Hydroxyalkylation intramolecular

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Chromans have been obtained by the Pd-catalysed intramolecular cross coupling reaction involving aryl halides containing an ortto-hydroxyalkyl substituent <96JA10333>. 

Reaction of the carbanion of chloromethyl phenyl sulphoxide 409 with carbonyl compounds yields the corresponding 0-hydroxy adducts 410 in 68-79% yield. Each of these compounds appears to be a single isomer (equation 242). Treatment of adducts 410 with dilute potassium hydroxide in methanol at room temperature gives the epoxy sulphoxides 411 (equation 243). The ease of this intramolecular displacement of chloride ion contrasts with a great difficulty in displacing chloride ion from chloromethyl phenyl sulphoxide by external nucleophiles . When chloromethyl methyl sulphoxide 412 is reacted with unsymmetrical ketones in the presence of potassium tcrt-butoxide in tert-butanol oxiranes are directly formed as a mixture of diastereoisomers (equation 244). a-Sulphinyl epoxides 413 rearrange to a-sulphinyl aldehydes 414 or ketones, which can be transformed by elimination of sulphenic acid into a, 8-unsaturated aldehydes or ketones (equation 245). The lithium salts (410a) of a-chloro-/ -hydroxyalkyl... 

The grem-dibromocyclopropanes 152 bearing a hydroxyalkyl group, prepared by the addition of dibromocarbene to allylic or homoallylic alcohols, undergo an intramolecular reductive carbonylation to the bicyclic lactones 153. bicyclic lactone derived from prenyl alcohol is an important precursor for the synthesis of ris-chrysanthemic acid. (Scheme 54)... 

Acid-catalyzed intramolecular attack of nucleophilic hydroperoxide function on an oxirane ring results in formation of 3-(l-hydroxyalkyl)endoperoxides. For example, epoxidation of unsaturated hydroperoxide 320 affords oxirane-hydroperoxide 321 (66%), which through acid-catalyzed regioselective cyclization gives 1,2-dioxolane 322 (70%) (Scheme 79) . This type of reaction is applicable also to a more complex epoxide-hydroperoxide such as 323, which cyclizes to polyfunctionalized 5-membered cyclic... 

Ring opening of a 4-(hydroxyalkyl)-substituted oxazolone using dimethylamine gives an amide 245 that can be used as an intermediate in a subsequent intramolecular cyclization to prepare lactones 247 (Scheme 1.19) ... 

D-Camphor-lO-sulfonic acid (CSA) has been utilized to form aj-fused bicyclic acetals from hexopyranosides (Scheme 20) <1997TL849>. A silver terrafluoroborate-promoted cyclization of a series of 3-hydroxyalkyl-2-cyanopiperidines has been used to prepare the octahydropyrano[2,3- ]pyridine of upenamide (Scheme 21) <2004EJ01057>. Related pyranopyr-idines have been prepared using an intramolecular Wadsworth-Emmons cyclization <2003TL8545>. 

Intramolecular substitution for chloride or fluoride is particularly effective. Oxygen heterocycles with fused benzo rings are obtained from Cr(CO>3 complexes of fluorobenzene with an o-(hydroxyalkyl) side chain.39,60 For example, complexation of 3-(2-fluorophenyl)-l -propanol with [Cr(CO>3(pyridine)3] at 25 C in ether (promoted by BF3 Et20) followed by reaction in DMSO with excess potassium f-butoxide for 3 h at 25 C gave the chroman complex (14).60 The yield in the cyclization step was 75% and iodine decomplexation was quantitative (equation 12). Efforts to produce the dihydrobenzofuran under the same... 

Several poly(urea urethane) oligomers 28 (Figure 12) were prepared by one-component polycondensation of iV-(hydroxyalkyl)-2 -oxo-1,3-diazepane-l-carboxamides, which act as intramolecular blocked isocyanates <2005PLM 1459>. These oligomers are semicrystalline materials and their melting points show the odd/even effect observed earlier for [ ]-polyamides, [ ]-polyurethanes, poly(ester amide)s, and poly (amide urethane)s. Further analysis showed that the polymers are stable up to ca. 205-230 °C, the polymers with the lower number of methylene groups in the amino alcohol decomposing at the lowest temperature. 

Similar hypervalent iodine radicals (9-1-2) are formed in the reaction of alkyl radicals with alkyliodides (R + RI — R2I ), and as an intramolecular complex they are stable enough that a reaction with 02 is only low (Miranda et al. 2000). Such 9-X-2 radicals have also been postulated as intermediates in the reduction of alkylhalides by a-hydroxyalkyl radicals (Lemmes and von Sonntag 1982). 

Monocyclic Phosphoranide Anion. The intramolecular oxidative addition of hydroxyalkyl phosphites, which gives P-H phosphoranes, is well known (10). Some P-H phosphoranes are so stable that the open-chain P(III) tautomers cannot be detected spectroscopically or even by attempted H2O2 oxidation (8). Thus, it is surprising to find no evidence for an equilibrium between phosphine alcohol 1 and its closed-ring tautomer phosphorane 2. Phosphine 1 is quaternized by alkyl halides giving phosphonium halides such as 3. These in turn are converted to alkoxyphosphor-anes, such as 4 by NaH (Scheme I). 

The intramolecular hydroxyalkylation of aromatic compounds is a ring closure reaction. In the reaction example in Figure 5.31, it is followed by an El elimination, which leads to a styrene derivative. 

Hydroxyalkyl derivatives of seleno- and thio- chromones can be formed by the reaction of aldehydes with appropriate propynones in which an intramolecular Michael reaction is followed by an aldol condensation (Scheme 9) <02TL7039>. 

However, a considerable difference should be noted between a-hydroxyalkyl nitrilium ions 24 which contain an intramolecular nucleophilic center (OH group), and N-alkylnitrilium ions 26 which are the intermediates of a Ritter reaction45. The transformation of ions 24 into the N-acyliminium ions 25 (equation 11) is evidently an intramolecular rearrangement (see Sections V.B and V.C), while the nitrilium salts 26 can be converted into ions 25 only by an oxidative dehydrogenation of amides 273 (equation 12). 

The Pechmann reaction catalyzed by solid acid catalysts (e.g. zeolite H-BEA) in refluxing toluene has been reported by H. van Bekkum et al. (64). The reaction proceeds via transesterification and intramolecular hydroxyalkylation, followed by dehydration (Eq. 15.4.2). 

The Pechmann synthesis of coumarins via condensation of phenols with / -keto esters also involves an intramolecular hydroxyalkylation, following initial... 

Tertiary amines form complexes with mercury(II) ion, which then give iminium ions by loss of a piotoa Addition of perchloric acid permits isolation of the iminium ion as the perchlorate salt and generally the more-substituted ion is favored (equation 14). Intramolecular trapping by a hydroxyalkyl group is also possible to form aminals (equation 15). The lactam products result from over-oxidation, which is promoted by heat. Basification on the other hand usually allows the isolation of enamines although hydroxyenamines have been obtained by reaction of enamines with mercury(II) acetate (equation 16), while dihydroaromatic systems undergo aromatization (equation 17). ... 

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