Catalytic Asymmetric Homologation of α‐Ketoesters with α‐Diazoesters: Synthesis of Succinate Derivatives with Chiral Quaternary Centers

Abstract

Unter milden Bedingungen und in Gegenwart des Katalysators L/Y(OTf)3 gelang erstmals die Titelreaktion. Über eine 1,2‐Aryl‐ oder 1,2‐Alkyl‐Verschiebung wurden hoch funktionalisierte Succinat‐Derivate mit einem quartären Stereozentrum mit ausgezeichneten Ausbeuten und Enantioselektivitäten erhalten. Tf=Trifluormethansulfonyl.

Synthesis and properties of novel helical 3-vinylpyridine polymers containing proline moieties for asymmetric aldol reaction

“…2-Amino-3-methyl-5-bromopyridine (97%, Alfa Aesar), phthalic 15 anhydride (AR, Beijing Chemical Co.), tetrachloromethane (CCl 4 , AR, Beijing Chemical Co.), N-bromosuccinimide (NBS, 99%, Aldrich), triphenylphosphine (PPh 3 , 99%, Acros), hydrazine hydrate (85%, Sinopharm Chemical reagent Co.), aqueous formaldehyde solution (40%, AR, Beijing Chemical Co.), 4-tert- 20 butylphenylboronic acid (98%, J&K Scientific Ltd.), tetrakis(triphenylphosphine)palladium(0) (Pd(PPh 3 ) 3 , 99%, Acros), dicyclohexylcarbodiimide (DCC, Beijing Ouhe Technology Co.), N-Boc-L-proline (99%, J&K Scientific Ltd.), and N-Boc-D-proline (99%, J&K Scientific Ltd.) were used as 25 purchased. Azobisisobutyronitrile (AIBN, AR, Wuhan Chemical Co.) was recrystallized from ethanol and dried under vacuum at room temperature.…”

“…It should be noted that P(S)-BPhVPyA displayed an [α] 365 25 value of -264°. The optical rotation sign alternation before and after de- 25 protection might be attributed to the change in the orientation of proline pendants. Boc groups are bulky and have strong steric conflicts with polymer backbone.…”

“…water and 0.4 eq. of 4-nitrobenzoic acid 25 together resulted in the best results in terms of chemical yield and stereoselectivity (Entries 7 and 8, Table 3). When the amount of water added was fixed, more or less 4-nitrobenzoic acid led poor ee% and dr values.…”

“…4-nitro- 20 benzoic acid, plays the key roles of activating the carbonyl groups of the both substrates. Furthermore, the additional protons benefit for the formation of the six-membered ring transition state 4 through the hydrogen bond, which dramatically enhance the influence from the chiral proline moiety and increase the enantio- 25 selectivity. On the other hand, the added water helps to accelerate the aldol reaction possibly because of the hydrogen bond bridge between the catalyst molecule with the substrate molecules.…”

“…3 Asymmetric aldol catalysis is one of the most powerful and widely applied C−C bond forming transformation to afford β-hydroxyketones with one or two new stereocenters by combining two molecules of carbonyl compounds. 4 Among many 25 aldolases, proline and its derivatives are the simplest but most effective, successful and commonly employed class of catalysts, that catalyze a great number of aldol reactions with excellent yield and high enantio-selectivity. [5][6][7][8] Apart from aldolization, proline and its derivatives via enamine catalysis are widely 30 utilized in asymmetric Mannich reactions, [9][10][11] Michael reactions, 12-14 D-A reactions, [15][16][17] and α-aminations.…”