Methylenation chemoselective

With higher alkenes, three kinds of products, namely alkenyl acetates, allylic acetates and dioxygenated products are obtained[142]. The reaction of propylene gives two propenyl acetates (119 and 120) and allyl acetate (121) by the nucleophilic substitution and allylic oxidation. The chemoselective formation of allyl acetate takes place by the gas-phase reaction with the supported Pd(II) and Cu(II) catalyst. Allyl acetate (121) is produced commercially by this method[143]. Methallyl acetate (122) and 2-methylene-1,3-diacetoxypropane (123) are obtained in good yields by the gas-phase oxidation of isobutylene with the supported Pd catalyst[144]. 

A solvent-dependent chemoselectivity, pointing to a dependence of the relative reactivities of the 1,2- and 1,1-disubstituted double bonds on solvent polarity and nucleophilicity, has been observed in the reaction of benzeneselenenyl chloride with 2-methylenebicyclo[2.2.1]hept-5-ene (159) which gives products 160-163140. In methylene chloride the reaction occurs with a moderate chemoselectivity, attack on the endocyclic bond being preferred over that on the exocyclic one in a 60 40 ratio. In methanol, the addition is completely chemoselective and the attack occurs exclusively on the endocyclic double bond (equation 132). It may be further noted that 162 and 163 isomerize and solvolyze at high temperatures, leading to the homoallylic products 160 and 161. 

In the carboxylate series, the TPA catalyst (entry 4) was the most selective for methine over methylene insertion. Should this remarkable chemoselectivity prove to be general, this complex may add a possibility for high chemoselectivity not previously observed with rhodium(ll) catalysts. The other carboxylate catalysts show less preference for CH over CH2 insertion. We expect that the CH/CH2 ratios would be more pronounced with a less carefully balanced substrate. In the carboxamidate class, MPPIM catalyst (entry 9) was more selective than the corresponding MeOX catalyst (entry 10), with the MEPY catalyst (entry 8) being the least discriminating for CH over CH2 insertion. 

One of the most impressive examples of the chemoselectivity that is possible in these C-H insertions is the reaction of ( )-silylated alcohol 33 [Eq. (17] [28]. Even though this compound contains three positions that might be expected to be susceptible to C-H insertion, only the methylene position adjacent to the N-Boc group is reactive as the other two sites are too sterically encumbered. Furthermore, this reaction is highly diastereoselective and displays a high level of kinetic resolution such that the C-H insertion product 34 is obtained essentially as a single diastereomer in 85% yield and 98% ee. 

Donor/acceptor-substituted carbenoids are usually much more chemoselective than the more established carbenoids functionalized solely with acceptor groups [lc]. The development of these donor/acceptor-substituted carbenoids has enabled enantioselective intermolecular C-H insertions to become a very practical process. These carbenoids have a strong preference for functionalizing C-H bonds where positive charge build-up at C in the transition state is favored but these electronic effects are counter-balanced by steric factors. Benzylic and allylic sites and C-H bonds adjacent to oxygen and nitrogen functionality are favored but these sites can also be sterically protected if desired. By appropriate consideration of the regiocontrolling elements, effective intermolecular C-H insertions at methyl, methylene, and methine sites have been achieved. 

Chemoselective reductions. The reactivity of NaBH4 can be decreased by use of a lower temperature or by a mixed solvent such as methanol or ethanolic methylene chloride. This simple strategy can be used to effect selective reduction of ketones in the presence of enones,1 and of aldehydes in the presence of ketones. ... 

Making the vinyllithium by a Shapiro reaction (section 8.1) from 164 bypasses the chemoselectivity problem altogether, and provides a useful cyclisation route to exo-methylene derivatives of five-, six- and seven-membered rings 165.78 The main by-products 166 are the result of protonating the vinyllithium. 

The first progress was made by Takai and Lombardo, who developed an in situ entry to titanium-alkylidene chemistry starting from the reagent combinations 5 and 6 (Scheme 4) [9]. These reactions proceed via a gem-dizinc compound 7 (its formation is catalyzed by traces of lead or lead(II) salts), which is subsequently transmetalated with TiCl4 to the titanium-alkylidene species 8, the actual olefination reagent. To date, 8 has not been characterized in detail [10]. These in situ reagents exhibit chemoselectivities similar to those of the structurally defined methylenation reagents 1-3. 

Although periodates also oxidize polycyclic aromatic hydrocarbons, phenols, hydrazines, active methylene compounds and sulfides, chemoselectivity can usually be achieved and glycol cleavage oxidation takes precedence. For example, the diol moiety in the diethyl dithioacetal derivative of o-glucose can be selectively oxidized in good yield (equation 6). In contrast, LTA is less selective dum periodate and oxidizes a far greater variety of oiganic compounds. Consequently, in order to minimize undesired reactions, it is customary to add LTA slowly to avoid contact of die initially formed products widi an excess of the oxidant (equation 7). ... 

Recently, the chemoselective addition of the a-silyimethyl anion to aldehydes has been accomplished with titanium (equation 7). In studies by Kau mann, the Grignard derivative was treated with TiCU to prepare the titanium species in situP As indicated in Table iP this reagent added in good yield to aldehydes to produce the desired methylene compounds but was ineffective for the conversion of ketones to the corresponding methylene compound. ... 

It is possible to exclusively methylenate a ketone in the presence of an aldehyde by precomplexing the aldehyde (e.g. 76) with Ti(NEt2)4, followed by treatment with the usual methylene zinc/TiCU reagent (equation 17). Takai also studied the chemoselective methylenadon of aldehydes (78) in the presence of ketones, and found the use of diiodomethane, zinc and titanium isopropoxide or trimethylaluminum to be effective (equation 18). ... 

During the total synthesis of (+)-phyllanthocin, A.B. Smith and co-workers installed the epoxide functionality chemo-and stereoselectively at the C7 carbonyl group of the intermediate diketone by using dimethylsulfoxonium-methylide in a 1 1 solvent mixture of DMSO-THF at 0 °C. The success of this chemoselective methylenation was attributed to the two a-alkoxy substituents, which render the C7 carbonyl group much more electrophilic than Cl 0. 

Alkylidenation. While methylenation of aldehydes with CHjfZnIIj proceeds smoothly, the presence of TiClj is essential for a similar reaction with ketones to give the alkenes in reasonable yields. It means that chemoselectivity is achievable by adjusting the reagent composition. 

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