Trimethylsilyl Reissert reaction with

The Reissert reaction of 3,4-dihydro-p-carboline (213) has also been studied 47,48). It has been shown that 3,4-dihydro-p-carboline (213) afforded 1-cyano-2,9-dibenzoyl-l,2,3,4-tetrahydro-P-carboline (214) with a phase-transfer catalyst and trimethylsilyl cyanide (Scheme 27). However, the normal Reissert product 2-benzoyl-l-cyano-l,2,3,4-tetrahydro-p-carboline (215) was obtained when a catalytic amount of anhydrous aluminum chloride was used in addition to the trimethylsilyl cyanide reagent. Reaction of 214 with sodium... 

Finally, a solid phase version of the Reissert reaction has been developed for combinatorial chemistry purposes, and differently substituted isoquinolines have been prepared (Figure 15.16). Starting from polymer-supported benzoyl chloride, isoquinoline was bound and treatment with trimethylsilyl cyanide (TMSCN), followed by alkylation, yielded resin 31. After performing synthetic transformations (carbonylation etc.), Reissert hydrolysis was induced with aqueous NaOH in THF. 

Pyrimidine reacts with trimethylsilyl cyanide and benzoyl chloride with aluminum chloride as catalyst, to give the Reissert-type compound (366) <81JHC443>. The intermediate acylpyrimidinium cation (367) adds a soft nucleophile such as the silyl ether of acetophenone, and the adduct rapidly undergoes a second A-quaternization to (368) with a subsequent nucleophilic attack to form (369) (Scheme 61). The reactive intermediate can also be trapped by reactions with heteronucleophiles <88JCS(P1)725>. Intramolecular nucleophilic addition is shown in the formation of the spiran derivative (370) <92JOC2526>. 

The most frequently used method for the preparation of isoquinoline Reissert compounds is treatment of an isoquinoline with acyl chloride and potassium cyanide in water or in a dichloromethane-water solvent system. Though this method could be successfully applied in a great number of syntheses, it has also some disadvantages. First, the starting isoquinoline and the Reissert compound formed in the reaction are usually insoluble in water. Second, in the case of reactive acyl halides the hydrolysis of this reaction partner may became dominant. Third, the hydroxide ion present could compete with the cyanide ion as a nucleophile to produce a pseudobase instead of Reissert compound. To decrease the pseudobase formation phase-transfer catalysts have been used successfully in the case of the dichloromethane-water solvent system, resulting in considerably increased yields of the Reissert compound. To avoid the hydrolysis of reactive acid halides in some cases nonaqueous media have been applied, e.g., acetonitrile, acetone, dioxane, benzene, while utilizing hydrogen cyanide or trimethylsilyl cyanide as reactants instead of potassium cyanide. 

The Reissert alkylation method was also utilized for synthesizing the basic skeleton of protoberberine alkaloids (Scheme 21). Reaction of 3,4-dihydroiso-quinoline derivatives 149, 150, and 151 with 2-chloromethylbenzoyl chloride and trimethylsilyl cyanide in methylene chloride gave the corresponding 2-chloromethylbenzoyl-l,2,3,4-tetrahydroisoquinaldonitriles (152, 153, and 154,... 

The formation of Reissert derivatives of the antineoplastic agent ellipticine (225) (Scheme 29) and their reactions have been extensively studied by Popp and co-workers 39,49-51). The ellipticine Reissert compound 226 could be prepared either with benzoyl chloride and potassium cyanide in a dichloromethane-water system or, better, with benzoyl chloride and trimethylsilyl cyanide in dichloromethane. In similar manner 9-methoxyellipticine and a number of 6-substituted ellipticines have also been converted to the corresponding Reissert compounds. 

Disubstituted pyrido[3,4- ]pytazines 90 were reacted with equivalent amounts of trimethylsilyl cyanide and acyl chlorides or chloroformates in the presence of a catalytic amount of AICI3 in CH2CI2 to give the Reissert compounds 91, where the reactions occurred across the C-5,N-6 bond <1994JHC819>. On the other hand, treatment of 90 (R = = Ph) with benzenesulfonyl chloride and trimethylsilyl cyanide in the presence of a catalytic amount of... 

Pyridazine or 3-methylpyridazine with trimethylsilyl cyanide and benzoyl cyanide gave Reissert compound 106, which is easily rearranged into 107. In addition, compound 108 is formed, resulting from the reaction of one mole of cyanide and three moles of benzoyl chloride (81JHC443 ... 

Reaction of quinazoline, benzoyl chloride, and trimethylsilyl cyanide in a 2 2 1 molar ratio in anhydrous dichloromethane affords l,3-dibenzoyl-2,4-dicyano-l,2,3,4-tetrahydroquinazoline in 25% yield. When the reaction of quinazoline with trimethylsilyl cyanide and benzoyl chloride or a,/ -unsaturated acid chlorides [molar ratio (1 2.2 2.2)] is carried out in the presence of a catalytic amount of anhydrous aluminum trichloride, a more vigorous reaction takes place and the quinazoline di-Reissert compounds 22 are obtained in higher yield. Attempted Reissert compound formation with benzoyl chloride and potassium cyanide using a dichloromethane/water solvent system leads to ring opening (cf. pp 84, 149). 

A novel method for the synthesis of 2-alkylpyridines and 2-pyridine-carbinols starts from pyridine and involves the pyridine Reissert analog 175. Anion formation with sodium hydride and alkylation with alkyl halides afford the 2-alkyl-l-ethoxycarbonyl-2-cyano-1,2-dihydropyridines 176, which on heating with HMPT/Nal (HMPT = hexamethylphosphorous triamide) give 2-alkylpyridines 177. Condensation of the anion with benzaldehyde or o-tolualdehyde leads to 2-pyridinecarbinols (85CI(L)125). The reaction of 1,4-bis(trimethylsilyl)-1,4-dihydropyridine (178) with aldehydes (and ketones) in... 

Nucleophilic addition of 1005 to an 7V-acyliminium ion, e.g., a Reissert salt, and oxidation of the resulting adduct affords a 2-(heteroaryl)oxazole 1019. Acylation of a nitrogen heterocycle 1016 with ethyl chloroformate generated the intermediate Reissert salts 1017 in situ (Scheme 1.272). Addition of 1005 to 1017 gave adducts 1018, which produced 1019 after oxidative deacylation with o-chloranil. Examples of 2-(heteroaryl)oxazoles prepared from thiazole, benzothia-zole, pyridine, quinoline, and isoquinoUne are shown in Table 1.77. Donodni and co-workers summarized their early work on preparation and reaction of 2-(trimethylstannyl)oxazoles and 2-(trimethylsilyl)oxazoles. 

Addition to Carbonyls, Imines (Strecker-type Reactions), and Heteroaromatic Rings (Reissert-type Reactions). Cyanohydrin trimethylsilyl ethers are of significant synthetic interest as they can be transformed into a variety of multifunctional intermediates. Aldehydes and ketones can be enantioselectively converted to cyanohydrin trimethylsilyl ethers when treated with cyanotrimethylsilane in the presence of a Lewis acid and a chiral ligand. Enantioselective and/or diastereoselective formation of cyanohydrins and their derivatives has been reported and most of these reactions involve chiral ligands and metal catalysts containing Ti (eq 24), Sm (eq 25), and A1 (eq 26). ... 

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