Silylketenimine – vielseitige Nucleophile für die katalytische asymmetrische Synthese

Denmark, Scott E.; Wilson, Tyler W.

doi:10.1002/ange.201202139

Cited by 34 publications

(14 citation statements)

References 113 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Likewise,a dditional derivatives bearing longer aliphatic chains also underwent the desired reaction with high efficiency (18)(19). We were pleased to observe that acrylonitrile was efficiently reacted with diphenylsilane at 25 8 8Ct og ive 2-silyl-1-propylamine, which was isolated as the HCl salt in good yield (17;T able 2).…”

mentioning

confidence: 98%

Chemoselective Silylative Reduction of Conjugated Nitriles under Metal‐Free Catalytic Conditions: β‐Silyl Amines and Enamines

et al. 2015

View full text Add to dashboard Cite

The B(C6F5)3-catalyzed silylative reduction of conjugated nitriles has been developed to afford synthetically valuable β-silyl amines. The reaction is chemoselective and proceeds under mild conditions. Mechanistic elucidation indicates that it proceeds by rapid double hydrosilylation of the conjugated nitrile to an enamine intermediate which is subsequently reduced to the β-silyl amine, thus forming a new C(sp(3))-Si bond. Based on this mechanistic understanding, a preparative route to enamines was also established using bulky silanes.

show abstract

mentioning

confidence: 98%

Chemoselective Silylative Reduction of Conjugated Nitriles under Metal‐Free Catalytic Conditions: β‐Silyl Amines and Enamines

et al. 2015

View full text Add to dashboard Cite

show abstract

“…[4b,d] As an alkyl nitrile equivalent, silyl ketene imines [7] (SKIs) are competent nucleophiles that can react to form C-substituted nitriles (Scheme 1). Moreover, owing to their unique structure and ready racemization, SKIs are attractive substrates for the construction of vicinal tertiary and quaternary stereogenic carbon centers, [8] which are difficult to synthesize. [9] Since Fu and co-workers reported the first asymmetric acylation of SKIs, [10a] they have become attractive nucleophiles for asymmetric catalytic reactions.…”

mentioning

confidence: 99%

“…It was envisioned that bases might facilitate the deprotonation of aldimine 1, thereby making it easier for it to coordinate with the Sc III center in a bidentate fashion. The substituent on the phenol protecting group of the imine also influenced the diastereoselectivity ( Table 1, entries [8][9][10]. When imine 1 c was used Scheme 1.…”

mentioning

confidence: 99%

“…A wide range of aldehydes are suitable substrates for the reaction of a-methyla-phenyl silyl ketene imine 2 a, and excellent diastereo-and enantioselectivity was achieved in most cases ( Table 2, entries [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. The reactions of imines derived from electron-rich and electron-deficient aromatic aldehydes gave the desired products in good yield and enantioselectivity (89-97 % ee; Table 2, entries 2-12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Asymmetric Synthesis of β‐Amino Nitriles through a Sc^III‐Catalyzed Three‐Component Mannich Reaction of Silyl Ketene Imines

