Acid-catalyzed intramolecular dehydration

Chemically amplified negative resists based on acid-catalyzed intramolecular dehydration... 

Full details of a careful study of the regio- and stereospecific intramolecular [4 + 2] cycloadditions of o-quinone methides generated by the thermal or acid-catalyzed (CF3CO2H) dehydration of o-hydroxybenzyl alcohols have been described 75 and have found application in the total synthesis of enantiomerically pure (3/ )-26 and (3/ )-27 possessing the ring system and correct absolute configuration of the cannabinol family [Eq. (47)]. 

Another example dealing with a, 3-unsaturated ketones was reported by Gems et al. [110], Ketones 327 were smoothly converted to cyanohydrins by treatment with TMSCN, which on reduction with LiAlH, afforded the aminoalcohols 328. Acid catalyzed intramolecular cyclization gave 329, which by dehydration gave the pyrroles 330 generally in good yields. 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

Figure 4 The biosynthesis of nisin A as a representative example of the posttranslational maturation process of lantibiotics. Following ribosomal synthesis, NisB dehydrates serine and threonine residues in the structural region of the prepeptide NisA. NisC subsequently catalyzes intramolecular addition of cysteine residues onto the dehydro amino acids in a stereo- and regioselective manner. Subsequent transport of the final product across the cell membrane by NisT and proteolytic cleavage of the leader sequence by NisP produces the mature lantibiotic. For the sequence of the leader peptide, see Figure 6. Adapted with permission from J. M. Willey W. A. van der Donk, Annu. Rev. Microbiol. 2007, 61, 477-501.

Step 2 Dimethyl acetal hydrolysis ester hydrolysis followed by decarboxylation intramolecular acid-catalyzed aldol condensation followed by dehydration. 

Another efficient synthesis of i7-norgestrel (209) begins with the condensation of 2-ethyl-1,3-cyclopentanedione (200, R = C2H5) with methyl vinyl ketone (199), producing (201). An asymmetric, intramolecular aldol condensation of (201) that is catalyzed by (T)-(—)-prohne followed by an acid-catalyzed dehydration yields hydrindandione (202) in 97% optical purity (205). Condensation of (202) with formaldehyde and benzenesulfinic acid generates (203) in 85% yield. 

The thiadiazoles are formed during the acid catalyzed dehydration of (XCa) or (XCb) which are themselves the reaction products of an intramolecular attack of the thioxo group on the carbonium ion (LXXXIX) that is formed by the protonization of the amide carbonyl function (LXXXVIIIa). 

Furthermore, 1,2-propyleneglycol and other polyols containing vicinal OH-groups could be reacted to valuable aldehydes and ketones. Thereby an acid catalyzed dehydration is subsequently followed by an intramolecular rearrangement according... 

Poly[4-(2-hydroxy-2-propyl)styrene] undergoes acid-catalyzed dehydration to yield a stable tertiary benzylic carbocation, which then eliminates a p-pro-ton to form a pendant olefinic structure (Fig. 119) [353]. This intramolecular dehydration reaction converts the hydrophilic alcohol to a highly lipophilic olefin and allows negative tone imaging with a polar alcohol as a developer. 

Sorbitan esters can be produced by transesterification in the presence of basic catalysts [104], This process does not, however, give satisfactory results-dehydra-tion of sorbitol is incomplete and, therefore, sorbitol esters can be the major products [105], Nowadays the acid-catalyzed direct esterification is the major route practiced in industry. Under these conditions both intramolecular dehydration and esterification occur to satisfactory extents [106]. When fatty acids in large excess are reacted for longer times sorbitan triesters are formed these can be used as water-in-oil emulsifiers. 

Intramolecular enamine formation between an aldehyde or ketone and the nitrogen atom of a piperidine ring can serve as the key step in the preparation of quinolizidine derivatives. For example, the ketal (184), prepared by double addition of the lithio derivative (183) to 6-methoxy-2,3,4,5-tetrahydropyridine, can be easily cyclized to the quinolizidine derivative (185) by double acid-catalyzed deprotection, cyclization, and dehydration (Scheme 31). These reactions constitute the first steps of a stereocontrolled total synthesis of the alkaloid ( )-porantherine <87JA4940>. 

Thieno[2,3-c]furan and thieno[2,3-c]pyrrole also behave as thiophene-2,3-quinodimethane equivalents. Thus, intramolecular Diels-Alder reaction of the furan (588) followed by acid-catalyzed dehydration affords the benzo[6]thiophene (589) in good overall yield (Scheme 122) <88TLI 137>. The Diels-Alder reaction of the pyrrole (590) with DMAD followed by oxidation of the resulting adduct (591) affords the benzo[ft]thiophene (592) with loss of nitrosomethane (Scheme 123) <90JOC2446>. 

A -piperideine-2-carboxylic acid which is subsequently converted into pipecolic acid, the molecule that is entirely incorporated. The other lysine unit provides the C5N (N-8, C-9 to C-13) through cadaverine, which is generated by stereospecific decarboxylation of the amino acid catalyzed by lysine decarboxylase. Intramolecular cyclization of cadaverine affords 2,3,4,5-tetrahydropyridiniuni, which undergoes nucleophilic attach by pipecolic acid to generate l,2-biperidine-2-carboxylic acid. A further intramolecular cyclization generates imidazo-dipyridin-one which upon reduction, dehydration, and subsequent oxidation produces anosmine (Figure 5.88) [333, 334]. 

Figure 7.21 Synthesis of sorbitan esters by intramolecular dehydration of sorbitol in the presence of an acid at 150-200°C and subsequent base-catalyzed esterification with fatty acids at 200-250°C.

The mechanism involves an aldol reaction with dehydration, followed by a Michael addition, and then an intramolecular aldol with dehydration (all base catalyzed). Loss of the two ester groups begins with an acid-catalyzed hydrolysis, followed by decarboxylation of each of the resulting carboxylic adds. 

Bradsher proposed that the mechanism initially involved reversible addition of the proton to the carbonyl group of 1 to form 7, followed by intramolecular Friedel-Crafls-type electrophilic attack on the aryl ring by the positively charged species in 8.2,5,13-15 Restoration of aromaticity through proton loss from 9 followed by acid-catalyzed 1,4-dehydration of carbinol 2 furnished the anthracene derivative 3. 

Reaction (5) is an intramolecular acid-catalyzed dehydration of a 1,5-diol to give a cyclic ether. 

Hajos and Parrish at Hoffmann La Roche discovered that proline-catalyzed intramolecular aldol reactions of triketones such as 104 and 107 furnish al-dols 105 and 108 in good yields and vith high enantioselectivity (Scheme 4.17). Acid-catalyzed dehydration of the aldol addition products then gave condensation products 106 and 109 (Eqs. (1) and (2)). Independently, Eder, Sauer, and Wiechert at Schering AG in Germany directly isolated the aldol condensation products vhen the same cyclizations vere conducted in the presence of proline (10-200 mol%) and an acid co-catalyst (Eqs. (3) and (4)). 

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