Acetals, acid catalyzed ethers

The first enantioselective total synthesis of tetracyclic sesquiterpenoid (+)-cyclomyltaylan-5a-ol, isolated from a Taiwanese liverwort, was accomplished by H. Hagiwara and co-workers. They started out from Hajos-Parrish ketone analogue, (S)-(+)-4,7a-dimethyl-2,3,7,7a-tetrahydro-6/-/-indene-1,5-dione, that could be synthesized from 2-methylcyclopentane-1,3-dione and ethyl vinyl ketone in an acetic acid-catalyzed Michael addition followed by an intramolecular aldol reaction. The intramolecular aldol reaction was carried out in the presence of one equivalent (S)-(-)-phenylalanine and 0.5 equivalent D-camphorsulfonic acid. The resulting enone was recrystallized from hexane-diethyl ether to yield the product in 43% yield and 98% ee. Since the absolute stereochemistry of the natural product was unknown, the total synthesis also served to establish the absolute stereochemistry. 

An interesting comparison of catalytic activities of synthetic beidellite and montmorillonite and PILCS prepared from them was recently reported [69]. The reactions examined included secondary amine formation from cyclohexylamine, ester production from 1-hexene and acetic acid and ether synthesis from pentanol. In all cases, the reactivity of the PILCS was much lower than that of the unpillared clays, whereas the montmorillonite was generally more effective than the beidellite. These results are not surprising in that all of the reactions are Br<(Jnsted-acid-catalyzed and the observed decreased activity of the PILCS may derive from a greater loss of protons to the layers by the pillared clays. This is also in keeping with the findings of Occelli and Tindwa [5] that the PILCS are mainly Lewis acids after heat treatment. 

Ether Cle va.ge, This is commonly observed as the initial step in the metaboHsm of the phenoxy herbicides 2,4-D (1), (2,4,5-trichlorophenoxy)acetic acid (2,4,5-T), and mecoprop (17). A wide variety of bacteria have been isolated which are able to catalyze this reaction (eq. 

The reactions of oxiranes with thiocyanate ion or with thiourea are usually done in homogeneous solution in water, alcohols or alcohol-acetic acid. The use of silica gel as a support for potassium thiocyanate in toluene solvent is advantageous for the simple work-up (filtration and evaporation of solvent) (80JOC4254). A crown ether has been used to catalyze reactions of potassium thiocyanate. 

The dimethyl acetal (94) is readily prepared from the 22-aldehyde (93) by direct reaction with methanol in the presence of hydrogen chloride. Ena-mines (95) are formed without a catalyst even with the poorly reactive piperidine and morpholine.Enol acetates (96) are prepared by refluxing with acetic anhydride-sodium acetate or by exchange with isopropenyl acetate in pyridine.Reaction with acetic anhydride catalyzed by boron trifluoride-etherate or perchloric acid gives the aldehyde diacetate. 

Symmetrical labile ethers such as cycloalkenyl ethers (15) or mixed acetals (16) can also be prepared from the 3-hydroxyl group by acid-catalyzed exchange etherification or by acid-catalyzed addition to cyclohexanone methyl enol ether. 

B-Homosteroids have also been prepared by acid-catalyzed reaction of diazomethane with a,/5-unsaturated ketones. 3/ -Hydroxycholest-5-en-7-one acetate (57) reacts with diazomethane in the presence of concentrated fluoroboric acid, boron trifluoride etherate or aluminum chloride to give 3yS-hydroxy-B-homo-cholest-5-en-7a-one acetate (67). The 7a-keto group is reported to be chemically less reactive than an 11-keto group. 

Procedures have been worked out which increased the yield of 2-bromothiophene to 78% on direct bromination in acetic acid-ether mixtures and to 67% in carbon tetraehlorided With the mild brominating agent, dioxane dibromide, quantitative yields of 2-bromothiophene are obtained. A very convenient procedure for the iodination of thiophenes consists of the acid-catalyzed (HzSOi) reaction with iodine and HIO3, giving 2-iodothiophene in 75% yieldd In contrast to the HgO method, all the iodine is utilized. 

For example, using (/ )-5-trimethylsilyl-2-cyclohexenone as the chiral Michael acceptor, optically active m // .v-3.5-disubstituied cyclohexanones 1 are obtained via a Lewis acid catalyzed addition of silylenol ethers or ketene acetals. 

The ionization of (E)-diazo methyl ethers is catalyzed by the general acid mechanism, as shown by Broxton and Stray (1980, 1982) using acetic acid and six other aliphatic and aromatic carboxylic acids. The observation of general acid catalysis is evidence that proton transfer occurs in the rate-determining part of the reaction (Scheme 6-5). The Bronsted a value is 0.32, which indicates that in the transition state the proton is still closer to the carboxylic acid than to the oxygen atom of the methanol to be formed. If the benzene ring of the diazo ether (Ar in Scheme 6-5) contains a carboxy group in the 2-position, intramolecular acid catalysis is observed (Broxton and McLeish, 1983). 

The Mukaiyama aldol reaction refers to Lewis acid-catalyzed aldol addition reactions of silyl enol ethers, silyl ketene acetals, and similar enolate equivalents,48 Silyl enol ethers are not sufficiently nucleophilic to react directly with aldehydes or ketones. However, Lewis acids cause reaction to occur by coordination at the carbonyl oxygen, activating the carbonyl group to nucleophilic attack. 

