Ketones, ethyl aldol reaction, stereoselection

Huang, X.-T. Chen, Q.-Y. Ethyl a-Fluoro Silyl Enol Ether Stereoselective Synthesis and Its Aldol Reaction with Aldehydes and Ketones. J. Org. Chem. 2002, 67, 3231-3234. 

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,... 

In a similar manner, syn aldol reactions can be carried out with ethyl ketones using the Ipc2BOTf reagent. We showed that the asymmetric induction using diethyl ketone is reasonable (66-91% ee), with best results for a,jS-unsaturated aldehydes [35]. We also showed that this reaction could be extended to chiral ketones, for example, the stereoselective synthesis of either syn adduct 51 or 52 was achieved, depending on the configuration of IpciBOTf reagent (Scheme 9-17) [II]. 

When we discussed how -enolates of ethyl ketones such as 207 gave 1,3-control in the aldol reaction, we noted that there was 1,4-control too. Paterson did the same reaction on the corresponding methyl ketones and found that the lithium enolate (M = Li in 234) was unselective. The boron enolate with an achiral group 9 (M = dicyclohexyl-B) was selective giving 88 12 syn anti-235 in 84% yield but with a chiral group [M = (-)-(Ipc)2B] the stereoselectivity was significantly better35 (92 8). 

A number of ethyl ketones and propionate esters derived from carbohydrates have been investigated in the aldol reaction. None of the compounds studied give useful levels of stereoselection. The most selective compound from this study is ketone (201 equation 121) syn aldols (202) and (203) are produced in a ratio of 79 21. 

The high syn stereoselectivity attained in zirconium enolate aldol reactions has proved useful in complex natural product synthesis. The zirconium-mediated aldol reaction of the chiral ethyl ketone (9) with a chiral aldehyde has been used by Masamune et al. to give selectively adduct (10), which was further elaborated into the ansa chain of rifamycin S (equation 1). Good enolate diastereofacial selectivity is also obtained here and leads to a predominance of one of the two possible syn adducts. A zirconium enolate aldol reaction also features in the Deslongchamps formal total synthesis of erythromycin A, where the di(cyclopentadienyl)chiorozirconium enolate from methyl propionate adds with high levels of Cram selectivity to the chiral aldehyde (11) to give the syn adduct (12 equation 2). A further example is... 

In some cases titanium enolates give as good, if not better, stereoselectivity as the corresponding boron enolate aldol reactions (Volume 2, Chapter 1.7). For example, the tri(isopropoxy)titanium enolate of the chiral ethyl ketone (27) has been found to undergo aldol reactions with aldehydes with very high dia-... 

Stereoselective aldol reactions of a-methyl aldehydesThe lithium enolatc of this ethyl ketone (1) reacts with various a-methyl aldehydes to form aldols, which after protection as silyl ethers and thermolysis (500 ) were isolated as the a, / -unsaturated ketones 2 and 3. The diastcrcoselectivity is highly dependent on the R group. Thus... 

An alternative route by the Danishefsky group was developed [142e-g] (Scheme 84). The aldol reaction of ethyl ketone 580, prepared from P-keto ester 579, with aldehyde 581 stereoselectively afforded 582 (dr = 5.4 1). After Troc protection followed by hydrolysis of the enol ether, Suzuki coupling with 583 followed by TBS deprotection gave the desired (12Z)-olefin 584. The Noyori reduction of the P-keto ester 584 gave 3a-alcohol with high stereoselectivity, which was converted into hydroxy carboxylic acid 585. Macrolactonization of 585 was accomplished by the Yamaguchi method, and subsequent deprotection and DMDO oxidation efficiently afforded epothilone B (5b). 

Masamune reports the selective formation of the ( )- or (Z)-vinyloxyboranes (103) from cyclohexyl ethyl ketone, depending on the boron triflate used. The intermediates undergo stereoselective aldol reactions giving the threo- and... 

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