Homoallyl ethers

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>. 

The conversion of anomerically linked enol ethers 29 into either the cis- or trans-substituted pyranyl ketones with high diastereoselectivity and yield involves a Lewis acid-promoted O —> C rearrangement (Scheme 19) <00JCS(P1)2385>. Under similar conditions, homoallylic ethers 30 ring open and the oxonium ions then recyclise to new pyran derivatives 31. Whilst the product is a mixture of alkene isomers, catalytic hydrogenation occurs with excellent diastereoselectivity (Scheme 20) <00JCS(P1)1829>. 

The efficient isomerization of allyl ethers and related compounds was accomplished by using NaHFe(CO)4 as catalyst. Isomerization of a homoallyl ether was also carried out in high yield (Scheme 32).56... 

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]. 

Acyclic acetals are simple protecting groups for aldehydes and ketones, and we have previously reported their synthesis catalyzed by Bi(OTf)3 [104]. Acyclic acetals can also be converted to other useful functional groups. For example, allylation of acyclic acetals to give homoallyl ethers has been well investigated, and we have reported a Bi(OTf)3-catalyzed method for the same [105]. The success of Bi(OTf)3-catalyzed formation and allylation of acyclic acetals prompted us to develop a one-pot method for the synthesis of homoallyl ethers from aldehydes, catalyzed by bismuth triflate. A one-pot process saves steps by eliminating the need for isolation of the intermediate and thus minimizes waste. Three one-pot procedures for the synthesis of homoallyl ethers were developed [106]. 

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). 

A three-component one-pot procedure was also developed. This method involves stirring the aldehyde, trialkylorthoformate, and allyltrimethylsilane in CH3CN in the presence of a catalytic amount of Bi(OTf)3. The homoallyl ethers were again obtained in moderate to good yields with a more simple and straightforward procedure (Scheme 11). 

Scheme 10 Bismuth(III) triflate-catalyzed method for the conversion of aldehydes to homoallyl ethers via an acetal intermediate...

We found that the desired homoallyl ethers could be synthesized in good to moderate yields using alkoxytrimethylsilanes in place of the trialkylorthoformates (Scheme 12). In addition, a lower catalyst loading was required. 

Yadav JS, Subba Reddy VB, Srihari P (2000) Scandium triflate catalyzed allylation of acetals and gem-diacetates a facile synthesis of homoallyl ethers and acetates. Synlett 673... 

Wieland LC, Zerth HM, Mohan RS (2002) Bismuth triflate catalyzed allylation of acetals a simple and mild method for synthesis of homoallyl ethers. Tetrahedron Lett 43 4597 1600... 

Anzalone PW, Baru AR, Danielson EM, Hayes PD, Nguyen MP, Panico AF, Smith RC, Mohan RS (2005) Bismuth compounds in organic synthesis a one-pot synthesis of homoallyl ethers and homoallyl acetates from aldehydes catalyzed by bismuth triflate. J Org Chem 70 2091-2096... 

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... 

The ruthenium indenylidene IX catalyzed the ring dosing metathesis of a homoallyl ether diene to give a bicydic compound, which is an intermediate for the synthesis of different marine natural products (Equation 8.10) [63]. 

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

HOMOALLYLIC ETHERS lodotri-methylsilane. Trimethylsilyltrifluoro-methanesulfonate. 

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

Cleavage of homoallyl ethers 2,4-dienols.1 3,6-Dihydro-2H-pyrans are cleaved to (Z)-2,4-pentadienols by this combination of bases in 35-75% yield. Example ... 

The same cleavage is observed with acyclic homoallyl ethers. Example ... 

Diazomethane-Alumina, 14 Ethers (see also Allylic compounds, Enol ethers, Homoallylic ethers)... 

Allyltributyltin, 10 Vinyltrimethylsilane, 343 Homoallylic ethers Allyltrimethylsilane, 11 Crotyltrimethylsilane, 86 Trityl perchlorate, 339 Homopropargylic alcohols Allenylboronic acid, 36 D imethoxy [ 1 -trimethylsilyl-1,2-buta-dienyljborane, 218 Lithium acetylide, 44 Triisopropoxy[l-(trimethylsilyl)-l,2-buta-dienyl]titanium, 218 Hydroperoxides Oxygen, singlet, 228 Hydroxy acids a-Hydroxy acids... 

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. 

Selective cleavage of 2-methoxyethyl hemiacetats. 2-Methoxyethyl hemiacetals react with allyltrimethylsilane in the presence of TiCl4 (1 equiv.) to give a homoallyl ether with selective cleavage of the 2-methoxyethoxy group (cf, 7,370-371).8 Examples ... 

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 acetal 14, activated by the iodotrimethylsilane 17, produces the oxonium cation 16 which can be intercepted by allylsilane 1 yielding homoallylic ether 15, one equivalent of methoxytrimethylsilane 18 and the catalyst 17. 

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). 

Optically pure crotylsilanes 70 were used by Panek et al. [37, 38] who prepared functionalized homoallylic ethers 72, Scheme 13.30. 

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