Intramolecular regioselectivity

This reaction is applied to the intramolecular regioselective cyclization of the 3-alkoxybenzoeyelobutenedione 60 to 61, a precursor of nanaomycin A 62 [33], (Scheme 23)... 

An intramolecular regioselective sulfenocyclization of unsaturated ureas 447 resulted in formation of 5,6-dihydro-4//-l,3-oxazine derivatives 449 (Scheme 86). The procedure employed phenylsulfenyl chloride and ethyldiisopro-pylamine to generate an episulfonium ion intermediate 448, from which the cyclic products 449 were formed by internal nucleophilic displacement <1995M609>. 

Nitrogen-based nucleophiles continue to remain popular in ring-opening reactions of aziridines. a-Substituted-a-methoxycarbonyl-V-nosylaziridines were opened with a variety of functionalized amines to provide access to enantiopure a,a -disubstituted (3-lactam scaffolds for ditopic peptidomimetics <07OL101>. A related intramolecular regioselective 3,Y-aziridine ring opening with an a-amino functionality was reported in the synthesis of... 

TL22 429 (1981) (intramolecular regioselectivity) 23 4891 (1982) (transidon state stereoselecdvity) ... 

Snieckus applied the intermolecular version of this reaction for a highly stereoselective synthesis of )8-amino acids (Scheme 31, Eq. 31.1) [118], Ikeda used an intramolecular regioselective reaction to synthesize the core of (+ )-epibatidine (Eq. 31.2) [119]. 

Intramolecular regioselective cycloadditions with unactivated olefins have been described by Sammes and Watt. Thermolysis of the pyridine betaine (254) at... 

The ability of the in situ generated aqflpalladium complexes to activate carbon-carbon triple bonds toward intramolecular nucleophilic attack emerged as a valuable tool for the synthesis of functionalized heterocycle derivatives (Scheme 9.28). The reaction is considered to proceed through the intramolecular regioselective nucleophilic attack across the carbon-carbon triple bond activated by coordination to the acylpalladium complex, followed by a reductive elimination step that produces the functionalized cyclic derivative and regenerates the catalytic species. 

We begin with the discussion of intramolecular reactions. An example of a regioselec-tive Dieckmann condensation (J.P. Schaefer, 1967) used an educt with two ester groups, of which only one could form an enolate. Regioselectivity was dictated by the structure of the educt. 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

In principle, the direct hydride addition or catalytic hydrogenation, which did not give chlorins, was replaced by an electrocyclic intramolecular addition which is much easier with the above system. Complete regioselectivity was also achieved since electrocyclization did not occur with the resonance-stabilized ring C. 

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-... 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

The regioselectivity of the reaction with unsymmetrical alkynes is poor. Mixtures of isomers are obtained with alkyl substituted acetylenes, if the alkyl groups do not differ much in size. A solution to this problem has been reported by Semmelhack et al. The reactants are connected by a -OCHaCHaO-tether, which can later be removed the coupling step thus becomes intramolecular ... 

Woodward s ingenious synthesis of chlorophyll a is based, in the first part of the synthetic approach, on a classical porphyrin synthesis using two dipyrrylmethanes for the formation of the macrotetracycle. The problem of regioselectivity in the connection of the two unsymmetric pyrrylmethane halves 1 and 2 was solved by the formation of SchifF base 3 between the two halves prior to the condensation so that the macrotetracycle formation occurred by an intramolecular reaction. 

As for chlorins and bacteriochlorins, reactions at the chromophore periphery of porphyrins can be used to prepare isobacteriochlorins. The lack of regioselectivity in these reactions necessitates the use of highly symmetric porphyrins as starting materials. In some cases, intramolecular reactions have been used to solve the problems of regioselectivity. 

Lindo-rv.ff oselecli ve oxacydization of polyepoxides is less common the first ster-eospedfic tandem endo-regioselective biomimetic oxacydization of polyepoxides to fused THP rings has only recently been reported [38a], The cyclization of the hydroxy-methoxymethyl-substituted triepoxide 75 (a 1,4,7-triepoxide), promoted and directed by La(OTf)3 through an intramolecular chelation and based on a procedure originally described for a monoepoxide system [38b], afforded the tri-... 

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