Nitriles carbinols

The lithium derivatives of 1-substituted pyrroles and indoles provide another general route of access to 2-acyl pyrroles and indoles. The ketones can be obtained directly by reaction with aryl nitriles or acid halides but, at least for 1-benzenesulfonylindole, a two-step procedure involving reaction with an aldehyde followed by oxidation of the carbinol to the ketone is frequently more convenient (equation 179) (73JOC3324, 75JOC2613). This method is probably the most general route to 2-acylindoles, although many have also been prepared by direct Fischer cyclization (see Section 3.06.3.4.2). 

The Ritter reaction has been applied to the reaction of a-naphthyl carbinols with nitriles. Rather than finding a mixture of regioisomers as feared, the only products were the 3,4-dihydrobenzo[/i]isoquinolines <03CHE184>. 

The reaction is specific for aldehydes. Aromatic ketones, esters, nitriles, halides (Cl, Br) were unreactive as evidenced by the recovery of these substrates. The steric hindrance around the boron atom retarded the reaction (entry 13), but those reactions of ort/io-monosubstituted arylboronic acids proceeded smoothly at 80 C (entry 12). The additions to aliphatic aldehydes such as hex anal and cyclohexanecarbaldehyde were very slow at 80 C due to their lower electrophilicity than that of aromatic aldehydes, but the reaction at 95 T2 in dioxane/H20 achieved high yields of the carbinols (entries 16 and 17). ( )- 1-Hexenylboronic acid also participated in the catalytic reaction, retaining its stereochemistry (entry 18). 

If one considers the general principle that the heterolytic breakage of a C-C bond results in the relative oxidation of one carbon end (the carbocation) and the simultaneous reduction of the other carbon end (the carbanion), or groups directly attached to these atoms, it is possible to infer that the nitrile group of II finds its antecedent in the oxime function and the aldehyde in the carbinol group of I, if one allows for the heterolytic mpture of the C-C bond that separates them. 

Now let me come back to primary substitutions at the ferrocene nucleus. Together with Vil chevskaya, we phosphorylated ferrocene and its derivatives to triferrocenylphosphine oxides [263, 264). An unusual reaction, discovered in collaboration with Perevalova and Yur eva, was the direct cyanation of ferrocene with hydrocyanic acid in the presence of ferric chloride [265,272). Initially, cyanide attacks the iron atom of the ferricinium cation, then the cyanide group transfers to the ring while the iron is simultaneously reduced. The reaction was termed by us as the ricochet (from the metal to the nucleus) substitution it may be applied to many substituted ferrocenes and to the ruthenocenium cation [273), and it is now the simplest route to ferrocene carboxylic acids through their nitriles. Further, ferrocene was studied in acid-medium reactions with oxo compounds. With aldehydes [274), the reaction was complicated by the transformation of ferro-cenylalkyl carbinol formed Initially via the carbonium ion, followed by transformation to a radical which, in its turn, was coupled to 1,2-bis-(ferrocenylalkyl)ethane (27.5). The reaction with acetone led to 2,2-di-ferrocenylpropane (276). 

Nitriles are easily reduced by Ni—A1 alloy, to the corresponding primary amine in aqueous alkali, and to the aldehyde in aqueous formic acid solution. Reductive hydrolysis may lead to the carbinol after furAer hydrogenation of the aldehydic group, as... 

In a related synthesis, acetylenic carbinols (63) have been claimed to condense directly with nitriles in the presence of concentrated sulfuric acid to give substituted oxazoles.133 Intermediates of the type represented by 64 have in fact been prepared independently as their hydrochlorides and are known to give oxazoles on treatment with sulfuric acid.140... 

USE In Claisen condensations, alkylation of nitriles and ketones, synthesis of ethynyl compds, acetylenic carbinols. 

Barbierreactions. In nitrile solvents, the condensation of alkyl halides with carbonyl compounds gives alcohols. The reaction between esters and iodoalkanes proceeds only in the presence of Nil. With an iron(IIl) salt as a catalyst, cyclic A-iodoalkyl imides form polycyclic enamides via carbinol lactams. ... 

In general, aldehydes, ketones, acids, esters, and acid chlorides are all reduced to the corresponding alcohols hy this reagent. Alkyl halides are unreactive towards DIBAL. Amides are reduced to amines, while nitriles afford aldehydes upon hydrolysis of an intermediate imine. Isocyanates are also reduced to the corresponding imines. Nitro compounds are reduced to hydroxy-lamines. Disulfides are reduced to thiols, while sulfides, suhbnes, and sulfonic acids are unreactive in toluene at 0°C. Tosylates are converted quantitatively to the corresponding alkanes. Cyclic imides can be reduced to carbinol lactams. 

On the methodological front of these broadly based endeavors, we have exploited pericyclic processes such as the dipolar cycloadditions of nitrile oxides together with the aldol reaction and related constructions as tactical devices for the formation of new carbon-carbon bonds with high levels of stereochemical control Another important focus of these explorations has been upon the development of techniques for the manipulation and refunctionalization of hydropyrans, since this structural subunit is not only common to a variety of natural substances, but it may also be effectively exploited as a conformationally-biased template for the stereoselective construction of various skeletal arrays present in numerous natural products. In this context, we have devised a novel and highly effective strategy for the asymmetric syntheses of oxygenated natural products. The fundamental approach features the intermediacy of the hydro-3-pyranones 12, which may be accessed from the chiral furfuryl carbinols 10 via the hydroxy enediones 11 by well-established oxidative techniques (Scheme 1). A critical element of this overall planll is that the hydro-3-pyranones 12 are admirably endowed with differentiated functionality that is suitable for further elaboration by reaction with selected nucleophiles... 

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