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Crystallization‐Induced Diastereomer Transformation (CIDT) of α‐bromo‐α'‐(R)‐sulfinylketones is reported. The utility of these 1,2‐difunctionalized synthons is convincingly demonstrated by their facile conversion into cyanohydrins and bromohydrins. Furthermore, bromohydrins can be converted into complex arrangements of functionality and stereochemistry through SN2‐like inter and intramolecular transformations. [ABSTRACT FROM AUTHOR]

• Nanoceria catalyzes the cyanosilylation of different ketones at rt in high yields. • Nanoceria acts as a bifunctional acid-base solid catalyst. • The solid catalyst can be reused ten times with a simple calcination. • The catalytic activity of nanoceria is independent of the crystalline phase. • Au-nanoceria catalyzes the aerobic oxidation of alcohols/cyanosilylation reaction. The cyanosilylation of carbonyl compounds is a fundamental reaction in organic synthesis, to give cyanohydrins. Ketones are particularly reluctant to cyanosilane addition and require the action of a catalyst, and despite many soluble Brönsted and Lewis acids have been employed for this task, it is difficult to find in the open literature catalytic solids able to carry out the reaction. Here, we show that commercially available nanoceria catalyzes the cyanosilylation of different ketones (21 examples) at temperatures between 0 and 50 °C, in high yields, under solventless conditions if required. The nanoceria network atoms act in a cooperative way to provide a bifunctional acid-base solid catalyst for the cyanosilylation reaction. The amorphization of nanoceria during reaction, due to acid release, does not hamper the catalytic activity and, indeed, different types of nanoceria, even with supported metal nanoparticles on surface, are active for the reaction, enabling extensive reuses after air calcination and the use of the catalytic material for the aerobic oxidation of alcohols / cyanosilylation reaction. [ABSTRACT FROM AUTHOR]

2,3-Secooleanane hydroxynitriles undergo dehydration and anionotropic 1,2-migration of the methyl group C(24)H3 under the action of the SOCl2-CH2Cl2 system to form a mixture of isomeric Δ4-alkenes. A similar E1-elimination process in the presence of the H2SO4—AcOH system is accompanied by hydrolysis of the CN group giving A-ring unsaturated C(2)-ketones and diastereomeric ε-lactones. Epimeric 4,23-epoxides and isopropyl ketone were synthesized by oxidative transformations of 4,23-alkene, which was selectively formed from 2,3-secooleanane hydroxynitrile under the action of the POCl3-Py system. The in vitro cytotoxic evaluation by the MTT assay showed that the synthesized compounds are not toxic (IC50 > 100 μmol L−1) against the human cancer cell lines HEp-2, HCT116, MS, RD TE32, MCF-7, A549, and PC-3. [ABSTRACT FROM AUTHOR]

Catalytic asymmetric cyanation reactions of aldehydes and ketones provide efficient routes for the synthesis of optically active cyanohydrins, which are versatile synthons for the preparation of natural products and chemical pharmaceuticals. This review aims to provide a summary of recent achievements concerning catalytic enantioselective cyanation reactions of aldehydes and ketones employed in the total syntheses of various natural products, drugs, and pharmaceutically active compounds. [ABSTRACT FROM AUTHOR]

Two known lanthanide complexes, [KLa(HL 1 ) 2 {(CH 3 ) 2 NCHO} 2 (H 2 O) 3 ] ( 1 ) and [Sm(H 2 O) 9 ]( E -H 2 L 2 ) 3 ·2H 2 O ( 2 ) were prepared by reaction of lanthanum(III) and samarium(III) nitrates with potassium 3-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)-2-hydroxy-5-nitrobenzenesulfonate (KH 2 L 1 ) and potassium ( E,Z )-5-chloro-3-(2-(1,3-dioxo-1-phenylbutan-2-ylidene)hydrazinyl)-2-hydroxybenzenesulfonate (KH 2 L 2 ), respectively. Catalytic activities of 1 and 2 were evaluated in the cyanosilylation of aldehydes with trimethylsilyl cyanide in different solvents such as tetrahydrofuran, dichloromethane or methanol. Complex 1 was found to be efficient catalyst for the cyanosilylation reaction in methanol medium at room temperature, producing cyanohydrin trimethylsilyl ethers with good yields (76–99%). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A NADPH-dependent benzil reductase (KRED1-Pglu) was used as recombinant enzyme for catalysing the reduction of different functionalised ketones. The reactions were carried out in the presence of a catalytic amount of NADP + and an enzyme-coupled transformation (oxidation of glucose catalysed by glucose dehydrogenase), for regenerating the cofactor and thus driving the reaction to completion. KRED1-Pglu showed remarkable versatility, being able to reduce different β-ketonitriles and α-haloketones at different pHs; notably, depending on the nature of the substrate, KRED1-Pglu can be used for efficient and clean enzymatic reduction, avoiding side-reactions due to the pH of the medium. The reduction generally occurred with high enantioselectivity, allowing the preparation of enantiomerically enriched β-hydroxynitriles and halohydrins in high yields; the stereochemical outcome of the reduction followed in all the cases the so-called Prelog's rule. [ABSTRACT FROM AUTHOR]

