Disubstituted allylsilanes

Finally, Szabo et al. examined the reactions of disubstituted allylsilanes 166 with aldehydes. In the presence of TMSOTf, the 2,3,5,6-tetrasubstituted tetrahydro-pyrans 167 are formed in good yields (Scheme 13.57). In complete analogy with the results of Ito [78] and Mohr [69], a remarkably high stereoselectivity was also observed. 

The aUylation of acetals with y-substituted allylsilanes is occasionally highly syn-selective [362]. Panek et al. have succeeded in highly diastereo- and enantioselective synthesis of homoallyl ethers by aUylation using homochiral a,y-disubstituted allylsilanes [334] (Section 10.3.1.3). 

Allylation of a-dUcetonesr Allyltrifluorosilanes react with a-diketones in the presence of Et,N at room temperature. iyn-Diols are obtained as the major products. y,y-Disubstituted allylsilanes give a-ketols under the same conditions. 

Conventional synthetic schemes to produce 1,6-disubstituted products, e.g. reaction of a - with d -synthons, are largely unsuccessful. An exception is the following reaction, which provides a useful alternative when Michael type additions fail, e. g., at angular or other tertiary carbon atoms. In such cases the addition of allylsilanes catalyzed by titanium tetrachloride, the Sakurai reaction, is most appropriate (A. Hosomi, 1977). Isomerization of the double bond with bis(benzonitrile-N)dichloropalladium gives the y-double bond in excellent yield. Subsequent ozonolysis provides a pathway to 1,4-dicarbonyl compounds. Thus 1,6-, 1,5- and 1,4-difunctional compounds are accessible by this reaction. 

No unusual products were formed with allylsilanes. Under similar conditions, allylsilanes made only 1,3-disubstituted propanes, and pro-penylsilanes were recovered if excess allylsilane was used. 

A diastereoselective synthesis of 3,5-disubstituted indolizidines based on an intermol. addition of an allylsilane on an acyliminium ion derived from (d )-pyroglutamic acid, is described <2006TA1253>. 

In addition to allylsilanes, CM can also be applied to allylstannanes, which serve as valuable reagents for nucleophilic additions and radical reactions.To date, only eatalyst 1 has been shown to demonstrate CM reactivity in the preparation of 1,2-disubstituted allylstannanes, as ruthenium catalysts were found to be inactive in the presence of this substrate class.Poor stereoselectivities were generally observed, with the exeeption of one instance of >20 1 Z-selectivity in the reaction of allyltributylstannane with an acetyl-protected allyl gluco-side. 

The first total synthesis of the marine dolabellane diterpene (- -)-4,5-deoxyneodolabelline 106 has been accomplished by Williams et alf" The /ra j -disubstituted dihydropyran moiety in key intermediate 69 was efficiently prepared from mixed acetal 103 by RCM with catalyst C and subsequent Lewis acid-catalyzed allylation of ethyl glycosides 104 with allylsilane 107 (Scheme 18). 

In contrast to the case of allylsilanes, anodic oxidation of disubstituted olefins provides in general four regioisomeric products because all the allylic carbon-hydrogen bonds can be cleaved. In the case of allylsilane, the cleavage of a C—Si bond takes place... 

Whereas an allylsilane can serve as an allyl anion synthon, the reaction of 1,3-bis(silyl)propene with electrophiles can afford the 1,3-disubstituted propene. Thus, treatment of a mixture of (If)- and (Z)-2-aryl-l,3-bis(trimethylsilyl)propenes 5 with 2 equivalents of NBS at —78 °C stereoselectively yields the corresponding (Z)-2-aryl-l,3-dibromopropene 6. When 1 equivalent of NBS is employed, the monobromo product 7 is obtained (equation 5). The reactions apparently proceed via the pattern of sequential displacement of allylsilane moieties40,41. 

TMSOTf-mediated intramolecular cyclization of allylsilanes with alkylidene 1,3-dioxo moiety gives almost exclusively the fraws-l,2-disubstituted cyclopentanes 76 in high yield (equation 50). Other Lewis acids or fluoride ion can also promote similar reactions114. In the presence of the chiral auxiliary, such intramolecular cyclization gives the corresponding iraws-l,2-disubstituted cyclopentanes and cyclohexanes 77 (equation 51) in excellent enantioselectivity115. 

Benzaldehyde (entry 3) and the hindered iso-butyraldehyde (entry 2) give the lowest yields. Sakurai and Hosomi next extended the addition of allylsilane 1 to enones 8 [7]. In the presence of TiCU, the 1,4-adduct 9 is obtained in good yields (Scheme 13.3). It is interesting to note that allylcuprates are less selective than allylsilanes and that / ,/ -disubstituted enones react efficiently, leading to ketones bearing a quaternary carbon center at the / position (entry 3). 

