Y-Keto nitriles

Tertiary amines capable of eliminating a secondary amine to form a conjugated system can react with hydrogen cyanide to form y-keto nitriles by amine replacement. Thus (I) yields p-benzoylpropionitrile (IV) ... 

In another procedure, acyl radicals derived from phenyl selenoesters ArCOSePh I by treatment of them with Bu3SnH) add to a,P-unsaturated esters and nitriles to give y-keto esters and y-keto nitriles, respectively. ... 

The y-keto nitriles shown in Table I were prepared by the cyanide-catalyzed procedure described here. This procedure is generally applicable to the synthesis of y-diketones, y-keto esters, and other y-keto nitriles. However, the addition of 2-furancarboxaldehyde is more difficult, and a somewhat modified procedure should be employed. Although the cyanide-catalyzed reaction is generally limited to aromatic and heterocyclic aldehydes, the addition of aliphatic aldehydes to various Michael acceptors may be accomplished in the presence of thioazolium ions, which are also effective catalysts for the additions. 

This method has been applied to a,(i-unsaturated ketones, esters, and nitriles to give the corresponding 1,4-diketones, y-keto esters, and y-keto nitriles, respectively (see also 6-54). 

Oxazolin-5-ones have also proven to be important intermediates in the homologation of carboxylic acids (71AG(E)655). The IV-acyl-DL-valine derivative (402), prepared from the acid chloride of the carboxylic acid and DL-valine by the Schotten-Baumann procedure, was treated with excess acetic anhydride to afford (403). Reaction of (403) with acrylonitrile and triethylamine led to (404) in good yield. Hydrolysis of (404) with dilute alkali or acid gave the y-keto nitrile or y-keto acid (Scheme 89). 

Two alternative routes to y-keto-nitriles 10 that have been used to generate unusual 2-aminofuran derivatives are noteworthy. Treatment of the isoquinolinedi-one-glyoxal products 13 with malononitrile and diethylamine in alcoholic solvent gave the furans 15 via the intermediates 14. The 5-methyl derivative tautomerises to the product 16 (m.p. 224 °C), which was isolated in low yield. The 2-phenyl derivative cyclises to the tetracyclic product 17 whose structure was confirmed by X-ray crystallography (85CPB2663) (Scheme 2). 

Startg. aldehyde reacted with 2 eqs. ethyl triphenylphosphoranylideneacetate in THF for 1 h intermediate thioenolether (Y 87% E Z 1 3), hydrolysed with trifluoroacetic acid-water (4 l)/methylene chloride at 20° for 3 h product (Y 94%). KOBu-r may be used to isomerize the initially-formed double bond. F.e. inch y-keto-nitriles and -amides, y-diketones, and 1,4,7-tricarbonyl compds., also via Horner synthesis, s. T. Sato et al., J. Am. Chem. Soc. 110, 5209-11 (1988). 

Carbanions 31, formed from azlactones of type 23 by deprotonation with bases, undergo Michael addition with alkenes possessing electron-withdrawing substituents such as acrylonitrile in general, the Michael acceptor attacks the anion 31 in the 2-position. The adducts 32 are cleaved on hydrolysis to give y-keto nitriles 33 [301] ... 

The use of the y-(trimethylsiloxy)nitrile derivatives (190) as a route to 1,4-bifunctional units is exemplified in a convenient synthesis of jasmonoid compounds. The addition of the Grignard reagent to the cyano group as the homologation step results in the keto alcohol (191) after subsequent hydration. The y-ketocarboxylic add (192) obtained from the... 

Cycloadditions. [2+1], [2 + 2], and [4 + 2] cycloadditions with electrophilic reactants such as carbenes (eq 5), tetracya-noethylene (eq 6), and a-keto-, Y-unsaturated nitriles (eq 7) lead to interesting products which are all enantiopure see, for instance, the 5-amino-6-hydroxy-2-keto acid (5). 

The 1,3-dipolar cycloaddition of nitrile oxide to an unsaturated ester is a useful synthetic strategy for the synthesis of heterocycles such as A -isooxazolines and a-hydroxy-y-keto or y-imino carboxylic acids. Thus, the 1,3-dipolar cyclo-addition of the 4-0-acryloyl derivative 115 (R = f-butyldimethylsilyl) with two nitrile oxides (R = Ph or t-Bu) was explored by the Tadano group [95] (O Scheme 33). In the case of benzonitrile oxide (R =Ph), a functionalized A -isooxazoline 124 was obtained as a single isomer in excellent yield. Thus, the cycloaddition proceeded smoothly at room temperature with extreme stereoselectivity. 

Hydroacylation of Michael acceptors. The organotetracarbonylferrates obtained by alkylation of disodium tetracarbonylferrate undergo insertion reactions with Michael-type acceptors to give eventually y-keto esters, ketones, and nitriles. The last example shows an interesting synthesis of a cyclopentanone by an intramolecular insertion reaction. ... 

Alkynyltrialkylborates are versatile intermediates to 1,4-dikelones and y-oxo-esters, -nitriles, and -alkynes, as well as substituted ketones. A route from a -unsaturated cycloalkenones to 1,4-diketones is available wherein an aldehyde undergoes photoaddition to the alkene unit, and a variety of 1,4-diones is obtained by thiazolium salt-catalysed addition of aldehydes to but-2-enone. Monoacetalized 1,4-diketones and y-keto-aldehydes are formed on reaction of acyl chlorides with the Grignard reagents (13) and (14), respectively. 

The ahain-lengthening of carboxylic acids by three carbon atoms to y-keto aaida (or nitriles) by way of oxazoline-5-one anions have been described. The conversion of aldehydic cyanohydrins to a-hydroxy-N-t-butylcarboxamides followed by oxidation and hydrolysis constitutes h new general procedure for the preparation of a-ketoaoida. ... 

Application of the Ritter reaction conditions on y-hydroxy-a,P-alkynoic esters, 102, produced ethyl 5-oxazoleacetates 103 or y-A-acylamino-P-keto ester 104 by reaction with aryl or alkyl nitriles respectively. The y-A-acylamino-P-keto ester 104 can also be transformed into oxazole derivatives using an additional step involving POCI3 <06TL4385>. 

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