Allylsilanes, Sakurai allylation reaction

The undefined mechanism of the aldol-type Mukaiyama and Sakurai allylation reactions arose the discussion and interest in mechanistic studies [143-145]. The proposed mechanism was proved to proceed through the catalytic activation of the aldehyde and its interaction with the silyl ketene acetal or allylsilane producing the intermediate. From that point the investigation is complicated with two possible pathways that lead either to the release of TMS triflate salt and its electrophihc attack on the trityl group in the intermediate or to the intramolecular transfer of the TMS group to the aldolate position resulting in the evolution of the trityl catalyst and the formation of the product (Scheme 51). On this divergence, series of experimental and spectroscopic studies were conducted. 

Sakurai allylation Reaction of allylsilanes with a variety of aldehydes and ketones in the presence of a Lewis acid. 392... 

Substituted allylsilanes are subject to ene reaction with aldehydes and a,/3-unsaturated carbonyl compounds in the presence of a Lewis acid. The Et2AlCl-promoted reaction of /3-siloxymethyl-substituted allylsilane 27 with aldehydes gives more functionalized allylsilanes (Equation (37)).148 The use of TiCU instead of Et2AlCl leads to the Hosomi-Sakurai allylation. Catalytic enantioselective carbonyl-ene reactions of methallylsilanes have been achieved by using chiral Ti and A1 complexes.149,150... 

The Lewis acidic character of reactive pentacoordinate silicon compounds has been unequivocally confirmed by Corriu, Sakurai and Hosomi [90]. Allylsilicates prepared from allylsilanes and catechol can undergo allylation reaction with aldehydes in the absence of Lewis acid promoter (Sch. 51). 

In 1976 we reported that aldehydes and ketones are efficiently allylated with allyl-trimethylsilane in the presence of a substoichiometric amount of I iLf, [332]. Subsequently, BU4NF, a fluoride ion source, was found to be an effective catalyst of this allylation reaction [333]. After these initial reports of the Hosomi-Sakurai reaction, several allylsilanes, including highly functionalized compounds, were used for regio- and stereoselective allylation of a variety of carbon electrophiles [6, 13, 14, 334]. In the nineteen-eighties, some Lewis acids (TMSOTf [335], TMSI [336]... 

The Hosomi-Sakurai-Prins reaction of the easily available enal 142 and allylsilane 143 was performed in the presence of Lewis acids to give the 4-methylene-tetrahydropyran with poor cis-trans selectivity ( 2 1), however, the pro tic acid provided only cis-144, which was converted into the aldehyde 145. The Takai iodoalkenylation, followed by desilylation and Sharpless asymmetric epoxidation, provided 146 with a 4 1 ratio of /Z, which was separable via the treatment of TBAE After protection of the primary alcohol, the alkenyllithium derived from the iodoalkene, reacted with aldehyde 147 to form 148, which was converted into epoxy-carboxylic add 149 in five steps. The key macrocyclization was performed by the treatment of 149 with Ti(Oi-Pr)4 [73] under high diluted conditions (2 mM) at 75 °C to provide the macrolactone 150 in moderate yield with 30% of the starting material recovery. After desilylation, the chemoselective oxidation of the allyl alcohol with 4-acetylamino-2,2,6,6-tetramethylpiperidine- 1-oxoammonium tetraflu-oroborate, followed by oxidative cleavage of the C20-C21 diol, produced (-)-dactyloUde (Scheme 30). 

Baba et al. found that the Sakurai-Hosomi reaction, a variant of the carbonyl allylation reaction using allylsilanes, was catalyzed by 5mol% of a InCl3-TMSCl catalytic pair [38]. Good to excellent yields of the products from the y-allylation... 

In the pioneering works by Hosomi and Sakurai, a stoichiometric or substoichio-metric amount of TiCU, a conventional Lewis acid, was used for the carbonyl allylation with allylsilanes [106]. Davis and coworkers found that TMS borates such as Me3Si[BX(OTf)3] (X = OTf, Cl) enables an efficient, catalytic Hosomi-Sakurai allylation of aldehydes although (la) and Me3SiI show low catalytic activities (Scheme 9.41) [18, 107]. Ishihara and Yamamoto have demonstrated the utility of (lb) as Lewis acid catalyst of the carbonyl allylation as well as the Mukaiyama aldol reaction [15]. The silicon Lewis acid (lb), generated in situ by the reaction of allyltrimethylsilane with HNTf2, efficiently promotes the allylation of aldehydes and ketones with a loading of 0.5 mol% (Scheme 9.41). 

CM with Allylic Compounds Allylic compounds such as allyl silanes, allyl phosphonates, allyl halides, and primary allylic alcohols are categorized as type I olefins and are used in CM reactions with various olefins for the synthesis of natural products. The CM reaction of allyl silanes has been reported to be combined with intramolecular Sakurai-type reaction for the construction of cyclic compounds.In the concise synthesis of the indolizidine alkaloid by Marsden and McElhinney, " allyltrimehylsilane (4 equiv) was employed as a CM partner of the type I olefin 80 giving rise to the desired allylsilane 81 in 73% yield as a 3 1 mixture of E- and Z-isomers (Scheme 24.21). After the... 

