Homoallyl ethers reaction

Homoallylic ethers Reaction of aldehydes with allyltrimethylsilane and Cl2Ti(OR)2 (prepared from LiOR and TiCl4) results in homoallylic ethers in 50-95% yield. 

The application of RCM to dihydropyran synthesis includes a route to 2,2-disubstituted derivatives from a-hydroxycarboxylic acids. In a one-pot reaction, the hydroxy esters undergo sequential O-allylation, a Wittig rearrangement and a second O-allylation to form allyl homoallyl ethers 8. A single RCM then yields the 3,6-dihydro-2//-pyran 9. The process is readily adapted not only to variably substituted dihydropyrans but also to 2-dihydrofuranyl and 2-tetrahydrooxepinyl derivatives and to spirocycles e.g. 10 through a double RCM (Scheme 4) <00JCS(P1)2916>. 

Ruthenium-carbenoid complex 1 catalyzed the isomerization of /3,7-unsaturated ethers to the corresponding vinyl ethers. This reaction is useful in the deprotection of allyl and homoallyl ethers (Scheme 39).65... 

Homoallyl ethers or sulfides.1 gem-Methoxy(phenylthio)alkanes (2), prepared by reaction of 1 with alkyl halides, react with allyltributyltin compounds in the presence of a Lewis acid to form either homoallyl methyl ethers or homoallyl phenyl sulfides. Use of BF3 etherate results in selective cleavage of the phenylthio group to provide homoallyl ethers, whereas TiCl effects cleavage of the methoxy group with formation of homoallyl sulfides. 

The reaction was achieved through transfer vinylation of 67 with 68 by action of the [IrCl(cod)]2 complex to afford allyl homoallyl ethers 69, followed by a Claisen rearrangement of the ether 70. The Claisen rearrangement of allyl homoallyl ethers to y,5-unsaturated aldehydes has been reported previously [6]. 

The first procedure is a one-pot sequential process in which the acetal is formed from the aldehyde in a Bi(OTf)3-catalyzed reaction with trialkylorthoformate and the corresponding alcohol. After the aldehyde was consumed, the remaining alcohol was removed under reduced pressure. Acetonitrile, allyltrimethylsilane, and additional Bi(OTf)3 were added and the desired homoallyl ethers were obtained in moderate to good yields (Scheme 10). 

Mekhalfia A, Marko IE (1991) The silyl modified Sakurai (SMS) reaction. An efficient and versatile one-pot synthesis of homoallylic ethers. Tetrahedron Lett 32 4779 1782... 

As a consequence of the cyclobutyl to homoallyl rearrangement, reactions of 1-chloro-, 1-bro-mo-l,2-dimethylcyclobutane, 1-chloro- or l-bromo-l,3-dimethylcyclobutane with silver(I) te-trafluoroborate in diethyl ether gave in each case the same open-chain compound 2-fluoro-4-mcthylpent-4-ene (14) as the major product. Thus, l-bromo-l,3-dimethylcyclobutane (13) was treated with silver(l) tetrafluoroborate in diethyl ether at 0 >C to give 2-fluoro-4-methylpent-4-ene (14).22... 

Homoallyl ethers. Trimethylsilyl triflate catalyzes a reaction between dimethyl ketals and allyltrimethylsilane to form homoallyl ethers. Allylation is not possible with the parent ketones. 

In order to explain why in 33 the bond from zirconium to C-l is selectively cleaved rather than the zirconium-C-4 bond it is necessary to take note that this reaction involves allylic and homoallylic ethers and alkoxides. With such species the magnesium cation also coordinates with an oxygen atom from the substrate, as in model system 36. It can further be shown that in the transition from 33 to 34 zirconium generally remains with the statically least hindered residue even if there is no heteroatom present12... 

Using liquid sulfur dioxide as a Lewis-acid solvent for the alkoxyalkylation and alkylation of allylsilanes has been investigated50. The reaction of acetals with allylsilanes results in the formation of homoallyl ethers 11 in excellent yields (equation 8). 

The coupling reaction of allylsilane with the w-thiomethoxyacetal is catalyzed by TMSOTf51. TiCLj-mediated reaction of a-bromoallylsilane 7 with 1,1-diethoxyethane leads to homoallylic ether 12 stereoselectively in excellent yield (equation 9)40. Under similar reaction conditions, double substitution of allylsilane to diketals 13 affords 14 in high diastereoselectivity (equation 10)52. 

Optically active crotylsilane 22 functions as a chiral carbon nucleophile in TMSOTf-catalyzed reactions with acetals giving homoallylic ethers 23 in high diastereo- and enantioselectivities (equation 14)58,59. 

Parallel to an earlier work on the highly diastereoselective reactions of aliphatic aldehydes with allylsilane in the presence of 3976, treatment of methyl ketones under the same conditions yields the corresponding tertiary homoallylic ether with a diastereomeric excess of up to 90% (equation 25)77. 

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 addition of trimethyl (2-methylallyl)silane 28 to acetal 27 was chosen as the key step. The reaction proceeded smoothly and generated homoallylic ether 29 with high diastereoselectivity. The desired homoallylic alcohol 30 could subsequently be obtained, in high enantiomeric purity, by oxidative deprotection of the chiral template (Scheme 13.12). 