et al. 2013

View full text Add to dashboard Cite

Chiral b-amino nitriles are versatile synthetic intermediates that are readily transformed into optically active compounds such as b-amino acids, and 1,3-diamines. [1] The asymmetric addition of alkyl nitriles to imines provides a straightforward route to such compounds. [2] Although many methods for the asymmetric Mannich reaction have been described, [3] the use of less nucleophilic alkyl nitriles as the nitrile species is a continuing challenge; [4][5][6] one reason for this issue is the poor acidity of the a protons of alkyl nitriles. [5,6] One strategy to solve this problem is the use of an N-metalloketene imine, generated from cyanocarboxylic acid or benzyl nitrile, as an active intermediate; two catalytic asymmetric systems have been reported for such Mannich reactions. [4b,d] As an alkyl nitrile equivalent, silyl ketene imines [7] (SKIs) are competent nucleophiles that can react to form C-substituted nitriles (Scheme 1). Moreover, owing to their unique structure and ready racemization, SKIs are attractive substrates for the construction of vicinal tertiary and quaternary stereogenic carbon centers, [8] which are difficult to synthesize. [9] Since Fu and co-workers reported the first asymmetric acylation of SKIs, [10a] they have become attractive nucleophiles for asymmetric catalytic reactions. [10] The asymmetric aldol-type reaction of SKIs has been reported. [10b,c,e] However, there is only a limited number of examples of the asymmetric addition of SKIs to aldimines and the addition of SKIs to similar substrates has proven somewhat more difficult to achieve and is generally characterized by a narrow substrate scope; the only asymmetric system, which uses stoichiometric quantities of a chiral silicon Lewis acid as the promoter, was reported by Leighton and co-workers. [11] Therefore, the development of a general and efficient asymmetric Mannich reaction of SKIs is particularly desirable. We have recently developed chiral N,N'-dioxide/metal catalysts, which we used for a variety of asymmetric transformations, [12] one of which is the three-component, [13] one-pot addition of N-aryl imines. [14] Herein, we describe a practical and highly efficient Mannich reaction of SKIs to address the challenges mentioned above. A three-component, one-pot method involving the use of a chiral N,N'-dioxide scandium(III) catalyst under mild reaction conditions was developed for the synthesis of bamino nitriles. The desired products, which contain a quaternary stereogenic center, were generated in excellent yield and stereoselectivity (up to 95 % yield, > 95:5 d.r., 97 % ee). The procedure is convenient as no exclusion of air and moisture is required.In the initial study, the reaction between aldimine 1 a [15] and SKI 2 a was performed in EtOAc at À20 8C with 10 mol % of a Lewis acid catalyst, which was prepared in situ from Sc(OTf) 3 and chiral N,N'-dioxide ligand L1. The desired bamino nitrile 3 a was obtained in moderate yield and enantioselectivity and extremely low diastereoselectivity (56:44 d.r.; Table 1, entry ...

show abstract

“…However, such ideas would not be applicable to anitrile carbanions, which probably cannot generate axially chiral intermediates because of the linear nature of a keteniminate. [18] We chose the N-carbamoyl a-amino nitrile (S)-4, which is readily derived from l-phenylalanine (see the Supporting Information), and investigated its enantioselective deprotonation/substitution reaction. [19] The optimized reaction conditions [2] found for the carbamoyloxy derivative (S)-1 were applied to (S)-4 and resulted in the formation of the acylated product 6 a in poor yield and with moderate enantioselectivity (Table 1, entry 1) together with the recovery of a significant amount of the starting material and no loss of enantiomeric purity.…”

mentioning

confidence: 99%

Enantiodivergent Deprotonation/Acylation of α‐Amino Nitriles

et al. 2013

View full text Add to dashboard Cite

show abstract

Silylketenimine – vielseitige Nucleophile für die katalytische asymmetrische Synthese

Cited by 34 publications

References 113 publications

Chemoselective Silylative Reduction of Conjugated Nitriles under Metal‐Free Catalytic Conditions: β‐Silyl Amines and Enamines

Chemoselective Silylative Reduction of Conjugated Nitriles under Metal‐Free Catalytic Conditions: β‐Silyl Amines and Enamines

Asymmetric Synthesis of β‐Amino Nitriles through a Sc^III‐Catalyzed Three‐Component Mannich Reaction of Silyl Ketene Imines

Enantiodivergent Deprotonation/Acylation of α‐Amino Nitriles

Contact Info

Product

Resources

About

Silylketenimine – vielseitige Nucleophile für die katalytische asymmetrische Synthese

Cited by 34 publications

References 113 publications

Chemoselective Silylative Reduction of Conjugated Nitriles under Metal‐Free Catalytic Conditions: β‐Silyl Amines and Enamines

Chemoselective Silylative Reduction of Conjugated Nitriles under Metal‐Free Catalytic Conditions: β‐Silyl Amines and Enamines

Asymmetric Synthesis of β‐Amino Nitriles through a ScIII‐Catalyzed Three‐Component Mannich Reaction of Silyl Ketene Imines

Enantiodivergent Deprotonation/Acylation of α‐Amino Nitriles

Contact Info

Product

Resources

About

Asymmetric Synthesis of β‐Amino Nitriles through a Sc^III‐Catalyzed Three‐Component Mannich Reaction of Silyl Ketene Imines