Bond additivity approach

Additivity schemes with fixed bond energy (or enthalpy) parameters plus a host of corrective factors reflecting nonbonded steric interactions have a long history in the prediction of thermochemical properties, such as the classical enthalpy of formation of organic molecules. AUen-type methods, for example, nicely Ulustrate the usefulness of empirical bond additivity approaches [1,2]. 

Ab initio calculations at the HF/6-31G level have been used to explore energy changes, structural variation, and electron density shifts during jr-face selective addition of substituted acetylide ions to cyclohexanone and cyclohexanethione. Charge polarization of the jr-bond on approach of the nucleophile is such that the carbonyl carbon becomes considerably electron deficient for most of the reaction path (and may... 

A method involving the use of atom equivalents for relating ab initio energies to heats of formation has also been suggested (Ibrahim et a/., 1985 and 1987). In this approach, atom equivalents were determined based on the environment in which they reside consequently, this method corresponds to an intermediate method between group and bond additivity methods. 

This [3 + 2] addition approach has been extended successfully to indole derivatives. The ready availability of the precursor tosylanilides provides a novel and useful complement to the current approach (94MI3). However, me(a-substituted tosylanilide yields a mixture of two regioisomeric indoles 107a and 107b in different ratios depending on the nature of substitutents (Scheme 30). Furthermore, the reaction of o-methyltosylamide with 102 does not produce any detectable amount of the desired indole, plausibly due to the repulsive peri-type steric interactions as indicated in 108, which would be unavoidable as the carbene approaches the CH bond. 

An alternative approach in the asymmetric catalysis in 1,3-dipole cycloaddition has been developed by Suga and coworkers. The achiral 1,3-dipole 106 was generated by intramolecular reaction of an Rh(ii) carbene complex with an ester carbonyl oxygen in the Rh2(OAc)4-catalyzed diazo decomposition of <9-methoxycarbonyl-o -diazoacetophenone 105 (Scheme 12). The asymmetric induction in the subsequent cycloaddition to G=G and G=N bond was achieved by chiral Lewis acid Sc(iii)-Pybox-/-Pr or Yb(iii)-Pybox-Ph, which can activate the dipolarophile through complexation. With this approach, up to 95% ee for G=0 bond addition and 96% ee for G=G bond addition have been obtained, respectively. ... 

A somewhat more chemically based empirical correction scheme is the bond-additivity correction (BAG) methodology. In the BAG-MP4 approach, for instance, the energy of a molecule is computed as... 

Scheme 3 illustrates retrosynthetic analysis of the E and F series of PGs. The widely used Corey synthesis (2) takes notice of the presence of the two olefinic bonds in the side chains of PGF2a. The actual synthesis consists of a two-fold Wittig-type chain extension of a chiral dialdehyde equivalent with four defined stereogenic centers derived from cyclopentadiene via a series of bicyclic intermediates. A similar sequential synthesis has been developed at Upjohn Co. (la). These chemical syntheses are much more economical than enzymatic methods and are used for commercial synthesis of certain PGs. An alternative pathway pioneered by Sih is the conjugate addition approach (3). Nucleophilic addition of an E-olefinic co side-chain unit to a cyclopentenone in which the a side chain is already installed leads directly to PGE-type compounds. Untch and Stork used an co chain unit with a Z-olefinic bond (4). The most direct and flexible synthesis is the convergent three-component coupling synthesis via consecutive linking of the two side chains to unsubstituted 4-hydroxy-2-cyclopentenone derivatives (5, 6). 

Compared with the single-bond construction approach of (3-lactam synthesis, the ketene-imine cycloaddition, which includes carbenoid insertion and the Staudinger reaction, have been widely used [56, 65]. Due to the ready availability of both imines and ketenes, the Staudinger reaction has provided a useful and economical approach for the synthesis of (3-lactams. In addition, the ketene-imine cycloaddition is efficient, which constructs the (3-lactam four-member ring in just one-step... 

This nitrene-addition approach was used by Knight to synthesize vinyl aziridines from 1,3-dienes using PhI=NTs and a copper catalyst. The more electron-rich double bond is selectively transformed in most cases. When the electronic difference is negligible the regioselectivity is then determined by steric hindrance. A mixture of cis and tram isomers is usually obtained [95SL949],... 

The observed absolute configuration of the products is in compliance with a simple transition state model where the phenyl group of the diox-ane moiety shields the Re face of the intermediate formed by addition of the nucleophilic carbene to the aldehyde, therefore, directing the attack of the enoate Michael acceptor to occur with the less hindered face, that is the Si face of the enamine (Fig. 16). The electrophilic part of the intermediate bearing the activated C=C double bond is approached by... 

Just as alkylidenes and alkylidynes may bridge M-M bonds, vinyli-denes may also be employed to support metal-metal bonds. This approach has included the addition of preformed terminal vinylidene complexes to unsaturated metal complexes or, occasionally, the direct assembly from terminal alkynes with unsaturated metal complex precursors (Figure 5.50). 

Other topological molecular descriptors can be obtained by using suitable functions applied to - local vertex invariants, the most common functions are atom and/or bond additives, resulting in descriptors which give correlation of physico-chemical properties that are atom and/or bond additives themselves. - Zagreb indices and -> ID numbers are derived according to this approach. 

Carbene reactions provide a versatile approach to the synthesis of five-membered nitrogen-containing rings. Of particular importance here are intramolecular insertion of a carbene into C — H and N — H bonds, addition onto multiple carbon-carbon bonds, intermediate formation of ylides as a result of carbene addition onto the heteroatom followed by rearrangement, cycloaddition, and cyclization. 

Reactions of transition metal carbonyls with an In(I) center also take place by oxidative addition here InX inserts into the M-X bond. Oxidative addition to the low-valent halides of Ga, In, or T1 thus provides a useful route to compounds with group IIIB-metal bonds This approach is particularly useful when the salt elimination route cannot be employed because a suitable transition metal nucleophile is lacking. 

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