Acid catalyzed intramolecular

The Pictet-Spengler reaction is an acid-catalyzed intramolecular cyclization of an intermediate imine of 2-arylethylamine, formed by condensation with a carbonyl compound, to give 1,2,3,4-tetrahydroisoquinoline derivatives. This condensation reaction has been studied under acid-catalyzed and superacid-catalyzed conditions, and a linear correlation had been found between the rate of the reaction and the acidity of the reaction medium. Substrates with electron-donating substituents on the aromatic ring cyclize faster than the corresponding unsubstituted compounds, supporting the idea that the cyclization process is involved in the rate-determining step of the reaction. 

The reaction conditions for the ene reaction of simple starting materials are, for example, 220 °C for 20 h in an aromatic solvent like trichlorobenzene. Lewis acid-catalyzed intramolecular reactions have been described, e.g. with FeCls in dichloromethane at -78 °C." Yields strongly depend on substrate structure. 

Acid catalyzed intramolecular Diels-Alder reactions in lithium perchlorate-diethyl ether acid promoted migration of terminal dienes prior to [4 + 2] cycioaddition in conformationally restricted substrates [101]... 

Base-catalyzed aldol reactions have been carried out intramole-cularly.241 The aqueous acid-catalyzed intramolecular aldol condensation of 3-oxocyclohexaneacetaldehyde proceeded diastereoselectively (Eq. 8.95).242... 

Finally in 2005, Hutt and Mander reported their strategy for the synthesis of nominine (Scheme 1.3) [29], The approach relies upon construction of the steroidal ABC carbocyclic ring structure followed by stepwise preparation of the fused aza-ring system. In the key sequence of the synthetic study, enone 50 was oxidized to dienone 51 with DDQ followed by Lewis acid-catalyzed intramolecular conjugate addition of the methylcarbamate to the newly formed dienone to deliver pyrrolidine 52. 

The amino pyrrole 29 derived from the reaction with phenylhydrazine <1998JOC9131> was found to undergo an acid-catalyzed intramolecular condensation with the carbonyl present to give the 3//-pyrrolo[l,2-A pyrazole 30 ring system in a good yield (75%) (Equation 2). 

Cycloheptane annelation.1 A new route to cycloheptanes is based on a Lewis acid-catalyzed, intramolecular addition of an allylsilane group to a 3-vinylcycloal-kenone (equation I). This annelation has been applied to a synthesis of the ses-... 

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

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... 

CEJ1358> and the ruthenium mediated isomerization of double bonds (cf. Scheme 89, Section 8.11.7) <2007TL137> are recent examples of transition metal catalyzed manipulations at the side chain carbon atoms of 1,3-heterocycles. A novel side-chain addition reaction of aldehydes to 6-alkylidene-l,3-dioxin-4-ones was used for the construction of intermediates of lophotoxin <2006CJC1226>. An acid-catalyzed intramolecular cycloaddition of a hydroxy group to an alkene has been effected by the presence of an adjacent 1,3-dithiane moiety <2006TL4549>. 

An equally important general type of synthesis which proceeds via heterocyclization with formation of a ring bond y to the heteroatom involves acid-catalyzed intramolecular electrophilic aromatic substitution, especially those in which a carbonyl group functions as the electrophile. The most common structural requirements are summarized in (18)-(2l) ... 

An interesting fur n synthesis based on acid-catalyzed intramolecular condensation has been reported by Fritel and Bamnger,t> a using l(2-epoxy-l (2-oxoprcpyl -cyclohexane. Attack is bolievcd by these authors to be led by the enolic form of the ketone, as shown in... 

Intramolecular Sakurai reaction. Allylic and propargylic silanes can undergo a Lewis acid catalyzed intramolecular Sakurai reaction.1 In cyclization to hydrin-danones, the stereochemical outcome can differ from that obtained by fluoride ion catalysis (presumably kinetically controlled cyclization), equation (I).2... 

In a Lewis-acid catalyzed intramolecular ene reaction,4 the alkene (ene) reacts in a pericyclic fashion with an enophile to form two new a bonds with concurrent migration of the allylic double bond. 

Lewis acid catalyzed intramolecular coupling of allylsilanes with aziridines serves as a useful route for the synthesis of carbocycles having the y-amino olefin unit 104 (equation 80)149. However, this reaction does not occur in an intermolecular manner. 

The use of the Fmoc-protected 4-nitrophenyl carbamate building blocks and resins with acid-labile linkers allows synthesis of the final products with C-terminal carboxylic acid or amide groups (Fig. 6). Unfortunately, Fmoc solid-phase synthesis of oligourea peptidomimetics with C-terminal carboxylic acid also leads to formation of corresponding hydantoin byproducts (53-56) (Fig. 7). In this case hydantoin formation arises as a result of an acid-catalyzed intramolecular cyclizafion reaction. It has been reported that the ratio of desired oligourea pepfidomimetic acid product and hydantoin byproduct is approximately 2 1 (53). However, these two compounds are in principle separable by preparative HPLC. 

A stereocontrolled synthesis of 2,4,5-trisubstituted tetrahydropyrans 331 can be achieved via a Lewis-acid-catalyzed intramolecular Prins cyclization of homoallylic acetals 332. Incorporation of a variety of substituents at C-4 of the resulting tetrahydropyrans is possible by simple variation of the reaction conditions (Equation 141, Table 13) <2001CC835>. 

Fig. 15.32. Sequence of a Lewis-acid-catalyzed inter-molecular and a Lewis-acid-catalyzed intramolecular Diels-Alder addition. The first Diels-Alder addition occurs with simple and the second with induced diastereoselec-tivity.

Lewis acid catalyzed intramolecular vinylogous aldol reaction of 5-substituted furoic acids afforded spiro compounds with high diastereoselectivity, which were converted to the zaragozic acids <02JOC4200>. 

Dimethyl-6-(trimethylsilyl)-5,8,9,10-tetrahydro-5-silabenzocyclooctane 53 (Figure 2) was obtained in 48% yield via the Lewis acid-catalyzed intramolecular fra r-hydrosilylation of l-(dimethylsilanyl)-2-[5-(trimethylsilyl)-pent-4-enyl]-benzene according to the procedure discussed above for its seven-membered ring analogue 31 <2000JOC8919>. 

Intramolecular Diels-Alder reactions. The Lewis acid-catalyzed intramolecular Diels-Alder reaction is useful for construction of cw-fused bicyclo[6.4.0]dodecanes. Thus... 

Diastereofacial-setective intramolecular Diels-Alder reactions. Trienecarbox-imides derived from ahiral oxazolidones undergo Lewis-acid-catalyzed intramolecular Diels-Alder reactions With high endo- and diastereofacial selectivity (endo/exo 100 1). 

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