Evans aldol reaction units

The Evans aldol reaction using chiral p-keto imide 23 as a dipropionate building block is also very effective for the construction of polypropionate segments in polyoxomacrolides (Scheme 2) [8]. The diastereoselective aldol reaction of 23 via different metal enolates (Ti, Sn, and B enolates) afforded three kind of aldols, syn-syn-24, anti-syn-25, and anti-anti-26, with high diastereoselectivity, respectively. The subsequent stereoselective reduction of the resulting p-hydroxy ketones 24-26 provides various types of dipropionate units. Based on this strategy, the... 

The Evans asymmetric alkylation [127] and aldol reactions were also effectively applied to the synthesis of the C10-C19 top segment 230 (Scheme 33). The starting chiral unit 223 was synthesized via the Evans asymmetric alkylation of 218a. The subsequent Evans aldol reaction of 223 with 224 followed by trans-amidation yielded 2,3-sy -diol derivative 225 with complete stereoselectivity. Addition of alkyl lithium 226 to the Weinreb amide 225 produced ketone 227, which was stereoselectively reduced and methylated to give dimethyl ether 228. The standard functional group manipulation afforded thioacetal 229, which was converted into phosphine oxide 230. 

The completion of the total synthesis of FK506 (1) is described in Scheme 34. The coupling of the two segments 222 and 230 was accomplished by phosphine oxide-mediated HW olefination. The addition of 222 to 230 afforded a separable 1 1 mixture, and the less polar diastereomer yielded ( )-olefin 231. After selective removal of the TES group, esterification of 231 with (S)-A-Boc-pipecolic acid (232) under DCC-DMAP conditions followed by dethioacetalization afforded aldehyde 233. The Evans aldol reaction of 233 with 218d installed a glycolate unit, and hydrolysis of the chiral auxiliary followed by TES protection provided 234 ready for macrocyclization. The macrolactamization of 234 was effectively... 

The aldol reaction is an important carbon-carbon bond formation reaction. The general concept of the reaction involves the nucleophilic addition of a ketone enolate to an aldehyde to form a P-hydroxy ketone, or aldol , a structural unit found in many naturally occurring molecules and pharmaceuticals. Since the aldol addition reaction creates two new stereocenters, up to four stereoisomers may result. The Evans aldol reaction performs a diasteroselective aldol transformation using an Evans s acyl oxazolidinone (also known as Evans chiral auxiliary), a chiral carbonyl compound that creates a temporary chiral enolate for the aldol addition. Upon subsequent removal of the auxiliary, the desired aldol stereoisomer is revealed. ... 

As an extension of the Evans aldol reaction, the so-called Evans-Mettemich variation [17] adds two polyketide units to the growing polyketide chain (Scheme 2.114). It should be pointed out that here not the chiral auxiliary controls the stereoselectivity but the a-chiral center, which in turn was previously generated by addition to the Evans propionate. Using different metals and reaction conditions, three out of four possible stereoisomers can be generated and subsequent reduction of the keto carbonyl group can construct an additional chiral alcohol (vide infra). 

Bravo and co-workers report asymmetric syntheses of fluoroalkylamino compoimds via chiral sulfoxides and the stereoselective synthesis of p-fluoroalkyl-p-amino alcohol units using chiral sulfoxides and the Evans aldol reaction. Begde and colleagues discuss the stereoselective and enantioselective synthesis of trifluoromethyl amino alcohols and fluoroalkyl isoserinates. Hoffman reports the aysmmetric fluorination of a-aminoketones, while... 

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