Peterson methylenation

Peterson methylenation (10, 433 11, 581). Methylenation with trimethyl-silylmethyllithium, (CH3),SiCH2Li, is not widely used in synthesis because of lack of selectivity and moderate yields. However, a modified reagent prepared from (CH3)3SiCH2Li and CeCl, adds to aldehydes or ketones (even enolizable ones) to form adducts in generally high yield, particularly in the presence of TMEDA. The 2-hydroxysilanes are converted into methylene compounds by aqueous HF (with or without pyridine).4... 

The most prevalent applications of the Peterson methodology are with the readily available lithium or magnesium anions, which have similar reactivity with both aldehydes and ketones. Recent examples of the Peterson methylenation in organic synthesis are presented in Table 1. 

In addition to the examples in Table 1, the Peterson methylenation has been used in several interesting natural product syntheses, as the examples in equation (2)-(6) indicate. Danishefsky and coworkers used the Peterson reaction in an approach to mitomycins (4 equation 2). This tq>plication demonstrated the use of unique elimination conditions. The hydroxysilane intermediate was stable to direct Peterson elimination. Therefore, the removal of the silyl protecting group and the elimination of the silyloxy group were carried out with DDQ in quantitative yield. 

Further examples of the Peterson methylenation successfully being applied when other techniques failed are shown in equations (S) and (6). In the synthesis of bicyclomycin, a diazabicyclodecane dione. 

Johnson has studied the cerium modification of the Peterson methylenation. (Trimethylsilyl)methyl-lithium was added to CeCh and the addition carried out in the presence of TMEDA (equation 8). The cerium lithium reagent proved to be superior to the lithium, magnesium or cerium magnesium mixed... 

In direct analogy to the Peterson methylenation, the triaryl- and trialkyl-stannylmethyllithiurn reagent (91) can be added to aldehydes and ketones (90), followed by elimination of the hydroxystannane (92) to obtain the methylene derivative (93 Scheme 20). This reaction, like the titanium and cerium modifications of the Peterson methylenation of Kaufmann and Johnson, may prove advantageous, in comparison to the Wittig reaction, for enolizible substrates. 

The Peterson methodology has seen wide application in the synthesis of carbohydrates. The preparation of 3-C-methylene sugars (6) was demonstrated by Carey and coworkers, with the methylenation proceeding without elimination of the anomeric alkoxy group (equation 3). A more recent example of Peterson methylenation of a carbohydrate is the synthesis of a deoxyamino sugar (8) by Fraser-Reid (equation 4). In this case, the carbonyl failed to react with the methylenetriphenylphosphorane at room temperature, and forcing conditions resulted in decomposition. Application of the Oshima-Takai-Lom-bardo method also failed. The Peterson reagent added in excellent yield, and the elimination resulted in the formation of the desired methylene (8a) as well as the vinylsilane (8b). 

Nafion resins have been used not only for the opening of epoxides but also for their isomerization to aldehydes or ketones [137]. Various other rearrangements and isomerizations are catalyzed by this solid acid, in some cases with selectivities higher than those obtained with other solid catalysts [138-140]. Other reactions that have been studied include the Peterson methylenation of carbonyl compounds [141], hetero-Michael additions to unsaturated ketones [142], the Koch-type carbon-ylation of alcohols to form carboxylic acids [143], dimerization of a-methylstyrene [144], addition of carboxylic acids to olefins [145] and Diels-Alder reactions [146]. Notably, in most cases, reutilization of the catalyst is considered but only after an appropriate washing protocol to regenerate its acidity/activity. 

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