The article presents a study to describe an efficient protocol for the conjugate addition of cyanide to alpha, beta-unsaturated ketones 1a-j using trimethylsilyl cyanide (TMSCN) as cyanide source and Amb-F as solid catalyst under solvent-free conditions (SolFC). It discusses the addition of TMSCN to (E)-hept-3-en-2-one (1a). The study suggests that an initial 1,2-addition of cyanide to the a,b-unsaturated ketone 1 occurs giving the cyanohydrin trimethylsilyl ether 2.

A convenient one-pot, two-step procedure for the synthesis of ketone cyanohydrin esters in aqueous media is reported using N -acylbenzotriazoles as the acylating agents. In saturated aqueous sodium bicarbonate containing a catalytic amount of tetrabutylammonium bromide, the reaction of ketones with potassium cyanide and N -acylbenzotriazoles proceeded readily at room temperature to provide the corresponding O -acyl cyanohydrin derivatives in good to excellent yields. [ABSTRACT FROM AUTHOR]

A novel Lewis base-promoted rearrangement of allylic cyanohydrins has been developed, in which the cyano group was rearranged, directly coupled with the generation of new functional groups. This protocol provides a unique and facile way to prepare highly functionalized nitriles bearing 1,3-diketone moieties under mild reaction conditions. Furthermore, the synthetic transformations of the functionalized products have also been demonstrated. [ABSTRACT FROM AUTHOR]

The potential of the hydroxynitrile lyase from Manihot esculenta towards ketone substrates was investigated. It was observed that the length of the aliphatic chain is a key parameter for the conversion of aliphatic, non-branched ketones. Smaller substrates are readily converted with high enantioselectivites, but the elongation of the chain length causes a significant loss in enzyme activity. For a number of halogenated, herein especially fluorinated, acetophenone derivatives the corresponding cyanohydrins have been synthesized with good to moderate enantioselectivities. [ABSTRACT FROM AUTHOR]

The 1,2-dianion reactivity of the reagent generated from EtMgBr and titanium isopropoxide was illustrated when N-acyl cyanohydrins were used as substrates (>20 examples), giving both aminocyclopropane derivatives and 1,4-dicarbonyl compounds. When the reaction was performed in diethyl ether, 5-hydroxy-1,4-diketones were the main product. Under specific conditions (use of tetrahydrofuran and a bulky carboxylic moiety), the cyclopropane derivatives were obtained in good yields. The observed dichotomy may be explained by a ring-opening of the five-membered titanacycle intermediate followed by a nonselective acyl addition. [ABSTRACT FROM AUTHOR]

Abstract: Cyanation-O-protection reaction of ketones with different cyanide sources catalyzed by N-heterocyclic carbenes is reported. Under the catalysis of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, various ketones coupled with diethyl cyanophosphonate to produce cyanohydrin-O-phosphates with a quaternary carbon center in moderate to excellent yield. Furthermore, the reaction can be scaled-up easily and high yield maintained. [Copyright &y& Elsevier]

This paper describes the solvent-assisted addition of trimethylsilyl cyanide (TMSCN) to cyclic α-fluorinated ketones. In DMF, this method gives TMS-protected cyanohydrins in good yields (70-95 %) and with good selectivities ( dr up to 22:1), and the products are readily reduced to the corresponding fluorinated 1,2-amino alcohols. [ABSTRACT FROM AUTHOR]

Reactions of 2-adamantan-2-one, acetone cyanohydrin, and amine lead to the formation of substituted 2-amino-2-cyanoadamantanes. The reaction is of a general character as has been proved by examples on a series of ketones and amines and it proceeds through the formation from the acetone cyanohydrin and amines of 2-amino-2-cyanopropane derivatives reacting further with the carbonyl compounds. [ABSTRACT FROM AUTHOR]

A highly regio- and stereospecilic rhodium-catalyzed allylic alkylation of tertiary allylic alcohol derivatives with a cyanohydrin pronucleophile is described. This direct and operationally simple protocol provides a fundamentally novel approach toward the synthesis of α-quaternary substituted ketones and circumvents many of the inherent problems associated with conventional enolate allrylation reactions. The stereospecific variant of this reaction provides the enantiomerically enriched a- quaternary substituted allylic aryl ketone, which is a particularly challenging intermediate for more conventional enolate-based strategies. [ABSTRACT FROM AUTHOR]

