Regio-and stereochemistry

Another strategy to control the regio- and stereochemistry of cycloaddidon is a silicon-tethered reacdon, as discussed in the secdon of nitronates fSecdon 8.2.3 fEq. 8.65. ... 

In this series both regio- and stereochemistry are markedly influenced by relatively small pressure changes, as illustrated by selected examples (9/). 

Scheme 36 RCM-based synthesis of aspicilin (189) effect of substrate substitution on regio-and stereochemistry [93]...

Among the many recent applications to natural products, syntheses of pyrrolizidine and indolizidine alkaloids that take advantage of the 1,3-dipolar cycloaddition methodology have been reviewed [8]. The regio- and stereochemistry [9] as well as synthetic appHcations [10] of nitrile oxide cycloadditions have also been discussed. 

Predict the products, including regio- and stereochemistry, for the following reactions ... 

Give the structure, including stereochemistry, of the expected products of the following reactions. Identify the critical factors that determine the regio- and stereochemistry of the reaction. 

The predictable regio- and stereochemistry make these reactions valuable in establishing stereochemistry in both acyclic and cyclic systems. 

These changes in regio- and stereochemistry are likely due to conformation changes and electrostatic factors within the cavity. The intrazeolite oxidations can be improved by use of fluorocarbon solvents, owing to an enhanced lifetime of 102 and to improved occupancy of the cavity by hydrocarbons in this solvent.176... 

Both the regio- and stereochemistry of Entry 6 are of interest. The regioselectivity is imposed by the rigid ring geometry, which favors enolization at the observed position. Inspection of a molecular model also shows that a-face of the enolate is more accessible. 

Diels-Alder reactions are attractive for synthetic application because of the predictable regio- and stereochemistry. There are, however, limitations on the types of compounds that can serve as dienophiles or dienes. As a result, the idea of synthetic equivalence has been exploited by development of dienophiles and dienes that meet the reactivity requirements of the Diels-Alder reaction and can then be converted to the desired structure. For each of the dienophiles and dienes given below, suggest a Diels-Alder reaction and subsequent transformation(s) that would give a product not directly attainable by a Diels-Alder reaction. Give the structure of the diene or dienophile synthetic equivalent and indicate why the direct Diels-Alder reaction is not possible. 

It should be noted that as early as 1993, Kurth and coworkers investigated the enzymatic transformation of bis-epoxides of type 8-51 using cytosolic epoxide hydrolase from rat liver. However, at that time the regio- and stereochemistry of the obtained THFs had not been investigated. 

Intermolecular Cycloaddition at the C=C Double Bond Addition at the C=C double bond is the main type of 1,3-cycloaddition reactions of nitrile oxides. The topic was treated in detail in Reference 157. Several reviews appeared, which are devoted to problems of regio- and stereoselectivity of cycloaddition reactions of nitrile oxides with alkenes. Two of them deal with both inter- and intramolecular reactions (158, 159). Important information on regio-and stereochemistry of intermolecular 1,3-dipolar cycloaddition of nitrile oxides to alkenes was summarized in Reference 160. 

This regio- and stereochemistry in these reactions can be accounted for as shown in Scheme 17.26 When coordinating electrophiles like ketones and aldehydes are used, the equilibrium between ij1- and 3-allyl complexes shifts to rj1, resulting in the formation of the least substituted -complex 52 preferentially. Carbon-carbon bond formation takes place via a six-membered ring transition state 53, leading to the formation of the branched homoallylic alcohols 54 with //-diastereoselectivity. 

Another Rh-catalyzed protocol that has potentially broad utility has come from the reactions of Cu(i) alkoxides with allylic carbonates.190,191 Under the action of Wilkinson s catalyst modified by P(OMe)3, a variety of primary, secondary, and even tertiary aliphatic alcohols undergo an allylic etherification process with a high degree of retention of regio- and stereochemistry, thus providing expeditious access to a and/or ct -stereogenic ether linkages (Scheme 5).192... 

Patterns for addition of the Schwartz reagent to multiple C—C bonds in terms of regio-and stereochemistry are well-established for most substituents, as is the fundamental chemistry of the newly formed Csp2—Zr and Csp3—Zr bonds. Conversion to halides and... 

The limited extent of intramolecular rearrangements undergone by the chiral oxonium ions 35 and 36 at 720 torr and at 40 °C (Table 22) allows their use for probing the regio- and stereochemistry of the displacement reactions of Scheme 19. In this case, the allylic alcohol, precursor of the chiral oxonium ions 35 and 36, acts as the nucleophile NuH. The relevant results are condensed in Scheme 21. 

Heck reactions, the hydroarylation methodology, has been a key tool in the synthesis of varions epibatidine analogues, due to the ability of this approach to address regio- and stereochemistry in substituted azabicyclo ring systems [6],... 

Subsequent monosilylation and Wittig reaction furnished unsymmetrical double diene 170. The synthesis of the other Diels-Alder partner started from bromophenol 173 (prepared in three steps from dimethoxytoluene), which was doubly metalated and reacted with (S,S)-menthylp-toluenesulfinate 173. CAN oxidation delivered quinone 171, which underwent a Diels-Alder reaction with double diene 170 to give compound 175 possessing the correct regio- and stereochemistry. Upon heating in toluene the desired elimination occurred followed by IMDA reaction to adduct 176, which was obtained in an excellent yield and enantioselectivity. Both Diels-Alder reactions proceeded through an endo transition state the enantioselectivity of the first cyclization is due to the chiral auxiliary, which favors an endo approach of 170 to the sterically less congested face (top face) (Scheme 27). 

Further efforts have been devoted to the synthesis of teUuro(thio)ketene acetals with high regio- and stereochemistry. The E and Z isomers were obtained by two different routes. The E isomer resulted by the syn hydroalumination of thioacetylenes with DIBAL-H followed by the addition of n-BuLi and capture of the obtained intermediate with BuTeBr. 

In particular, the formal positive charge present in polar cycloaddition would be expected to influence the formation and geometry of intermediate charge-transfer complexes and the electrophilic character of the reaction with alkenes. As will be seen later, these effects result in important influences upon the regio- and stereochemistry as well as the concertedness of polar cycloaddition. 

To rationalize the enantioselectivity of the TADDOL-catalyzed HDA reaction between Danishefsky s diene and benzaldehyde, eight possible diastereomeric transition states of different regio- and stereochemistry should in principle be considered for comprehensive analysis. The cycloaddition between the model diene and benzaldehyde can take place along two regio-isomeric meta (C1-06, C4-C5 bond formation) and ortho (C1-C5, C4-06 bond formation) reaction channels. For both of these pathways, an exo- and an endo-approach can be formulated (Scheme 11) [64]. 

The complexation of the base with the oxirane in nonpolar solvents drives the fi-deprotonation to occur from the syn face (see above), but also influences its regio- and stereochemistry. During the aggregation step, two conformational structures can be formed depending on which lone pair of the oxygen is used as the donor site. The relative stabilities of these complexes are largely influenced by nonbonded interactions between the base and the syn substituents on the epoxide (Scheme 16). 

Effect of Choice of Geometry on Relative Energies of Regio and Stereochemistry of Diels-Alder Cycloadditions of Substituted Cyclopentadienes with Acrylonitrile/ 6-31G Model... 

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