Lewis acid-promoted allylation

The pioneering works by Flosomi and Sakurai described that conventional Lewis acids (TiCLt, S11CI4, and BFj OEtd are effective in the allylation of aldehydes, ketones, and acetals with a (sub)stoichiometric quantity.72 

The BF3 OEt2-promoted allylation of 4-substituted 2-hydroxytetrahydrofurans (7-lactols) shows high trans-selectivity as in the allylation of 4-substituted 2-acetoxytetrahydrofurans.81 

Tandem acetalization-allylation reaction of aldehydes with allylsilanes provides a convenient route to homoallyl ethers.82 Under catalysis by Sc(OTf)3, various aldehydes can be converted into homoallyl ethers by treatment with 

HNTf2 (Me3SiNTf2) Aldehyde, ketone CH2C12, Et20, PhCl 75 

Deoxygenative allylation of aromatic ketones can be performed by the InCI (-catalyzcd reaction with HSiMe2Cl and 10 (Equation (17)).85 

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Lewis acid-promoted allylation, 9, 304 titanacyclopropane and titanacylcopropene reactions,... 

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. 

Generally, the Lewis acid-promoted allylation of aldehydes with allyltrimethylsilanes proceeds via carbonyl activation. However, the SnCU-promoted allylation with allylsilanes bearing a coordinate site is rationalized by a transmetallation mechanism, in which allyltrichlorostannanes work as the actual allylating agents (Equation... 

Allylsilanes are available for Lewis acid-promoted allylation of reactive alkyl electrophiles such as allyl halides and esters. 6 Recently, much attention has been focused on catalytic allylation of alkyl esters, ethers, and alcohols with allylsilanes.217-221... 

The advantage of aluminum reagents over other metal reagents was also seen in the Lewis acid-promoted allylation of fluoro carbonyl compounds. For instance, MesAl-promoted selective allylation of an equimolar mixture of 2- and 4-fluorobenz-aldehydes with allyltributyltin afforded the homoallylic alcohol 53 almost exclusively. Unsatisfactory chemical yield and/or selectivity were obtained with Ti, Mg, Li, Sn, and Si Lewis acids (Sch. 38). 

In the Lewis acid-promoted allylation of aldehydes with allyltributyltin, virtually complete chemoselective functionalization of aldehyde carbonyls is also observable and the opposite chemoselectivity is easily accessible by use of TiCU as promoter, as shown in Sch. 148 [106],... 

Lewis acid-promoted allylation reactions of carbonyl compounds with allyltrialkyltin were reported, (a) Yamamoto, Y Yatagai, H. Naruta, Y Maruyama, K. J. Am. Chem. Soc. 1980, 102, 7107. (b) Pereyre, M. Quintard, J.-R Rahm, A. Tin in Organic Synthesis, Butterworths, London, 1987, p 216. 

In this chapter, an overview of the electrophilic snbstitntion chemistry of allyltin compounds leading to the formation of a new C—C bond is presented. Mechanistic considerations and a synopsis of information derived from detailed studies of allyltin reactions develop a perspective, which serves as a guide for planning new reactions. The major emphasis of the chapter is devoted to Lewis acid-promoted allylation reactions of aldehydes and related species. 

In general, the Lewis acid-promoted allylation and propargylation of aldehydes wifh y-substituted allylsilanes [357] and aUenylsilanes [358] are syn-selective. Information about the preferred orientation of fhe reactive double bonds in fhe transition structure is essential for rationahzing fhe stereochemistry. Denmark et al. examined the Lewis acid-promoted cychzation of fhe formyl-substituted allylsilane 119 to clarify fhe transition structure (Scheme 10.124) [359]. It was found that fhe allylation occurs from the synclinal and antiperiplanar arrangements, and the former is somewhat important. Thus, synchnal and antiperiplanar transition state models have been frequently used to explain fhe origin of the simple diastereoselection [14, 334]. 

In the Lewis acid-promoted allylation with allylsilanes, the promoter is usually regarded as activating electrophiles. Thomas [374] and Dias [375] have, however, described SnCLj-promoted allylation reactions proceeding via a transmetalation mechanism (Scheme 10.130). In the latter equation of Scheme 10.130, the formation of the allylstannane species has been observed by NMR spectroscopy [375 b]. 

Lewis acid-promoted allylation of imines [30] and allylative substitution of selenides have been reported [31]. Displacement of selenide results in formation of a contiguous quaternary C-C bond with retention of configuration (Scheme 12.10). 

Compared with aldehyde, the corresponding aldimine is less reactive toward nucleophilic addition however, aldimine is able to coordinate to transition metals more strongly. This latter property of aldimine may be more important than the former in the present reaction, and the allylation of aldimine proceeds much easier than the aUylation of aldehyde. In order to achieve the Lewis acid promoted allylation of aldehydes and aldimines with allylstannane, an excess amount of Lewis acid (>2 equiv) is required. Under such conditions, both aldehyde and aldimine may be equally activated toward allylation, and the allylation of aldehyde takes place selectively. 