Employing a silyl ether instead of 38 provided a connective assembly of homoallylic ethers. This three-component reaction leads to the formation of homoallylic ethers 45 via activation of carbonyl 6 by Lewis acid 17. The in situ generated oxo-nium cation 43 can then be trapped by the nucleophilic silyl ether 42 affording 44. The new species can then react with allyltrimethylsilane 1, to form the desired ether 45 with subsequent regeneration of the catalyst and loss of TMSOTMS 47 (Scheme 13.16). 

A wide variety of silyl ethers can be employed, leading to functionalized homo-allylic alcohols or ethers. This three-component coupling reaction, which generates in a single operation a range of homoallylic ethers, does not require the initial and independent synthesis of the acetal (or ketal) derived from 6. 

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). 

Palladium-catalyzed oxidative cyclization of aryl homoallyl ethers affords 4-methyl-2//-chromenes in moderate yield. The reaction is proposed to proceed via activation of the alkene by coordination to Pd(ll) followed by intramolecular nucleophilic attack by the arene. Subsequent [1-hydride elimination and isomerization then affords 4-methyl-27/-chromenes (Scheme 13). Electron-rich aryl homoallyl ethers give the best yield and good regio-selectivity is observed for the reaction of unsymmetrical arenes <2005OL3355>. 

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... 

A radical approach to cyclization is offered by the intramolecular homolytic substitution (ShO reaction at a silicon center. Reaction of phenyl bromoacetate with a stannylated silyl homoallyl ether under atom transfer conditions provides cyclic alkoxysilanes (Equation (119)).2... 

Homoallylic ethers appeared much less reactive towards the f-elimination reaction with the zirconocene-alkyne complexes or zirconacyclopentenes [21]. No -elimination products were observed in these cases. In contrast, Szymo-... 

In several cases, cyclopropylcarbinyl-homoallyl rearrangements involving zirconium species were observed (Scheme 16), similar to those reported for some other transition metals [23]. Examples of reactions are depicted in Table 3. The lack of rearrangement for the homoallylic ethers in entries 3-5 was attributed to the Thorpe-Ingold effect, i.e., angle compression at the substituted carbon [24]. 

Acetalization and allyUuion of carbonyl compounds. lodotrimethyisilane is an effective catalyst for acetalization with an alkoxysilane. Addition of allyltrimcthylsilanc to this reaction results in allylation of the acetal to form a homoallyl ether. 

When examining the silylene transfer to gi OT-disubstituted alkenes to form silacyclopropenes, an unprecedented reaction of homoallylic ethers was discovered. Two di-/-butylsilylene units were found to be incorporated into the molecule followed by a complete rearrangement of the carbon backbone (Equation 6) <20050L5531 >. This reaction opens a new route to prepare organic synthetically useful allylic silenes to be used in annulation reactions. 

Under electrochemical conditions it is possible to couple two silanes. The reaction of 34 and aUyltrimethylsilane, for example, gave the corresponding homoallylic ether. 

The reaction of aldehydes 3 with crotyl silanes (e.g. 5) yields 3-methylated homoallylic products such as 6 and 9. Since crotyl silanes are only weak nucleophiles, the carbonyl compound 3 must be activated. This can be done by addition of a Lewis acid (LA) to form the C2ixhony -Lewis acid complex 4. After addition of 5 and aqueous workup, the homoallylic alcohol 6 is obtained. An alkyl-oxo-carbenium ion 8 is available when treating an acetal 7 with acid or when the aldehyde 3 reacts with a silyl ether 10 in the presence of a Lewis or a Brousted acid (multicomponent crotylation). Crotylation of this alkyl-oxocarbenium ion 8 yields homoallylic ethers 9. 

In the case of an acyclic anti homoallyl ether or alcohol, the zirconium-catalyzed ethylmagnesiation reaction leads to the same sense of stereoinduction [93], whereas... 

Panek and co-workers have demonstrated that crotylsilanes 217 and 343 react with a variety of electrophiles including aldehydes, a, ff-unsaturated ketones, acetals and imines under appropriate activation conditions (usually Lewis acidic) to form homoallylic ethers [149, 261], homoallylic alcohols [58, 150, 151], tetrahy-drofurans [262, 263], cyclopentanes [264], pyrrolidines and homoallylic amines [265] with high levels of enantio- and diastereoselectivity [12]. This review will focus on the reactions of crotylsilanes 217 with Lewis acid-activated acetals and aldehydes, and the application of these reactions to the synthesis of polypropionate natural products [266-271]. 

Panek has reported the reactions of chiral crotylsilanes, e.g. (S)-217c, with a variety of achiral acetals, resulting in the formation of homoallylic ethers 348 with high enantio- (>95% ee) and variable diastereoselectivities (Table 11-20) [149, 261]. The acetals can be formed in situ from the corresponding aldehydes via treatment with TMSOBn or TMSOMe in the presence of catalytic TMSOTf. 

Silver-initiated ring cleavage of bicyclo[1.1.0]butanes in protic solvents leads predominantly to mixtures of cyclopropanes and the corresponding dienes, e.g. a mixture of the norcarane ether 32 and the corresponding homoallylic ether 33 is observed in the reaction of 2,6-dimethyl-tricyclo[4.1.0.0 ]heptane (31) with silver perchlorate. This reaction is of little practical value for the synthesis of cyclopropane derivatives from bicyclo[1.1.0]butanes. 

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