Sakurai condensation

In 1991, Marko and Mekhalfia [23] employed the readily available trimethylsilyl-triflate (TMSOTf) as the catalyst and decided to call this reaction SMS for silyl-modified Sakurai condensation. Carbon tetrachloride appeared to be the best solvent and the presence of two chlorine atoms at the ortho,ortho positions of the aromatic ring provided good selectivity (Scheme 13.21). 

The intramolecular Sakurai condensation (IMSC) can be considered as one of the most powerful synthetic tools for the stereocontrolled construction of polysubsti-tuted tetrahydropyran rings [48-50]. Using this methodology, the synthesis of five- [51-54] or seven-membered [55, 56] rings, their nitro analogues [57, 58] and spiro [59] compounds is possible. 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

H. Ohta, T. Sakurai, S. Okubo, M. Saruhashi, T. Kunimoto, Y. Uwatoko, and J. Akimitsu, Journal of Physics-Condensed Matter, 2002,14,10637. 

A nearly fully ordered polysilane copolymer has been synthesized by careful condensation of a 1,3-dibromotrisilane, yielding the AABAAB-type copolymer shown in equation (30).118 The best method for obtaining ordered polysilane copolymers is however by the anionic polymerization of masked disilenes (Section 5.3.3). Formation of an ABAB-type copolymer is illustrated in equation (31).119 These polymers show only two narrow lines in their 29Si NMR spectra, consistent with their ordered structure. In a similar reaction, the Sakurai group synthesized an exactly alternating polysilastyrene polymer, (PhMeSi-SiMe2) .120... 

Sakurai et al. reported the condensation of allylsilane 1 with acetals [8], leading to the preparation of homoallylic ethers 15 (Scheme 13.6). The reaction occurs at —78 °C, in dichloromethane. The yields are usually excellent, even though the condensation is slower than with aldehydes and ketones. 

At the end of his review [7] dealing with the acetalization of carbonyl compounds, Sakurai reported a previously unpublished observation. In the presence of catalytic amounts of iodotrimethylsilane and one equivalent of tetramethoxysilane 38, allyl-trimethylsilane 1 underwent smooth condensation with benzaldehyde 39, leading to adduct 41 in good yield. The silyl-modified Sakurai reaction was born (Scheme 13.15). 

In summary, the SMS reaction is a truly efficient process, possessing a broad scope and applicable to a number of carbonyls, allylsilanes, alcohols (silyl ethers) or amines. Its usefulness has been validated in several total syntheses and demonstrated by the preparation of chiral homoallylic alcohols. During the development of the SMS reaction, Melkafia and Marko [48] realized that the homoallylic alcohol (ether), if connected to an allylsilane, would form novel annelating agents that would lead to tetrahydropyran derivatives via condensation with carbonyl compounds. This reaction was called IMSC for intramolecular Sakurai cydization and will be discussed in the next section. 

Nowadays, the intramolecular Sakurai cyclization stands as one of the most suitable methodologies for the assembly of such subunits [62-64], However, in 1991, when Marko et al. [48] initially published the TMSOTf-catalyzed condensation (ISMS) of aldehyde 105 with TMS-ether 106a, the results of this reaction were far from perfect (Scheme 13.40). Indeed, this condensation resulted in the formation of three products. Surprisingly, not only the expected product 107 was formed, but the isomerized adducts 108 and 109 were also present in the reaction mixture. 

A related coupling reaction is the condensation of aldehydes with alkyl trichlorotitanium compounds (RTiCl3). When methyltrichlorotitanium (MeTiCl3) was coupled with aldehyde 468 in dichloromethane at -78°C, a 91 9 mixture of 470/471 was formed via the chelated complex 469. Sakurai and co-worker had previously noted the coupling of allylsilanes to aldehydes in the presence of TiCl4.305... 

Like Sakurai s general introduction to quantum theory [45], this advanced volume also offers plenty of insight condensed into a single volume. It can be warmly recommended. 

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