Magnesium enolates conjugate addition

The introduction of asymmetry in conjugate additions can be promoted by chiral acceptors. The preparation of regio-defined magnesium enolates from copper(I)-mediated conjugate addition of Grignard reagents has been extensively used in many important... 

The copper-catalyzed conjugate addition of methyl magnesium iodide to cyclohexenone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloro-antinomate-catalyzed Mukaiyama reaction, is apphed to / -(—jcarvone. C-2, C-3 functionalized chiral cyclohexanones are converted into their a-cyano ketones, which are submitted to Robinson annulation with methyl vinyl ketone. Highly functionalized chiral decalones are obtained that can be used as starting compounds in the total synthesis of enantiomerically pure clerodanes (equation 70). 

Methyltryptophan derivatives have been synthesized stereoselectively using chiral auxiliaries. Conjugate addition of magnesium methylcuprate to the indole acrylic add (392) gives an enolate which can be trapped by bromination to give the product (393), which can then be transformed into the tryptophan (394) by azide displacement, reduction and hydrolysis (Scheme 131) <92TL7491>. 

In the enantioselective conjugate addition, the use of p,P-disubstituted enones to create quaternary chiral centers is more difficult because of the steric hindrance of the P-position [21]. Alexakis showed that Cu complexes with the chiral carbene ligand 49 are capable of catalyzing domino conjugate additions to the trisubstituted enone 50 in a one-pot process (Scheme 11.11). The magnesium enolates reacted poorly with alkyl halides, but their reactivity improved with use of an HMPA/THF... 

The magnesium enolate (216) generated from copper(i)-catalysed conjugate addition of MeMgl to 3-methylcyclohex-2-enone in ether at 0°C has been used as a substrate in a study of acylation, alkylation, and the aldol condensation, particularly with respect to regiospecificity. With acetyl chloride in ether the ratio of C-alkylated (217) to 0-alkylated (218) product was 62 38 in a total yield of 39—53%, whereas in dimethoxyethane (218) only was formed in 63% yield. Predominant C-acylation also occurred with crotonyl chloride in ether, where the isolated product contained 86% of (219) in dimethoxyethane the extent of 0-acylation was 95 %. No evidence was adduced for intermediacy of the equilibrated enolate anion (216b). Product ratios were discussed in terms of hardness and softness of the reaction sites. 

Copper Conjugate addition of Grignard reagents to cyclic enones (249), catalysed by the Cu complex of Taniaphos (248), followed by Mannich reaction of the resulting chiral magnesium enolates with Af-protected imines, has been shown to produce the adducts (250) with <98% ee. Diastereoselectivity turned out to be dependent on the... 

Naphthol derivatives with an acrylic pendant (251) undergo a conjugate addition of Grignard reagents, catalysed by Cu(I)-(254). The resulting magnesium enolate (252) can be oxidatively coupled in situ by copper(II) to afford spirocyclic cyclohexenones (253) in >20 1 dr and <94%... 

Scheme 2.37 Copper catalyzed generation of magnesium enolate 123 by conjugate addition.

---