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M. Rueping, E. Sugiono
Scheme 5. Brønsted acid catalyzed imino aza-enamine reaction
Scheme 6. Useful derivatizations of chiral amino hydrazones
Given the value of these products we decided to develop an enantioselective Brønsted acid catalyzed synthesis of amino hydrazones. Optimization of the reaction showed that N-Boc protected aldimines 23
in combination with the pyrrolidine-derived hydrazine 22a gave goodyields of amino-hydrazones 24. With regard to the chiral Brønsted acid
catalysts used, the use of octahydro-BINOL-phosphate 5c resulted in
the best enantioselectivities. The results are summarized in Table 9. In
general, a series of N-Boc-protected aldimines bearing electron-withdrawing or electron-donating groups could be applied in the enantioselective aza enamine reaction resulting in the corresponding hydrazones
24a–h in good isolated yields and with the so far highest enantioselectivities (77%–90% ee). The mild reaction conditions of this metal-free
process, together with the operational simplicity and practicability, render this approach not only a useful procedure for the synthesis of optically active aminohydrazones but additionally, it further expands the
M. Rueping, E. Sugiono
Scheme 5. Brønsted acid catalyzed imino aza-enamine reaction
Scheme 6. Useful derivatizations of chiral amino hydrazones
Given the value of these products we decided to develop an enantioselective Brønsted acid catalyzed synthesis of amino hydrazones. Optimization of the reaction showed that N-Boc protected aldimines 23
in combination with the pyrrolidine-derived hydrazine 22a gave goodyields of amino-hydrazones 24. With regard to the chiral Brønsted acid
catalysts used, the use of octahydro-BINOL-phosphate 5c resulted in
the best enantioselectivities. The results are summarized in Table 9. In
general, a series of N-Boc-protected aldimines bearing electron-withdrawing or electron-donating groups could be applied in the enantioselective aza enamine reaction resulting in the corresponding hydrazones
24a–h in good isolated yields and with the so far highest enantioselectivities (77%–90% ee). The mild reaction conditions of this metal-free
process, together with the operational simplicity and practicability, render this approach not only a useful procedure for the synthesis of optically active aminohydrazones but additionally, it further expands the