Allylsilane-aldehyde condensation

Kocovsky and coworkers have recently described a triple allylation that leads to tetrahydrofurans in high diastereo- and enantioselectivity (Scheme 34) [34]. From bis-allylsilane 128, a chiral base-catalyzed aldehyde condensation gives homoallylic alcohol 131. The best catalysts for the reaction were dioxides 129... 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

The most direct route to the 1,4-dicarbonyl equivalent required for the aldol condensation would be to couple the enol ether of an aldehyde with the enol ether of a ketone. However, this sequence proved impractical due to the hydrolytic instability of the ketone enol ether. Even after an extensive effort, the substrate for the electrolysis reaction could not be reproducibly prepared in high yield. These problems were readily avoided with the use of an allylsilane based... 

Sakurai et al. reported the condensation of allylsilane 1 with acetals [8], leading to the preparation of homoallylic ethers 15 (Scheme 13.6). The reaction occurs at —78 °C, in dichloromethane. The yields are usually excellent, even though the condensation is slower than with aldehydes and ketones. 

The aza-analogue of the SMS condensation has been reported [35, 45-47]. Veenstra and Schmid in 1997 [46] were the first to perform the three-component condensation between an aldehyde 6, an amine 92 and an allylsilane 1. A stoichiometric amount of Et20-BF3 was generally used and the yields were good (Scheme 13.37). 

The reaction is based upon the two components condensation between an aldehyde or ketone 6 (or their synthetic equivalents) and alcohol 95, which contains an allylsilane (or vinylsilane) moiety. The IMSC reaction is mediated by Lewis or Bronsted acids, which activate the carbonyl group of 6 towards nucleophilic attack. After addition of alcohol 95 on the activated carbonyl, the oxonium cation 96 is formed, which is intramolecularly captured by the pendant allylsilane function, leading to oxygen-containing rings 97 (Scheme 13.38). This process typically requires a stoichiometric (or more) amount of Lewis acid. 

Dihydropyrans of general structure 110 can be prepared by two complementary strategies starting from aldehyde 113 (or its synthetic equivalent). Condensation with vinylsilane 114 or allylsilane 115 affords in each case the adduct 110 (Scheme 13.41). 

The synthesis of optically active vinyl oxepans 234 [55], was reported by Ito et al. starting from the enantioenriched allylsilanes 240. This annelating agent reacted with various aldehydes in the presence of TMSOTf (2.0 equivalents), leading to the oxepans 234 in good yields and excellent stereoselectivity (Scheme 13.89). The condensation of benzaldehyde with 237 is the only case in which an erosion of the tram cis stereoselectivity is observed, though this ratio still remains an impressive 50 1 (Scheme 13.87, entry 3). 

Condensation of achiral aldehydes with allylsilanes promoted by CAB catalyst (2) (20 mol %) at —78 °C in propionitrile produces homoallylic alcohols with excellent enantioselectivity (eq 7). 

HomoaUylic amines. A three-component condensation involving an aldehyde, a carbamate ester, and an allylsilane is accomplished in the presence of BFj-OEt. ... 

Chiral boronales are generated m situ by reaction of binaphthols 3.7 (R = H, Ph) [231] with BH3 in the presence of acetic acid [778], with H BBr [781] or with B(OPh)3 [782, 783], Chiral borates are formed by reactions of substituted (S)-prolinol derivative 2.13 (R =- CPl OH) and BBr3 [784], These boronates and borates are valuable catalysts in asymmetric Diels-Alder reactions [73, 231, 601, 780], Tartaric acid derivatives, such as borate 3.8 and acyloxyboranes 3.9 recommended by Yamamoto and coworkers [73,601,778,780,785-791], are very efficient catalysts in asymmetric Diels-Alder reactions and in condensations of aldehydes with allylsilanes, enoxysilanes or ketene acetals. These catalysts are generated in situ from substituted monobenzoates of (RJl)- or (S -tartaric acid and BH3 (R = H) or an arylboric acid (R = Ar). The best asymmetric inductions are observed with catalysts 3.9, R = /-Pr. 1,3,2-OxazaboroMnes 3.10, prepared from a-aminoacids [44, 601, 780, 792, 793], are efficient catalysts in asymmetric Diels-Alder reactions. The catalyst generated from A -tosyltrytophan 3.11 is more efficient than borolidines 3.10 (R = Et, /-Pr). The catalysts 3.10 prepared from 3.11, 3.12 and 3.13 are also useful in asymmetric condensations of aldehydes with ketene acetals [794-797]. 

The allylsilane 32 was used to prepare dienones via the tin tetrachloride catalyzed condensation with acetals or aldehydes followed by an elimination reaction81 (equation 76). Interestingly, when the condensation is catalyzed with fluoride ion only the a-adduct is observed (equation 77). 

A related coupling reaction is the condensation of aldehydes with alkyl trichlorotitanium compounds (RTiCl3). When methyltrichlorotitanium (MeTiCl3) was coupled with aldehyde 468 in dichloromethane at -78°C, a 91 9 mixture of 470/471 was formed via the chelated complex 469. Sakurai and co-worker had previously noted the coupling of allylsilanes to aldehydes in the presence of TiCl4.305... 

K. -I. Serita, S. Hiraoka, T. Yokozawa, Tetrahedron Lett. 2000, 41, 7075-7078. Lewis acid-catalyzed three-component condensation reactions of aldehydes, A-silylcarbamates, and allylsilane synthesis of A-homoallylcarbamates. 

It has been shown recently that the condensation of an allylsilane, of which a double bond is conjugated to an amide (silylacrylamide), onto aldehydes in the presence of TBSOTf and NEts gives direct access to dienamides after a p-eliminati(Mi on the intermediate aldol product [120]. Another paper based on a Knoevenagel craidensa-tion involves p-diketones or P-ketoesters and enals. Proline catalysis leads to the expected conjugated dienones in good yields and after short reaction times [121],... 

Multi-component reactions open a direct access to poly-functional derivatives/ For instance, reactions of unsaturated substrates and aldehydes in the presence of EtaSiH opened a rapid access to allyllic, homo-allylic or co-unsatu-rated alcohols, and NHC-Ni complexes were recently reported to be efficient catalysts for such oxidative coupling. Mori and co-workers described the first example of such condensation in 2001. They showed that an in situ generated IPr/Ni 1 1 complex led to the stereoselective formation of (Z)-homoal-lylic silyl alcohols [eqn (10.33)], while classical Ni -PPhj catalyst produced only (Ej-coupling products. Of note, IPr/Ni 1 2 and IMes/Ni 1 2 were less efficient in this reaction. These first results were extended to silylated dienes. Interestingly, it was shown that a mixed complex [(IPr)Ni(PPh3)] stereoselectively produced (Z)-allylsilanes while [Ni(PPh3)4] led only to (Ej-isomeric products. 

Cycloadditions have become a valuable means of generating tetrahydrofurans. They typically involve the condensation of an aldehyde with a 1,3-dipole in an overall [3+2]-cycloaddition process. With one exception, the focus of this section is on tetrahydrofuran formation from dipolar cycloadditions of either push-pull cyclopropanes or allylsilanes with aldehydes. 

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