And the Sakurai reaction

LiC104 was shown to be a more compatible Lewis acid for chelation in an ethereal solvent—when TiCU, a typical chelation agent for a-alkoxyaldehydes, was used in EtaO for alkylation of 79, moderate diastereoselectivity (68 32) was obtained. Rapid injection NMR studies of the TiCU-promoted chelation-controlled Mukaiyama aldol reaction and the Sakurai reaction show that an acyclic transition state must be involved in which the silyl groups never reach the carbonyl oxygen atom. In LPDE-mediated enolsilane additions silylated products predominate. Obviously, the mechanism is different—it is a group-transfer aldol reaction [107]. 

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. 

Entries 4 and 5 are examples of use of the Sakurai reaction to couple major fragments in multistage synthesis. In Entry 4 an unusual catalyst, a chiral acyloxyboronate (see p. 126) was used to effect an enantioselective coupling. (See p. 847 for another application of this catalyst.) Entry 5 was used in the construction of amphidinolide P, a compound with anticancer activity. 

The bromoallene (-)-kumausallene (62) was isolated in 1983 from the red alga Laurencia nipponica Yamada [64a], The synthesis of the racemic natural product by Overman and co-workers once again employed the SN2 -substitution of a propargyl mesylate with lithium dibromocuprate (Scheme 18.22) [79]. Thus, starting from the unsymmetrically substituted 2,6-dioxabicyclo[3.3.0]octane derivative 69, the first side chain was introduced by Swern oxidation and subsequent Sakurai reaction with the allylsilane 70. The resulting alcohol 71 was protected and the second side chain was attached via diastereoselective addition of a titanium acetylide. The synthesis was concluded by the introduction of two bromine atoms anti-selective S -substitution of the bulky propargyl mesylate 72 was followed by Appel bromination (tetrabromo-methane-triphenylphosphine) of the alcohol derived from deprotection of the bromoallene 73. 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

As with allylsilanes, increased steric hindrance at silicon favours annulation (equation 105)172 rather than the Sakurai reaction (equations 103 and 104). 

The ene reaction is the major side reaction in the Sakurai-Hosomi coupling reaction. Thus, treatment of 221 with carbonyl or with azo compounds in the presence of TiCl2(OPr-/)2 furnishes a mixture of ene-type product 222 and the Sakurai-Hosomi-type product 223 (equation 182)327. Allylsilylation of alkenes328 and alkynes329-330 proceeds regioselectively to give 224 (equation 183) and 225 (equation 184), respectively when aluminum catalysts are used. 

Since the 1980s, chemists have attempted to develop novel Lewis acids and Lewis bases able to catalyze the Sakurai reaction with full diastereo- and enantiocontrol. A review by Denmark and Fu [19] summarizes the most recent advances in this area. Thus, we will not discuss these aspects of the Sakurai reaction but shall focus our attention on the one-pot three-component synthesis of homoallylic alcohols and ethers. 

Sakurai reaction (7, 371)/ BlumcnkopI and Hcathcock have examined the ster-etKhcmistry of the Sakurai reaction and of the Ji-n-alkyl cuprate addition as applied to 4- and 5-methylcyclohexcnones. The stercoselcciivity of the former reaction can be higher than that of the latter reaction, and can even be in a different sense. 

These results can be explained in terms of an interplay of stereoelcctronic and steric factors. Steric factors are evidently more important in the reaction of bulky cuprate clusters than in the Sakurai reaction. Thus stereoelcctronic factors predominate in the allylsilanc reaction. Similar effects are observed in conjugate additions to substituted cycloheptcn-ones. 

Yamamoto, Y., Sasaki, N. The stereochemistry of the Sakurai reaction. Stereochemistry of Organometallic and Inorganic Compounds 1989, 3, 363 1. 

Hollis, T. K., Robinson, N. p., Whelan, J., Bosnich, B. Homogeneous catalysis. Use of the TiCp2(CF3S03)2] catalyst for the Sakurai reaction of allylic silanes with orthoesters, acetals, ketals and carbonyl compounds. Tetrahedron Lett. 1993, 34,4309-4312. 

Polla, M., Frejd, T. Lewis Acid-induced alkoxyalkylation of aiiyisiianes with acetals (the Sakurai reaction) regio- and stereochemical aspects. Acta Chem. Scand. 1993,47, 716-720. 

The complex [Cp 2Ti(F[20)2](CF3S03)2 is an efficient catalyst for the Diels-Alder reaction even when water is present, while Cp2Ti(CF3S03)2 is an efficient catalyst for the Diels-Alder and Mukaiyama reactions1560 as well as for a variety of reactions between allylic silanes and orthoesters, acetals, ketals, aldehydes, and ketones for the Sakurai reaction.1561... 

An example of attaching a carbon nucleophile to an o, j8-unsaturated ketone is the Sakurai reaction. This involves the reaction of allyltrimethylsilane with an a,fi-unsaturated ketone to form a -unsaturated ketone in the presence of a Lewis acid. Howarth used indium(iii) chloride to catalyze this reaction in the ionic liquids [BMIM][BF4] and [BMIM][PF6] [207]. An example ofthis is shovm in Scheme 5.2-83. 

An intermolecular version of the Sakurai reaction has been developed. It proceeds at temperatures as low as —78°C, using substoichiometric amounts of the Lewis acid, to form five-or six-membered oxygenated heterocycles from cyclic allylsilox-anes and aldehydes through a chairlike transition state (eq 65). Acetals may also act as electrophiles in this kind of reaction. /3-Borylallylsilanes also undergo nucleophilic allylation to lead to the preparation of functionalized alkenylboranes, which may participate in further transformations. ... 

If the aldehyde carries a chiral a-methyl group, as in 50, the major product is the syn-syn adduct, in accordance with the Cram and Felkin-Anh model (Table 4). For a reminder of the Cram and Felkin-Anh rules, see The Sakurai reaction . 

For some reviews about S akurai reaction, see (a) Y. Yamamoto, N. Sasaki in Chemical bonds—better ways to make them and break them (I. Bernal, Ed.). Elsevier, Amsterdam, The Netherlands, 1989, pp. 363 441. The stereochemistry of the Sakurai reaction, (b) D. Schinzer, Synthesis 1988, 263-273. Intramolecular addition reactions of allylic and propargylic silanes, (c) Y. Yamamoto, N. Asao, Chem Rev. 1993, 93, 2207-2293. Selective reactions using allylic metals. 

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