Homoallyl methyl ethers

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. 

Homoallyl methyl ethers.4 Trityl perchlorate catalyzes a reaction of allyltri-methylsilanes with dimethyl acetals or ketals to form homoallyl methyl ethers in 60-90% yield. Diphenylboryl triflate is a somewhat less efficient catalyst. Example ... 

Tetrahydrofurans.s The (tributylstannyl)methyl ethers (1) of homoallylic alcohols (9, 475) on treatment with butyllithium undergo tin-lithium exchange to a-... 

The copper-catalyzed photobicyclization of acyclic 1,6-dienes to bicyclo[3.2,0]heptanes using the bis[copper(l) lrifluoromethanesulfonate]benzene complex has found general and synthetic utility in the conversion of diallyl and homoallyl vinyl ethers to 3- or 2-oxabicyclo[3.2.0]heptanes,5 6 of /V-allyl-A -2-methyl-2-propenecarbamates to iV-carboethoxy-3-azabicyclo[3.2.0]heptanes 7 and of allylic alcohols to the corresponding hydroxy-substituted bicyclo[3.2.0]heptanes.8 9 Examples of such reactions are summarized below. 

Asymmetric allylboration has also been applied to y-methoxyallyl derivatives. Isomerically pure (Z)-y-methoxyallyldiisopinocampheylborane (rf31), prepared from Ipc2lSOMe and the lithium anion of allyl methyl ether, reacts with various aldehydes to afford the yyn - j-m e (boxy homoallylic alcohol (32a) in a highly regio- and stereoselective manner17 (Scheme 3.In). This one-pot synthesis of enantiomerically pure 1,2-diol derivatives went as smoothly as the asymmetric Brown crotylation, affording products with uniformly high diastereoselectivity. 

Asymmetric hydroboration 2171 of prochiral alkenes with monoisopinocampheyl-borane in the molar ratio of 1 1, followed by a second hydroboration of non-prochiral alkenes with the intermediate dialkylboranes, provides the chiral mixed trialkylbo-ranes. Treatment of these trialkylboranes with acetaldehyde results in the selective, facile elimination of the 3-pinanyl group, providing the corresponding chiral borinic acid esters with high enantiomeric purities. The reaction of these intermediates with base and dichloromethyl methyl ether provides the chiral ketones (Eq. 130)2l8>. A simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities via B-allyldiisopinocampheylborane has been also reported 219),... 

Maiti and Roy reported a selective method for deprotection of primary allylic, benzylic, homoallylic and aryl TBS ethers using aqueous DMSO at 90° C. All other TBS-protected groups, benzyl ethers, THP ethers as well as methyl ethers remain unaffected. 

Asymmetric Coupling Reactions of Chiral Grignard Reagents Derived from Ephedrine Derivatives. Asymmetric coupling reactions of Allyl Bromide and chiral Grignard reagents derived from ephedrine methyl ether in the presence of Copper(I) Iodide (10 mol %) followed by oxidation affords optically active homoallyl alcohols with 60% ee (eq 12). ... 

The final approach was elegantly presented by Panek [44]. Several optically active ( )-crotylsilanes are available via stereoselective Ireland-Claisen rearrangement of enantiomerically pure vinylsilanes. Addition of the chiral crotylsilanes to acetals or to mixtures of aldehyde and trimethylsilyl methyl ether is effected by la to afford homoallylic ethers in exceedingly high diastereo- and enantioselectivity (Sch. 13). Occasionally a stoichiometric amount of la is required for allylation of aliphatic acetals, preserving the excellent level of asymmetric induction. The synthesis of (-F)-macbecin I involving triple use of the strategy imderscores the utility of the la-catalyzed asymmetric allylation [44c]. 

However, Narayanan and Iyer found that cleavage can be effected with boron trifluoride and acetic anhydride alone and that a lithium halide slows down the reaction and does not decrease elimination to the olefin. They obtained cholesteryl acetate from cholesteryl methyl ether (homoallylic) in 93% yield (15 hrs, at 0°). Cleavage of an allylic methyl ether (A -cholestene-3y3-ol methyl ether) required only 3 min. at —18° (90% yield) under less mild conditions the main product was the A Miene. Cleavage of saturated ethers was attended with considerable elimination. R. D. Youssefyeh and Y. Mazur, Tetrahedron Letters, 1287 (1962)... 

With rhodium as transition metal the product formation is strongly dependent on the substitution pattern and the solvent used. With dicarbonylchlororhodium dimer in methanol, 1,2,2-trimethylbicyclo[1.1.0]butane(34, = Me R = H) exclusively affords the cyclopropylmethyl methyl ether 35 in almost quantitative yield. However, when R = Ph and R = H or Me the formation of the homoallylic ether 36 is strongly favored. When an aprotic solvent is used, such as chloroform instead of methanol, no cyclopropylmethyl derivative is obtained. Instead the corresponding diene is isolated. ... 

Ethylmagnesiation of homoallylic alcohols (ethers). Ethylmagnesium chloride can add to the double bond of homoallylic alcohols on catalysts with Cp2ZrCl2 with high stereoselectivity. In the case of the an/i-homoallylic alcohol 1 (R=H) the reaction proceeds with high an/i-selectivity in the case of both the alcohol and the methyl ether. In contrast to the reaction of the syn-homoallylic alcohol 3, the reaction proceeds with... 