Abstract: A series of cis-2,6-tetrahydropyran-4-ones was synthesized from the intramolecular cyclization reaction of β-hydroxy allyl ketones in the presence of Me3SiOTf as catalyst. The β-hydroxy allyl ketone was prepared from allylation reaction with β-hydroxynitrile without protection of hydroxy functionality under the Barbier-type reaction condition. [Copyright &y& Elsevier]

Abstract: We describe efforts to achieve a multigram synthesis of the tricyclic spiroacetal core of the lituarines based on the addition of acyl anion equivalent to 4-(2-furyl)butan-2-one (18). We report the first cases of chemoselective Achmatowicz reaction in the presence of a second furan ring that lacks an α-hydroxyl group. The use of lithiated methoxyallene provides an efficient one-step conversion of ketone 18 into a tricyclic Diels–Alder adduct (27). In the final route, asymmetric cyanosilylation of ketone 29 achieved the construction of the stereogenic C(12) 3°-alcohol centre. Subsequent butenylation, diastereoselective reduction of keto-alcohol (+)-33 and alkene cross metathesis set up an oxy-Michael reaction to close the C(8–12) tetrahydropyran ring. The second ring-closure, which completed the route, was achieved by oxidative spirocyclisation following our earlier work. [Copyright &y& Elsevier]

Abstract: The enantioselective preparation of both enantiomers of the benzo-fused cyanohydrin derived from α-tetralone via lipase catalyzed processes is described. The (S)-enantiomer has been obtained as the remaining substrate in the CAL-A catalyzed aminolysis of the methoxyacetylated derivative, using a structurally related amine as the nucleophile. The (R)-enantiomer has been obtained as the product of CAL-A or PSL-C catalyzed hydrolysis of the methoxyacetylated derivative in organic solvents. The resolutions of several structural analogs of this cyanohydrin have been also tested under similar conditions. [Copyright &y& Elsevier]

Chiral α-ethylphenylamine tartaric acid salts were synthesized from α-ethylphenylamine by direct reaction with chiral tartaric acid. The crystal structure of S-(−)-α-ethylphenylamine-(2 R,3 R)-(−)-dihydroxybutanedioic acid was determined. The crystal is monoclinic, of space group P21/ n, with a = 6.331(5) Å, b = 14.209(11) Å, c = 7.495(6) Å, α = 90.00º, β = 107.000(13)º, γ = 90.00º, λ = 0.7103 Ǻ, V = 644.7(9), Z = 2, Dc = 1.397 g/cm3, M r = 271.27 and F(000) = 288, R = 0.0477, and ω R = 0.0838 for 1388 observed reflections with I > 2σ( I). We then used the chiral α-ethylphenylamine tartaric acid salts as catalysts in the cyanosilylation of prochiral ketones, and moderate conversions were obtained. The crystal structure of a chiral α-phenylethylamine tartaric acid salt, and novel application to the cyanosilylation of prochiral ketones Chiral α-ethylphenylamine tartaric acid salts were synthesized from α-ethylphenylamine by direct reaction with chiral tartaric acid. The crystal structure of S-(−)-α-ethylphenylamine-(2 R,3 R)-(−)-dihydrobutanedioic acid was determined. When the chiral α-ethylphenylamine tartaric acid salts were used as catalysts in the cyanosilylation of prochiral ketones, moderate conversions were obtained[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: One-pot three components synthesis of O-acetylcyanohydrins has been developed in the presence of B(C6F5)3 as the catalyst. Variety of aldehydes or ketones reacts with TMSCN and acetic anhydride (Ac2O) under the influence of 1mol% of B(C6F5)3 to give good to excellent yield of the products without solvent at rt. [Copyright &y& Elsevier]

The absolute configuration of ketone cyanohydrins can be assigned from analysis of the 1H NMR spectra of the corresponding (R)- and (S)-MPA ester derivatives and use of ΔδRSsigns. This is an application of the NMR methodology for stereochemical assignment to tertiary alcohols possessing polar groups as substituents. [ABSTRACT FROM AUTHOR]

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 O2-/O- (Lewis basic site) of nanocrystalline magnesium oxide. [ABSTRACT FROM AUTHOR]

