Titanium tetrachloride allylsilane reactions

Another study by Fleming and coworkers examined the stereoselectivity of the titanium tetrachloride catalysed reaction of the allylsilane 137 with 1-adamantyl chloride... 

Conventional synthetic schemes to produce 1,6-disubstituted products, e.g. reaction of a - with d -synthons, are largely unsuccessful. An exception is the following reaction, which provides a useful alternative when Michael type additions fail, e. g., at angular or other tertiary carbon atoms. In such cases the addition of allylsilanes catalyzed by titanium tetrachloride, the Sakurai reaction, is most appropriate (A. Hosomi, 1977). Isomerization of the double bond with bis(benzonitrile-N)dichloropalladium gives the y-double bond in excellent yield. Subsequent ozonolysis provides a pathway to 1,4-dicarbonyl compounds. Thus 1,6-, 1,5- and 1,4-difunctional compounds are accessible by this reaction. 

Titanium tetrachloride promoted a three-component cyclization involving a carbonyl compound, an allylsilane, and an acetal, as shown in Eq. (69) [188]. The reaction was initiated by allyl addition to the aldehyde this was followed by acetal exchange and intramolecular Friedel-Crafts-type alkylation of the olefinic moiety. 

In the absence of Lewis acids, allylsilanes react only with very electrophilic ketones like hexafluo-roacetone, when they undergo ene reactions rather than electrophilic replacement of the silyl group. In the presence of Lewis acids, allylsilanes react with aldehydes and ketones with clean allylic transposition (Scheme 1) and the formation of homoallylic alcohols. The range of Lewis acids used is wide, but titanium tetrachloride and boron trifluoride etherate are the most common. Typically, reaction takes place somewhere between -78 °C and 0 C in dichloromethane solution, and a molar proportion of Lewis acid is used. 

Acetals and ketals are exceptionally good electrophiles for allylsilanes, often giving better yields than the corresponding aldehyde or ketone, because the products are less prone to further reaction. Typically the reactions are catalyzed by stoichiometric amounts of titanium tetrachloride in dichloromethane at -78 °C, and the regiospecific reaction is complete in a few minutes (Scheme 37). Other Lewis acids used are boron trifluoride etherate, tin(IV) chloride and, in catalytic amounts, trimethylsilyl tri-flate, - trityl perchlorate and montmorillonite clays. With the unsymmetrical acetal (53), the meth-oxyethoxy group departs selectively (Scheme 38), presumably because it chelates the Lewis acid. ... 

Lewis acids used for acylation of allylsilanes with acid chlorides include titanium and tin tetrachlorides, aluminum, gallium and indium trichlorides and zinc dichloride, and boron trifluoride for reactions with acid anhydrides. Although gallium and indium chlorides have been used successfully in catalytic (ca. 2 mol %) amounts, most frequently aluminum chloride has been used as catalyst, with titanium tetrachloride also commonly employed, both in molar quantities. With these catalysts, acylations can often be carried out at low temperatures, and with short reaction times. 

The reaction of acetals and ketals with enol silyl ethers, usually catalyzed with the more traditional Lewis acids such as boron trifluoride etherate or titanium tetrachloride, can be carried out with trimethylsilyl triflate catalysis50. In the example shown in equation 42 the resulting allylsilane was annulated with titanium tetrachloride. 

Although the direct generation of titanium enolates is typically the most useful method of generating titanium enolates for aldol reactions, other methods have been described. Grubbs and Stille reported that titanium enolates could be generated by reaction of biscyclopentadienyltitanium al-kylidene complexes and acyl halides [93]. Oshima and coworkers reported the formation of titanium enolates from a-iodoketones with allylsilane and titanium tetrachloride [94]. Mukaiyama and coworkers reported the generation of titanium enolates from a-bromoketones on treatment with TiCh and copper powder [95]. 

In 1976, Akira Hosomi and Hideki Sakurai of Tohoku University in Sendai, Japan, published a letter entitled Syntheses of y,S-Unsaturated Alcohols From Allylsilanes And Carbonyl Compounds In The Presence of Titanium Tetrachloride"The letter describes the reaction depicted in equation 1, in which allyl silanes react with aldehydes or ketones to provide homoallylic alcohols. The following year, Hosomi and Sakurai extended their finding to ketals, which provide homoallylic ethers (eq. 2)," and to a,P-unsaturated ketones (eq. 3), in which case the addition occurs in a 1,4-fashion and becomes a valuable method to generate quaternary centers. 

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