Steric congestion

The chemoselective desilylation of one of the two different silyi enoi ethers in 10 to give the monosilyl enol ether II is realized by the Pd-catalyzed reaction of Bu3SnF. The chemoselectivity is controlled by steric congestion and the relative amount of the reagent[7,8]. An interesting transformation of the 6-alkoxy-2,3-dihydro-6//-pyran-3-one 12 into the cyclopentenone derivative 13 proceeds smoothly with catalysis by Pd(OAc)2 (10 mol%)[9]. 

A sterically restricted nucleophile is less reactive than a more accessible one because of nonbonded repulsions which develop in the transition state. The trigonal bipyramidal geometry of the 8 2 transition state is sterically more demanding than the tetrahedral reactant, so steric congestion increases as the transition state is approached. 

Several groups have used the Paal-Knorr reaction to synthesize trialkylfurans. Ballini prepared a series of 3-alkyl-2,5-dimethylfurans (53) in 60-94% yield by treatment of the corresponding diones (52) with tosic acid. Weirsum produced the sterically congested tri-r-butylfuran 55 from dione 54, but was unable to use the same strategy to furnish the tetra-t-butyl derivative. ... 

The Paal-Knorr reaction offers an excellent method for the preparation of tetrasubstituted furans however, it does not work for some sterically congested substrates. Similar to di- and trisubstituted furans mentioned previously, tetrasubstituted furans have been investigated for biological acitivity. Katzenellenbogen has prepared numerous alkyl triarylfurans by the Paal-Knorr condensation (e.g. 65 to 66) and investigated their activity toward the estrogen... 

The first condensation is conducted selectively on a variety of 3-ketoesters and a-formylesters. The first step works well on most simple anilines even when sterically congested and is mostly affected by basicity. Formation of intermediate 3 is problematic when strong electron-withdrawing groups (EWG) are attached to the aniline (e.g., nitro). The cyclization step is promoted thermally in inert solvents as well as using acidic solvents at elevated temperature. When there exists an opportunity to form isomers on cyclization (e.g., m-substituted anilines) a mixture of the 5- and 7-substituted quinolines usually results. 

The exact position of the aldol equilibrium depends both on reaction conditions and on substrate structure. The equilibrium generally favors condensation product in the case of aldehydes with no a substituent (RCH2CHO) but favors reactant for disubstituted aldehydes (R2CHCHO) and for most ketones. Steric Factors are probably responsible for these trends, since increased substitution near the reaction site increases steric congestion in the aldol product. 

To explain this extremely high anti selectivity, a cyclic transition state has been proposed in which the a-substituent of the inline and the methyl group of the allenic reagent are aligned in a less sterically congested anti relationship15. 

In contrast, the fluoride ion induced cyclization proceeds via an anticlinal approach which minimizes steric congestion between the allylsilane and the substituent in the 3-position of the cyclohexenone50. Thus, the product having a cis relationship between the vinyl group and R2 at the ring junction is formed preferentially 48 " 51. The controlling element is the substituent R2. In its absence (R2 — H) the diastereoselectivity disappears (see Table 1). 

Despite the favorable thermodynamics associated with the cyclization of unsaturated organolithiums, the isomerization is often sluggish when the ring closure involves generation of a quaternary center or formation of a strained framework. In such cases it has been found that addition of lithiophilic Lewis bases such as THF or TMEDA facilitate the reaction.7 9 The preparation of cuparene, a sterically congested sesquiterpene possessing two adjacent quaternary centers, illustrates the methodology.11... 

The reactions of the butadiynediyldimetal(Fe, Ru) complexes with Fe2(CO)ci at room temperature afforded mixtures of products, from which three types of products, viz. the ps-acetylide cluster compound 4, the pj-ti -propargylidene-ketene compound 5 and zwitterionic cluster compound 6, were isolated. While the reaction with an excess amount of Co2(CO)g results in addition to the sterically congested Fp -C=C part [6]. The distributions of the products were dependent on the metal fragments situated at the other end of the conjugated carbon rod. The cluster compounds so obtained were characterized by spectroscopic and... 

These empirical linear relations should be applied to groups of compounds with a common steric background. Thus, a negative deviation from these linear relations most probably indicates specific steric congestion assisting the dissociation. In this context, it is known that, in radical dissociation of carbon-carbon cr bonds, steric congestion is a major enhancing factor (Riichardt and Beckhaus, 1980). 

As shown in Fig. 3, the observed values of A/fhet(R-R ) in DMSO for the hydrocarbons [3-2] and [25-2] are 15kcalmol less than the values predicted from (28) and (29), respectively, while A/fi,et(R-R ) for the nitro-cyano compound [4-102] in acetonitrile (30) is close to the value predicted from (29). Therefore, this departure of the dissociative hydrocarbons from the predicted behaviour can be ascribed to steric congestion in the hydrocarbon, predominantly caused by the carbanion moiety [2 ]. 

The AGhet(R-R ) values observed in acetonitrile are almost identical with A//het(R-R ) values for the compounds [4-6] and [5-6] (Troughton et al., 1984). Thus, provided that this is the case also for a nitro-cyano compound, (tri-t-butylcyclopropenyl)(phenyl)malononitrile [101-102], its AGhet(R-R ) value should be close to the A//het(R-R ) value predicted from (29). In practice, as indicated in Fig. 3, the AG°het(R-R ) observed in acetonitrile is 6kcalmol less than that predicted (Miyabo et al., 1993). Hence this departure from linearity can be most probably ascribed to steric congestion, which is mainly derived from the cation moiety [lOT ] in [101-102]. 

On the basis of the results in acetonitrile, it might be reasonable to assume that the values for A//het(R-R ) and AG°het(R-R ) are apparently close to each other also in sulfolane, since the dielectric constant (43.3) and the donor number (14.8) of this solvent are close to those of acetonitrile (37.5 and 14.1, respectively). On the basis of this assumption, Arnett s equation (28) was examined for reactions of type (23). For these reactions, except for [3-2], only the AGhet(R-R ) values are avtiilable. As shown in Fig. 3, the values for this system are about 10 kcal moP less than predicted from (28). The negative deviation can also be ascribed to steric congestion in these hydrocarbon molecules. The large negative deviations, similar to those observed in sulfolane, are also seen in Fig. 3 for the values of AGSet(R-R ) in DMSO. 

To sum up, in addition to the electronic stabilization and solvation, classical steric congestion caused by either the cation or anion moieties effectively controls the ease of ionic dissociation of the carbon-carbon a bond in hydrocarbons. 

With the right choice of catalyst even very sterically demanding transformations are possible. Catalyst Rul s low steric congestion proved it superior to others in the... 

In 2005, Kunieda et al. developed sterically congested 2-iminothioethers as novel and highly efficient chiral ligands for the test reaction, providing the product in excellent yield and enantioselectivity, as shown in Scheme 1.38. ... 

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