2-Cyclohexenone addition reaction

A comparison of the configuration of the substrates and reaction products shows that the oxiranyl anions arc configurationally stable under the reaction conditions. Only one example is known in which isomerization was observed. When the ci.v-tm-butyl-substituted epoxysilane27 was metalated and quenched with 2-cyclohexenone, addition product 27 was obtained under inversion of the anionic center. Presumably the strain created in forcing the ter/-butyl and the trimethylsilyl group cis on the oxirane ring facilitates the isomerization process13. 

Henry reactions 317-20 hydrosilylations 333 organozinc reagents, addition to ketones 156-80 PrMgCl to cyclohexenone with crown thioether ligands 100-1 see also specific ZnEt2 and ZnR2 addition reactions... 

Cyclization reactions of vinyl- and alkynylsilanes have been reviewed100. The course of the reaction of the cyclohexenone derivative 184 depends on the catalyst employed ethylaluminium dichloride gives solely the product 185 of 1,6-addition, whereas tetrabuty-lammonium fluoride yields a mixture containing 69% of the 1,4-adduct 186 and 31% of the bridged compound 187 (equation 89)101. Intramolecular addition reactions of allylic silanes102 may also be catalysed by Lewis acids (equation 90) or fluoride ions, and in this case an allyl anion or a pentavalent silicon intermediate may be involved (equation 91). Such reactions are exemplified by the formation of a 1 5 mixture of the diastereomers 189 and 190 when the cyclohexenone derivative 188 is treated with ethylaluminium dichloride (equation 92). In the presence of fluoride anion the ratio of the isomers is reversed103. 

Li and co-workers also reported a highly efficient conjugate addition reaction with arylsilanes as nucleophilic reagents. The reaction of 2-cyclohexenone with 4 equiv. of either diphenyldichlorosilane or phenylmethyldichlorosilane in water generated the conjugate addition product in 97% and 95% yields, respectively (Scheme 55).143 An excess of sodium fluoride additive was important in this reaction. 

This work was initiated in 1988 when Villacorta et al.71a reported the asymmetric conjugate addition of a Grignard reagent to 2-cyclohexenone. This study showed that 1,4-adducts with 4-14% ee were obtained in the presence of aminotroponeimine copper complex.713 Enhanced results (74% ee) were obtained by adding HMPA or silyl halides.71b Several other copper complexes were also used for inducing asymmetric conjugate addition reactions. Moderate results were obtained in most cases when THF was used as the solvent and HMPA as the additive. 

Japanese workers (50,51) were the first to observe optical activity in the addition of thiols to electron-poor olefins (eq. [9]) The e.e. was not determined, but these observations led us to attempt using a cinchona alkaloid as the catalyst in the addition of thiophenol to cyclohexenone. The reaction lends itself admirably to a scope, limitations, and mechanism study, and the results have been published in detail (19). An important mechanistic difference between the addition of the dodecanethiol to isopropenyl methyl ketone and the addition of thiophenol to a cyclohexenone (eq. [1]) lies in the sequence of chirality-producing steps. In the former case, chirality is produced when the proton adds to the a-caibon atom of the ketone—after thiol addition has taken place. In the latter... 

Although the mechanism of this reaction has not been studied as thoroughly as that of the thiol addition reaction, there appears to be considerable similarity in the main features of the reaction. Thus, although the transition state may well differ in a number of details, the transition state shown earlier (Figure 10) appears to predict the correct configuration for the products of the selenophenol addition as well as of the thiophenol addition to cyclohexenones. 

Wipf has shown that this method is quite general and tolerates several functional groups, such as ethers, thioethers, silanes, halides, aromatic rings, and olefins. The iodoalkyne 64 is readily carbometalated and after treatment with the dialkynylcuprate 59 furnishes the functionalized copper reagent 65, which smoothly undergoes 1,4-addition reactions with enones. Thus, in the case of 2-cyclohexenone, the functionalized ketone 66 is produced in 85% yield (Scheme... 

