Ketones 2-methoxy- 2-

After the initial claim of the synthesis of an oxirene (by the oxidation of propyne Section 5.05.6.3.1) this system reappeared with the claim 31LA(490)20l) that 2-chloro-l,2-diphenyl-ethanone (110) reacted with sodium methoxide to give diphenyloxirene (111), but it was later shown (52JA2082) that the product was the prosaic methoxy ketone (112 Scheme 97) (the formation of 111 from 110 would be an a-elimination carbene-type reaction). Even with strong, nonnucleophilic bases, (110) failed to provide evidence of diphenyloxirene formation (64JA4866). 

The reaction with a-hydroxy and a-methoxy ketones under these conditions are chelation controlled. 

Hayakawa and Shimizu developed a novel C-C bond-forming reaction by epoxi-dation of methoxyallene 145 with m-chloroperbenzoic acid, which provides a meth-oxyallene oxide intermediate capable of adding to aldehydes. This reaction sequence provides 3-hydroxy-2-methoxy ketones 234 (Scheme 8.59) [133]. The best anti/syn selectivity was obtained by application of a 1 1 mixture of Til4 and Ti(OiPr)4. They also observed the formation of a,/3-unsaturated ketones 236 under comparable reaction conditions when 1-silylated methoxyallene 235 was employed as starting material (Scheme 8.60) [134]. 

By the use of chiral oxazolidines derived from a chiral norephedrine and methyl ketones, an asymmetric aldol reaction proceeds in a highly enantioselective manner. In the case of ethyl or a-methoxy ketones, the corresponding anti aldol products were obtained with high diastereo- and enantioselectivities. A chiral titanium reagent, generated from... 

Table 3. Asymmetric Aldol Reaction of Or-Methoxy Ketone...

Oxyberberine (49), when further oxidized by pyridine chlorochromate and then treated with methanol, gives the methoxy-ketone (50 R = Me) the tetra-methoxy-analogue of (49) behaves similarly.132 The carbinolamine (50 R = H) is obtainable, together with the keto-acid (53), by the photolysis of oxidoberberine (51), in the presence of oxygen and rose bengal, to produce the peroxide (52), followed by treatment with pyridine hydrochloride a tetramethoxy-analogue of oxidoberberine, prepared by the reduction of norcoralyne with zinc and acetic acid, followed by oxidation with a peracid, behaves in the same way.133... 

In 1984, Nakata and co-workers reported that zinc borohydride reduces the ot-mcthyI-p-hydroxy or a-methyl-ft-methoxy ketone 28 stereoselectively to afford... 

Protonated carbonyl compounds can be electron sinks too (remember the dienone-phenol rearrangement from Chapter 37 ), and this bicyclic methoxy ketone fragments to a seven-membered ring in acid. Note the same 1,2,3,4 arrangement, with the bond between carbon atoms 2-3 fragmenting. 

The reactions of enol ester radical cations formed in anodic oxidations were pioneered by Shono [220-225] almost two decades ago. A reaction mode was identified that formally corresponds to that of enol cation radicals. Depending on the electrolysis conditions enol acetates were either converted to a-acetoxy ketones (high concentration of acetate) or to enone products (absence of acetate). Similarly, a-methoxy ketones were obtained through electrolysis in methanol-Et4NOTs. Yields for additional reactions not listed here varied between 29% and 90% [222,223]. 

However, when the carboxy enone rac-5 was irradiated in methanol, both the cis- and transfused bicyclic methoxy ketones trans-6 and cis-6 were isolated24. Clearly, epimerization at the bridgehead carbon atom may occur due to Norrish type-I reactivity of the product ketones rac-2, rac-4 and rac-6. Therefore, subsequent photochemical equilibration may well account for the observed product distributions. 

Maruoka and his colleagues reported that B(CeF5)3 is capable of forming a penta-coordinate complex in the reduction of alkoxy-substituted carbonyl compounds with Bu3SnH [156]. Reduction of an a-methoxy ketone and its deoxy analog (1 1 ratio)... 

In 1913, Kishner observed in one instance that under standard Wolff-Kishner reduction conditions, 2-hydroxy-2,6-dimethyloctan-3-one underwent eliminative reduction upon treatment with hydrazine hydrate and base at elevated temperatures to afford 2,6-dimethyloctan-2-ene (Scheme 7). This same reaction was later found to occur in the case of a-methoxy ketones and has since been referred to as the Kishner eliminative reduction. The reaction entails initial formation of the hydrazone and elimination of the a-substituent to afford the intermediate alkenyldiazene, which subsequently collapses to the desired alkene. Given the facile transformation of ketones into a-halo ketones, these conditions have been used to introduce alkenes regioselectively in the 2a-halocholestan-3-one series as shown in Scheme 8. Yields of 2-cholestene parallel the resistance of the a-halogen to undergo competitive elimination reactions. 

Cr03-H2S04-Hg(II) salts/" and Hg(OAc)2 followed by PdCl2. The reaction has also been accomplished electrochemically. Terminal alkenes react with ceric ammonium nitrate in methanol to give a-methoxy ketones. 

Unsymmetrical ketones can be obtained from symmetrical ketones by anodic oxidation of their enol ethers to the or-methoxy ketone (III) [29], reaction with R MgX, and anodic oxidation of the glycol monomethyl ether. Alternatively, the ketone may be oxidatively aminated, alkylated at C=0, and oxidized (y = OCH3 or NR2) ... 

This general procedure has also been extended to allow for the insertion of a methoxy-containing carbon. The uncatalyzed addition of the lithium anion of methoxymethyl enyl sulfone to ketones proceeds readily at low temperature in dimethoxyethane to form the intermediate adduct. Addition of a Lewis acid (ethylaluminum dichloride or diisobutylaluminum diisopropylamide) directly to the reaction mixture effects the rearrangement reaction to produce the ring-expanded a-methoxy ketone. This sequence, illustrated by the example in Scheme 28, is limited to the expansion of four- and five-membered ring ketones. ... 

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