The chemistry of acylals. 3. Cyanohydrin esters from acylals with cyanide reagents

[reaction: see text] When treated with KCN in DMSO at room temperature, acylals from aliphatic aldehydes gave the corresponding cyanohydrin esters in good to excellent yields. Acylals from aromatic aldehydes were less reactive and gave several byproducts in addition to fair yields of cyanohydrin under the same conditions. Trimethylsilyl cyanide mixed with titanium(IV) chloride afforded cyanohydrin esters in good to excellent yields from both aliphatic and aromatic aldehydes.     

Remarkable acceleration of cyanosilylation by the mesoporous Al-MCM-41 catalyst

The presence of the heterogeneous mesoporous Al-MCM-41 catalyst remarkably accelerated the cyanosilylation of various aldehydes and ketones with trialkylsilyl cyanide, giving the corresponding cyanohydrin silyl ethers in quantitative yields under mild reaction conditions.     

Cyanobenzoylation and hydrocyanation of aldehydes with benzoyl cyanide using no catalyst

[reaction: see text] In the presence of MS 4A in DMSO, cyanobenzoylation of various aldehydes with benzoyl cyanide proceeded very smoothly to give the corresponding cyanohydrin benzoates in high to excellent yields without an acid or a base. On the other hand, reaction of aldehydes with BzCN in DMSO-H(2)O also occurred readily to afford the corresponding free cyanohydrins exclusively.     

Iodine as novel reagent for the 1,2-addition of trimethylsilyl cyanide to ketones including α,β-unsaturated ketones

Molecular iodine is found to catalyze efficiently the addition of trimethylsilyl cyanide to a range of simple and functionalized ketones under very mild and convenient conditions to afford the corresponding cyanohydrin trimethylsilyl ethers in excellent yields in a short reaction period with high selectivity. α,β-Unsaturated ketones selectively afford the corresponding 1,2-adducts without the formation of 1,4-adducts under similar reaction conditions.     

Cyanosilylation of Aldehydes and Ketones Catalyzed by Nanocrystalline Magnesium Oxide

Abstract

Cyanosilylation of various aldehydes and ketones with TMSCN proceeded smoothly under mild conditions to give the corresponding cyanohydrin trimethylsilyl ethers in the presence of nanocrystalline magnesium oxide. The cyanohydrin trimethylsilyl ethers of aldehydes produced cyanohydrins in good to high yields on treatment with 2 N HCl. ²⁹Si NMR spectral evidence proved that the reaction proceeds through the hypervalent silicate species by coordination to O^2?/O^? (Lewis basic site) of nanocrystalline magnesium oxide.     

Organocatalysts of tertiary-phosphines and amines catalyzed reactions of α-keto esters with cyclopent-2-enone

The reaction of α-keto esters with cyclopent-2-enone catalyzed by tertiary-phosphines provides the corresponding Baylis-Hillman adducts. Among the catalysts, diphenylmethylphosphine was found to be the most effective promoter allowing the reaction to proceed smoothly at room temperature and to give the corresponding adducts in higher yields in the presence of p-nitrophenol. Whereas, the similar reaction of α-keto esters with cyclopent-2-enone catalyzed by tertiary-amine of DBU furnishes the corresponding aldol adducts with syn-configuration exclusively.     

The first broad application of alkynyl sulfides as dienophiles in cobalt(I)-catalyzed Diels-Alder reactions

The cobalt(I)-catalyzed Diels-Alder reaction of nonactivated aryl alkynyl sulfides with acyclic 1,3-dienes generates dihydroaromatic vinyl sulfides under very mild reaction conditions, and these products can be oxidized with mild oxidants to the corresponding diaryl sulfides in good overall yields. The steric and electronic effects of substituents on the aryl, as well as on the alkynyl, moieties of the aryl alkynyl sulfide are discussed. While the cobalt catalyst system is quite efficient in converting alkynyl sulfides to the Diels-Alder adducts, the transformation of the corresponding aryl alkynyl sulfoxides and sulfones under similar mild reaction conditions gave only moderate yields of the desired adducts.     

A facile direct conversion of aldehydes to esters and amides using acetone cyanohydrin

Aromatic aldehydes with electron-withdrawing groups undergo rapid reactions with a variety of alcohols and secondary amines to afford the corresponding esters and amides, respectively, in high yields, when treated with NaCN or acetone cyanohydrin and base under ambient reaction conditions. In case of α,β-unsaturated aldehydes, simultaneous reduction of the CC bond along with esterification occurred to produce the saturated esters in high yields.     

Solvent‐free cyanosilylation of aldehydes catalyzed by SmI2

A novel method to obtain racemic cyanohydrin silylethers by reaction of trimethylsilyl cyanide with a variety of aldehydes promoted by catalysis of SmI₂ is reported. The corresponding cyanosilylethers were obtained in high yields (up to 99%) in solvent‐ free conditions at room temperature within a relatively short time using 0.01–0.5 mol% catalyst loadings. Copyright © 2007 John Wiley & Sons, Ltd.     

A novel synthesis of α-fluoroacetonitriles. Application to a convenient preparation of 2-fluoro-2-phenethylamines

α-Fluorophenylacetonitriles (3) are readily prepared by the treatment of the corresponding benzaldehyde cyanohydrin trimethylsilylethers (2) with diethylaminosulfur trifluoride (DAST). This method for the introduction of fluorine alpha to a cyano group is also applicable to the cyanohydrin trimethylsilylethers of aromatic ketones. Diborane reduction of the α-fluorophenylacetonitriles (3) yields 2-fluoro-2-phenethylamines (4).     

