Methylenation titanium salt

Aldehydes are methylenated by bis(iodozincio)methane (3) without the mediation of titanium salt. Commercially available Nysted reagent 1 is also effective for this transformation in this case, the addition of a catalytic amount of BF3 OEt2 improved the yield (Table l)31a c. 

TABLE 2. Titanium salt mediated methylenation of ketones with bis(iodozincio) methane (3)... 

The role of titanium salt is to activate the carbonyl compounds as Lewis acid. As described above, bis(iodozincio)methane (3) is nucleophilic enough to attack the carbonyl group of aldehydes or ce-alkoxyketones. In the reaction with simple ketones or esters, however, the addition of titanium salt is necessary to facilitate the nucleophilic attack. Instead of this Lewis acid activator, simple heating may induce the nucleophilic attack. Treatment of 2-dodecanone with 3 without titanium salt at higher temperature, however, does not improve the yield of alkene (Scheme 13). The reason for the low reactivity of 3 at higher temperature comes from the structural change of 3 into the polymeric methylene zinc 4 through the Schlenk equilibrium shown in equation 740. 

ALKENES Dimethyl(methylene)-ammonium salts. Methylene bromide-Zinc-Titanium(IV) chloride. Methylene bromide-Zinc-Trimethylaluminium. 

Sharpless epoxidation of allyl alcohols (Sharpless, 1985, 1988 Pfenninger, 1986 Rossiter, 1985 Woodard et al., 1991 Finn and Sharpless, 1991 Corey, I990a,b), an example of which is included in Table 9.6, is perhaps the most recent and one of the most remarkable applications of asymmetric catalysis. The reaction is normally performed at low temperatures (-30 to 0°C) in methylene chloride with a titanium complex consisting of a chiral component [diethyl tartrate (DET) or diisopropyl tartrate (DIPT)] and a titanium salt (titanium tetraisopropoxide) as the catalyst. The beauty of the synthesis is that both enantiomers of the tartrate are available so that either form of the product can be prepared in more than 90% ee. 

Methylenation reactions of ketones with 4 required the addition of a titanium salt. As shown in Table 5.2, 2-dodecanone was treated with bis(iodozincio)methane 4 in the presence of various titanium salts. Titanium chloride, yS-TiCb, prepared from titanium(IV) chloride and hexamethyldisilane by following Girolami s procedure [21], was shown to be the most effective. This report by Girolami corrected an earlier report by Naula and Sharma, in which it was erroneously claimed that TiGl2 was formed from the reaction of titanium(IV) chloride with hexamethyldisilane... 

The problem about the aging period for preparation of reactive species 3, argued by Lombardo, should not be attributed only to the formation of gem-dizinc species. As titanium(IV) chloride is also reduced with zinc powder, [17] the titanium salt that works as a mediator would be the low-valent one. The reduction process of titanium(IV) may also sometimes cause the problem of reproducibility of methylenation reaction. In 1998, Matsubara and coworkers reported a general... 

As shown in Scheme 8.14, various ketones were converted into alkenes in good to moderate yields by i ts(iodozincio)methane (4)/ [bmim] [PF ]. Instead of 4, Nysted reagent was also examined for the methylenation of 2 in the presence of ionic liquid, but did not give the corresponding alkene. Although the titanium salt is still the best additive for the effective methylenation of ketones with 4, use of an ionic liquid shows the new possibility for an activation of gem-dizinc reagents [27]. 

The substrate itself also activates the reagent 4. Alkoxy group at a-position of ketone will form a chelate intermediate that activates the f)is(iodozindo)methane to react with carbonyl group of ketone. Such substrates with 4 undergo methylenation in the absence of any additive. As shown in Scheme 8.15, a substrate that has a-benzyloxyketone and simple ketone groups in the same molecule can be converted into the chemoselective methylenated product. In the methylenation reaction, activations of bis(iodozindo)methane (4) have been done with titanium salt, a-alkoxy group of ketone, THT, or ionic liquid. This means that the readivity of 4 can be tuned to perform a seledive methylenation. In Scheme 8.16, a keto alkanal and a keto ester were examined for the chemoseledive methylenation [18,23,27]. 

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. 

The titanium carbene complex TiCl2[C(Ph2P=NSiMe3)2] has been synthesized by metathetical reaction of the dilithium bis(phosphoranimine) salt with TiCl4 (Scheme 107).215 In this bis(iminodiphenylphosphorano)methylene... 

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