Homoenolates conjugate addition

The homoenolate conjugate addition has been used very recently by Paquette and Cheney [17] to synthesise the key diquinane intermediate 18 in their studies directed towards the total synthesis of trixikingolide (Scheme 5.13). 

Unsymmetrical cyclopropane homoenolates Conjugate addition of zinc homoenolates Zirconium homoenolates Enantioselective cyclopropane homoenolates An enantioselective amino acid homoenolate Homoenolate equivalents from three-membered rings The Defensive Strategy d3 Reagents with Protected Carbonyl Groups Acetals Sulfones... 

COPPER-CATALYZED CONJUGATE ADDITION OF A ZINC HOMOENOLATE ETHYL 3-[3-(TRIHETHYLSILYL0XY)CYCL0HEX-... 

Table 8. Products of conjugate addition of zinc homoenolate in the presence of Cu(I) and Me3SiCl (Ref. [28, 29]...

The allylation and the conjugate addition (vide supra) of zinc homoenolate proceed under essentially the same conditions except that the latter requires the presence of Me,SiCl as well. Due to this subtle difference, selective allyl substitution is possible even with an enone function is present in the same molecule (Table 9). 

In place of a Grignard reagent, several homoenolate equivalents have also been employed. Kempt 1 7 reported the titanium-mediated addition of /V-alkylmethylacrylamide dianions to N-protected a-amino aldehydes (Scheme 8). Pyrolytic cyclization affords a 3-methylenetetrahydrofuran-2-one and the side chain of C3 is appended via conjugate addition. The resulting lactone can be converted into the 1-hydroxyethylene dipeptide by hydrolysis. The stereochemistry of the C6 atom is the same as that of the a-amino aldehyde. However, the stereoselectivities of the reactions regarding the C3 and C5 atoms are unsatisfactory. 

Carboalkoxycyclopentenones.3 The zinc homoenolate 1, prepared as shown (13, 349-350), can undergo a formal [3 + 2]cycloaddition to acetylenic esters in the presence of CuBr-S(CH3)2, ClSi(CH3)3, and HMPA to give 2-carboalkoxycyclopen-tenones. The reaction probably involves conjugate addition to give an allenolate followed by intramolecular cyclization. 

Apart form the aforementioned highly enantioselective hetero-Diels-Alder reactions, that proceed with very low catalyst loadings, the catalytically accessible enolates have also been used for related intramolecular Michael reactions (Philips et al. 2007) and for the desym-metrization of 1,3-diketones yielding cyclopentenes via an intramolecular aldol reaction (Wadamoto et al. 2007). The formation of cyclopentenes, however, presents a special case, so—depending on the stereochemical nature of the enone substrates (s-cis or s-trans) and the stereochemistry of the final products—two different mechanisms are discussed in the literature. Whereas /ran.v-cycl open (cries are proposed to be available upon conjugate addition of a homoenolate to chalcones,... 

Reformatsky reagent which then adds to carbonyl derivatives according to Scheme 20. These authors also observed conjugate addition of the homoenolate anion to a,)5-unsaturated ketones in the presence of copper ion as shown ... 

Conjugate addition of catalytically generated zinc homoenolate (cf. Eq. 39) has been used for the stereoselective synth b of a key inl mediate to ( )-cortisone (38). Precedents of the cuprate addition onto a tronr-fused hydrindane such as 35 was expected to give 36 but attack of the nucleophilic copper reagent from the desirable, le hindered oc-side. Although treatm t of the enone 35 with the zinc homoenolate under standard condition (Eq. 39, MCjSiCI/HMPA/ cat. CuBr - MejS) afforded the adduct in quantitative yield, the product was a 1 1 mixture of 36 and 37. In contrast, use of BFj EtjO instead of M iO gave the desired isomer 36 with better than 9S% selectivity with some additional steps... 

An open chain example44 153 of asymmetric homoenolates from allylic amines uses the proline derivative 152 and the p-stannyl ketone 153 made by conjugate addition of Bu3SnLi to the enone 150. 

Just as anions of allyl derivatives can be homoenolate equivalents (chapter 13) so anions of vinyl derivatives can be acyl anion equivalents. Vinyl (or enol) ethers can be lithiated reasonably easily, especially when there is no possibility of forming an allyl derivative, as with the simplest compound 81. The most acidic proton is the one marked and the vinyl-lithium derivative 82 reacts with electrophiles to give the enol ether of the product17 84. However, tertiary butyl lithium is needed and compounds with y-CHs usually end up as the chelated allyl-lithium 85. These vinyl-lithium compounds add directly to conjugated systems but the cuprates will do conjugate addition.18... 

---