Tetrahydrofuransp- A new route to tetrahydrofurans involves cydization of an alkoxymethyl radical derived from a homoallylic alcohol. The precursor is obtained by conversion of the alcohol (1) to the (tributyltin)methyl ether (9,475), followed by Sn-Li exchange, and quenching with (C6HsS)2 to form an a-phenylselenenylmethyl ether 2. Treatment of 2 with BujSnH (AIBN) generates an alkoxymethyl radical that cyclizes... 

The reaction of allyltrimethylsilane with acetals to give homoallylic ethers, previously conducted with stoicheiometric amounts of Lewis acids, has now been shown to proceed in high yield under very mild conditions with catalytic quantities of trimethylsilyl trifluoromethanesulphonate. No reaction could be achieved with aldehydes (or ketones) in place of the acetals. By contrast, 3-chloroallyltrimethylsilane reacts with aromatic and aliphatic aldehydes, though not with ketones, in the presence of Lewis acids, to give methyl ethers of homoallylic alcohols (e.g. Scheme 67), a process involving an unusual methyl group transfer. 

Typical experimental procedure for the methoxyallylboration of aldehydes with (B)-(Z)-y-[methoxyallyl]diisopmocampheylborane scc-Butyl lithium (100 mmol) is added drop-wise to a weU-stirred solution of aUyl methyl ether (110 mmol) in 200 mL THF at-78°C and stirred for 0.5 h. lpC2BOMe (120 mol, 1.0 M solution in THF) is added to the reaction mixtnre and stirred at -78 C for 1 h. BF3 Et20 (150 mmol) is then added and the reaction mixtnre cooled to -lOO C. A precooled solution of the appropriate aldehyde (90 nunol) in 50 mL THF is added drop-wise to the reaction mixture at -100°C and stirred nntil complete consnmption of the reactants (analyzed based on "B NMR). The reaction mixtnre is oxidized with 50 mL of 3.0 M sodinm hydroxide and 50 mL of 30% hydrogen peroxide and stirred overnight at room temperatnre. The prodnct is extracted with Et20, washed with water, and dried over MgS04, concentrated in vacuo and pnrilied via colnmn chromatography to obtain the homoallylic alcohol. 

A Schlenk tube is charged with the allylic stannane (2.0 equiv.) and benzaldehyde (1.0 eq.), and the resulting mixture is maintained at 150 °C for 24-36 h. The crude homoallylic alcohol is directly loaded on a small portion of silica gel and purifred by flash chromatography Rf= 0.27, cyclohexane terf-butyl methyl ether = 10 1) to give the adduct in 76% yield (d.r. = 90 10,99% ee). 

In our efforts, we found that ethers other than methyl transfer efficiently as long as steric or electronic differences were insignificant. In fact, benzyloxymethyl substrates 57, readily prepared from protection of homoallylic alcohols with commercially available BOMCl, underwent efficient benzyl ether transfer (Scheme 37.16). This process significantly expands the scope of the reaction because, in contrast to methyl ethers, benzyl groups can be easily cleaved by hydrogenolysis. Thus, the ether transfer can provide access to orthogonally protected iy -l,3-diol units. 

Deamination of 19-amino-A Manosten-3p-ol provides a 9(10- 19)-<3Z t -lanostene derivative analogous to (341) (Cio methyl ether in place of Cio hydroxyl), presumably by way of a homoallyl-cyclopropylcarbinyl-homoallyl rearrangement 435). The initial product was considered to be the 3,10-diol, which underwent methanolysis to the Cio methyl ether during recrystallization. 

Another example is the hydrogenation of the homoallylic eompound 4-methyl-3-cyclohexenyl ethyl ether to a mixture of 4-methylcyclohexyl ethyl ether and methylcyclohexane. The extent of hydrogenolysis depends on both the isomerizing and the hydrogenolyzing tendencies of the catalysts. With unsupported metals in ethanol, the percent hydrogenolysis decreased in the order palladium (62.6%), rhodium (23 6%), platinum (7.1%), iridium (3.9%), ruthenium (3.0%) (S3). 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

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. 

A highly selective synthesis of homoallylic alcohols has been reported by Tietze et al.,917 who reacted methyl ketones, the chiral norpseudoephedrine derivative 285, and an allylsilane in the presence of a catalytic amount (0.2 mol%) of triflic acid [Eq. (5.340)]. The transformation was interpreted as an SN2 attack of the allylsilane to the protonated mixed acetal 286. The obtained ethers were then cleaved to the final product, homoallylic alcohols. 

Oxidation of allylic andhomallylic acetates (cf. 10,175-176).1 This system is an efficient catalyst for oxygenation of terminal alkenes to methyl ketones (Wacker process). Similar oxidation of internal olefins is not useful because it is not regioselective. However, this catalyst effects oxygenation of allylic ethers and acetates regioselectively to give the corresponding /i-alkoxy ketones in 40-75% yield. Under the same conditions, homoallylic acetates are oxidized to y-acetoxy ketones as the major products. 

Unsaturated 1,5-dicarbonyl compounds. The phenylthioalkylation of silyl enol ethers of carbonyl compounds (9, 521-522) can be extended to the synthesis of unsaturated 1,5-dicarbonyl compounds. In a typical reaction the enol silyl ether of a ketone is alkylated with the unsaturated chloride 1 under ZnBr2 catalysis to give a homoallyl sulfide. Ozonolysis of the methylene group is accompanied by oxidation of the phenylthio group sulfoxide elimination results in an unsaturated 1,5-aldehydo ketone (equation I). Alkylation with 2 results in a methyl ketone (equation II). 

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