- Palladium-catalyzed asymmetric benzylation of azlactones
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Asymmetric benzylation of prochiral azlactone nucleophiles enables the catalytic introduction of a benzyl group towards the synthesis of α,α-disubstituted amino acids. Herein, we report an enantioselective palladium-catalyzed process using chiral bis(diphenylphosphinobenzoyl)diamine (dppba) ligands. Naphthalene- and heterocycle-based methyl carbonates react with a number of azlactones derived from both natural and unnatural amino acids. Monocyclic benzylic electrophiles, for which the barrier to ionization is higher, must employ a phosphate leaving group in order to react. Reaction conditions for electron-rich and -neutral benzylic electrophiles have been developed, and the scope of the reaction has been explored with respect to both reaction partners. The high levels of asymmetric induction, as well as the reactivity pattern of the electrophiles, suggest an η3-benzyl intermediate that arises through two distinct pathways. Attack on benzyl: Palladium-catalyzed asymmetric benzylation methodology is demonstrated on prochiral azlactone nucleophiles. The use of naphthyl, heterocyclic, and monocyclic benzylic electrophiles demonstrates the wide reaction scope (see scheme; Cp=cyclopentadienyl). The benzylation products are readily converted into enantioenriched α,α-disubstituted amino acids.
- Trost, Barry M.,Czabaniuk, Lara C.
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p. 15210 - 15218
(2013/11/06)
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- Novel open-chain and cyclic conformationally constrained (R)- and (S)-α,α-disubstituted tyrosine analogues
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A series of novel open-chain and cyclic conformationally constrained (R)- and (S)-α,α-disubstituted tyrosine analogues 1a-e were synthesized in good yields and high optical purities. The absolute configurations of these tyrosine analogues were unambiguously determined based on the X-ray structures of the precursor diastereoisomeric peptides of type 4 and 5. Four of these structures are deseribed, showing β-turn type-I geometries for dipeptides 4b, 5b, and 4c and an extended conformation for peptide 5c. The conversion of the free amino acids 1a-c into suitably protected building blocks 11a-d and 15d,e for peptide synthesis is discussed.
- Obrecht,Lehmann,Ruffieux,Schonholzer,Muller
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p. 1567 - 1587
(2007/10/02)
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