Stereochemistry and Regioselectivity

Two issues are of essential for predicting the structure of 1,3-DCA products (1) What is the regiochemistry and (2) What is the stereochemistry Many specific examples demonstrate that 1,3-dipolar cycloaddition is a stereospecific syn addition with respect to the dipolarophile, as expected for a concerted process. 

With some 1,3-dipoles, two possible stereoisomers can be formed by syn addition. These result from two differing orientations of the reacting molecules that are analogous to the endo and exo TS in D-A reactions. Phenyldiazomethane, for example, can add to unsymmetrical dipolarophiles to give two diastereomers. 

Each 1,3-dipole exhibits a characteristic regioselectivity toward different types of dipolarophiles. The dipolarophiles can be grouped, as were dienophiles, depending upon whether they have ERG or EWG substituents. The regioselectivity can be 

Apart from the role of substituents in determining regioselectivity, several other structural features affect the reactivity of dipolarophiles. Strain increases reactivity norbornene, for example, is consistently more reactive than cyclohexene in 1,3-DCA reactions. Conjugated functional groups usually increase reactivity. This increased reactivity has most often been demonstrated with electron-attracting substituents, but for some 1,3-dipoles, enol ethers, enamines, and other alkenes with donor substituents are also quite reactive. Some reactivity data for a series of alkenes with several 1,3-dipoles are given in Table 10.6 of Part A. Additional discussion of these reactivity trends can be found in Section 10.3.1 of Part A. 

Concerted. Cycloadditions, Unimolecular Rearrangements, and Thermal Eliminations 

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Reactivity. Explain the regioselectivity and stereochemistry observed in the transformations below. 

Reactivity. Propose a mechanism for each of the following transformations to explain the observed regioselectivity and stereochemistry. 

Hydroboration of alkenes.2 Wilkinson s catalyst is effective for catalysis of hydroboration with catecholborane (CB), which can differ from the regioselectivity and stereochemistry of uncatalyzed hydroboration with 9-BBN. In the case of... 

A mechanism is reported141 for the transformation of alkenes and cycloalkanes by trimethylchlorosilane and dimethyl sulfoxide into 2-chloroalkyl methyl sulfide and 2-chlorocycloalkyl methyl sulfide (equation 98). The regioselectivity and stereochemistry of... 

Huisgen and co-workers reported, in three papers (02T507, 02T4185 and 02HCA1523> the conversion of various 1,3,4-thiadiazolines 86 into thiocarbonyl ylides 87 via extrusion of N2. They then described cycloaddition reactions of these ylides 87 with various a,P-unsaturated esters and nitriles and postulated reaction mechanisms for the regioselectivity and stereochemistries observed in the transformations. 

Regioselectivity and stereochemistry have been studied in the case of the anodic methoxylation of A-acylpiperidines and A-acylmorpholines [234]. Because of steric constraints imposed by the intermediate formation of the planar A-acyhminium ions, substitution is directed to the secondary carbon rather than to the tertiary position. The same reason accounts for the axial methoxylation in this reaction. 

Kobayashi et have also investigated other modes of enzymatic polymerization to produce a novel cellulose-chitin hybrid polysaccharide. A sugar fluoride monomer of GlcNAc/3(l 4)Glc (17) was designed as a TSAS monomer for polymerization catalyzed by cellulase from Trichoderma viride. In the polymerization, monomer 17 was recognized by cellulase from T. viride, leading to a cellulose-chitin hybrid polysaccharide 18 with perfect regioselectivity and stereochemistry (Scheme 17). 

The mechanisms of the regioselectivity and stereochemistry of the ring-opening reactions of y3-butyrolactones by activated anions has been reviewed. A study of the mechanism of hydrolysis of y3-propiolactone has been reported. A mechanistic appraisal of diastereoselective and enantioselective syntheses of optically active j8-lactones has been made. An ab initio study on the thermal decomposition of y-butyrolactone has shown that decarbonylation is easier energetically than decarboxylation. ... 

Perugini R, Ruzziconi R, Sebastiani GV (1983) Synthesis of 2,3-dihalogeno-2,3-dihydrobenzofurans regioselectivity and stereochemistry. Gazz Chim Ital 113 149-152... 

Variously substituted oxazoline monomers, 2-ethyl, 2-n-pro-pyl, and 2-vinyl oxazoline monomers for HA, were newly prepared and polymerized with HAase catalysis. The reactions proceeded with total control of regioselectivity and stereochemistry, to afford the corresponding HA and Ch derivatives (unnatural polysaccharides) possessing N-propionyl, N-butyryl, and N-acryloyl group in every hexosamine unit (Scheme 40). Similarly, Ch derivatives were also achieved. The resulting N-acryloyl HA and Ch are functional polymers having a reactive vinyl group. 

The addition of primary phosphines to activated alkynes proceeds in the presence of KOH (Scheme 4.288) [451]. Representative substrates included several primary phosphines and a number of cyanoacetylenes. For the vast majority of examples, the conditions were mild, and moderate to excellent yields of the addition products were obtained. The addition reaction was regioselective for the addition of beta to the cyano group and stereoselective for the formation of the Z-isomer. While the addition of secondary phosphines to activated alkynes proceeded without the addition of a catalyst, no reaction was observed with the primary phosphines without the addition of the potassium hydroxide. The authors expanded upon this observation to investigate the addition of secondary phosphines to activated propargyl alcohols. In the absence of added bases, the addition reaction proceeded to generate the vinylphosphine in excellent yield with retention of the alcohol moiety. The regioselectivity and stereochemistry were the same in these reactions and resulted in the formation of Z-isomers. The authors have also reported the addition of... 

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