High-yielding cyanosilylation of ketones with NaCN and various chlorotrialkylsilanes in DMSO proceeds smoothly without catalysis to give silyl-protected ketone cyanohydrins. The unique role of DMSO consists in rendering naked cyanide anions that reversibly add to the C=O bond at the rate-determining step followed by fast trapping of the transient tertiary sodium cyanoalcoholates with chlorotrialkylsilanes or in situ generated cyanotrialkylsilanes. Preparatively, the reaction matches the best known catalytic cyanosilylation systems applying expensive Me3SiCN and demonstrates unprecedented efficiency in the synthesis of sterically congested trialkylsilyl-protected cyanohydrins. [ABSTRACT FROM AUTHOR]

The addition of TMSCN to aldehydes and ketones under microwave irradiation in the absence of any Lewis or Brønsted acid and solvent yielded the corresponding cyanohydrins in good yields in short reaction times (less than 30 min). [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of (R)- and (S)-cyanohydrins from a range of aromatic methyl and ethyl ketones, including the first examples from substituted variants of phenylacetone, benzylacetone and propiophenone, is described. Commercially available hydroxynitrile lyase (HNL) enzymes were used to catalyze the asymmetric addition of cyanide to the ketones, including the first successful application of the flax HNL (LuHNL) to the synthesis of any aromatic (S)-cyanohydrin. Both reaction yields and stereoselectivities were shown to be influenced by the carbon chain length between the ketone and phenyl functional groups, and the type of aromatic substitution present on the starting material. Substrates converted with the greatest degree of productivity and selectivity were phenylacetones with large, electron withdrawing meta-substituents, such as 3-Cl, 3-Br and 3-CF3 phenylacetones, from which cyanohydrins are formed with 93–99% ee and 61–71% yield. [Copyright &y& Elsevier]

Abstract: Trimethylsilyl cyanide asymmetrically adds to various ketones by catalysis of 1 /triphenylphosphine oxide. This is a double activation where 1 acts as Lewis acid and Ph3PO Lewis base. Various ketones were subjected to the enantioselective addition so as to give up to 92% ee and >90% yield. [Copyright &y& Elsevier]

Optically pure functionalized cyanohydrins derived from 1-[2-(p-tolylsulfinyl)phenyl] ethanone can be obtained by the reaction of 2-p-tolylsulfinyl benzaldehyde derived cyanohydrins with bases and further treatment with suitable electrophiles. High yields and excellent stereoselectivities (up to de »98%) were obtained for these remote 1,4-asymmetric induction processes controlled by a sulfinyl chiral inductor. [ABSTRACT FROM AUTHOR]

Abstract: Trimethylsilylcyanide addition to different carbonyl moieties, i.e. saturated ketones, an enone and an aldehyde, at the steroid side-chain, was studied in the presence of a convenient catalyst. Depending on the nature of the carbonyl group, different outcomes were noticed. Saturated 20-keto pregnanes yielded epimerically pure silylated cyanohydrins, being the absolute configuration unambiguously established by X-ray crystallographic analysis. [Copyright &y& Elsevier]

Heterocyclic saturated five- and six-membered ring ketones sometimes bearing a methyl substituent were reacted with HCN under enzyme catalysis using recombinant hydroxynitrile lyase from Hevea brasiliensis, as a rule (S)-selective, and Prunus amygdalus, (R)-selective. The resulting cyanohydrins were stereochemically characterised. The steric outcome of these transformations was interpreted by molecular modelling. [Copyright &y& Elsevier]

(S)-Hydroxynitrile lyase fromManihot esculenta(MeHNL) was shown for the first time to be able to catalyze the enantioselective transcyanation of acetyltrimethylsilane (ATMS) with acetone cyanohydrin to form (S)-2-trimethylsilyl-2-hydroxyl-propionitrile in an aqueous/organic biphasic system. To better understand the reaction, various influential variables were examined. The most suitable organic phase, optimal buffer pH, aqueous phase content, shaking rate, temperature, concentration of ATMS, acetone cyanohydrin and crude enzyme were diisopropyl ether (DIPE), 5.4, 13% (v/v), 190 rpm, 40°C, 10 mM, 20 mM, and 35 U/ml, respectively, under which the initial reaction rate, substrate conversion and product enantiomeric excess (e.e.) were 19.5 mM/h, 99.0% and 93.5%, respectively. A comparative study demonstrated that silicon atoms in the substrate had a great effect on the reaction, and that ATMS was a much better substrate for MeHNL than its carbon analogue 3,3-dimethyl-2-butanone (DMBO) with respect to the initial reaction rate, substrate conversion and product e.e. MeHNL has greater affinity towards ATMS than its carbon analogue as indicated by the much lowerKm. The activation energy of MeHNL-catalyzed transcyanation of ATMS was also markedly lower than that of DMBO. The silicon effect on the reaction was rationalized on the basis of the special characteristics of silicon atoms and the catalytic mechanism of MeHNL. [ABSTRACT FROM AUTHOR]