Sakurai reactions proceed regiospecifically with a large variety of electrophiles due to the so-called /1-effect5-9. However, allylsilanes are also known as masked allyl carbanions, which may be activated by the presence of fluoride ion10-12. 

In the synthesis of spirocyclic systems via an intramolecular Sakurai reaction, allylsilanes with an allyl moiety attached to the 3-position of the 2-cyclohexenone are required as starting materials. 

Allylation of aldehydes or ketones using allylsilanes, known as the Hosomi-Sakurai reaction, is a useful method for obtaining homoallylic alcohols. TiIV compounds have been successfully applied to this reaction (Scheme 21) 80 Besides aldehydes and ketones, acylsilanes, 0,0-acetals, and A-,(7-acetals can be employed.81-83 1,4-Addition of an allyl group to an a,/ -unsaturated ketone has been also reported.84... 

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). 

The Hosomi-Sakurai reaction is a powerful method for conjugate allylation of a,fi-unsaturated ketones [425], In the presence of TiCl4 the allylation occurs smoothly at the y-position of allylsilanes and the / -position of a, -unsaturated ketones. This highly regioselective process has been widely used for introduction of functionalized carbon chains and construction of carbocycles in natural product synthesis [6, 426]. When TBAF is used as catalyst, both conjugate addition and 1,2-addition occur competitively [333]. The fluoride ion-catalyzed procedure is, however, effec-... 

Allylsilanes have enjoyed widespread use as reagents in allyl-transposition reactions with electrophiles [i.e. ( )- (12)]. Now Sakurai et aV have found that the corresponding homoallylsilanes (13) can be used in the synthesis of cydopropyl ketones (14) from acid chlorides in the presence of Lewis acids. 

The allylation of a carbonyl compound, or equivalent thereof (aldehydes, ketones, acetals, ketals, enones, acid chlorides, epoxides, etc.), performed with an allylsilane 39 promoted by a Lewis acid (TiCl, SnCl, BF3-OEt2, AICI3, EtjAlCl, etc.) is known as Hosomi-Sakurai reaction (Scheme 12.11, Eq. 1) [68, 69]. This reaction was first described in 1976, allowing the synthesis of homoallylic alcohols 43 from aldehydes and ketones 40 [70]. A year later, the authors extended the method to ketals 41, which provide homoallylic ethers 44 (Scheme 12.11, Eq. 2) [71], and to a,p-unsaturated ketones 42 (Scheme 12.11, Eq. 3) [72]. 

Allylsilanes are intrinsically nonnucleophilic. We believe that addition of fluoride ion to an allylsilane forms a silicate anion, which can react at either end of the tc-system. Thus from a mechanistic viewpoint, substitution of an allylsilane under nucleophilic conditions is more appropriately considered an addition-elimination reaction with the terms Se2 and Se2 aptly representing the elimination process. For recent evidence of pentacoordinate silicate intermediates in fluoride ion catalyzed allylation using trimethylallylsilane, see a) M. Kira, M. Kobayashi and H. Sakurai, Tetrahedron Lett.. 28. 4081 (1987) b) M. Kira, K. Sato and H. Sakurai. J. Am. Chem. Soc.. 110, 4599 (1988) c) T. Hayashi, Y. Matsumoto, T. Kiyoi, Y. Ito, S. Kohra, Y. Tominaga and A. Hosomi, Tetrahedron Lett., in press d) H. Sakurai, Lewis Acid Character and Selective Reactions of Pentacoordinate Silicon Compounds, this volume. 

The reaction between allyl nucleophiles and aldehydes or ketones in the presence of titanium Lewis acids gives the homoallylic alcohols that are widely applicable in organic synthesis. The first allylation was reported by Hosomi and Sakurai in 1976 [69]. TiCU was utilized as the promoter to facilitate the addition of allylsilane to aldehydes or ketones. This allylation has the advantage of complete S 2-regiospecificity with regard to the allylic system. Later, Hayashi and Kumada established the acyclic stereochemical outcome of this allylation with a few electrophiles in the presence of TiCU, indicating the anti 8 2 mode of the reaction [70] (Scheme 14.15). 

The Sakurai reaction can be defined as the allylation of a carbonyl compound, or equivalent thereof, performed with an allylsilane and promoted by a Lewis acid. 

This book chapter is limited to Lewis acid-mediated reactions, and does not discuss the important field of Lewis base-mediated allylations, nor does it describe the reactions of allylsilanes with other electrophiles such as epoxides, imines, and allyl-X (X = -Cl, -OR, -OAc). The SaJcurai reaction has been covered under different forms in reviews focusing on The Stereochemistry of the Sakurai reaction , Intramolecular Addition Reactions of Allylic and Propargylic Silanes ," Selective Reactions Using Allylic Metals , Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , and Modem Carbonyl Chemistry . ... 

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. 

In conclusion, the Sakurai reaction is a powerful method to introduce a nucleophilic allyl synthon. Similar allylations include the Keck reaction of allylstannanes, and the Roush reaction of allylboranes. What sets the Sakurai reaction apart is the exceptional stability of allylsilanes, which are stable to air and water, and can easily be chromatographed, unlike most other allylmetal species. In addition, allylsilanes are easily accessible by a variety of reactions. These factors have allowed the Sakurai reaction to find widespread use, from basic methodology to total synthesis. 

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