The same reaction was studied by Roush et al. [50]. However, in this case, the cyclization of anti-allylsilane 126 resulted in the production of only cis-2,6-disubstituted dihydropyrans 127. No trans-2,6-disubstituted dihydropyrans 128 were formed. Moreover, significant amounts of adducts 129 and 130 were observed (Scheme 13.45). These products probably originate from a side-chain exchange process (vide infra). 

This side reaction, which complicates the condensation of allylsilanes anti-126, was suppressed by using a-acetoxy acetals such as anti-131 as the oxonium cation precursor. Under these conditions, the desired cis-2,6-disubstituted dihydropyran 132 was isolated in moderate yields but high diastereoselectivity (dr = 94 6 Scheme 13.46). 

Three years later, in 1998, Ito et al. published [78] a similar reaction using the enantio-enriched allylsilane 161 (Scheme 13.55). This condensation reaction furnished the trans-2,3-disubstituted tetrahydropyranes 162 with 92.1 to 93.4% ee (indicating that the reaction proceeded with nearly complete chirality transfer), high diastereoselectivity and very good yields. In this case, the reaction was mediated by TMSOTf (1.1 equivalents) and the first steps presumably involved the silylation of the free alcohol function. It is noteworthy that the double bond in 162 possesses exclusively the E-geometry. 

Previously, Ireland-Claisen ester-enolate rearrangement of the corresponding a-propionyloxy-allylsilane led to model system 5.44 Therefore, elaboration to 4 via rearrangement of 15 was pursued. To complete our retrosynthetic analysis, a plausible route to 15 was devised, involving straightforward homologation of 2P,3a-disubstituted cyclohexanone 17 to cyclohexene-carboxaldehyde 16, which in turn undergoes silylanion addition and subsequent acylation (Eq. 8). 

THF at - 20°. All other anions should be prepared separately, and 2 should be added to 1 at - 20°. By these procedures mono- and disubstituted olefins, vinyl sulfides, vinyl ethers, and allylsilanes are available in 35-80% yield, usually as cis-trans mixtures. Trisubstituted olefins are best prepared by similar routes from a -branched nitrile anions. 

In addition to Ni and Pd catalysts, Li2CuCU is also an effective catalyst for the coupling of alkenyl iodides with Grignard reagents. Since the stereochemistry of alkenyl iodides is also retained, the coupling reactions are useful for the stereoselective synthesis of disubstituted alkenes, - trisubstituted al-kenes, allylsilanes, allyl alcohols and tetrasubstituted alkenes (equations 25-29). ... 

Heterocyle assembly. The allylation of aldehydes using functionalized ( )-allylsilanes is followed by cyclization to give frans-2,3-disubstituted tetrahydropyrans and piperidines. Using a (Z)-allylsilane of shorter chain length cii-2,3-disubstituted tetrahydrofurans are obtained. ... 

Dichlorocyclopropanation of allylsilanes, mono- or disubstituted at C3, afforded 1,1-dichloro-2-trimethylsilylcyclopropanes which were treated with cesium fluoride in dimethylformamide to give derivatives of 3-chlorobuta-l,3-diene. 

The alkylidene-1,3-dicarbonyl moiety is also a highly reactive enophile. Thus, the Knoevenagel adduct (223) obtained from aldehyde (222) and dimethyl malonate in the presence of piperidinium acetate, cy-clizes by treatment with Lewis acids such as FeCb on AI2O3 exclusively to the rranr-substituted cyclohexane (224 trans.cis > 99.5 0.5 Scheme 44).7 °3 The sesquiterpene veticadinol (225) has been synthesized in enantiomerically pure form by this method.Contrary to the expectation, rranr-sub-stituted cyclopentanes can also be obtained with excellent induced and noninduced dia-stereoselectivities. Similarly, aldehydes containing an allylsilane moiety can be used for a highly stereoselective formation of rran.r-l,2-disubstituted cyclopentanes and cyclohexanes by a Knoevenagel... 

In a similar fashion, palladium- or nickel-catalyzed hydrosilylative cyclization of bis-diencs 6 stereoselectively leads to //( / .< -1,2-disubstituted cyclopentanes 761. This reaction resembles telomerization of dienes with 1,4-carbosilylation of one of the diene subunits, leading to allylsilanes. Both stereoisomers are formed with the same relative configuration of the ring substituents, solely differing with respect to the Z/E configuration of the (wo different unsaturated side chains. 

Diels-Alder reaction Allylsilanes and propargylsilanes condense with A-aryl-aldimines in the presence of Gads to provide 2,4-disubstituted tetrahydroquinolines and quinolines, respectively. 

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