The silylcuprate conjugate addition reaction has been used for the protection of an enone double bond, which can be regenerated with CuBr2 [22a], and for the strategic introduction of the silyl substituent for stereocontrol and regiocontrol purposes. Enantiopure 5-trimethylsilyl-2-cyclohexenone can be prepared by conjugate addition reaction [44] and the appropriate enantiomer has been converted into a number of natural products (Scheme 3.4) [38]. These synthetic strategies exploit... 

Addition of Lewis acids may not only accelerate the reaction rate of a conjugate addition but may also alter the stereochemical outcome of a cuprate addition. Interestingly when the 6-t-butyl-substituted cyclohexenone derivative 17 was exposed to dibutylcuprate, followed by silylation of the resulting enolate, the cis enol ether 18 was obtained (Scheme 6.3) [8]. If, however, the cuprate addition was performed in the presence of chlorotrimethylsilane, the stereochemical outcome of the conjugate addition reaction was reversed to give trans enol ether 19. 

Although the presence of BINOL in the ligands so far discussed has shown itself to be particular effective, modification of the diol moiety provides new classes of ligands for this addition reaction. Alexakis, screening a number of chiral phosphites in the Cu(OTf)2-catalyzed 1,4-addition, showed that an ee of 40% could be obtained for the addition of Et2Zn to 2-cyclohexenone and of 65% for addition to chalcone, by using cyclic phosphites derived from diethyl tartrate [51]. 

Ss2 reaction with a,fi-epoxy ketones.6 The enolate 1 of 2,3-epoxycyclohexanone reacts with methyllithium to give, after acidic work-up, 2-methy -2-cyclohexenone (3), the product of SN2 addition. Reaction of 1 with lithium dimethyl cuprate on the other hand results in 6-methyl-2-cyclohexcnonc (2), the product of Sv2 addition. 

The photosensitized addition of 1,3-dioxolane and 1,3,5-trioxane to, alkenes was developed a number of years ago as a route to a-alkylated ethers (68JOC805). It has now been shown that 2-methyl-l,3-dioxolane will undergo a photochemically induced conjugate addition reaction to cyclohexenone to afford an adduct (327) in 54% yield which can be hydrolyzed to the diketone (328) (77CJC3986). Functionalized dioxolane (330) was also... 

Highly enantioselective Michael addition reactions of 2-mercaptopyridine (11) to 2-cyclohexenone (10) have been accomplished by treatment of the 1 1 inclusion... 

Metallodendrimer Go-20 was used as a catalyst in the 1,4-addition reaction of diethylzinc to 2-cyclohexenone in a variety of solvents. The results obtained showed that this dendritic catalyst provides activities similar to or even higher than those observed for the unsupported aminoarenethiolato copper(I) complexes, depending on the solvent used. Applying Go-20, this reaction could also be performed using a solvent as apolar as hexane, whereas the unsupported complexes are not soluble in this medium. 

Catalytic, Enantioselective Addition of Arylboronic Acids to Cycloalkenones. A complex between ligand 1 and a rhodium(I) salt was found to catalyze the asymmetric 1,4-addition reaction of arylboronic acids to cyclohexenone and cyclohep-tenone. The reaction proceeds with high enantiocontrol and excellent yields (eq 4). Lower enantiomeric excesses were observed with cyclopentenone (83% ee), but a variety of substituted phenyl-boronic acids could be used. 

The first chiral aluminum catalyst for effecting asymmetric Michael addition reactions was reported by Shibasaki and coworkers in 1986 [82], The catalyst was prepared by addition of two equivalents of (i )-BINOL to lithium aluminum hydride which gave the heterobimetallic complex 394. The structure of 394 was supported by X-ray structure analysis of its complex with cyclohexenone in which it was found that the carbonyl oxygen of the enone is coordinated to the lithium. This catalyst was found to result in excellent induction in the Michael addition of malonic esters to cyclic enones, as indicated in Sch. 51. It had previously been reported that a heterobimetallic catalyst prepared from (i )-BINOL and sodium and lanthanum was also effective in similar Michael additions [83-85]. Although the LaNaBINOL catalyst was faster, the LiAlBINOL catalyst 394 (ALB) led to higher asymmetric induction. 

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