DMAP-catalyzed cyanation of aldehydes and ketones with ethyl cyanoformate

Aoki, Shohei; Kotani, Shunsuke; Sugiura, Masaharu; Nakajima, Makoto

doi:10.1016/j.tetlet.2010.04.123

Cited by 31 publications

(12 citation statements)

References 51 publications

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“…Based on our kinetic data, and the findings of the groups of North, Moberg, Shibasaki,4 and others, a probable mechanism for the cyanoethoxy carbonylation reaction is suggested in Scheme . Ti IV could act as a Lewis acid to activate the carbonyl group and DMAP as a Lewis base to activate ethyl cyanoformate via the formation of intermediate species III , the probable structure of which is shown in Figure 7 d 9. This was confirmed further by 13 C NMR analysis, in which a set of new peaks at δ =154.182, 109.882, 38.854, 14.113 ppm appeared (Figure 7).…”

Section: Resultsmentioning

confidence: 73%

Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a Ti^IV Macrocyclic Complex: An Efficient Synthetic Protocol for β‐Blocker and α₁‐Adrenergic Receptor Agonists

et al. 2013

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Chiral macrocyclic TiIV–salen complexes were used as efficient catalysts in the asymmetric cyanoethoxy carbonylation of aldehydes. The TiIV catalysts demonstrated excellent performance (product yields and ee values up to 99 %) with ethyl cyanoformate as the cyanide source and a catalyst loading of 0.5 mol %, which is the lowest known. The macrocyclic TiIV–salen complex retained its performance at multigram level and was conveniently recycled for a number of times. The product obtained was straightforwardly transformed to the pharmaceutically important chiral drugs (R)‐proethalol (β‐blocker) and (R)‐phenylephrine (α1‐adrenergic receptor agonist) in good yields. To understand the mechanism of the catalytic reaction, a kinetic investigation was conducted with various concentrations of the catalyst, ethyl cyanoformate and benzaldehyde as the representative substrate. The reaction of benzaldehyde was first order with respect to the concentration of the catalyst and the ethyl cyanoformate but did not depend on the initial concentration of the substrate. A possible mechanism of the cyano‐ethoxy carbonylation reaction was proposed.

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Section: Resultsmentioning

confidence: 73%

Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a Ti^IV Macrocyclic Complex: An Efficient Synthetic Protocol for β‐Blocker and α₁‐Adrenergic Receptor Agonists

et al. 2013

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“…In the case of aliphatic ketones, good results were obtained for both acyclic and cyclic ketones. The reaction proceeded more smoothly than the reported example [17]. Only 1,2-addition products were observed for unsaturated ketones.…”

Section: Resultsmentioning

confidence: 55%

“…Several catalytic reactions have been recently studied. To date, reactions using tributyltin cyanide [9], K 2 CO 3 [10], tertiary amines [11,12], DABCO (1,4-diazabicyclo[2.2.2]octane) [13,14], dimethyl sulfoxide [15], TTMPP (tris(2,4,6-trimethoxyphenyl)phsphine) [16], DMAP ( N , N -dimethyl-4-aminopyridine) [17], and N -heterocyclic carbenes [18] as catalysts or activators have been reported. Asymmetric catalytic reactions have also been reported using cinchona alkaloids [19,20,21,22,23,24,25], Y complexes [26,27,28], Al complexes [29,30], Ti complexes [31,32,33,34,35,36,37,38,39,40], and V complexes [41].…”

Section: Introductionmentioning

confidence: 99%

TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds

2016

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Cyanation reactions of carbonyl compounds with methyl cyanoformate or acetyl cyanide catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) were examined. Using methyl cyanoformate, the corresponding cyanohydrin carbonates were readily obtained in high yield for aromatic and aliphatic aldehydes and ketones. Similar results were obtained when acetyl cyanide was used as the cyanide source. The polymer-supported catalyst, PS-TBD, also acted as a good catalyst for this reaction. PS-TBD was easily recovered and reused with minimal activity loss.

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“…With lower concentrations of DMAP and acetonitrile as solvent, O -ethoxycarbonyl cyanohydrins have been synthetized from aldehydes and ketones [ 23 ]. Table 4 shows the results.…”

Section: Synthesis Of O -Protected Cyanohydrinsmentioning

confidence: 99%

“…The mechanism involves the formation of complex H from the reaction of DMAP with ethyl cyanoformate, followed by addition of CN − to the aldehyde to give compound I which decomposes into the product and regenerates DMAP (Scheme 8). With lower concentrations of DMAP and acetonitrile as solvent, O-ethoxycarbonyl cyanohydrins have been synthetized from aldehydes and ketones [23]. Table 4 shows the results.…”

Section: Entrymentioning

confidence: 99%

Recent Advances on O-Ethoxycarbonyl and O-Acyl Protected Cyanohydrins

2021

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Ethoxycarbonyl cyanohydrins and O-acyl cyanohydrins are examples of O-protected cyanohydrins in which the protecting group presents an electrophilic center, contributing to additional reaction pathways. The first section of this review describes recent advances on the synthesis of O-ethoxycarbonyl and O-acyl protected cyanohydrins. Reactions using KCN or alkyl cyanoformates as the cyanide ion source are described, as well as organic and transition metal catalysis used in their preparation, including asymmetric cyanation. In a second part, transformations, and synthetic applications of O-ethoxycarbonyl/acyl cyanohydrins are presented. A variety of structures has been obtained starting from such protected cyanohydrins and, in particular, the synthesis of oxazoles, 1,4-diketones, 1,3-diketones, 2-vinyl-2-cyclopentenones through various methods are discussed.

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DMAP-catalyzed cyanation of aldehydes and ketones with ethyl cyanoformate

Cited by 31 publications

References 51 publications

Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a Ti^IV Macrocyclic Complex: An Efficient Synthetic Protocol for β‐Blocker and α₁‐Adrenergic Receptor Agonists

Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a Ti^IV Macrocyclic Complex: An Efficient Synthetic Protocol for β‐Blocker and α₁‐Adrenergic Receptor Agonists

TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds

Recent Advances on O-Ethoxycarbonyl and O-Acyl Protected Cyanohydrins

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DMAP-catalyzed cyanation of aldehydes and ketones with ethyl cyanoformate

Cited by 31 publications

References 51 publications

Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a TiIV Macrocyclic Complex: An Efficient Synthetic Protocol for β‐Blocker and α1‐Adrenergic Receptor Agonists

Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a TiIV Macrocyclic Complex: An Efficient Synthetic Protocol for β‐Blocker and α1‐Adrenergic Receptor Agonists

TBD- or PS-TBD-Catalyzed One-Pot Synthesis of Cyanohydrin Carbonates and Cyanohydrin Acetates from Carbonyl Compounds

Recent Advances on O-Ethoxycarbonyl and O-Acyl Protected Cyanohydrins

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Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a Ti^IV Macrocyclic Complex: An Efficient Synthetic Protocol for β‐Blocker and α₁‐Adrenergic Receptor Agonists

Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a Ti^IV Macrocyclic Complex: An Efficient Synthetic Protocol for β‐Blocker and α₁‐Adrenergic Receptor Agonists