An expeditious synthesis of cyanohydrin trimethylsilyl ethers using tetraethylammonium 2-(carbamoyl)benzoate as a bifunctional organocatalyst

Phthalimide and tetraethylammonium hydroxide react via an unusual pathway to afford tetraethylammonium 2-(carbamoyl)benzoate (TEACB) which is of interest as a bifunctional organocatalyst. TEACB (0.5 mol %) was found to catalyze the addition of trimethylsilyl cyanide (TMSCN) to carbonyl compounds under solvent-free conditions at room temperature with very short reaction times. A wide variety of aldehydes and ketones were transformed into the corresponding cyanohydrin trimethylsilyl ethers in high to quantitative yields.     

Asymmetric aza-Henry reaction of chiral fluoroalkyl α,β-unsaturated N-tert-butanesulfinyl ketoimines: an efficient approach to enantiopure fluoroalkylated α,β-diamines and α,β-diamino acids

The aza-Henry reaction of chiral fluoroalkyl α,β-unsaturated N-tert-butanesulfinyl ketoimines and nitromethane was achieved in the presence of 0.2 equivalent of anhydrous potassium carbonate to give the corresponding adducts diastereoselectively in high yields. Transformations which highlighted the synthetic potential of these aza-Henry adducts were also performed.     

Catalytic and enantioselective aza-ene and hetero-Diels-Alder reactions of alkenes and dienes with azodicarboxylates

Lewis acids such as Cu(OTf)(2), Zn(OTf)(2), Yb(OTf)(3) and Nd(OTf)(3) catalyze the aza-ene reaction of alkenes with azodicarboxylates, giving the allylic amination adducts. The use of bis(2,2,2-trichloroethyl)azodicarboxylate as the amination reagent and Cu(OTf)(2) and Yb(OTf)(3) as the catalysts gave the aza-ene reaction of different alkenes, leading to the corresponding allyl amines in high yields. Chiral copper complexes prepared from Cu(OTf)(2) and chiral bisoxazoline ligands were found to catalyze the enantioselective aza-ene reaction of azodicarboxylates with alkenes and the hetero-Diels-Alder reaction with cyclopentadiene, giving the corresponding aza-ene- and hetero-Diels-Alder adducts, respectively, in good yields and moderate enantioselectivities.     

Protonation of acyl anion equivalents generated from acylphosphonates: nonhydride access to the aldehyde oxidation state from the carboxylic acid oxidation state

Acylphosphonates, which are easily available from carboxylic acids, are potent acyl anion precursors and undergo cyanide ion promoted phosphonate-phosphate rearrangement to provide the corresponding acyl anion equivalents as reactive intermediates. The protonation of these acyl anion equivalents furnished cyanohydrin O-phosphates in good yields. For the high yield formation of cyanohydrin O-phosphates from arylphosphonates THF should be used and from alkylphosphonates DME was used.     

Enantioselective cyanosilylation of alpha,alpha-dialkoxy ketones catalyzed by proline-derived in-situ-prepared N-oxide as bifunctional organocatalyst

Bifunctional N,N'-dioxide catalysts have been developed for highly enantioselective cyanosilylation of alpha,alpha-dialkoxy ketones. This process, catalyzed by in-situ-prepared proline-derived N,N'-dioxide 2b, produced the corresponding cyanohydrin trimethylsilyl ethers in excellent yields (up to 99%) with high enantioselectivities (up to 93% ee). A reasonable mechanism was proposed according to the observation of the linear effect, 1H NMR spectra, isolated cyanohydrin, and the roles of the NH and N-oxide moieties of the catalyst.     

Cycloadditions of 8,8-dicyanoheptafulvene to styrenes: manifestation of dual reactivity modes

A facile cycloaddition reaction of 8,8-dicyanoheptafulvene with styrenes leading to the corresponding [8+2] and [4+2] adducts in excellent yields is described.     

Trimethylsilyl Cyanide Addition to Carbonyl Compounds Under Neutral Condition Catalyzed by Iodine

Reaction of trimethylsilyl cyanide with aliphatic or aromatic aldehydes and ketones in the presence of a catalytic amount of elemental iodine produced the corresponding cyanohydrin trimethylsilyl ethers in very short time and high yields.     

SYNTHESIS OF 3-PER(POLY)FLUOROALKYLPYRAZOLES

ＳＹＮＴＨＥＳＩＳＯＦ３－ＰＥＲ（ＰＯＬＹ）ＦＬＵＯＲＯＡＬＫＹＬＰＹＲＡＺＯＬＥＳＳＹＮＴＨＥＳＩＳＯＦ３－ＰＥＲ（ＰＯＬＹ）ＦＬＵＯＲＯＡＬＫＹＬＰＹＲＡＺＯＬＥＳ￥ＸｉａｏＱｉｎｇＴＡＮＧａｎｄＣｈａｎｇＭｉｎｇＨＵ（ＳｈａｎｇｈａｉＩｎｓｔｉ...     

Candida antarctica lipase A in the dynamic resolution of novel furylbenzotiazol-based cyanohydrin acetates

A series of novel (R)-furylbenzotiazol-based cyanohydrin acetates were prepared in over 90% isolated yields from the corresponding furancarbaldehydes. The one-pot method combines a basic resin to produce hydrogen cyanide from acetone cyanohydrin, an equilibrium between the formation and decomposition of furylbenzotiazol-based cyanohydrins and the unique enantioselectivity of Candida antarctica lipase A, allowing the acylation of (R)-cyanohydrins in the presence of vinyl acetate in anhydrous acetonitrile.     

Aza-Baylis–Hillman reaction of N-tosylated imines with β-substituted α,β-unsaturated esters

Aza-Baylis–Hillman reaction of N-tosylated imines with β-substituted α,β-unsaturated esters can take place under mild reaction conditions to give the corresponding Baylis–Hillman adducts in moderate to excellent yields.