Homoenolate cyclopropanols

DePuy, as early as 1966 [14], reported that cw-1-methyl-2-phenylcyclopropanol gave exclusively deuterated 4-phenyl-2-butenone in 0.1 M NaOD/D20/dioxane. However, homoenolates derived from simple cyclopropanols by base-induced proton abstraction fail to react with electrophiles such as aldehydes and ketones, which would afford directly 1,4-D systems. Lack of a reasonably general preparative method was another factor which impeded the studies of homoenolate chemistry. For this reason, in the past twenty years more elaborated cyclopropanols, which might be suitable precursors of "homoenolates", have been prepared and studied. 

Vicinally donor-acceptor-substituted cyclopropanol carboxylic esters have been proven to be versatile synthetic building blocks in organic synthesis [11]. They readily undergo a retroaldol reaction, thus creating a stable enolate that at the same time can be considered as a homoenolate in relation to the newly formed carbonyl function. Shimada et al. applied this strategy to the preparation of y-substituted lactones starting from cyclopropane 21 (Scheme 3) [12]. 

Unlike their enolate counterparts, homoenolates have been underrated because of a prior lack of synthetic accessibility. Many of the previously known homoenolates cyclize readily to the cyclopropanolate tautomer and behave chemically as the latter. 1-Alkoxy-l-silyloxycyclopropanes have provided,... 

The chemistry of cyclopropanol [7] has long been studied in the context of electrophilic reactions, and these investigations have resulted in the preparation of some 3-mercurio ketones. As such mercury compounds are quite unreactive, they have failed to attract great interest in homoenolate chemistry. Only recent studies to exploit siloxycyclopropanes as precursors to homoenolates have led to the use of 3-mercurio ketones for the transition metal-catalyzed formation of new carbon-carbon bonds [8] (vide infra). 

The concept of homoenolization was recognized by Nickon in the 1960s but attempts at direct formation of homoenolates were frustrated by cyclopropanolate formation. This lack of success has prompted the development of homoenolate equivalents19 of which the first example, the 3-propionaldehyde anion equivalent (112), was previously discussed (Sections 1.2.2.1.2 and 1.2.2.1.3). Ghosez has shown that a-cyanoenamines (249 and 250) add preferentially in the 1,4(7)-mode to cycloalkenones. The versatility of (250) which serves as either a (3-carboxyvinyl anion equivalent [-CH=CHCChR] or 3-propionate anion equivalent ["Cl ClfcCChR] (Scheme 85) is notable.191... 

Cyclopropanols in general, can well serve as homoenolate anion precursors, i.e., the P-anion of ethyl propionate 99), however, to avoid the easy base or acid induced ring opening the hydroxyl function of 42 must be protected when necessary. On simple addition of one equivalent of 3,4-dihydro-2H-pyran to a CH2C12 solution of the a-hydroxy acid 42, the tetrahydropyranyl ether 163 was obtained exclusively,... 

Cyclopropanol may be regarded as the simplest homoenol, the cyclopropylalkoxide ion structure is one of the pair of hybrid structures which constitute the parent homoenolate ion (equation 14). 

For an interesting application of a cyclopropanolate as a homoenolate in a Heck-type aiylation see F. A. Khan, R. Czerwonka, H.-U. Reissig, Synlett 1996, 533-535. 

Enolisation 1 involves the removal of the a-proton from a carbonyl compound to form an enolate ion 2. Homoenolisation involves the removal of a (i-proton 3 to form the homoenolate ion 4 or 5. Both the enolate and the homoenolate can be represented as carbanions, but whereas the enolate version 2b is merely a different way of representing a single delocalised structure, the homoenolate 5 is a different compound from the cyclopropane 4. No literal examples of homoenolates 5 are known so they have the status of synthons which may be represented in real life by reagents derived from cyclopropanols 4 among many other possibilities.1... 

In the presence of a Lewis acid, alkyl 2-silyloxycyclopropanecarboxylates (14) react with a wide range of carbonyl compounds to give a diester (15), which has b n converted to a variety of furan derivatives (Scheme 18). An interesting use of the oxyanionic tautomer of a homoenolate involves the reaction of a magnesium cyclopropanolate (12) with the lithium enolate of cyclohexanone, from which a tricyclic ring containing a functionalized cycloheptanone (13) is formed in a single step (Scheme 18). ... 

Scheldt and coworkers reported the addition of amide enolates to acylsilanes for generation of p-silylojq homoenolate equivalents 62, based on the fact that less electrophilic p-carbonyl groups disfavor the formation of cyclopropanolates 63 by internal carbanion attack (Scheme 6.30). Instead, the carbanion generated in situ can be trapped by allq l halides, aldehydes, ketones, and imines. The use of optically active amide enolates delivers p-hydroxy amides with high levels of diastereoselectivity. 

The cyclopropanol also serves as a source of homoenolate radical species. Treatment of a mixture of the cyclopropanol and an enol silyl ether with manganese(III) 2-pyridinecarboxylate in DMF gives a 1,5-dicarbonyl compound (eq 15). ... 

Transition metal cyclopropanolates underwent ring opening by P-carbon elimination to generate transition metal homoenolates. Palladium(ll)-catalyzed ring opening of substituted cyclopropanols predominantly occurred at the less substituted C-C bond to give conjugated enones (Scheme 2.31) [47]. When the reaction was performed under non-oxidative conditions, a mixture of unsaturated and saturated ketones was obtained [48]. 

Representative reactions that are thought to proceed through a CMD pathway and that use KOAc as the optimum base include the benzolactone formation via direct arylation of a tethered carboxylic acid (eq 33), indanone formation via direct arylation of cyclopropanol-derived homoenolates (eq 34), and the direct arylation of thiophenes with aryl bromides (eq 35). ... 

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