Aldehydes allylic silanes

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

Allylic silanes react with aldehydes, in the presence of Lewis acids, to give an allyl-substituted alcohol. In the case of benzylic silanes, this addition reaction has been induced with Mg(C104)2 under photochemical conditions. The addition of chiral additives leads to the alcohol with good asymmetric induction. In a related reaction, allylic silanes react with acyl halides to produce the corresponding carbonyl derivative. The reaction of phenyl chloroformate, trimethylallylsilane, and AICI3, for example, gave phenyl but-3-enoate. ... 

While trifluoro and other halosilanes function by increased electrophilicity at silicon, nucleophilic reactivity of allylic silanes can be enhanced by formation of anionic adducts (silicates). Reaction of allylic silanes with aldehydes and ketones can... 

Scheme 9.4. Reactions of Alkenyl and Allylic Silanes with Aldehydes, Ketones, Acetals,...

The stereochemistry was controlled by Lewis acid-induced addition of these allylic silanes to aldehydes. The reaction of the silane with O-protected (S)-3-hydroxy-2-methylpropanal provides 15. The silane reacted with the benzyl-protected analog to provide 16. 

Condensation of sulfoximine 717 with an aldehyde and benzotriazole produces Ar-[ -(bcnzotnazol-l -yl)alkyl]sul-foximine 718. Treatment with allyl silanes in the presence of BF3 etherate or with organozinc reagents allows substitution of the benzotriazolyl moiety in compound 718 to produce variety of substituted sulfoximines 719... 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

Scheme 3.7. Diastereoselective formation of /S-silyl ( )- or (Z)-ester enolates by silylcuprate conjugate addition followed by alkylation with aldehydes [49]. Stereoselective synthesis of ( )-and (Z)-allyl silanes [50].

Non-racemic a-substituted allylic silanes, in particular crotylsilanes, are very attractive reagents despite their rather tedious preparation. They were found to provide very high transfer of chirality in their additions to achiral aldehydes under Lewis acid catalysis (Eq. 114). These reagents have been tested several times in the context of natural product synthesis. Their diastereoselectivity (syn/anti) depends on several factors, including the natme of the aldehyde substrate, the reagent, and the natme of the Lewis acid employed. For example, the syn product can be obtained predominantly in the reaction of Eq. 114 by switching to the use of a monodentate Lewis acid such as BF3. 

Although the allylation reaction is formally analogous to the addition of allylboranes to carbonyl derivatives, it does not appear to occur through a cyclic transition state. This is because, in contrast to the boron in allyl boranes, the silicon in allylic silanes has no Lewis acid character and would not be expected to coordinate at the carbonyl oxygen. The stereochemistry of addition of allylic silanes to carbonyl compounds is consistent with an acyclic transition state. Both the E- and Z-stereoisomers of 2-butenyl(trimethyl)silane give the product in which the newly formed hydroxyl group is syn to the methyl substituent.64 The preferred orientation of approach by the silane minimizes interaction between the aldehyde substituent R and the methyl group. 

Section B of Scheme 9.4 gives some additional examples of Lewis acid-mediated reactions of allylic silanes with aldehydes and acetals. 

Reaction of allylic silanes with aldehydes and ketones can also be induced by fluoride ion, which is usually supplied by the THF-soluble salt tetrabutylammonium fluoride (TBAF). Fluoride adds at silicon to form a hypervalent anion with much enhanced nucleophilicity.73 An alternative reagent to TBAF is tetrabutylammonium triphenyldi-fluorosilicate.74... 

The alcohol 10 looks like it might be formed by the addition of a Grignard reagent to an aldehyde. In fact, Patrick Steel of the University of Durham prepared 10 (Tetrahedron Lett. 44 9135,2003) by Diels-Alder addition of the transient silene derived from 7 to the diene 8. More highly substituted dienes lead to more complex arrays of stereogenic centers. The intermediate silacyclohexenes, exemplified by 9, should also engage in the other reactions of allyl silanes. 

Condensation of the allyl silane 4 with 3 proceeded to give exclusively the desired trans dihydropyran 5. McMurry coupling of the derived keto aldehyde gave the diol 13 as a mixture of diastereomers. Oxidation of the mixture gave 2 and its C-8 diastereomer in a ratio of 8 1. 

Penladienylation. This allylic silane in the presence of TiCl4 adds to aldehydes and ketones to give (E)-2,4-pcntadienyl substituted alcohols of the type CH2 CHCH-CHCH2C(OH)R R2. 

Polystyrene-derived phenylboronic acids have been used for the attachment of diols (carbohydrates) as boronic esters [667]. Cleavage was effected by treatment with acetone/water or THF/water. This high lability towards water and alcohols severely limits the range of reactions that can be performed without premature cleavage of this linker. Arylboronic acids esterified with resin-bound diols can be oxidatively cleaved to yield phenols (Entry 8, Table 3.36). Alcohols have also been prepared by nucleophilic allylation of aldehydes with polystyrene-bound, enantiomerically enriched allyl-silanes [668], as well as by Pummerer reaction followed by reduction of resin-bound sulfoxides [669]. 

PEG-grafted polystyrene is also well suited for reactions with highly reactive orga-nometallic reagents, provided that the support has been dried. PEG-containing polymers are generally more difficult to dry than pure polystyrene. Cross-linked PEG is stable towards Lewis acids, and can be used for SnCl4-mediated allylations of aldehydes with allyl silanes [21],... 

The reaction of allyl silanes with aldehydes and ketones activated as electrophiles by Lewis acids is a very useful method for preparing homoallylic alcohols. Since allyl silanes are only modestly nucleophilic, strong electrophiles are needed to ensure a good reactivity match. 

Carbamate and amide groups have been found to be stable under these coupling conditions73. In the presence of TiCLt or SnCLt, chiral a-keto amides 36 react with allyl-silane to produce, after hydrolysis, optically active tertiary alcohols 37 with extremely high optical selectivity (equation 23)74. The addition reaction appears to occur from the Si face of the carbonyl group. In a similar manner, a high degree of stereoselectivity is obtained from the reactions of A-Boc-a-amino aldehydes 38 with 2-substituted allylsilanes (equation 24)75. 

Ketones were also reacted under these conditions, leading to tertiary ethers. Thus, by mixing equimolar quantities of a carbonyl (aldehyde or ketone), allyl-silane and a silylated alcohol, followed by the addition of a catalytic amount of TMSOTf, homoallylic ethers can be obtain in good yields via a three-component coupling reaction (Scheme 13.22). 

Miginiac et al. [97] synthesized oxepin 233 and oxocin 234 starting from allyl-silane silyl ether 237, which was condensed with various aldehydes in the presence of Et20 BF3 (1.0 equivalent) (Scheme 13.85). The resulting seven- and eight-membered rings were obtained in moderate to excellent yields. 

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