Enantiopure Derivatives of Aza-Baylis-Hillman Adducts by Subsequent SN′-SN′ Reactions of Acylcarbamates Bearing a Chiral Auxiliary

(S)-Butane-1,2,4-triol (2) has been investigated as a potential chiral auxiliary for the formation of non-racemic acetals derived from η6-arylcarbonyl complexes of tricarbonylchromium. Predominantly the cis dioxan (5) was formed from benzaldehyde, leading to preparation of the η6-Cr(CO)3 complex (16), and of the derived complexes (23) and (24). Lithiation{electrophile quenching of these complexes gave a mixture of products arising fromortho and benzylic functionalization. Reaction of acetophenone, or of the η6-Cr(CO)3 complexes (45) or (46), with either the triol (2) or its tris(silyl) ether (15) under conditions of kinetic or thermodynamic control gave an inseparable mixture of acetals.

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Stereoselective and enantioselective synthesis of five-membered rings via conjugate additions of allylsulfone carbanions

Pure and Applied Chemistry ◽

10.1351/pac200072091671 ◽

2000 ◽

Vol 72 (9) ◽

pp. 1671-1683 ◽

Cited By ~ 32

Author(s):

Alfred Hassner ◽

Eugene Ghera ◽

Tamar Yechezkel ◽

Victoria Kleiman ◽

Thiagarajan Balasubramanian ◽

...

Keyword(s):

Membered Ring ◽

Optically Active ◽

Enantioselective Synthesis ◽

Ring Closure ◽

Chiral Auxiliary ◽

Asymmetric Induction ◽

Conjugate Additions ◽

Derivatives Of ◽

The Michael Addition ◽

High Stereoselectivity

This lecture describes some of our studies of lithio derivatives of allyl sulfone carbanions which add α-regioselectively as well as anti diastereoselectively to Michael acceptor olefins. This can be ascribed to chelation in the Michael addition step. When the reaction leads to subsequent ring closure by using a bromoallyl sulfone, the latter acts as a methylenemethane synthon in a (3+2) Michael-initiated ring closure, affording highly functionalized cyclopentane derivatives. Such additions proceed with high stereoselectivity and with asymmetric induction leading to nonracemic substituted cyclopentanones. Additions of allyl sulfone carbanions also proceed stereoselectively to C=N systems containing a chiral auxiliary on N. These can be used in the synthesis of optically active five- and six-membered ring N-heterocycles. Furthermore, chiral groups on the allyl sulfone moiety can induce significant remote asymmetric induction, made possible by the presence of an aromatic π-system which promotes intramolecular chelation to the Li cation.

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Preparative Method for Asymmetric Synthesis of (S)-2-Amino-4,4,4-trifluorobutanoic Acid

Molecules ◽

10.3390/molecules24244521 ◽

2019 ◽

Vol 24 (24) ◽

pp. 4521 ◽

Cited By ~ 6

Author(s):

Jianlin Han ◽

Ryosuke Takeda ◽

Xinyi Liu ◽

Hiroyuki Konno ◽

Hidenori Abe ◽

...

Keyword(s):

Schiff Base ◽

Drug Design ◽

Asymmetric Synthesis ◽

Large Scale ◽

Preparative Method ◽

Chiral Auxiliary ◽

Enantiomerically Pure ◽

Great Demand ◽

Derivatives Of

Enantiomerically pure derivatives of 2-amino-4,4,4-trifluorobutanoic acid are in great demand as bioisostere of leucine moiety in the drug design. Here, we disclose a method specifically developed for large-scale (>150 g) preparation of the target (S)-N-Fmoc-2-amino-4,4,4-trifluorobutanoic acid. The method employs a recyclable chiral auxiliary to form the corresponding Ni(II) complex with glycine Schiff base, which is alkylated with CF3–CH2–I under basic conditions. The resultant alkylated Ni(II) complex is disassembled to reclaim the chiral auxiliary and 2-amino-4,4,4-trifluorobutanoic acid, which is in situ converted to the N-Fmoc derivative. The whole procedure was reproduced several times for consecutive preparation of over 300 g of the target (S)-N-Fmoc-2-amino-4,4,4-trifluorobutanoic acid.

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