Science of Synthesis

Kruiswijk, E.; Deck, J. A., Science of Synthesis, (2009) 40, 838.

Enantioselective organocatalysis is a field of central importance in asymmetric synthesis,[‌50‌,‌51‌–‌56‌] and novel modes of substrate activation are achieved using organic catalysts that now compete with, or even surpass, transition-metal catalysts or biocatalysts. The concept of organocatalysis, which can be defined as the acceleration of chemical reactions with less than a stoichiometric amount of an organic compound that does not contain any metal atom, is not new;[‌57‌] indeed, the first example of an enantioselective transformation of this type dates back to 1904.[‌58‌] Since then much progress has been made and, for example, the efficient asymmetric synthesis of α-amino acids under phase-transfer conditions is now well-established.[‌59‌] Thus, pioneering work using phase-transfer catalysts derived by the N-alkylation of cinchona alkaloids[‌60‌] was followed by the first catalytic enantioselective synthesis of amino acids in 1989.[‌61‌] In this work the quaternary salts ‌74‌ (R1 = H) or ‌76‌ (R1 = H), based upon cinchonine and cinchonidine, respectively, are employed to promote the C-alkylation of tert-butyl N-(diphenylmethylene)glycinate (‌73‌) with 4-chlorobenzyl bromide. After alkylation, both the imino and ester functions of the product are hydrolyzed to release the amino acid ‌75‌ (‌Scheme 33‌).[‌62‌] While modest enantioselectivities (up to 66% ee) are obtained for alkylations with these catalysts, it is possible in related cases to prepare optically pure higher α-amino acids by recrystallization or by enzymatic resolution of the initial C-alkylated imines. In 1994 an improvement on the first-generation catalysts became possible when it was recognized that the active species in these alkylations is formed by O-alkylation of the hydroxy group of the N-benzylated alkaloid in situ.[‌63‌] Indeed, an O-allyl group is shown to be the optimal substituent in a second-generation of enantiocomplementary catalysts ‌74‌ (R1 = CH2CH=CH2) and ‌76‌ (R1 = CH2CH=CH2) (‌Scheme 33‌) and enantioselectivities of up to 81% are obtained using them for the alkylation of certain Schiff bases.

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References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 88/8, 888.
• 8.Meeeee-Meee, (8888) M 88e8, 888.