Recent Advances in the Synthesis of Nitriles

RECENT ADVANCES IN THE SYNTHESIS OF NITRILES-G.P. Ellis and I.L. Thomas... 

When recent advances in the chemistry of isoxazoles were reviewed by Kochetkov and Sokolov1 in this Series in 1963 (and by Quilico2 in 1962), the main features of isoxazole chemistry had been established. Since then some important new discoveries have been made, but probably the most significant advances have concerned the exploitation of the known features of their chemistry in synthesis. Particularly noteworthy developments include the further application of the cycloaddition of nitrile oxides in the synthesis of isoxazoles (Section II,C and D), the use of isoxazolium salts in peptide synthesis (Section III,B,2), syntheses involving the products of reductive cleavage of isoxazoles as intermediates (Section III,D and E) and annelation reactions via deprotonation of alkylisoxazoles (Section 1II,E). 

The Mukaiyama-Hoshino reaction between a nitroalkane and phenyl isocyanate generates a nitrile oxide, and this method has been used in the synthesis of 1,2,4-oxadiazoles as discussed in CHEC-II(1996) <1996CHEC-II(4)179>. In a more recent advance, nitroethane undergoes ultrasound-mediated cycloaddition with trichloroacetonitrile to give the extremely useful (see Equation 11) 5-trichloromethyl-l,2,4-oxadiazole 228 (Equation 45) <1995TL4471>. 

Various routes are used for the synthesis of 1,2-benzisothiazole 1,1-dioxides, and recent advances are the cyclization of 7V-acyl-benzenesulfonamides using two equivalents of LDA, and a one-pot procedure in which or/Ao-lithiated V,V-diphenylbenzenesulfonamides are reacted with nitriles <92J0C5328, 89S394) (see Sections 3.05.9.1.3 and 3.05.9.2.2). 

A comprehensive review (260 refs.) on the synthesis of carbohydrates from noncarbohydrate sources covers the use of benzene-derived diols and products of Sharpless asymmetric oxidation as starting materials, Dodoni s thiazole and Vogel s naked sugar approaches, as well as the application of enzyme-catalysed aldol condensations. The preparation of monosaccharides by enzyme-catalysed aldol condensations is also discussed in a review on recent advances in the chemoenzymic synthesis of carbohydrates and carbohydrate mimetics, in parts of reviews on the formation of carbon-carbon bonds by enzymic asymmetric synthesis and on carbohydrate-mediated biochemical recognition processes as potential targets for drug development, as well as in connection with the introduction of three Aldol Reaction Kits that provide dihydroxyacetone phosphate-dependent aldolases (27 refs.). A further review deals with the synthesis of carbohydrates by application of the nitrile oxide 1,3-dipolar cycloaddition (13 refs.). ... 

Recent advances in the catalytic 2- -2 + 2-cycloadditions of alkenes, alkynes, and nitriles for the synthesis of carbo- and hetetro-cycles have been reviewed. Propar-gylic oxanorbornadiene esters (87) undergo facile intramolecular 2- -2- -2-homo-Diels-Alder cycloaddition in polar solvents (Scheme 27). ... 

Recent advances in the stereoselective olefination of phosphorus-stabilized carbon nucleophiles have been reviewed. Applications of the Horner-Wadsworth-Emmons reaction to the synthesis of natural products have been highligted. A highly Z-selective synthesis of a, -unsaturated nitriles using the Homer-Wadsworth-Emmons reaction has been reported this involves a new nitrile reagent, (o-t-BuC6H40)2P(0)CH2CN, which reacts with various types of aldehydes with 86 to >99% Z selectivity. 

The RuH2(PPh3)4-catalyzed addition of active methylene compounds can also be applied to conjugate additions to a,/3-unsaturated carbonyl compounds (Michael additions). In 1989, Murahashi reported the first example of the transition metal-catalyzed Michael addition of active methylene compounds [74]. One of the notable advances of this catalytic reaction is that the addition of C-H bonds to a,/3-unsaturat-ed carbonyl compounds give Michael adducts without contamination by the corresponding aldol products (Eq. 9.56) [74]. Recently, Murahashi applied their aldol and Michael addition reactions to a solid-phase synthesis using polymer-supported nitriles (Scheme 9.12) [76]. In this case, four component reactions took place with high diastereoselectivity. 

Among transition-metal complex catalyzed reactions of alkynes with carbon-heteroatom unsaturated compounds the most studied is co-cyclotrimer-ization of alkynes with nitriles to pyridines. For this process the same complexes can be used as for the cyclotrimerization of alkynes. The first report of a cyclopentadienylcobalt complex catalyzed co-cyclotrimerization of alkynes with nitriles appeared in 1973 [92] and was soon followed by other papers [93]. Co-cyclotrimerization of alkynes and nitriles with all its aspects has been recently reviewed [94] and because of that we will focus only on recent developments in this area. In this regard, advances have been made in simple co-cy-clotrimerization of ethyne with various nitriles [95], combinatorial synthesis of substituted pyridines [96], and co-cyclotrimerization of hydroxyalkynes with nitriles in aqueous media catalyzed by cobalt complex with hydrophobic chain attached to the cyclopentadienyl ring [97]. 

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