Conjugated ketones => alkoxy

Alcohols add to conjugated ketones with a PMe3 catalyst to give the p-alkoxy ketone.The conjugate addition of peroxide anions (HOO and ROO ) to cx,p-unsaturated carbonyl compounds is discussed in 15-48. 

Danishefsky used a variety of silyloxybutadienes in Diels-Alder reactionsin place of alkoxy and acetoxy derivatives. Treatment of these cycloadduct siloxy derivatives with fluoride (sec. 7.3.A.i) will unmask an enol moiety, which tautomerizes to the carbonyl under very mild conditions. Silyloxy dienes have become very popular for this type of reaction. In Weinreb s synthesis of phyllanthine,150 imine 144 reacted with diene I43151 in the presence of Yb(OTf)3 to give 145. Hydrolysis converted this functionality to the conjugated ketone 146 in 84% overall yield. The previous development of 143 as a reagent was due to several unsuccess-... 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

The isolated double bonds in the dihydro product are much less easily reduced than the conjugated ring, so the reduction stops at the dihydro stage. Alkyl and alkoxy aromatics, phenols, and benzoate anions are the most useful reactants for Birch reduction. In aromatic ketones and nitro compounds, the substituents are reduced in preference to the Dissoiving-Memi... 

In addition to solvolysis and nitrenium ion formation, Af-aLkoxy-A-chloroamides (2) also undergo bimolecular reactions with nucleophiles at nitrogen. Not only is the configuration destabilized by the anomeric effect, it also parallels that of a-halo ketones, where halogen on an sp carbon is activated towards reactions by the adjacent carbonyl. This rate-enhancing effect on 8 /2 processes at carbon is well-known, and has been attributed to conjugation of the p-orbital on carbon with the carbonyl jr-bond in the S 2 transition state stabilization of ionic character at the central carbon as outlined by Pross as weU as electrostatic attraction to the carbonyl carbon. The transition states are also affected by the nature of the nucleophile. ... 

Absorption at 240-250 nm by 4//-pyrans has been noted (61CB1784), although this has been disputed and in general 4//-pyrans are characterized by a weak shoulder at ca. 225 nm (69JOC3169). Introduction of an ethoxycarbonyl or acetyl group at C-3 causes a shift of the maximum to 270 and 284 nm, respectively, which are further shifted to 285 and 296 nm by a second of these substituents. These maxima are considerably different from those of 0-alkoxy a,/3-unsaturated esters and ketones indicative of additional conjugation with the second double bond of the pyran. 

There is no stereochemical bias in the conjugate addition of nucleophiles to bridgehead enones. Nevertheless, it should be mentioned here that the /i-alkoxy ketones roc-29-31 were prepared by addition of alcohols to the corresponding unstable enones21,22. 

The reduction of a,p-unsaturated aldehydes and ketones by NaBH4 leads, in general, to substantial amounts of fully saturated alcohols. In alcoholic solvents, saturated -alkoxy alcohols can be formed via conjugate addition of the solvent. This latter process becomes the main reaction path when reduction is performed in 2-propanol in the presence of sodium isopropoxide. In base, a homoallylic alcohol can become the major product of borohydride reduction of an enone. Analysis of the influence of substrate structure on NaBH4 reduction has shown that increasing steric hindrance on the enone increases 1,2-attack. ... 

Mono-enol ethers of -diketones (26) are formally alkoxy substituted enones, and by reductive coupling followed by hydrolysis they yield conjugated bis-enones [Eq. (8)]. This is the more stable product, independent of whether the initial coupling product is a pinacol, a bis-ketone, or mixed coupling product. Reduction of the substrates (26a-b) in ethanol/water (1 1) (Me4NCl) gave the corresponding bis-enones in 20-40% yield [101]. 

The addition of metalated sulfones to aldehydes or ketones is a reversible reaction and the principal cause of failure in the Julia alkenation results from an unfavorable equilibrium at this stage. The reverse reaction is favored when the P-alkoxy sulfone adduct is sterically encumbered. Adducts derived from ketones are more vulnerable than those derived from aldehydes. Stabilization of the sulfone anion by conjugation with an aromatic ring or chelation with a proximate heteroatom are also important contributors to favoring the reverse reaction. However, by varying the metal counterion, the position of equilibrium can be adjusted. For example, the lithio derivative of the sulfone (61 Scheme 24) failed to... 

Subsequent research showed the SrnI mechanism to occur with many other aromatic compounds. The reaction was found to be initiated by solvated electrons, by electrochemical reduction, and by photoinitiated electron transferNot only I, but also Br, Cl, F, SCeHs, N(CH3)3, and 0P0(0CH2CH3)2 have been foimd to serve as electrofuges. In addition to amide ion, phosphanions, thiolate ions, benzeneselenolate ion (C HsSe"), ketone and ester enolate ions, as well as the conjugate bases of some other carbon acids, have been identified as nucleophiles. The SrnI reaction was observed with naphthalene, phenanthrene, and other polynuclear aromatic systems, and the presence of alkyl, alkoxy, phenyl, carboxylate, and benzoyl groups on the aromatic ring does not interfere with the reaction. ... 

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