Asymmetric Synthesis of Bicyclic Diol Derivatives through Metal and Enzyme Catalysis: Application to the Formal Synthesis of Sertraline

Krumlinde, Patrik; Bogár, Krisztián; Bäckvall, Jan‐Erling

doi:10.1002/chem.200903114

Cited by 47 publications

(30 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent application, the Shvo catalyst 1 was used to oxidize enantiomerically pure bicyclic diols (R,R)-3 to the hydroxyketones (R)-4 in acetone [46]. The acetone acts as the hydrogen acceptor and, interestingly, under these conditions, it was possible to stop the reaction after oxidation of one of the hydroxyl groups to give the hydroxyketones 4 in 82-85% yield and 97-98% ee (5).…”

Section: Oxidation Of Alcoholsmentioning

confidence: 98%

“…The acetone acts as the hydrogen acceptor and, interestingly, under these conditions, it was possible to stop the reaction after oxidation of one of the hydroxyl groups to give the hydroxyketones 4 in 82-85% yield and 97-98% ee (5). The hydroxyketones obtained are useful starting materials for the synthesis of natural products and biologically active compounds, and (R)-4b was used for the synthesis of Sertraline [46].…”

Section: Oxidation Of Alcoholsmentioning

confidence: 99%

See 1 more Smart Citation

Shvo’s Catalyst in Hydrogen Transfer Reactions

Warner

Casey

Bäckvall

2011

Bifunctional Molecular Catalysis

Self Cite

View full text Add to dashboard Cite

This chapter reviews the use of Shvo's catalyst in various hydrogen transfer reactions and also discusses the mechanism of the hydrogen transfer. The Shvo catalyst is very mild to use since no activation by base is required in the transfer hydrogenation of ketones or imines or in the transfer dehydrogenation of alcohols and amines. The Shvo catalyst has also been used as an efficient racemization catalyst for alcohols and amines. Many applications of the racemization reaction are found in the combination with enzymatic resolution leading to a dynamic kinetic resolution (DKR). In these dynamic resolutions, the yield based on the starting material can theoretically reach 100%. The mechanism of the hydrogen transfer from the Shvo catalyst to ketones (aldehydes) and imines as well as the dehydrogenation of alcohols and amines has been studied in detail over the past decade. It has been found that for ketones (aldehydes) and alcohols, there is a concerted transfer of the two hydrogens involved, whereas for typical amines and imines, there is a stepwise transfer of the two hydrogens. One important question is whether the substrate is coordinated to the metal or not in the hydrogen transfer step(s). The pathway involving coordination to activate the substrate is called the inner-sphere mechanism, whereas transfer of hydrogen without coordination is called the outer-sphere mechanism. These mechanistic proposals together with experimental and theoretical studies are discussed.

show abstract

Section: Oxidation Of Alcoholsmentioning

confidence: 98%

Section: Oxidation Of Alcoholsmentioning

confidence: 99%

Shvo’s Catalyst in Hydrogen Transfer Reactions

Warner

Casey

Bäckvall

2011

Bifunctional Molecular Catalysis

Self Cite

View full text Add to dashboard Cite

show abstract

“…[8] The authors showed that the oxidation of the first alcohol function was faster than that of the second, and this provided a different access to (R)-3 which was then transformed into a sertraline precursor. [8] While this is elegant and of interest, our new one-step asymmetric mono-reduction of 1 (Scheme 3) is more efficient and operationally simpler than the two-step double reduction/mono-oxidation sequence.…”

Section: Resultsmentioning

confidence: 98%

Efficient Enantioselective Syntheses of Sertraline, 2‐Epicatalponol and Catalponol from Tetralin‐1,4‐dione

et al. 2010

View full text Add to dashboard Cite

Tetralin-1,4-dione, the stable tautomer of dihydroxynaphthalene, was reduced with catecholborane in the presence of 3,3-diphenyl-1-butyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole as catalyst to give enantiomerically highly enriched 4-hydroxy-1-tetralone (99% ee) in an efficient one-pot procedure. The R-enantiomer provided a rapid access to sertraline while the S-enantiomer was converted into 2-epicatalponol and catalponol. A more selective enantioselective route to the antithermitic catalponol made use of the planar chiral tricarbonylchromium complex of hydroxytetralone. Its precursor chromium(tricarbonyl)[η6-(1-4,4a,8a)-tetralin-5,8-dione] was obtained via direct complexation of 1,4-dihydroxynaphthalene using chromium(tricarbonyl)- tris(ammonia) and boron trifluoride etherate as source of the chromium(tricarbonyl) fragment. Enolate prenylation was best carried out in the presence of a tetraamine ligand. Complete inversion of the stereogenic center bearing the prenyl group of the initially obtained tetralone complex was achieved via enolate formation followed by protonation

show abstract

“…The excellent properties displayed by enzymes in terms of selectivity and reactivity under mild reaction conditions make biocatalysis an attractive alternative for the production of enantiopure building blocks and pharmaceuticals . Interestingly, the plethora of reported syntheses of 1 includes one chemoenzymatic approach based on a stereoselective enzyme‐ and ruthenium‐catalyzed dynamic kinetic asymmetric transformation (DYKAT) employing Candida antarctica lipase B . Very recently, Pfizer unveiled an imine reductase (IRED) capable of producing sertraline by diastereoselective reduction of the enantiopure ( S )‐ N ‐methylimine precursor .…”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Synthesis of Sertraline

Marx

Ríos‐Lombardía

Süss³

et al. 2020

Eur J Org Chem

View full text Add to dashboard Cite

A chemoenzymatic approach has been developed for the preparation of sertraline, an established anti-depressant drug. Ketoreductases (KREDs) were employed to yield a key chiral precursor. The bioreduction of the racemic tetralone exhibited excellent enantioselectivity (>99 % ee) and diastereomeric ratio (99:1) at 29 % conversion (the maximum theoretical yield Scheme 1. Synthesis of the API sertraline (S,S-1). The first step 1) is a KRED-catalysed selective bioreduction to the alcohol precursor (S,S)-4. The second step can either be achieved chemically 2a) by NaOCl/AZADO or enzymatically 2b) by Trametes versicolor laccase/AZADO.Step 3) comprises a direct amination employing methylamine followed by reduction with NaBH 4 .[a] 510 is 50 %) after 7 hours. The resulting (S,S)-alcohol was efficiently oxidized to an enantiopure (S)-ketone, an immediate precursor of sertraline, by using sodium hypochlorite as oxidant and 2azaadamantane N-oxyl (AZADO) as organocatalyst. Alternative routes aiming at the direct biocatatalytic amination using imine reductases and transaminases were unsuccessful.

show abstract

Asymmetric Synthesis of Bicyclic Diol Derivatives through Metal and Enzyme Catalysis: Application to the Formal Synthesis of Sertraline

Cited by 47 publications

References 41 publications

Shvo’s Catalyst in Hydrogen Transfer Reactions

Shvo’s Catalyst in Hydrogen Transfer Reactions

Efficient Enantioselective Syntheses of Sertraline, 2‐Epicatalponol and Catalponol from Tetralin‐1,4‐dione

Chemoenzymatic Synthesis of Sertraline

Contact Info

Product

Resources

About