Cyanohydrin phosphates 2a-2c were prepared in high yield from ketones (or aldehyde), diethyl phosphorochloridate, and sodium cyanide by using acetonitrile as solvent. GC analysis proved that the two reactions of cyanohydrin sodium with diethyl phosphorochloridate and with diethyl phosphorocyanidate resulted in the formation of cyanohydrin phosphates. [ABSTRACT FROM AUTHOR]

An efficient method of addition of trimethylsilylcyanide to ketones by employing cesium fluoride as catalyst has been described. A variety of aromatic, aliphatic, cyclic and heterocyclic ketones have been converted into their corresponding trimethylsilyl ethers in excellent yield. [Copyright &y& Elsevier]

Optically active 2-trimethylsilyl-2-hydroxyl-ethylcyanide was prepared by enzymatic enantioselective transcyanation of acetyltrimethylsilane with acetone cyanohydrin in a biphasic system at 35 °C and pH 5. (R)-Oxynitrilase from apple seed meal was the best among all the enzymes explored and diisopropyl ether was the most suitable organic phase. Acetyltrimethylsilane was a better substrate of the enzyme than its carbon analogue. The substrate conversion and product enantiomeric excess of 2-trimethylsilyl-2-hydroxyl-ethylcyanide were >99% and >99%, respectively. [ABSTRACT FROM AUTHOR]

Methods for the catalytic asymmetric synthesis of cyanohydrins derived from both aldehydes and ketones are reviewed. Successful catalysts based on enzymes, peptides and transitional metal complexes are included, and mechanistic detail is included where appropriate. Illustrations of the many synthetic applications of non-racemic cyanohydrins are given. [Copyright &y& Elsevier]

The crystal structures of hydroxynitrile lyase from Manihot esculenta (MeHNL) complexed with the native substrate acetone and substrate analogue chloroacetone have been determined and refined at 2.2 Å resolution. The substrates are positioned in the active site by hydrogen-bond interactions of the carbonyl O atom with Thr11 OG, Ser80 OG and, to a lesser extent, Cys81 SG. These studies support a mechanism for cyanogenesis as well as for the stereospecific MeHNL-catalyzed formation of (S)-cyanohydrins, which closely resembles the base-catalyzed chemical reaction of HCN with carbonyl compounds. [ABSTRACT FROM AUTHOR]

The article presents information on a study conducted on a three-component reaction of perimidines with carbonyl compounds and sodium nitrite in polyphosphoric acid (PPA). In the study, acetophenone is nitrosated and the formed nitroso ketone 3 alkylates the perimidines to give new compounds. Further reaction involves dehydration to give the unsaturated nitroso compounds which yield the 1,3,6-triazapyrenes and cyanohydrins.

Abstract: An easily amenable method is presented to produce acetone cyanohydrin on mole scale (output 39g/h), using a continuous flow system to overcome the high risks associated with the large-scale use of hydrogen cyanide. [Copyright &y& Elsevier]

Abstract: The cyanation of carbonyl compounds with ethyl cyanoformate is catalyzed by 4-dimethylaminopyridine (DMAP) to afford the corresponding cyanohydrin carbonates in excellent yields. The system provides a convenient method for cyanation of carbonyl compounds without using metal catalysts or solvents. [Copyright &y& Elsevier]

Various types of ketone substrates can be efficiently reduced in the presence of the title enzyme, isolated from P. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of cyanohydrins from aldehydes and ketones represents a useful avenue for the synthesis of important organic intermediates, for example, a-hydroxy acids and their derivatives and β-amino alcohols. For this reason there has been intense research activity in this area in recent years, leading to the development of a large and diverse array of chiral catalysts. In this article authors describes a new chiral catalyst system that is based on boron and the recognition of a novel cyanide donor. A variety of aldehydes, aromatic and aliphatic, have been transformed into cyanohydrins with greater than 90% enantiomeric purity under standardized conditions. The chiral precursor of the catalyst is readily recoverable. Finally, the absolute stereochemical course of the reaction is predicted clearly by a well-precedented mechanism.

The title compound, C14H23NO, the cyanohydrin of dicyclohexyl ketone, was prepared as an intermediate in the synthesis of dicyclohexyl(hydroxy)acetic acid. The cyclohexyl rings adopt chair conformations. The central C atom is in a slightly distorted tetrahedral environment of three C atoms and one O atom. Intermolecular hydrogen bonds are present in the crystal structure, forming dimers. [ABSTRACT FROM AUTHOR]