A High-Yielding Preparation of β-Ketonitriles

Ji, Yaohui; Trenkle, William C.; Vowles, James V.

doi:10.1021/ol053164z

Cited by 72 publications

(36 citation statements)

References 14 publications

(18 reference statements)

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“…The known compounds 2a and 2b are available in excellent yields from the 1,3-diketones 1a and 1b employing aqueous ammonia in the presence of silica gel [21]. Compound 2c was prepared from 1c in 87% yield with ammonium formate [22–23]. Interestingly, treatment of 1c with aqueous ammonia/silica gel failed to give 2c , deacetylation to 1-phenylpropan-2-one (76% yield) was observed instead.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

Hommes¹,

Reißig²

2016

Beilstein J. Org. Chem.

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SummaryThe scope of a flexible route to unsymmetrically functionalized bipyridines is described. Starting from 1,3-diketones 1a–e, the corresponding β-ketoenamines 2a–e were converted into different β-ketoenamides 3a–g by N-acylation with 2-pyridinecarboxylic acid derivatives. These β-ketoenamides were treated with a mixture of TMSOTf and Hünig’s base to promote the cyclocondensation to 4-hydroxypyridine derivatives. Their immediate O-nonaflation employing nonafluorobutanesulfonyl fluoride provided the expected 4-nonafloxy-substituted bipyridine derivatives 5a–g in moderate to good overall yields. The bipyridyl nonaflates are excellent precursors for palladium-catalyzed reactions as demonstrated by representative Suzuki and Sonogashira couplings. Thus, a library of specifically substituted bipyridine derivatives was generated, showing the versatility of the simple 1,3-diketone-based approach to this important class of ligands.

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Section: Resultsmentioning

confidence: 99%

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

Hommes¹,

Reißig²

2016

Beilstein J. Org. Chem.

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“…The starting nitrile is easily accessible from either substituted α,β-unsaturated ketone via cyanation or from the coupling between acetonitrile and an ester. [127] The production entails the use of purified CmCR, as the presence of ethanol (in whole cell biotransformation) can lead to alkylated side-products. [52] Monomers with > 4 carbon chain length can be produced from renewable fatty acids in a three-step biocatalytic process.…”

Section: Comparison Of Different Routes and Assessing Feasibility Of mentioning

confidence: 99%

Chemo-enzymatic routes towards the synthesis of bio-based monomers and polymers

Ahmed

Leferink

Scrutton

2019

Molecular Catalysis

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Scheme 7. Kinetic resolution of aromatic mandelic acid derivatives. Enantioselective hydrolysis of α-hydroxynitriles using nitrilases offer a facile approach to chiral hydroxy acids with theoretical yields of 100% in a dynamic kinetic resolution (DKR) process. Robertson et. al. identified 137 nitrilases after screening 651 environmental samples of which 44 were found to be (R) and 4 were (S)-selective on mandelonitrile. [36] Further investigation revealed nitrilase I and II to be proficient in the DKR of arylnitriles (rac-14 and 15) towards the synthesis of a panel of mandelic acid (R)-14 and phenyllactic acid derivatives (S)-15.[37] Scheme 8.Chemo-enzymatic DKR of α-hydroxynitriles towards the production of aromatic hydroxy acids. Dehydrogenases provide an alternative route to hydroxy acids via the asymmetric reduction of the pro-chiral ketone in α-keto esters. Fusion proteins consisting of glutathione Stransferase N-terminally linked to putative dehydrogenases from S. cerevisiae (Ypr1p and Gre1p) were used to reduce ethyl 2-oxo-4-phenylbutanoate to the corresponding alcohol with high enaniopurity.[38] Further systematic investigation by the same group on 18 reductases fused with GST showed activity towards α-and β-keto esters. [39] Five enzymes encoded from the yeast gene YDLI24w, YAL060w, YGL157w, YDR541c and YGL151w displayed excellent enantioselectivity across all three α-keto esters, affording the corresponding alcohol in >99% ee. Xu and co-workers engineered a highly stereoselective D-lactate dehydrogenase (D-LDH) towards a panel of aliphatic and aromatic αketoesters.[40] The Y52L mutant of D-LDH showed enhanced activity compared to the wildtype across the whole substrate panel (scheme 9). Scheme 9. Panel of α-keto acids using engineered D-lactate dehydrogenase (D-LDH). Values in brackets show % change in specific activity between wt and Y52L mutant.

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“…The crude residue was purified by silica gel column chromatography using ethyl acetate: hexanes to give pyrimidine compound 11(a-m). 10 17 : Acetonitrile (1.5 eq) was charged to a flask containing NaOMe (1.…”

Section: General Procedures For the Preparation Of Biginelli Compound mentioning

confidence: 99%

Successful utilization of $$\upbeta $$ β -ketonitrile in Biginelli reaction: synthesis of 5-cyanodihydropyrimidine

et al. 2018

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A Biginelli reaction of β-ketonitriles, aldehydes and urea in principle can yield 5-cyano substituted dihydropyrimidinones. Although potentially very useful, this substituted heterocycle is often difficult to synthesize via the three component reaction, presumably due to the lack of stability of β-ketonitriles. The present work describes the development of reaction conditions yielding the desired product. Interesting mechanistic observations have also been noted. Thirteen new compounds (derivatives) of 5-cyanodihydropyrimidin were synthesized.

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A High-Yielding Preparation of β-Ketonitriles

Cited by 72 publications

References 14 publications

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

Chemo-enzymatic routes towards the synthesis of bio-based monomers and polymers

Successful utilization of $$\upbeta $$ β -ketonitrile in Biginelli reaction: synthesis of 5-cyanodihydropyrimidine

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