Conjugate additions polar

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

Carbon-Carbon Bond-Forming Reactions TABLE 9.30. POLAR CONJUGATE ADDITION REACTION ... 

Using these optimized conditions, the conjugate addition of 45 to the malonates 49 in the presence of the solid base provided access to the Michael adducts in good yields and high diastereoselectivities. The removal of the chiral TADDOL auxiliary could be accomplished without epimerization or racemization in this case, too. After esterification of the very polar acid intermediates with diazomethane the corresponding dimethyl esters 52 were obtained with yields of 72-94% and enantiomeric excesses ee of 84-94% (Scheme 1.1.13). 

Table 1, a kinetic study suggested both polar and homolytic mechanisms for conjugate addition, depending on the substrate and the substrate conformation . ... 

The first examples of nitrofluorination of alkenes were demonstrated by the reaction in a solution of 10% nitric acid in hydrogen fluoride at — 10 C.204 Further investigation has shown that the rate of this conjugate addition is determined predominantly by the nature of the tr-bond (electron density, polarity).205 As a rule, the reaction is carried out at temperatures between - 60 C (i.e., 1,1-dichloro-or 1,1-difluoroethene) and + 20 C. However, nitrofluorination of hexafluoropropene is only successful at higher pressure and temperature, i.e. if the alkene rc-bond is less polar the regioselectivity of the addition is also unsatisfactory,205 e.g. reaction of 1 and 2.206... 

The effect of a remote substituent on the facial selectivities in a nucleophilic conjugate addition has been investigated for the reaction of EtSH with a series of dibenzobicyclo[2.2.2]octatrienes (84). Syn-addition proved to be favoured for nitro substituent and polar solvents increased the selectivity (Table 5).19... 

The simplest way to make such a derivative is to treat a 3-halocarbonyl compound 59, easily made from the enone 58 by conjugate addition, with zinc metal to give a species that we might write as 60 but perhaps should be 61 or even 62. Whichever is correct, it is nucleophilic at the (3-carbon atom and the polarity of the enone 58 has been reversed. 

At least 19 has the natural polarity of the enone but conjugate addition would lose the alkene so we need to add a leaving group at the site of the plus charge 22. One possibility is an enol ether 23 as these are easily made from 1,3-diketones 24 and a suitable alcohol. 

The choice of solvent and temperature also plays a significant role in the selectivity between the formation of 96 and 98 in the reaction between the 2,5-dimethylpyrrole complex 22 and MVK (Table 7). For polar aprotic solvents such as acetonitrile or DMF, an approximate 1 1 ratio of the two products is obtained, while in protic solvents such as methanol or water, the formation of conjugate addition products is favored. 

Vaupel and Knochel developed sequential nickel(0)-catalyzed radical 5-exo cyclizations of allylic bromo- or iodoacetaldehyde acetals 67, which were followed by polar alkylation, acylation, or conjugate addition reactions providing functionalized butyrolactols 69 (Fig. 15) [106-108]. Cyclization precursors 67 are... 

A special case of conjugate addition involves diaryl ketones. As noted in Section 4.2, conjugate addition of organomagnesium compounds may lead to products formally derived from addition to a ring. Such reactions are favoured by conditions promoting electron transfer, particularly when polar addition to the carbonyl group is sterically hindered [3]. 

Michael addition of ketene sUyl acetals. TASF catalyzes the conjugate addition of ketene silyl acetals to enones in THF at room temperature. A similar addition can be effected without a catalyst in a polar solvent, acetonitrile at 55° (ref. 2) or CH,NO, at 25°, in the case of some less hindered ketene silyl acetals. The addition shows no dia-stcreoselection. The adducts can be alkylated to provide 2,3-disubstitutcd cycloalkanoncs as a 1 1 mixture of two diastereomers (both probably Irons). 

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