Magnesium enolates diastereoselective addition reactions

Tin(Il) shows considerable affinity towards nitrogen, therefore is expected to activate the imino group. The diastereoselective addition of tin(II) enolates derived from thioesters 1 to x-imino-esters 2 is reported12. This reaction proceeds smoothly to afford. vi w-/j-amino acid derivatives 3 (d.r. 95 5) in good yields. Lithium, magnesium, and zinc enolates do not react while titanium enolates give the adducts in low yield with preferential formation of the anti-isomer. 

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... 

S, entries 1-9). The stereoisomer ratios observed seem to be kinetic, rather than thermodynamic, since the same yield and enantiomeric excess are observed at reaction times of 3 or 60 min (Table 25, entries 3 and 4). Stereoselectivity decreases as the size of increases (entries 1,2,3 and 6). Addition of HMPA has a deleterious effect on stereoselectivity. The magnesium enolate shows excellent diastereoselectivity. Again, stereoselectivity diminishes as the size of increases (Table 25, entries 10, 11, 14 and 16) and HMPA has a detrimental effect (entry 18). The analogous thioamide was prepared and studied, but it appears to offer no advantage over the oxoamide. ... 

As expected, other enol ethers work well in these procedures. For example, Jones and Selenski find that implementation of method F, which occurs by addition of MeMgBr to benzaldehyde 5 in the presence of dihydropyran (DHP) at 78 °C affords a 66% yield of the corresponding tricyclic ketal 59 with better than 50 1 endo diastereoselectivity (Fig. 4.31).27 On the contrary, Lindsey reports use of method H with the benzyl alcohol 35 and diethylketene acetal. The cycloaddition reaction occurs almost instantaneously upon deprotonation of the benzyl alcohol 35 by f-butyl-magnesium bromide in the presence of the ketene acetal and yields the corresponding benzopyran ortho ester 60 in a 67% yield.29... 

Addition to 632 of chiral enolates generated from mandelic acid-derived (S) or (i )-2-hydroxy-l,2,2-triphenylethyl acetate (HYTRA) produces syn or /-dihydroxypentanoates of the type 647 or 648 [195]. In order to achieve the highest diastereoselectivity, the lithium enolates are transmetallated to magnesium in conjunction with carrying out the reaction at —125 to — 135 °C in THF/2-methylbutane cosolvent. 

Phenols have been condensed with alkenoylesters to give chromans by an oxa-Michael addition/electrophilic aromatic addition sequence with magnesium(II)- or copper(II)-bis-oxazoline complexes as chiral Lewis acid catalysts (Scheme 17b) [97]. This reaction may be initiated by an oxa-Michael reaction, followed by a hydroarylation of a carbonyl group. The authors suggest that the initial stereodetermining oxa-Michael addition is followed by a fast diastereoselective aromatic substimtion [97]. A nickel Lewis acid, derived from Ni(hfacac)2 (hfacac = 1,LL5,5,5-hexafluoro-3,5-dioxopentane enolate) and chiral Al-oxide ligands, catalyzes the enantioselective oxa-Michael cyclization of 2-tert-butyloxycarbonyl-2 -hydroxy-chalcones to 3-ferf-butoxycarbonyl flavanones, which can be decarboxylated to flavanons in a separate step (Scheme 17c) [98]. A Lewis acid activation of the unsaturated p-ketoester unit can be assumed. 

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