Asymmetric 1,4-Reductions of Hindered β-Substituted Cycloalkenones Using Catalytic SEGPHOS−Ligated CuH

Lipshutz, Bruce H.; Servesko, Jeff M.; Petersen, Tue B.; Papa, Patrick; Lover, Andrew A.

doi:10.1021/ol0400185

Cited by 119 publications

(33 citation statements)

References 13 publications

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“…Attempts to generalize these procedures to alkenes conjugated with less polar groups such as aldehydes or ketones have been much less successful, [6] although some exceptions have been reported. [24][25][26] Therefore, ERs are interesting for the hydrogenation of unsaturated aldehyde or ketone substrates, rounding off the chemists toolbox. The stereoselective application of these enzymes has been reported recently.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Three Enoate Reductases and their Potential Use for Biotransformations

et al. 2007

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Enoate reductases (ERs) selectively reduce carbon-carbon double bonds in a,b-unsaturated carbonyl compounds and thus can be employed to prepare enantiomerically pure aldehydes, ketones, and esters. Most known ERs, most notably Old Yellow Enzyme (OYE), are biochemically very well characterized. Some ERs have only been used in whole-cell systems, with endogenous ketoreductases often interfering with the ER activity. Not many ERs are biocatalytically characterized as to specificity and stability. Here, we cloned the genes and expressed three non-related ERs, two of them novel, in E. coli: XenA from Pseudomonas putida, KYE1 from Kluyveromyces lactis, and Yers-ER from Yersinia bercovieri. All three proteins showed broad ER specificity and broad temperature and pH optima but different specificity patterns. All three proteins prefer NADPH as cofactor over NADH and are stable up to 40 8C. By coupling Yers-ER with glucose dehydrogenase (GDH) to recycle NADP(H), conversion of > 99 % within one hour was obtained for the reduction of 2-cyclohexenone. Upon lowering the loadings of Yers-ER and GDH, we discovered rapid deactivation of either enzyme, especially of the thermostable GDH. We found that the presence of enone substrate, rather than oxygen or elevated temperature, is responsible for deactivation. In summary, we successfully demonstrate the wide specificity of enoate reductases for a range of a,b-unsaturated carbonyl compounds as well as coupling to glucose dehydrogenase for recycling of NAD(P)(H); however, the stability limitations we found need to be overcome to envision large-scale use of ERs in synthesis.

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Section: Introductionmentioning

confidence: 99%

Comparison of Three Enoate Reductases and their Potential Use for Biotransformations

et al. 2007

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“…MeOH, 50 °C 50 bar H 2 , S/C 75,000 92% (38) A chiral tetrahydropyridine ester was hydrogenated with a catalyst prepared in situ from [RhCl(nbd)] 2 and (R)-MeOBIPHEP to afford the desired (1 S, 2R, 4R) product with only 36% de (eq 39). 60 Fortunately, when ferrocenyl-based chiral diphosphines were used (e.g., Mandyphos), de values up to 97% were achieved.…”

Section: Asymmetric Hydrogenation Of C=c Double Bonds 2-mentioning

confidence: 99%

“…3,5-Xyl-MeOBIPHEP shows promise in the reduction of cycloalkenones providing ee values >90%. 38 An interesting application of the parent MeOBIPHEP ligand is the dynamic-kinetic resolution by means of asymmetric Cu-catalyzed conjugate reduction of an α,β-unsaturated lactone (eq 21). 39 The saturated lactone product that is formed as single diastereomer in 93% ee is an intermediate in the total synthesis of eupomatilone-3.…”

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confidence: 99%

(R)- and (S)-2,2′-Bis(diphenylphosphino)-6,6′-dimethoxy-1,1′-biphenyl

Schmid

Michelet

Scalone

et al. 2016

Encyclopedia of Reagents for Organic Synthesis

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“…Outstanding results have so far been obtained in the 1,4 -hydrosilylation of cycloalkenones [50] , α , β -unsaturated esters [51] and β -silyl -α , β -unsaturated esters [52] . The choice of ligand is critical to the success, with each class of starting material having different requirements.…”

Section: Coppermentioning

confidence: 99%

Alkene Reduction: Hydrosilylation

Mayes

Perlmutter

2008

Modern Reduction Methods

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4.1 IntroductionCatalytic, asymmetric hydrosilylations of alkenes were fi rst reported in 1971 when the platinum complex cis -PtCl 2 (C 2 H 4 ) was used to catalyze the hydrosilylation of 1 -methylstyrene in 5% ee [1] . Through the use of nickel this was raised to 18% ee [2] . A palladium complex with a ferrocene -based ligand successfully catalyzed the hydrosilylation of norbornene and styrene giving moderate ee (52 -53%) [3] . The breakthrough came with the development of Hayashi ' s monophosphine ( MOP ) ligands in 1991 (see below), used in the palladium -catalyzed hydrosilylation of aliphatic alkenes with good regioselectivities and ee values greater than 90% being obtained. Early research into catalytic, asymmetric hydrosilylations of alkenes has been covered in reviews by Nishiyama and Hayashi [4] , this review therefore focuses on research published after 1998. Isolated Alkenes Palladium Aromatic AlkenesMuch of the recent research into catalytic, asymmetric hydrosilylation of alkenes has focused on developing catalysts for the hydrosilyation of aromatic alkenes, with many groups employing styrene (1) as the test substrate for their catalysts. These reactions generally require low catalyst loadings (0.1 to 0.25 mol% palladium) and often proceed at or below room temperature. The reactions are usually highly regioselective and often yield benzylsilane (2) as the only product (Scheme 4.1 ). Oxidation, generally employing the Tamao procedure, then yields alcohol (3) [5] .

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Asymmetric 1,4-Reductions of Hindered β-Substituted Cycloalkenones Using Catalytic SEGPHOS−Ligated CuH

Cited by 119 publications

References 13 publications

Comparison of Three Enoate Reductases and their Potential Use for Biotransformations

Comparison of Three Enoate Reductases and their Potential Use for Biotransformations

(R)- and (S)-2,2′-Bis(diphenylphosphino)-6,6′-dimethoxy-1,1′-biphenyl

Alkene Reduction: Hydrosilylation

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