Ketones, 2-cyano synthesis

Ketose (Section 25 1) A carbohydrate that contains a ketone carbonyl group in its open chain form Kiliam-Fischer synthesis (Section 25 20) A synthetic method for carbohydrate chain extension The new carbon-carbon bond IS formed by converting an aldose to its cyanohydnn Reduction of the cyano group to an aldehyde function com pletes the synthesis... 

Stork s elegant use of a protected cyanohydrin function in the synthesis of PGF2a (2) is also noteworthy. The electron-withdrawing cyano substituent in intermediate 21 (Scheme 7) confers nucleophilic potential to C-9 and permits the construction of the saturated cyclopentane nucleus of PGF2a (2) through intramolecular alkylation. In addition, the C-9 cyanohydrin function contained within 40 is stable under the acidic conditions used to accomplish the conversion of 39 to 40 (see Scheme 7), and it thus provides suitable protection for an otherwise labile /J-hydroxy ketone. 

Unfortunately, it quickly became apparent that a shortfall in this proposal was an inability to prepare the desired vinyl halide 25 in a straightforward and selective manner [19]. In contrast, we reasoned that the selective formation of an enol sulfonate, such as the enol triflate 26a, could be controlled by judicious tuning of enolization conditions starting from the corresponding ketone, and that such an enol sulfonate would possibly be a substrate for a palladium-mediated coupling (Scheme 9.17). In this way a common intermediate from the previously defined synthesis, that is, the racemic ketone rac-13 or its cyano equivalent rac-5 could be used to generate the required enamide. 

A facile synthesis of 5-substituted 3-aminopyrrole-2-carboxylates has been developed wherein condensation of diethyl aminomalonate with a-cyano ketones 46 was facilitated by prior formation of the p-toluenesulfonyl enol ether 47 <00JOC2603>. Addition of the amine component is followed by cyclization and decarboxylation to afford the pyrroles 48. 

Cyanohydrination (addition of a cyano group to an aldehyde or ketone) is another classic reaction in organic synthesis. Enantioselective addition of TMSCN to aldehyde, catalyzed by chiral metal complexes, has also been an active area of research for more than a decade. The first successful synthesis using an (5,)-binaphthol based complex came from Reetz s group142 in 1986. Their best result, involving Ti complex, gave 82% ee. Better results were reported shortly thereafter by Narasaka and co-workers.143 They showed that by... 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

Electroreduction of y- and 5-cyano ketones in isoPrOH with a Sn cathode gave a-hydroxyketones with good diastereo-selectivities as cyclization products. The reaction has been used as a key step for the synthesis of, for example, guaiazulene, triquinanes, and dihydrojasmone. Similarly, the corresponding intermolecular couplings were realized [315]. 

This process presents a typical procedure applicable to preparation of cyanohydrins from ketones and aldehydes of low reactivity. l-Cyano-6-methoxy-3,4-dihydronaphthalene is useful as an intermediate for synthesis of polycyclic compounds. 

Song et al. extended this methodology to include cyanosilylation of aldehydes and ketones (Eq. 32) [160], They propose that NHC 276 interacts with TMSCN to form complex LXXVIII followed by cyano group transfer to the aldehyde (Scheme 48). The carbene is then regenerated and the desired product is obtained when LXXIX fragments. Concurrently, Kondo, Aoyama and co-workers describe similar reaction conditions for the synthesis of cyanohydrins in high yields [161, 162], while Suzuki and co-workers reported a cyanosilylation of aromatic and aliphatic aldehydes in good yields [163]. 

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