Allylsilanes reactions with carbonyls

Allylsilanes react with carbonyl compounds to transfer the allyl group with 1,3-transposition, in the presence of Lewis acids, typically titanium(IV) chloride47. Recently this reaction has been carried out under super-acid catalysis48. Transfer of the allyl group is also induced by tetrabutylammonium fluoride, but in this case reaction takes place regioselectively at the less substituted end of the allyl fragment49. 

Fluoride ion promoted cleavage of propynylsilanes and subsequent reaction of the carbanion with carbonyl compounds produces allenic compounds. The reaction with formaldehyde and pivaldehyde fails, but both the allenic and acetylenic products are obtained from the reaction with acrolein and benzaldehyde [49]. Allylsilanes react with carbonyl compounds to produce but-3-en-l-ols [50],... 

Silyl-l,3-dienes undergo anodic methoxylation in methanol to give 1,4-addition products with an allylsilane structure as intermediates. Therefore, they are further oxidized to give l,l,4-trimethoxy-2-butene derivatives as the final products. The products are easily hydrolyzed to provide the corresponding y-methoxy-a, /t-unsaUirated aldehydes. Since 1-trimethylsilyl-l,3-dienes are readily prepared by the reaction of the anion of l,3-bis(trimethylsilyl)propene with aldehydes or ketones, l,3-bis(trhnethylsilyl)propene offers a, /i-formylvinyl anion equivalent for the reaction with carbonyl compounds (equation 15)16. 

Allylsilane and Propargylsilane Synthesis. (lodomethyl)-trimethylsilane has been used to prepare aflylsUanes, which are t)q)icafly utilized in Lewis acid or fluoride ion-promoted reactions with carbonyl compounds to provide homoallylic alcohols. Treatment of Mc3SiCH2l with methyltriphenylphosphonium bromide and base produces an intermediate phosphonium salt which can be further utilized to prepare allylsilanes from carbonyl compounds. This procedure has been modified so that this series of transformations can be done as a one-pot procedure (eq 1). ... 

Essentially all allylsilanes (M = SiR3, Section D.l.3.3.3.5.) with the exception of fluorosil-iconates11 and most of the trialkyl(allyl)stannancs (Section D.l. 3.3.3.6.), which have only very weak Lewis acidic properties, require a strong Lewis acid to trigger the reaction with a carbonyl compound by the preceding formation of an x-oxycarbenium ion, which attacks the allylic compound in an ionic open-chain pathway. These Lewis acid catalyzed carbonyl additions offer new possibilities for the control of the simple and induced diastereoselectivity12. 

T.3.3.3.5.2. Reactions of Allylsilanes with Carbonyl Compounds Introduction... 

Allyltrialkoxy- or -tris(dialkylamino)titanium reagents are not capable of chelation-controlled addition reactions with oxy- or amino-substituted carbonyl compounds due to their low Lewis acidity87. To attain chelation control, the application of allylsilanes (Section 1.3.3.3.5.2.2.) and allylstannanes (Section I.3.3.3.6.I.3.2.) in the presence of bidentate Lewis acids like titanium(IV) chloride, tin(lV) chloride or magnesium bromide are the better options. 

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

Apart from the tandem metathesis/carbonyl o[efination reaction mediated by the Tebbe reagent (Section 3.2.4.2), few examples of the use of stoichiometric amounts of Schrock-type carbene complexes have been reported. A stoichiometric variant of cross metathesis has been described by Takeda in 1998 [634]. Titanium carbene complexes, generated in situ from dithioacetals, Cp2TiCl2, magnesium, and triethylphosphite (see Experimental Procedures 3.2.2 and 3.2.6), were found to undergo stoichiometric cross-metathesis reactions with allylsilanes [634]. The scope of this reaction remains to be explored. 

Allyl transfer does not take place with 76 under nucleophilic conditions39. By contrast, the reactions of allylsilanes with carbonyl compounds are activated by fluoride ion353. 

The TiCU-induced three-component coupling reaction of an a-haloacylsilane, allylsilane and another carbonyl compound gives 48 in good yield. A silyl enol ether intermediate is suggested (equation 31)82. The reaction of a cyclopropyl ketone with allylsilane yields a mixture of skeletal rearranged products83. 

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. 

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... 

Indium-mediated allylation of trialkyl(difluoroacetyl)silane 70 in aqueous media gives homoallylic alcohol 71 exclusively (Scheme 60). Both water and THF are essential for the allylation reaction. It is worth noting that homoallylic alcohol 71 is formed exclusively under these reaction conditions. On the contrary, enol silyl ether 72 is a major product of the fluorinated acylsilanes reaction with other organometallic compounds than indium via a Brook rearrangement and defluorination. Indium-mediated allylsilylation of carbonyl compounds provides a facile route to 2-(hydroxyethyl)allylsilanes. The allene homologs are similarly prepared (Scheme 61).244,244a... 

Alkylation of ketones, As expected 1 reacts readily with carbonyl compounds to form allylsilanes. The reaction can be conducted as a one pot procedure with yields of 60-85%. In the presence of Lewis acids, allylsilanes react with various electrophiles (alkyl halides, acid chlorides, ethylene oxide). A typical sequence is shown in equation (I). 

