Ketones, conjugated reaction with organometallics

The reduction of unsaturated carbonyl compounds by metal hydrides, and the reaction of organometallic nucleophiles with them, is a complicated story.87 It is more common than not, in each case, to get direct attack at the carbonyl group, but reaction in the conjugate position is well known. Conjugate reduction of a/i-unsaturated ketones by metal hydrides increases88 in the sequences Bu2iAlH < LiAlH4 < LiAlH(OMe)3 < LiAlH(OBu )3 and... 

Figure 12.13 shows that the iso-A enols of the /3-diketones A react with an a,/3-unsaturated carboxonium ion C that acts as a C electrophile. This oxocarbenium ion is formed by reversible protonation of the oc,/3-unsaturated methyl vinyl ketone in acetic acid. However, the oxocarbenium ion C in this figure does not react with the iso-A enols at its carbonyl carbon atom—as the protonated acetone in Figure 12.12 does with the enol of acetone—but at the center C-/3 of the conjugated C=C double bond. Accordingly, an addition reaction takes place whose regioselectivity resembles that of a 1,4-addition of an organometallic compound to an 0C,/3-unsaturated carbonyl compound (see Section 10.6). 1,4-additions of enols (like in this case) or enolates (as in Section 13.6) to a,/3-unsaturated carbonyl and carboxyl compounds are referred to as Michael additions. 

Protection or reductive deoxygenation of alcohols and ketones. Ireland et al.2 have found that N,N,N, N -tetramethylphosphoroiiamidates (TMPDA derivatives) of alcohols and of ketone enolates are reduced in high yield by lithium-ethylamine. They are readily prepared by phosphorylation of alcoholate or enolate anions. The complete sequence is as follows. The alcoholate anion is simply prepared by treatment of an alcohol with a slight molar excess of n-butyllitliium. The enolate anions of saturated ketones are prepared by treatment with lithium diisopropylamide. In the case of a,/J-unsaturated ketones, lithium-ammonia reduction or conjugate organometallic addition is suitable. For phosphorylation of the Jnion a fivefold excess of N,N,N, N -tetramethyldiamidophosphorochloridate in 4 ] dimethoxyethane (or THF)-N,N,-N. N -tetramethylethylenediamine (TMEDA) is used. The reaction is complete after... 

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