Ketones a alkoxy

Ozonolysis of double bonds as a route to ketones and aldehydes is well known. Thiourea may be used for the reduction of the ozonide to afford aldehydes from suitable alkenes. Electrolytic reduction of ozonization products from the oxidation of trisubstituted cyclic alkenes in acetic acid offers a route to hydroxy-ketones. a-Alkoxy-peroxides, from ozonolysis in alcoholic solution, are stable... 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

The nucleophilic addition of Grignard reagents to a-epoxy ketones 44 proceeds with remarkably high diastereoselectivity70. The chelation-controlled reaction products are obtained in ratios >99 1 when tetrahydrofuran or tetrahydrofuran/hexamethylphosphoric triamide is used as reaction solvent. The increased diastereoselectivity in the presence of hexamethylphos-phoric triamide is unusual as it is known from addition reactions to a-alkoxy aldehydes that co-solvents with chelating ability compete with the substrate for the nucleophile counterion, thus reducing the proportion of the chelation-controlled reaction product (vide infra). 

Reaction of a-alkoxy phosphoranes with aldehydes or ketones... 

If the alkoxy group at the C-6 atom in nitroso acetals (475) is absent, silyl derivatives (476) are generated instead of nitroso ketones A, and methanolysis of compounds (476) gives rise to y-hydroxy oximes (479). 

Dynamic kinetic resolution is possible for a-alkyl or a-alkoxy cyclic ketones in the presence of KOH, which causes mutation of the stereogenic center syn-alco-hols were obtained selectively with high enantioselectivity using ruthenium-3,5-xyl-binap. Dynamic kinetic resolution of 2-arylcycloalkanones also proceeded with extremely high syn-selectivity and with high enantioselectivity using ruthenium-binap-diamine as catalyst (Table 21.23) [12, 139, 140]. 

Dondoni pioneered the use of 2-(trimethylsilyl)thiazole (71) as a formyl anion equivalent for the homologation of aldehydes. Extension of this reaction to ketones would be very useful, but has thus far been restricted to tritluoromethyl cases. However, it has now been widened to include several a, a -alkoxy ketones, as demonstrated in a new route to branched-chain monosaccharides. Aldehydes catalyse the reaction, although the scope is still limited electrophilic aldehydes, such as 2-fluorobenzaldehyde, promote the addition of (71) to electrophilic ketones. 

SCHEME 22. Stereochemical outcome of the addition of polar organometallic compounds R"M to a-alkoxy aldehydes and ketones (G = protecting group)... 

Substituted malondialdehydes form pyrimidines substituted in the 5-position with an alkyl, aryl, halo, or hetero substituent. The pyrimidine is unsubstituted in the 4- and 6-positions. /3-Dialdehyde equivalents are frequently used in these reactions, for example, 3-alkoxy- or 3-aminoacroleins. With aldehydo ketones, the pyrimidine carries a substituent in the 4- or 6-position. The formyl group in the ketone is normally masked as an alkoxymethylene ketone or as an aminomethylene ketone. A commonly used procedure involves the preparation of a dimethylaminomethyl-ene ketone 645 by reaction of a methyl ketone 644 with DMF dimethylacetal and subsequent reaction with an amidine or guanidine to form the target pyrimidine 646 <2003MI237, 2004JHC461>. 

Bandini and co-workers studied the zinc triflate-bis(oxazohne)-catalyzed reduction of a-alkoxy-ketones with catecholborane. The example in Figure 9.76 shows the reduction of a-methoxyacetophenone 252. l-Phenyl-2-methoxyethanol 254 was isolated in 78% yield and 82% ee. 

Tellers, D.M., Bio, M., Song, Z.J., McWilliams, J.C. and Sun, Y. Enantioselective Hydrogenation of an a-Alkoxy Substituted Ketone with Chiral Ruthenium (Phosphino-ferrocenyl)oxazohne Complexes. Tetrahedron Asymmetry 2006, 17, 550-553. 

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