Aldehydes, acetals, and acid chlorides have been cyclopropylmethylated stereo-selectively with homoallylstannanes, exploiting the y-effect of tin " a Lewis acid-promoted allylation of aldehydes with allyltin shows stereospeciflcity, as does an addition of highly substituted cyclic aUylzinc reagents. ... 

Consideration of the mechanism of the catalytic effect of rare earth ions on addition of organometallics to a, 8-unsaturated compounds has included addition of allyl-tributyltin to benzaldehyde catalysed by Sc. Stereospecificity in the Lewis acid-promoted allylation reaction of 3,3-disubstituted allyltins towards aldehydes has been attributed to an acyclic jyn-synclinal transition state. ... 

An interesting and stereoselective synthesis of 1,3-diols has been developed which is based on Lewis acid promoted reactions of /f-(2-propenylsilyloxy (aldehydes. Using titanium(IV) chloride intramolecular allyl transfer takes place to give predominantly Ag/r-l,3-diols, whereas anti-1,3-diols, formed via an / / /-molecular process, are obtained using tin(IV) chloride or boron trifluoride diethyl ether complex71. 

Lewis acids, particularly the boron trifluroride diethyl ether complex, are used to promote the reaction between allyl(trialkyl)- and allyl(triaryl)stannanes and aldehydes and ketones52-54. The mechanism of these Lewis acid promoted reactions may involve coordination of the Lewis acid to the carbonyl compound so increasing its reactivity towards nucleophilic attack, or in situ transmetalation of the allyl(trialkyl)stannane by the Lewis acid to generate a more reactive allylmetal reagent. Which pathway operates in any particular case depends on the order of mixing of the reagents, the Lewis acid, temperature, solvent etc.55- 58. 

Therefore, in order to obtain a 1,4-addition of an allyl residue to an enone, two activation modes can be used reactions take place either under electrophilic conditions with Lewis acid promotion, or in the presence of fluoride ions. This is important as the stereochemical outcome often depends on the activation mode selected. 

Upon treatment with Me3SiOTf, the 2,5-dihydrofuran-containing 14-membered marine cembranoid sarcophytoxide was converted to a 10-membered ring product as shown below <06OL2957>. Presumably, the Lewis acid promoted the cleavage of the dihydrofuran ring to provide a transient allylic cation, leading to a transannular cyclization. 

Suitably protected glycosyl halides or acetates, upon Lewis-acid promoted SN1 heterolysis, generate glycosyl cation intermediates that can react with electron-rich arenes, heteroarenes, Me3SiCN, enoxysilanes, enamines, allyl silanes and stannanes, acetylenyl silanes and stannanes affording C-glycosyl compounds. 

Lewis-acid promoted C-allylations of furanose acetates 101 with allyl-(trimethyl)silane are a-selective and the selectivity is governed by the alkoxy group at C-3. The lowest energy conformers bear the 3-alkoxy group in a pseudoaxial orientation (Scheme 35). To a lesser extent, the 2-substituent... 

Furthermore, the use of a Lewis acid promoter leads to increased stereoselectivities (Table 19, entry C)252,254. Compared to the aprotic reaction, where allyl silane was used instead of allyl bromide and indium chloride, an almost complete reversal of the diastereos-electivity was found. It was demonstrated recently that the Lewis acid catalysed allylation reaction can be carried out efficiently without any organic solvent in saturated ammonium chloride solution255. Finally, Lewis acid catalysed Mannich reactions can be carried out conveniently in mixtures of organic solvents and water. However, the exact role of the Lewis acid catalyst has not been clarified (Table 19, entry D)253. The same reaction can be carried out in pure water with catalysis by indium trichloride256. 

The synthesis of fenozan BO-7 4 involves two key steps, the first of which employs a 4 + 2 cycloaddition of singlet oxygen to the diene 83a122-20 123. This provides the endoper-oxide 83b that can be transformed into the target cis-fused 1,2,4-trioxane by treatment with the Lewis acid, TMSOTf, in the presence of a carbonyl compound. The reaction proceeds by Lewis acid promoted heterolysis of the C—O bond to give an intermediate peroxy allyl cation 83c that is captured by the carbonyl compound (in this case, cyclopen-tanone) to give the product (Scheme 30). A number of different carbonyls have been used in this reaction along with a number of different endoperoxide templates and detailed SAR have been developed (Scheme 30). 

Lewis acid-promoted asymmetric conjugate addition of an allylsilane to a series of 8-arylmenthol-derived A -acy I-2.3-di hydro-4-pyri doncs (122) has been reported to lead to 2-allyl-4-piperidones with moderate to high levels of asymmetric induction the highest levels were attained with Ar = 2-naphthyl. The stereochemical course of the reaction was attributed to re-stacking and the method was applied to the asymmetric synthesis of (—)-A-mcthy Icon i i nc.9 5... 

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