Sakurai-Hosomi allylation, aldehydes

Most desirable, however, would be chiral catalysts for the addition of the more readily available and less toxic allyl silanes, but so far the efforts towards an enantioselective variant of the Sakurai-Hosomi reaction have been less successful. Some time ago Ketter and Herrmann [3a] obtained 24 % ee for the addition of allyl silane to aldehydes catalyzed by the dichlorotitanate 1. 

Better results (80 % ee) have been reported by Mikami, Nakai and co-workers [3c] for the addition of crotyl silane also catalyzed by complex 1. Yamamoto and co-workers [3b] used chiral acyl-oxy boranes to catalyze the Sakurai-Hosomi-reac-tion. While an excellent 96 % ee was obtained for the addition of 2,3 -disubstituted allyl groups, the conversion with parent allyl silane was low (46 %) and the asymmetric induction mediocre (55 % ee). Gauthier and Carreira [5] then made a big leap forward by using the difluorotita-nium-binaphthol complex 3. The catalyst 3 is prepared in situ via the TiF4-binaphthol adduct 4 and formal HF elimination mediated by allyl silane 5. The addition of 5 to aldehydes 6 ( 7) catalyzed by 10 % of 3 proceeds with 61 - 94 % < e and good yields (69-93 %), the best results being observed for aldehydes with tertiary alkyl residues (Scheme 1). 

The CAB 2 catalyst has powerful activity in the Sakurai-Hosomi allylation of aldehydes and gives homoallylic alcohols in excellent enantiomeric excess (Eq. 66) [49a]. 

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). 

Asymmetric allylation is a valuable method for constructing chiral functionalized structures, and therefore many chiral allylmetal reagents directed toward a high level of asymmetric induction have been designed and synthesized. Although some of them have exhibited good to excellent enantio- and diastereoselectivities in reactions with achiral aldehydes, Yamamoto et al. developed the first method for a catalytic process in 1991 [43a]. CAB 3a has a powerful activity in the Sakurai-Hosomi allyla-... 

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). 

With this strategy in mind, Keck s construction of the 2,6-cii-tetrahydropyran unit commenced with the asymmetric allylation [185] of aldehyde 2.275 with allystannane 2.276 promoted by BEMOL titanium tetraisopropoxide (BITIP) to furnish the homoaUyl alcohol 2.274 (95 %, 95 % ee) [186]. The formation of the key 2,6- s-tetrahydropyran 2.277 was accomplished by the Hosomi-Sakurai-Prins cychzation in the presence of TMSOTf in 85 % yield as a single diaste-reomer. SUyl deprotection and oxidation, followed by Homer-Wadsworth-Em-mons olefination proceeded to provide 2.278, which was further elongated to the phosphonoacetate 2.279. Exposure of the resulting phosphonoacetate to NaHMDS after desilylation and subsequent oxidation afforded the macrocycle 2.280 via the Homer-Wadsworth-Emmons olefination protocol. 

More than a decade ago, Yamamoto and coworkers demonstrated that the chiral acyloxyborane (6) is an excellent catalyst for the Sakurai-Hosomi allylation of aldehydes to furnish the homoallylic alcohols in good yields and enantioselectivities (Equation 60) [59]. This system remains to date, the most effective catalytic enantioselective allylation of aldehydes based on boron Lewis acids. 

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... 

At the same time, Sakurai and Hosomi [6] extended this reaction to a wide range of non-activated carbonyl compounds 6, using TiCl4 as Lewis acid (Scheme 13.2). The allylation occurred rapidly at room temperature and is applicable to both aldehydes and ketones. 

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... 

A one-pot synthesis of 2,3>S-trisubstituted tetrahydrofurans by a double Hosomi-Sakurai reaction has been described. The product was obtained without the contamination of any regio- or stereoisomers. This remarkable selectivity has been explained by the difference in reactivity between the allylic starting material and the allylic silane formed in situ and between that of the two aldehydes employed (Scheme 80) <2004AGE1417>. 

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 use of C2-symmetric 1,2- and 1,3-diols as chiral auxiliaries is a reliable method for asymmetric allylation of acetals [382]. Acyclic acetals derived from homochiral 1-phenylethanol undergo the Hosomi-Sakurai allylation with high diastereoselectivity [383]. Tietze et al. have, on the other hand, reported that the TMSOTf-catalyzed successive acetalization-allylation reaction of aliphatic aldehydes with homochiral silyl ethers 123 and allyltrimethylsilane gives the corresponding homoallyl ethers with complete diastereocontrol these ethers can be readily converted into enantiomerically pure homoallyl alcohols without epimerization (Scheme 10.135) [384]. This method is applicable to asymmetric allylation of methyl ketones [385]. 

Since the discovery of thermally promoted allylation of aldehydes [9], allylstannanes have been widely used in organic synthesis as stable and stereodefined reagents for C-C bond formation. Although it had been reported that activated aldehydes [10] or allylstannanes with chloride on the tin [11] could be used for allylation, remarkably innovative technology for allylation was advanced by Naruta and by Sakurai and Hosomi [12]. They disclosed that allylation was promoted by addition of a Lewis acid this substantially expanded the versatihty of the aUylstaimane procedure. Because many allylation reactions have already been documented [1], the most recent progress in this field will be described after brief description of fundamental aspects. 

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). 

The aldehyde 218 possessing 2,6-frans-tetrahydropyran, was synthesized as shown in Scheme 48. /3-Keto ester 220 was reduced by Noyori hydrogenation [97] to give 6-hydroxy ester 221 in 94% ee, which was converted into iodide 222. Asymmetric alkylation using Myers chiral auxiliary [98] with 222, followed by acid treatment, furnished 5-lactone 223 with high stereoselectivity. Reductive acetylation, axial allylation by the Hosomi-Sakurai reaction, and ozonolysis completed the synthesis of 218. 

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]. 

Allylation of Aldehydes. Reiser s group has developed a stereoselective synthesis of substituted cyclopropyl carbaldehydes and has demonstrated their diastereoselective Hosomi-Sakurai aUyl-ations with several aUylsDanes, including 1 (eq 39). ... 

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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