Umpolung homoenolates

Another common umpolung synthon is a homoenolate. Normally the ft position of a carbonyl compound is an electrophilic center (by Michael addition to an 0, /3-unsaturated carbonyl derivative). To make it a nucleophilic center, an organometallic is needed since it is unactivated and nonconjugated. A common way to do this is to use a /3-bromo acetal. 

The reactions discussed above have focused on an a1 to d1 umpolung, as exemplified by the reaction of the resulting d1 nucleophile with aldehydes (benzoin condensation [9]) or with Michael acceptors (Stetter reaction [38]) [3]. In contrast, a,/ -unsaturated aldehydes can react as d3 nucleophiles by utilizing a conjugated umpolung that involves a homoenolate reactivity. 

Therefore acceptor cyclopropanes 1 will be ring opened by nucleophiles N to provide products like 2 (homo Michael addition) as depicted in Eq. 1. On the other hand, electrophiles E+ cleave donor activated cyclopropanes 3 affording adducts 4 or 5 which demonstrates that the cyclopropane serves as a homoenolate equivalent in this sequence (Eq. 2). Seebach consequently classified these methods as umpolung with the cyclopropane trick 4. ... 

The first step of this unprecedented umpolung reaction is identical to the standard MBH mechanism. Only the tautomerization event differentiates between a- (enolate) and -functionalization (homoenolate). 

The umpolung of a,p-unsaturated aldehydes promoted by /V-heterocyclic carbenes generating a homoenolate equivalent is the key procedure in a synthesis of 3-alkylcoumarins from salicylaldehydes carried out in ionic liquids (Scheme 31) <07EJO943>. 

The acyl cation 2a or acylium ion 2b is a familiar intermediate in the Friedel-Crafts reaction. It is easy to make (acid chloride + Lewis acid 1) and it can be observed by NMR as it expresses the natural reactivity pattern of the acyl group. The acyl anion by contrast has umpolung or reverse polarity.1 One might imagine making it from an aldehyde by deprotonation 3 and that it would be trigonal 4a or possibly an oxy-carbene 4b. Such species are (probably) unknown and their rarity as well as their potential in synthesis has led to many synthetic equivalents for this elusive synthon. The acyl anion, the d1 synthon, is the parent of all synthons with umpolung2 and should perhaps have been treated before the homoenolates dealt with in the previous chapter. 

The synthetic value of homoenolates, in exact analogy to that of enolates, stems from their amphoteric nature (equations 1 and 2). In addition, homoenolates represent archetypal synthons in the concept of umpolung , acting as inverse polarity nucleophilic synthons of Michael acceptors. 

N-Heterocyclic carbenes catalyzed umpolung reactions via homoenolates 07Y1009. 

Abstract The discovery and development of new A-heterocyclic carbene-catalyzed reaction is described. Based on inspiration from nature, we have taken thiazolium-based approaches to umpolung reactivity and invented a suite of related reactions involving acyl anions, homoenolate, and enolate nucleophiles all generated under catalytic conditions. 

Our initial studies uncovered a novel class of unconventional homoenolate nucleophiles accessible from the addition of an NHC to an unsaturated aldehyde. The umpolung addition of an alcohol across an enal to generate saturated esters has opened new possibilities for the development of useful acylatirai and oxidation reactions [99-106]. 

Another group of synthetic equivalents has been developed which correspond to the propanal homoenolate, CH2CH2CH=0. This structure is the umpolung equivalent of an important electrophilic reagent, the a,jS-unsaturated aldehyde... 

The abiUty of enals to react as homoenolates [84] in the presence of NHC catalysts was first noted in 2004 independently by the groups of Glorius and Bode [85]. In both cases, the use of stericaUy-hindered catalyst 99 and a strong base (DBU or Bu OK) allowed a -d umpolung through the extended Breslow intermediate (101), thereby attacking an aldehyde electrophile and ultimately forming a y-lactone diastereoselectively (105, = H) (Scheme 18.18). Whereas two aldehydes can... 

The NHC-catalysed umpolung of enals into homoenolate equivalents is an efficient tactic to develop cyclization reactions. Substituted cyclopentanones (132) have been prepared in a diastereoselective manner via the reaction of enals and 4-nitro-5-styrylisoxazoles (133) in the presence of imidazolium salt (134) as... 

Masked lithium homoenolates of type XII are of interest in synthetic organic chemistry and can be considered as three-carbon homologating reagents with umpolung reactivity [122]. The lithiation of the jS-chloro orthoester 147 with lithium in the presence of a catalytic amount of DTBB, under Barbier-reaction conditions, and using carbonyl compounds as electrophiles, followed by acidic hydrolysis, led to lactones 149 as reaction products, the masked lithium homoenolate 148 bang proposed as a reaction intermediate (Scheme 2.20) [123]. 

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