1,4-addition reactions to enone

The copper)I) arenethiolate complexes 19 [30], first developed and studied by van Koteris group, can be used as catalysts for a number of copper-mediated reactions such as 1,4-addition reactions to enones [31] and 1,6-addition reactions to enynes [32]. 

Although lower-order cuprate reagents will often engage in displacement reactions with alkyl halides, such reactions are usually slow. They are generally much less facile than 1,4-addition reactions to a,P-unsaturated enones or enoates. The latter processes are particularly facile when trimethylsilyl chloride is employed as an additive. It was Corey and Boaz10 who first recognised the accelerating effect of trimethylsilyl chloride on cuprate addition reactions to a,p-unsaturated carbonyls. Buszek therefore capitalised on Corey s earlier observations in his reaction of 10 with lithium dimethylcuprate to obtain 15. 

Most recently, B-halo-l-alkenyl-9-BBN s have revealed to undergo a 1,4-addition reaction to ae,P-unsaturated ketones such as methyl vinyl ketone. Hydrolysis of the initially formed intermediates produces the corresponding (Z)-5-halo-y,5-unsaturated ketones in good yields stereospecifically (>98%),88). In the reaction with methyl vinyl ketone, the major products isolated after hydrolysis are not the expected halo-enones but the aldol adducts, which are readily converted into the halo-enones by treatment with sodium hydroxide, as depicted in Scheme 3. No aldol adducts are formed in the case of enones other than methyl vinyl ketone. 

The addition of the anions of racemic cyclic allylic sulfoxides to various substituted 2-cyclopentenones gives y-l,4-adducts as single diastereomeric products22. The modest yields were due to competing proton-transfer reactions between the anion and enone. The stereochemical sense of these reactions is identical to that for the 1,4-addition reaction of (Z)-l-(/erf-butylsulfinyl)-2-methyl-2-butene to 2-cyclopentenone described earlier. 

Acyclic Enones as Substrates Compared to cyclic enones, acyclic enones are generally more challenging substrates for the copper-catalyzed asymmetric 1,4-addition reactions. Several ligands have been reported that can achieve high ee when p-aryl acyclic enones are used as substrates in the 1,4-addition of diethyl-zinc (Figure 3.5). ° ... 

Following the initial work by Hayashi and Miyaura using (5)-binap, several other chiral ligands were reported to achieve high enantioselectivity in the rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to ot,p-enones (Figure 3.18). A polymer-supported (X)-binap analog 42 was also synthesized and it was successfully utilized in the rhodium-catalyzed asymmetric 1,4-addition reactions in water (Figure 3.19)." The stereoselectivities observed in this system are comparable to those obtained in the unsupported Rh/(5)-binap system. It was also... 

For examples of the rate-increasing effect of NMP in 1,4-addition reactions of R2Zn to enones, see ... 

The choice of the organometallic nucleophile (Zn, B, or Si) has been shown to facilitate the straightforward conversion of enone (195) into the opposite diastereoisomers g) of 2-substituted pyrrolizidinones (196)/(197) via the rhodium-catalysed 1,4-addition reaction.244... 

In a similar fashion, diastereoselective addition of the vinylcuprate 103 to the glyceraldehyde-derived enone 102 was used for the construction of the precursor 104 of iso[7]-levuglandin D2.92 Besides enones and enoates, heteroatom-substituted nitroolefins and a,/3-unsaturated phosphine oxides also participate in diastereoselective copper-mediated 1,4-addition reactions.93,93 1,938... 

A similar bidentate ligand containing a ferrocenyl bridge between two BINOL moieties was described by Reetz and co-workers. Copper-catalyzed 1,4-addition reactions of diethylzinc to cyclohex-2-enone and cyclohept-2-enone in... 

The metal-catalyzed addition reaction of organoboron compounds have not yet been well developed, but die reaction of NaBPh4 or arylboronic acids with enones in the presence of Pd(OAc)2 and NaOAc or SbCL, was recently reported by Uemura and his coworkers.2 The reaction was proposed to proceed through the oxidative addition of the C-B bond to the Pd(0) species however, another probable process, the transmetalation to transition metals, may allow a similar catalytic transformation by the use of organoboronic acids. We report here the 1,4-addition reaction of organoboronic acids to oc, J-unsaturated ketones or esters and 1,2-addition to aldehydes or imines catalyzed by a (acac)Rh(CHj=CH2)2/phosphine complex, which may involve the B-Rh transmetalation as the key step. 

The 1,4-addition reaction of stabilized allylic carbanions with conjugated enones is normally complicated by the ambident reactivity of the carbanion. Clean 7-selective conjugate addition to cyclic enones, however, has been observed with lithiated allylic sulfoxides, phosphine oxides and phosphonates... 

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