Methoxymethylation of alcohols is generally achieved through alkylation with chloromethyl methyl ether. The procedure described here for the preparation of Bu3SnCH20CH20CH3 avoids the use of the highly toxic chloromethyl ether by employing an acid-catalyzed acetal exchange reaction with dimethoxymethane for the... 

Still another possibility in the base-catalyzed reactions of carbonyl compounds is alkylation or similar reaction at the oxygen atom. This is the predominant reaction of phenoxide ion, of course, but for enolates with less resonance stabilization it is exceptional and requires special conditions. Even phenolates react at carbon when the reagent is carbon dioxide, but this may be due merely to the instability of the alternative carbonic half ester. The association of enolate ions with a proton is evidently not very different from the association with metallic cations. Although the equilibrium mixture is about 92 % ketone, the sodium derivative of acetoacetic ester reacts with acetic acid in cold petroleum ether to give the enol. The Perkin ring closure reaction, which depends on C-alkylation, gives the alternative O-alkylation only when it is applied to the synthesis of a four membered ring ... 

The scope of the acid-catalyzed formation of C-glycosyl compounds has been greatly expanded with the finding that enol ethers and ketene acetals can be used as the carbon source in electrophilic substitution reactions at the anomeric center.126 Treatment of 198 with the trimethylsilyl enol ether derived from cyclohexanone, in the presence of stannic chloride, led to 2-(2,3,5-tri-0-benzoyl-/J-D-ribofuranosyl)cyelohexanone (206), presumably by way of the inter-... 

Gronowitz adapted this technology to one-pot syntheses of indole-3-acetic acids and indole-3-pyruvic acid oxime ethers from A-BOC protected o-iodoanilines [328, 329]. Rawal employed the Pd-catalyzed cyclization of A-(o-bromoallyl)anilines to afford 4- and 6-hydroxyindoles, and a 4,6-dihydroxyindole [330], and Yang and co-workers have used a similar cyclization to prepare 8-carbolines 287 and 288 as illustrated by the two examples shown [331]. The apparent extraneous methyl group in 288 is derived from triethylamine. 

Furans.2 Enol ethers, p-dicarbonyl compounds, and Mn(III) acetate (2 equiv.) react in acetic acid (25°) to form l-aIkoxy-l,2-dihydrofurans, which form furans readily on acid-catalyzed elimination of ROH. 

Izumi and Urabe [105] found first that POM compounds could be entrapped strongly on active carbons. The supported POMs catalyzed etherization of ferf-butanol and n-butanol, esterification of acetic acid with ethanol, alkylation of benzene, and dehydration of 2-propanol [105], In 1991, Neumann and Levin [108] reported the oxidation of benzylic alcohols and amines catalyzed by the neutral salt of Na5[PV2Mo10O40] impregnated on active carbon. Benzyl alcohols were oxidized efficiently to the corresponding benzaldehydes without overoxidation ... 

Lewis acid-catalyzed ene reactions proceed between allenyl sulfides, e.g. 330, and aldehydes 329 to afford cis-trans mixtures of 1,3-butadienes 331 (Scheme 8.90) [168, 175b], Similar ene reactions observed with imines such as 332 provide the corresponding allylamines [168,177]. It was also found that the ene reaction of 1-silylated allenyl sulfide 333 with various aldehydes (or acetals) furnishes a,/l-unsaturatcd acyl compounds such as 334 and 335 under BF3-etherate catalysis [175b]. 

Vinyl ethers are important raw materials in the production of glutaraldehyde, as well as of vinyl polymer materials which contain oxygen and are expected to degrade easily in Nature. The [IrCl(cod)]2 catalyzes an efficient exchange reaction between vinyl acetate 57 and alcohols or phenols 58, leading to the corresponding vinyl ethers 59 (Equation 10.11) [27]. Usually, the acid-catalyzed exchange reaction between alcohols and vinyl acetate results in alkyl acetates 60, and also to vinyl alcohol 61 which is readily isomerized to acetaldehyde 62. 

This protective group is introduced by an acid-catalyzed addition of the alcohol to the vinyl ether moiety in dihydropyran. />-Toluenesulfonic acid or its pyridinium salt is used most frequently as the catalyst,3 although other catalysts are advantageous in special cases. The THP group can be removed by dilute aqueous acid. The chemistry involved in both the introduction and deprotection stages is the reversible acid-catalyzed formation and hydrolysis of an acetal (see Part A, Section 8.1). 

The methylthiomethyl (MTM) group is a related alcohol-protecting group. There are several methods for introducing the MTM group. Alkylation of an alcoholate by methylthiomethyl chloride is efficient if catalyzed by iodide ion.9 Alcohols are also converted to MTM ethers by reaction with dimethyl sulfoxide in the presence of acetic acid and acetic anhydride10 or with benzoyl peroxide and dimethyl sulfide.11 The latter two methods involve the generation of the methylthiomethylium ion by ionization of an acyloxysulfonium ion (Pummerer reaction). 

The procedure described illustrates a new general synthetic method for the preparation of (E)-3-allyloxyacryl ic acids and their conversion to a-unsubstituted y,5-unsaturated aldehydes by subsequent Claisen rearrangement-decarboxyl at ion. Such aldehydes are traditionally prepared by Claisen rearrangements of allyl vinyl ethers. Allyl vinyl ethers are typically prepared by either mercury-catalyzed vinyl ether exchange with allylic alcohols or acid-catalyzed vinylation of allylic alcohols with acetals. The basic conditions required for alkoxide addition to the betaine to produce carboxyvinyl allyl ethers, as described in this report, nicely complements these two methods. In addition, this Claisen rearrangement is an... 

---