolidinyl tetrazole associated with a basic additive (such as piperidine), diethyl malonate reacted smoothly with 2-cyclohexen-l-one to provide the Michael addition product in 94% yield with 93% ee. The use of dimethyl malonate substrate furnished 87%... 

TABLE 9.7. Michael Addition Catalyzed by Pyrrolidinyl Tetrazole... 

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