Additive aldol reaction

Recently, the Texier-Boullet group [26] has prepared nitrocyclohexanols 10-77 by a twofold Michael addition/aldol reaction sequence (Scheme 10.19). Simply mixing chalcone 10-75 with nitromethane in the presence of a mixture of KF and A1203 under microwave irradiation gave 10-79 via the proposed intermediates 10-76, 10-77 and 10-78 as a single diastereomer in 65 % yield. One possible explanation for the stereoselectivity of the transformation is fixation of the reactive species onto the solid KF/A1203, as depicted in 10-79. 

Several attempts to take advantage of the intermediate boron enolate to achieve tandem conjugate addition-aldol reaction have been proposed [71]. Recently, Chandrasekhar [72] reported the addition of triethylborane to methyl vinyl ketone followed by the in situ trapping of the enolate by aromatic aldehyde (Scheme 26). 

Scheme 26 Tandem conjugate addition-aldol reaction...

Tandem addition-aldol reaction with methyl propiolate... 

Scheme 7.14. Enantioselective tandem conjugate addition-aldol reactions.

Very recently, a catalytic enantioselective route to prostaglandin i methyl ester was developed based on a tandem 1,4-addition-aldol reaction [84]. 

Subsequent ion exchange of the metal cation with the quaternary ammonium ion catalyst provides a lipophilic ion pair (step 2), which either reacts with the requisite alkyl electrophile at the interface (step 3) or is partitioned into the electrophile-containing organic phase, whereupon alkylation occurs and the catalyst is reconstituted. Enantioselective PTC has found apphcation in a vast number of chemical transformations, including alkylations, conjugate additions, aldol reactions, oxidations, reductions, and C-X bond formations." ... 

Krische reported an intramolecular version of the tandem conjugate addition-aldol reaction. The reaction of enone-ketone 58 with phenylboronic acid 2 m occurs in diox-... 

The three-component method is applicable to the synthesis of various C(6)- or C(7)-functionalized PGs. Scheme 11 illustrates the tandem conjugate addition-aldol reaction that affords 7-hydroxy-PGE derivatives (18). Both saturated and unsaturated C7 aldehydes can be used as a side-chain units. The aldol adducts can be transformed to naturally occurring PGs (5a, 19) and, more importantly, to a variety of analogues such as tumor-suppressing A7-PGA, (20) or 7-fluoro-PGI2, a stabilized prostacyclin (21). The unique cellular behavior displayed by A7-PGA methyl ester is well correlated to its chemical reaction with thiols (20). 

Conjugate addition-aldol reactions. A novel synthesis of a-substituted a,(3-enones involves conjugate addition of 1 to an a,p-enone the resulting 0-phenyl-selenoboron enolate undergoes aldol condensation with aldehydes. The adduct on oxidative elimination furnishes unsaturated p-hydroxy ketones.1 Example ... 

In another study Feringa et al. [20] reported a catalytic enantioselective three-component tandem conjugate addition-aldol reaction of dialkyl zincs. Here, zinc enolates were generated in situ via catalytic enantioselective Michael addition of dialkylzinc compounds to cydohexenone in the presence of a chiral Cu catalyst. Their diastereoselective reaction with an aldehyde then gave trans-2,3-disubstituted cyclohexanones in up to 92% yields and up to >99% ees (Scheme 9.11). 

Scheme 9.11. Catalytic enantioselective tandem conjugate addition-aldol reaction of dialkylzincs.

Naphthoquinone and 2-acylbenzenethiols react by sequential conjugate addition, aldol reaction, and atmospheric oxidation to produce 1277-benzo[3]thioxanthene quinones 423. The exact conditions required depend on the nature of the thiol, but are quite mild (Equation 123) <2004BCJ2095>. 

A remarkable example of tandem conjugate addition-aldol reaction has been recently reported by Tomioka and coworkers. The transient lithium enolate, generated by 1,4-addition of benzyl lithium thiolate onto the corresponding a,-unsaturated ester182,595, is followed by an intramolecular aldol tandem cyclization, resulting in a five-membered... 

Diastereoselective addition aldol reaction with (A)- HYTRA ... 

A general two-step synthesis of arylnaphthalenes from 0-/-butyldimethyl-silylcyanohydrins involving a tandem conjugate addition-aldol reaction, followed by... 

Acetylallene Is a valuable starting material in a,p-unsaturated y-lactones synthesis the tandem nucleophilic addition-aldol reaction of 1, iodide ion and aldehydes gives 3-iodohomoallylic alcohols in good yields, which can be further... 

---