Acyl nitriles, trimethylsilylation

Tricarbonylchromium stabilized benzylic carbocations can be captured by a large variety of nucleophiles, such as alcohols, amines, thiols, nitriles, trimethylsilyl enol ethers, allylsilanes, electron-rich aromatics, dialkylzincs, and tri-alkylaluminums (eq 19). The relative stereochemistry formed during these reactions via carbocations in acyclic systems proceeds with net retention. Friedel-Crafts acylation of (styrene)chromium complexes has been explored via the benzylic cations (eq 20). Tricarbonylchromium-stabilized oxonium ions are also utilized for steroselective carbon-carbon bond forming reactions (eq 21). ... 

Allylalion of the alkoxymalonitrile 231 followed by hydrolysis affords acyl cyanide, which is converted into the amide 232. Hence the reagent 231 can be used as an acyl anion equivalent[144]. Methoxy(phenylthio)acetonitrile is allylated with allylic carbonates or vinyloxiranes. After allylation. they are converted into esters or lactones. The intramolecular version using 233 has been applied to the synthesis of the macrolide 234[37]. The /i,7-unsaturated nitrile 235 is prepared by the reaction of allylic carbonate with trimethylsilyl cyanide[145]. 

The addition of unstabilized a-nitrile carbanions to a,3-unsaturated carbonyl acceptors affords predominantly 1,2-addition products, 56 while lithiated acetonitrile derivatives having a-alkoxy, a-aromatic, a-dialkylamino, a-phenylselenyl, a-phenylthio or a-trimethylsilyl substituents afford 1,4-adducts. However, some of these are acyl anion equivalents (Section 1.2.2.3.2) so this discussion is limited to a-stabi-lized nitriles in which the nitrile function is retained after removal of the activating group. Notable examples are trimethylsilylacetonitrile (208),157 phenylthioacetonitriles (209),158a b phenylselenylacetoni-... 

Condensation of an MSMA isonitrile with an aroylfluoride gives a salt which undergoes loss of trimethylsilyl fluoride to form a nitrile ylid. This transient species reacts with DMAD to form 2-aroyl pyrrole in high yield.162 Substitution of acyl chloride for acyl fluoride in the reaction affords only poor yields of adducts.465... 

Orthoesters react with hydrocyanic acid, catalyzed by ZnCh, to give 2,2-dialkoxycarbonitriles (424 equation 201)." These nitriles can also be obtained by treatment of orthoesters with acyl cyanides" or trimethylsilyl cyanide in the presence of Lewis acids (BF3, SnCh)." Cyanoselenation of ketene 0,0-acetals affords the nitriles (425 Scheme 77)," " from which other compounds of this type can be prepared, e.g. (426) and (427), by splitting off the phenylselenyl group. The acetonitrile derivative (428 equation 202) is a byproduct (23%) in the photochemical cycloaddition of ketene diethylacetal to 6-cyanouracil." ... 

N-Trimethylsilyl amides may be prepared in excellent yield from the amide, trimethylsilyl chloride and triethylamine in boiling benzene. These derivatives react with acyl chlorides to give the nitrile corresponding to the amide [36]. 

Johnson s group developed a catalytic asymmetric cyanation/1,2-Brook rearrangement/C-acylation of acylsilanes with cyanoformates (Scheme 19.14). In the presence of (i ,/ )-(salen)Al 19, the corresponding cyanohydrin trimethylsilyl ethers of a-keto esters were obtained in moderate to good enantioselectivities (61-82% enantiomeric excess). Access to chiral (silyloxy)nitrile anions is facilitated by metal cyanide-promoted Brook rearrangement reaction of acylsilanes. 

Several routes to /3-keto-acids, -esters, and -nitriles, based on the acylation of malonate derivatives, have been reported. The dianion of monoethyl malonate is acylated by acid chlorides to give -keto-esters in a one-pot synthesis,and the lithio-derivative of bis(trimethylsilyl) malonate reacts with acid chlorides, giving /3-keto-acids directly.The magnesium derivatives of monomethyl or mono-thioalkyl esters of malonic acid give j8-keto-esters or -thioesters respectively in high yield under virtually neutral conditions with acid imidazolides. Similarly, the trimethylsilyl ester of cyanoacetic acid, after lithiation, reacts with mixed anhydrides to give high yields of j8-keto-nitriles. ... 

The reaction of 3-[(trimethylsilyl)methyl]-3-butenoic acid methyl ester with various simple nitriles in the presence of BCI3 has afforded varying mixtures of pyridones, pyridines, and acylation products (eq 5). 4... 

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