Ketone, /-butyl ethyl reaction with benzaldehyde

E -Enolates often react with lower stereoselectivity than those of the corresponding Z-enolates. A classic example to illustrate this point is a study carried out by Heathcock et al.6 (Scheme 2.IV). When the carbonyl compounds 1 were deprotonated with lithium diisopropylamide (LDA) and the resulting enolates were subsequently treated with benzaldehyde at -72° C, the aldol products desired (2) were obtained in 83 to 99% yield. The Z-enolates derived from t -butyl and 1-adamantyl ethyl ketones afforded syn -products in excellent levels of diastereoselectivity. The fact that the syn/anti ratios directly reflect the isomeric purity of the reacting enolates hints that the Z-enolates in these cases undergo aldol reaction through a chairlike six-membered transition state (Scheme 2.III,... 

Treatment of a-iodo ketone and aldehyde with an equimolar amount of Et3B yielded the Reformatsky type adduct in the absence of PhaSnH (Scheme 21), unlike ot-bromo ketone as shown in Scheme 15 [22], Ethyl radical abstracts iodine to pro-duee carbonylmethyl radical, which would be trapped by EtsB to give the corresponding boron enolate and regenerate an ethyl radical. The boron enolate reacts with aldehyde to afford the adduct. The three-component coupling reaction of tert-butyl iodide, methyl vinyl ketone and benzaldehyde proceeded to give the corresponding adduct 38, with contamination by the ethyl radical addition product 39. The order of stability of carbon-centered radical is carbonylmethyl radical > Bu > Pr > Ef > Me . 

When the aldol addition reaction is carried out under thermodynamic conditions, the difference in stability of the stereoisomeric anti and syn products determines the product composition. In the case of lithium enolates, the adducts can be equilibrated by keeping the reaction mixture at room temperature. This has been done, for example, for the product from the reaction of the enolate of ethyl r-butyl ketone and benzaldehyde. The greater stability of the anti isomer is attributed to the pseudoequatorial position of the methyl group in the chairlike product chelate. With larger substituent groups, the thermodynamic preference for the anti isomer is still greater. 

Enol silyl ethers react with aldehydes with a catalytic amount of TBAF to give the aldol silyl ethers in good yields. These reactions generally proceed under very mild conditions and within shorter periods of time than conventional strong acidic or basic conditions. The products from4-f-butyl-l-methyl-2-(trimethylsilyloxy) cyclohexene and benzaldehyde show very good axial selectivity and a little anti-syn selectivity (eq 20). The aldol condensation of ketones and aldehydes can be achieved in one pot when ethyl (trimethylsilyl)acetate is used as a silylation agent with TBAF (eq 21). 

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