Aldehydes cyanomethylation

The cyano-substituted five-ring oligomers were formed in good yields in a Knoe-venagel condensation between an aldehyde and a cyanomethyl-substituted compound, according to a procedure previously reported by Greenham el at. [6. The Knoevenagel condensation needs careful control of reaction conditions in order to... 

Similarly, compound 58 [in both (R)- and (b )-forms] has been found to be a good ligand for the enantioselective addition of cyanomethyl zinc bromide to various aldehydes. Products with up to 93% ee are obtained.53b Scheme 8-22 shows one example. When R = Ph, product is obtained in 78% ee. 

N,N-dialkylhydrazines 93, prepared either by reduction of nitrosamines 91 or by Hofmann degradation of ureas 92 [84] are cyanomethylated with aldehydes and... 

Compounds 133, prepared by the condensation of benzotriazole with aldehydes R HO (R1 = H, Pr or Ph) and 7V-octylaminoacetonitrile, react with sodium tetrafluoroborate to give the cyanomethyl derivatives 134. The latter are de-cyanomethylated by the action of copper(II) sulphate. Treatment of 133 with Grignard reagents affords the analogues 135 (R2 = Ph or PhCH2) and thence the secondary amines 136130. 

The phase-transfer catalysed alkylation of S-cyanomethyl dithiocarbamates provides a high yielding and convenient route to aldehydes (from monoalkylation) and ketones (from dialkylation) [128]. The procedure has been used to produce a range of alicyclic and small-ring ketones (>85%). 

Fig. 12 Formation of A-(cyanomethyl)amides in the MCR between primary isocyano amides, aldehydes/ketones, and amines...

Dialkyl allyl telluronium bromides and dibutyl ethoxycarbonylmethyl (cyanomethyl, benzoylmethyl) telluronium bromide generated dialkyl alkylidene telluriums on treatment with potassium ferf-butoxide in tetrahydrofuran at low temperatures (s. p.837). The tellurium ylides were not isolated but were trapped with aldehydes and ketones4-6. 

Once again, ( )-carvone was chosen as starting material (Scheme 48) (727). Aldol reaction with formaldehyde led to 6-hydroxymethylcarvone. The primary alcohol was protected as silylether 415 to permit addition of (cyanomethyl)lithium. The 5 1 mixture of epimeric tertiary alcohols was separated and the main product, 416, the alcohol generated by axial attack, was protected stereoselectively as bromoether 417 utilizing pyridinium hydrobromide perbromide. To introduce the necessary alkyne, the nitrile was reduced to the aldehyde with diisobutylaluminum hydride and subsequent hydrolysis. Addition of the alkyne led to a 2 1 mixture of... 

Aromatic and aliphatic aldehydes in the presence of dialkylamines and an equivalent of acid such as hydrochloric, perchloric or p-toluenesulfonic acid give iminium salts, which add cyanide ion to form a-(dialkylamino)nitriles. An alternative preparation involves the reaction of the aldehyde with dialkylamines in the presence of acetone-cyanohydrin, a-(A, -dialkylamino)isobutyronitiiles, diethyl phosphorocyanidate or TMS-CN. Another route to a-aminonitrile starts with an aldehyde, the salt of an amine and KCN in organic solvents under solid-liquid two-phase conditions by combined use of alumina and ultrasound. Chiral a-aminonitriles were prepared by Strecker-type reactions, cyano-silylation of Schiffs bases, amination of a-siloxynitriles or from an A -cyanomethyl-l,3-oxazolidine synthon. Reaction of tertiary amines with CIO2 in the presence of 5.1 mol equiv. of aqueous NaCN as an external nucleophile affords a-aminonitrile. °... 

In the laboratory of S.M. Weinreb, the total synthesis of the potent antibiotic natural product streptonigrin was accomplished. In order to obtain a fully substituted pyridine moiety under mild conditions, the modified Sommeiet-Hauser rearrangement was utilized. The quaternary ammonium salt was derived from A/-(cyanomethyl)pyrrolidine which could be efficiently deprotonated using KOf-Bu. Upon deprotonation the expected [2,3]-sigmatropic shift took place, and the resulting amino nitrile was immediately hydrolyzed to afford the corresponding aldehyde. 

Cyanomethyl groups can be a convenient source of pyridine rings treatment with acetic anhydride-perchloric acid [3934], acetonitrile-aluminium chloride [2884], Vilsmeier reagent [2727], a 1,3-diketone (or its enol) [2714] and malon-aldehyde bisacetal [2714] have been used successfully and sometimes give high yields. Pyrido[4,3-A]indoles have been reviewed [2535]. 

Enantioselective cyanomethylation. Cyanomethylzinc bromide, prepared by reaction of BrCH2CN with Zn/Cu, adds to aryl aldehydes in the presence of (S)-l (1 equiv.) to give / -hydroxy nitriles in 87-93% ee. If only 0.3 mol% of (S)-l is present the optical yield is markedly decreased (in the case of QIlsCHO cc falls from 93 to 78%). Therefore, 1 serves both as a ligand and a catalyst. 

The latter is also prepared by condensation of 2-cyanomethyl-1,3-benzothiazole (184 R=H)[from 2-aminobenzene thiol and malono-nitrile] with aromatic aldehydes in the presence of NEt at room temperature. In THF at reflux (184 R=H) and ArCHO/NEt yield the fused system (185). ... 

Typically, in the Knoevenagel polycondensation, a terephthalic aldehyde is condensed with a bis-(cyanomethyl)-benzene compound. Since two monomers are used, PPVs with a strictly alternating structure can be synthesized. The Knoevenagel polycondensation allows the convenient synthesis of compounds in that the backbone double bond is substituted. PPV modified with cyano groups show a high EL activity. The synthesis is shown in Figure 3.8. In a quite similar way, PPV can be formed by the Wittig... 

A similar VNS cyanomethylation of 3-nitropyridine and subsequent hydrogena-ti(Mi of the so-formed ort/io-nitropyridyl-substituted acetonitriles provided 4- and 6-azaindoles. The VNS of hydrogen in 2-methoxy-5-nitropyridine with the carb-anion of aiyloxyacetonitrile leads to pyridylacetonitrile. Alkylation of the latter with hromoacetOTiitrile followed by a two-step reduction efficiently results in the formation of 5-azamelatonin (Scheme 69) [187]. Condensation of pyridyl-substituted acetonitriles with aromatic aldehydes followed by catalytic reduction gave 3-benzyl-4-azaindoles [187],... 

Typically, in the Knoevenagel polycondensation, a terephthalic aldehyde is condensed with a bis-(cyanomethyl)-benzene compound. Since two... 

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