Deoxygenation cyclic ketones

An interesting deoxygenation of ketones takes place on treatment with low valence state titanium. Reagents prepared by treatment of titanium trichloride in tetrahydrofuran with lithium aluminum hydride [205], with potassium [206], with magnesium [207], or in dimethoxyethane with lithium [206] or zinc-copper couple [206,209] convert ketones to alkenes formed by coupling of the ketone carbon skeleton at the carbonyl carbon. Diisopropyl ketone thus gave tetraisopropylethylene (yield 37%) [206], and cyclic and aromatic ketones afforded much better yields of symmetrical or mixed coupled products [206,207,209]. The formation of the alkene may be preceded by pinacol coupling. In some cases a pinacol was actually isolated and reduced by low valence state titanium to the alkene [206] (p. 118). 

Codeposition of Magnesium and a Ketone. A further interesting observation [9] by the same group was the interaction between metal atoms and a ketone, a reagent often present in a Barbier reaction mixture. Cocondensation of magnesium with cyclic ketones leads to both deoxygenation and dimerization ... 

Salicylaldehyde reacts with trimethylsilylketene dithioacetal in the presence of a Lewis acid to form the chroman 502, the product of a deoxygenative divinylation (Equation 208) <2001JOC3924>. This reaction can also be applied to salicylaldimines <2003JOC4947>. Treatment of 3,5-dibromosalicylaldehyde with methyl vinyl ketone (MVK) in the presence of DABCO leads to a chroman-4-ol as the major product <2002J(P1)1318>. A stereoselective one-pot synthesis of vy/z-fused chromans from salicylaldehydes, aromatic amines and cyclic enol ethers is carried out in the... 

Fig (4) The transformation of the ketone (24) to the cyclic ether (9) applying the standard organic reactions is described It wa subjected to three sequencial reactions with reagents mentioned for the conversion to cyclic ether (30). Isopropylation and by aromatization, it produces the phenol (31), which is converted to pisiferol (4). This on subjection to oxidation, esterification and deoxygenation respectively, furnish O-methyl pisiferate (5) and this is easily converted to pisiferic acid (1). 

Fig (14) Olefin (107) has been converted to cyclic ether (114) by standard reactions. Its transformation to enone (115) is accomplished by annelation with methyl vinyl ketone and heating the resulting diketone with sodium hydride in dimethoxyethane. The ketoester (116) is subjected to Grignard reaction with methyllithium, aromatization and methylation to obtain the cyclic ether (117). Its transformation to phenolic ester (119) has been achieved by reduction, oxidation and esterification and deoxygenation. 

Aluminum atom reactions are relevant to interfacial chemistry associated with aluminum-polyimide junctions. Al deposited under ultra high vacuum will reduce surface carbonyl functional groups (22). MVS co-condensation experiments show that besides ketones, aldehydes and epoxides, atomic aluminum will deoxygenate ethers. Chapter 7 of the monograph by Klabunde (12) includes tables of deoxygenation products of a variety of cyclic and acyclic ketones and ethers. 

Mai and co-workers have reported that the deoxygenation of cyclic a,/3-epoxy ketones (and acyclic a,/3-epoxy esters) is accomplished in high yields under mild and neutral conditions by the use of Mo(CO)6 (Table 14) <2003TL2355>. 

However, this sequence can be reversed. - Thus, the activated cyclopropane can be de-protonated by lithium diisopropylamide, reacted with an appropriate ketone and opened by various methods such as treatment with acid or desilylation with fluoride. Using this reaction sequence, y-lactones 52 with various substituents can be obtained by the intramolecular attack of the ketone oxygen on the siloxy-substituted carbon followed by oxidation with pyridinium chlorochromate. The cyclic hemiacetal intermediates 53 can be converted to the tetrahyd-rofuran derivatives 55 by deoxygenation with triethylsilane/boron trifluoride. 

The epoxide 4.2.1.2 proved resistant to nucleophilic attack, but the diol 4.2.1.1 could be converted into a number of new analogs. These included simple analogs such as various C-6 acyl derivatives 4.2.1.4 (167) but also various derivatives produced by deoxygenation at C-7. Thus diol 4.2.1.1 could be protected as its 2 -(triethylsilyl)ether, converted to its cyclic 6,7-a-thiocarbonate, and deoxygenated to the 7-deoxyanalog 4.2.I.5. Analog 4.2.1.5 can be oxidized to the ketone 4.2.1.6, which can then be reduced to the /5-alcohol 4.2.1.7 (176). Both compounds 4.2.1.5 and 4.2.1.7 were as active as taxol in a tubulin-assembly assay, but were 4 and 10 times less potent than taxol in a cytotoxicity assay with the HCT-116 human colon tumor cell line (176). 

Thioethers. A mixture of diphenyl sulfoxide and HMPA treated with SmL in THF under N2 at 20 for 1 min, diluted with hexane, and filtered through Florisil - diphenyl sulfide. Y 94%. The method can also be used for the rapid deoxygenation of sulfones (which may be viewed as protected thioethers). E Diphenyl sulfone under the same conditions - diphenyl sulfide. Y 93%. Esters remained intact and, in some cases, sulfoxides were selectively reduced in the presence of ketones. F.e. inch formation of cyclic tert. amines from N-oxides, tert. phosphines from phosphine oxides, and distannanes from distannoxanes, s. Y. Handa et al., J. Chem. Soc. Chem. Commun. 1989, 298-9 review of synthesis and use of polysulfoxides s. V.A. Nikonov, G.V. Leplyanin, Sulfur Reports 9, 1-23 (1989). 

Cyclic or-dioxo substrates such as acenaphthenequinone (148) and also N-alkylisatins (149) are deoxygenated in the presence of C o and P(NEt2)3 reductant, giving methanofiillerenes bearing ketone or lactam functionality, respectively. Carbene intermediates are implicated, and the electrochemical properties of the new fullerene derivatives are also reported. ... 

Reaction with Allylic Halides, Alcohols, and their Derivatives. Allylation of allyl and propargyl trimethylsilyl ethers as well as benzyl and propargylic alcohol derivatives proceeds in the presence of a catalytic amount of Lewis acids, such as ZnC, TMS(OTf), and B(C6F5)3. Direct substitutions of the hydroxyl group of allylic, ben-zylic, and propargylic alcohols are catalyzed by HN(S02F)2, a rhenium-oxo complex, and InCls (eq 27). A combination of chlorodimethylsilane and allyltrimethylsilane effectively promotes the deoxygenative allylation of aromatic ketones in the presence of a catalytic amount of an indium compound, such as indium trihalide or metallic indium (eq 28). Allylation of cyclic allylic acetates with allyltrimethylsilane can be catalyzed by molecular iodine. ... 

---