7-Cyanoketones

The synthesis of this series involved the reaction of disubstituted or benzo fused 6-keto(formyl)-2-cyclohexenones with hydroxylamine (Scheme 176), Base degradation gave a-cyanoketones which can be further degraded to diacids (67AHC(8)277, 80IJC(B)406). 

Cyclic a-cyanoketones, when treated with hydroxylamine, yielded 3-amino-4,5,6,7-tetrahydro-2,1-benzisoxazole. This compound could also be obtained by sodium or potassium cyanide interaction with chlorocyclohexanone oxime (Scheme 187) (67AHC(8)277, 66Bail25>. 

Tliis reaction can be extended to cyanoketone dltliioacrtals [117]. Alkenyltellu-... 

Ketoesters, synthesis of 608, 615 Ketones - see also a-Cyanoketones, Hydroxyketones, Sulphinylketones synthesis of 811-814 y-Ketonitriles, synthesis of 322 /3-Ketosulphones... 

Enolizahon of cyanoketone rac-5 under the previously optimized conditions, followed by reaction with p-toluenesulfonic anhydride afforded a 90 10 ratio of the two expected enol tosylates in 90% yield. An immediate advantage of the tosylates compared to the triflate was seen on isolation, when the desired compound 32 was found to be a crystalline solid. In this way an 85% isolated yield of 32 as a single isomer could be achieved without the need for chromatography (Scheme 9.24). Use of p-toluenesulfonyl chloride in place of the anhydride led to a-chlorination... 

The preparation of 2-aminopyrroles was accomplished with type Ilae zinc-catalyzed cyclocondensation reactions between (i-cyanoketones and primary amines <06T1452>. 

Under cathodic reduction condition, 2-bromo-2-cyanoacetophenone is transformed into 5-amino-4-benzoyl-3-phenylfuran-2-carbonitrile in good yield <00H(53)1337>. Cyanoketones react with glycolate under Mitsunobu conditions to produce vinyl ethers which give rise to 3-... 

Shono and Kise have investigated the electroreductive coupling reaction of y- and -cyanoketones, yielding bicyclic a-hydroxy ketones 218 and their dehyd-roxylated equivalents 221 [198], Optimized yields are obtained when the electroreduction is carried out in i-propanol at a controlled potential of — 2.8 V using a divided cell equipped with a ceramic diaphragm and an Sn or Ag cathode. The product ratio is controlled by the reaction temperature. When the reaction is carried out at 25°C, almost exclusively the a-hydroxy ketone 218 is obtained, whereas at 65°C the obviously thermally dehydroxylated ketone 221 is the predominant product (Scheme 42). Furthermore, this methodology has been... 

Figure 2). -Diketones 35 and j5-ketoesters 36-38 are commonly used as CH-acidic ketones 24. Cyanoketones 39 and 40, nitroketones 41, as weU as ketones substituted with beteroaromatic 42, sulfur-containing 43, and phosphorus-containing groups 44 and 45 are also favored (Figure 2). Syntheses... 

Unsaturated cyanoketone 40 forms pyran 60 in reactions only with benzalmalononitrile 30 cyanoester 31 gives complex mixtures (86M247) (Scheme 10). 

Scheme 6.129 Products prepared from the 121- and 124-catalyzed stereoselective Michael additions of a-chloroacrylonitrile and acrylonitrile to a variety to cyclic a-cyanoketones and acyclic a-substituted cyanoesters.

The first manufacturing route of the GEM side-chain relied on a-cyanoketone 125 however, the number of chemical steps from 125 to the final side-chain was reduced by one step (Noh et ah, 2004a). The sequence began with a selective hydrogenation with Raney nickel followed by double bond migration to enamine 131 (Scheme 4.25). The amino functionality of 131 was then monoprotected, and the double bond was reduced under hydrogenation conditions to afford pyrrolidine-3-one 133. Treatment of 133 with methoxylamine yielded methoxyoxime 129. Deprotection of the carbamate functionality was achieved with methanesulfonic acid to afford the C7-side-chain as the bis-methansulfonate salt. 

Formation of the d bond by the reductive cyclization of a,oj- nitroketones (68CRV747, p. 778), -cyanoketones and -cyanoesters (74MIP51800) has been used in the preparation of both 1,4- and 1,5-benzodiazepines. 

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