As we mentioned before, a classical Grignard reaction is formally described by the coupling of a covalent (albeit polarized) electrophile with an anionic nucleophile. Reactions shown in Scheme 2.41 (opposite) exemplify the alternative approach involving an interaction between cationic intermediates generated from carbonyl compounds (or their derivatives) under the action of Lewis acids and a purely covalent nucleophile, an allylsilane such as I09a or 109b. Similar electrophiles used in reactions with covalent silyl enolates such as 110 result in the formation of the aldol-Iike products (the Mukaiyama reaction ). 

Allenic alcohols.3 The reaction of allylsilanes with carbonyl compounds catalyzed by this salt to give homoallylic alcohols (9, 455-446) has been extended to a synthesis of a-allenic alcohols. Use of TiCl4 as catalyst results in a 2-chloro-l,3-diene. 

The addition of an allylsilane to an electrophile was first documented in 1948 by Sommer et al. [6]. These workers predicted that the allylsilane would react with an electrophile to generate a silicon-stabilized cationic intermediate. In 1956, Galas and co-workers demonstrated that allylsilanes undergo an allylic shift in the protiodesilylation of a cyclohexenylsilane to afford a methylidenecyclohexane [7], The first report of the reaction of allylsilanes with carbonyl compounds (1974) is also due to Galas [8]. These authors used activated substrates such as perfluoro-acetone and chloroacetone and AIGI3, GaGl3 or InGl3 as Lewis acids to promote... 

The reactions of ailylboranes, -silanes and -stannanes with carbonyl compounds and imines always take place with double-bond migration, and the structural stability of the reagent is a common problem that is encountered ( 2.7). The reactions of ailylboranes and -boronates occur without catalysis, while those of allylsilanes and -stannanes usually require the presence of a Lewis add [253], The mechanism of the reactions of allylboron derivatives is concerted, and the addition occurs via a six-membered cyclic transition state. A slightly distorted chair transition state model in which the oxygen of the carbonyl group is coordinated to the boron atom is usually invoked (Figure 6.42). Various steric and polar interactions dictate whether the Si or Re face of the prochiral aldehyde is attacked (models C j... 

The ene and Prins reactions are not mechanistically distinct. Coverage will therefore be organized by the nature of the carbonyl compound, with intermolecular reactions presented first, followed by intramolecular reactions. The emphasis will be on material published since the field has been reviewed " and on examples demonstrating the stereo-, regio- and chemo-selectivity of these reactions. Coverage is restricted to the addition of carbonyl and thiocarbonyl compounds to simple alkenes. Addition of carbonyl compounds to vinylsilanes, allylsilanes and enol ethers is covered in the following chapters. Addition of imines and iminium compounds to alkenes is presented in Part 4 of this volume. Ene reactions with alkenes and alkynes as enophiles are covered in Volume 5, Chapter 1.1. Use of aldehydes and acetals as initiators for polyene cyclizations is covered in Volume 3, Chapter 1.6. 

Allylation. The reaction of allylsilanes with carbonyl compounds, acetals, and ortho esters is catalyzed by Cp2Ti(OTf)2. Rapid reaction rates and good conversion... 

Remuson and coworkers reported that highly diastereoselective synthesis of 2,6-cis-disubstituted-4-methylenepiperidines based on a Mannich type intramolecular cyclization of allylsilane [37]. Reaction of p-aminohydroxysilane 116 with carbonyl derivative in the presence of TFA in a mixture of H2O-THF (1 1) led to 4-methylenepiperidine 117. Oxidation with osmium tetraox-ide in the presence of Na3H3lOe in AcOH led to piperidin-4-one followed by the stereoselective reduction with NaBH4 afforded (- -)-241D (13) and its C-4 epimer 118 in a ratio of 83 17 (Scheme 20). 

In this chapter, only the most recent multicomponent versions of the Hosomi-Sakurai reaction will be covered [68b], in particular those that allowed the synthesis of homoallylic ethers through the combination of an aldehyde (or ketone) with a silyl ether or the corresponding alcohol and an allylsilane (Scheme 12.13, Eq. 1). And also, the synthesis of homoallylic amines where the allylsilane reacts with an imine in situ formed from the carbonyl compound and an amine is known as aza-Sakurai reaetion (Scheme 12.13, Eq. 2). 

Other Lewis acid mediated C-C bond forming reactions of silylated C-nucleophiles include the Mukaiyama aldol and Michael additions of enolsilanes ), the related reaction of allylsilanes described by Sakurai ) as well as similar reactions of Me3SiCN ). Other "inert C-nucleophiles such as dialkylzinc compounds also react with carbonyl compounds in the presence of Lewis acids ). We ourselves have utilized many of these processes in performing stereoselective reactions, particularly in achieving diastereofacial selectivity in the reactions... 

Reaction with Carboxylic Acid Derivatives. In addition to carbonyl compounds, reagent (1) also reacts with carboxylic acid derivatives. Thus lactones provide hydroxy allylsilanes (3) (eq 3). ... 

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