Enantioselective Synthesis of β-Hydroxy Acid Derivatives via a One-Pot Aldol Reaction−Dynamic Kinetic Resolution

Abstract

[reaction: see text]. Combining dynamic kinetic resolution with an aldol reaction provides access to beta-hydroxy ester derivatives with high enantiomeric purity (up to 99% ee) in a one-pot procedure. Only simple starting materials are required in this enantioselective process, and preformation of a silyl enol ether is not necessary.

Shvo’s Diruthenium Complex [(η5-C4Ph4COHOCC4Ph4-η5)(μ-H)(CO)4Ru2]

“…(B) The combination of enzyme-catalyzed DKR and an aldol reaction provided an access to b-hydroxy ester derivatives with high enantiomeric purity in a one-pot procedure using Shvo complex as catalyst for racemization. 10 (C) Oxidation of 5-unsaturated 3b-hydroxy steroids to the corresponding 4-en-3-one derivatives can be achieved by acetone at reflux in the presence of a Shvo catalyst. The reaction proceeds via a ruthenium-catalyzed dehydrogenation and subsequent hydrogen transfer to acetone with concomitant double bond migration.…”

Highly Compatible Metal and Enzyme Catalysts for Efficient Dynamic Kinetic Resolution of Alcohols at Ambient Temperature

“…[4] In 1997 our group reported [5] an efficient DKR process for the synthesis of enantiopure secondary alcohols by the use of ruthenium catalyst 1 [6] in combination with an immobilized lipase. This method has also been applied to the DKR of different functionalized alcohols, such as hydroxyacid derivatives, [7] hydroxynitriles, [8] azidoalcohols, [9] haloalcohols, [10] hydroxyphosphonates, [11] and diols.…”

One-pot synthesis of enantiopure syn -1,3-diacetates from racemic syn / anti mixtures of 1,3-diols by dynamic kinetic asymmetric transformation

“…In particular, lipases have emerged as efficient and robust biocatalysts that give good selectivities for a broad range of substrates (3, 4). The determination of the first crystal structure of lipases in 1990 (5, 6), preceded by a low-resolution crystal structure of a lipase from Geotrichum candidum in 1979 (7), and the observation that lipases work well in organic solvents (8-12) were factors that stimulated the development and use of these enzymes.More recently, the combination of enzymes and transition metals in coupled catalytic processes has attracted considerable attention (13)(14)(15)(16)(17)(18)(19)(20)(22)(23)(24)(25)(26)(27)(28)(29)(30). Simultaneous in situ racemization of the substrate by a transition metal and enzymatic resolution has resulted in efficient deracemization processes via so-called dynamic kinetic resolution (DKR).…”

“…In 1999 also, a Korean group (27) reported on the combination of a lipase and a ruthenium catalyst for DKR of secondary alcohols. Since then a large number of functionalized alcohols have been shown to undergo efficient DKR by combination of an enzyme and a ruthenium catalyst (18)(19)(20)(22)(23)(24)(25)(26)(27)(28)(29)(30).In the present work we applied the combined transition metal͞ enzyme system to the enantioselective synthesis of acyclic 1,3-diols. Stereoselective synthesis of acyclic 1,3-diols has attracted much attention, because these units occur as structural elements in a large number of polyketide natural products (31, 32) and polyene macrolide antibiotics (33, 34).…”

“…In 1999 also, a Korean group (27) reported on the combination of a lipase and a ruthenium catalyst for DKR of secondary alcohols. Since then a large number of functionalized alcohols have been shown to undergo efficient DKR by combination of an enzyme and a ruthenium catalyst (18)(19)(20)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”