Promoters Sakurai allylation reaction

Sakurai pioneered the field of nucleophilic activation of reagents 21.5 by employing stoichiometric amounts of CsF or dilithium catecholates for highly diastereoselective allylation of aldehydes with allyltrihalosilanes 21.5. Later, it was demonstrated that the common dipolar aprotic solvents possessing a strongly Lewis basic ojg gen promote the allylation reaction. Thus, Kobayashi revealed that DMF can act both as a solvent and a Lewis-base activator. Denmark further established that, in contrast to DMF that was required in large excess to promote the allylation of aldehydes, HMPA can be used in substoichiometric quantities. 

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). 

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. 

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). 

A variety of electrophilic catalysts promote the addition of allylic silanes to carbonyl compounds.86 The original catalysts included typical Lewis acids such as TiCl4 or BFj.87 This reaction is often referred to as the Sakurai reaction. 

The Hosomi Sakurai Reaction involves the Lewis acid-promoted allylation of various electrophiles with allyltrimethysilane. Activation by Lewis acids is critical for an efficient allylation to take place. 

TMSOTf also promotes an intramolecular addition of allyl-silanes to aldehydes (Sakurai reaction), when used with 2,6-di-rert-butyl-4-methylpyridine (2,6-DTBMP) (eq 64), and ketones. ... 

Allylation. The use of allyl-TMS and TfzNH to generate TMSNTf2 in situ has also been applied to the aUylation reaction. Robertson reported the highly regioselective and diastereo-selective Sakurai reaction to cyclopentenones (eq 5). Again, TMSNTf2 was required for reactivity whereas TfOH or standard conditions (TiCL, 24 h) gave no Sakurai product. This system was even able to promote the 1,4-addition to a less reactive a, p- unsaturated ester (eq 5). 

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]. 

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). 

Annulations. The primary allylic halide 2-chloromethyl-3-trimethylsilyl-l-propene or the mesylate derived from the corresponding alcohol behaves as a hifunctional reagent possessing both nucleophilic and electrophilic reaction centers. For example, they have been shown to participate in [3 + 2] carbon annulations for the constmction of methylenecyclopentanes. The reaction proceeds through a Lewis acid-promoted conjugate addition (Sakurai reaction) followed by an internal alkylation of the derived ketone enolate (eq 3). 

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. 

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