Steric hindrance hydride

The use of (TMSlsSiH with acyl selenides can also yield new C-C bond formation, as shown with the a,/l-unsaturated lactam ester (Reaction 67). The resulting ketone can be envisaged as potentially useful for the synthesis of 2-acylindole alkaloids. Both the effects of H-donating ability and steric hindrance by the silicon hydride are evident. 

Tucci (54), studying mainly terminal olefins, cited two reasons for the high selectivity for linear products in the phosphine-modified cobalt catalysts (a) stereoselective addition of the hydride species to the olefinic double bond, and (b) inhibition of olefin isomerization. However, the results obtained with internal olefins as substrate tended to discount the likelihood of the second reason, and it is generally accepted that selective anti-Markovnikov addition arising from steric hindrance is the principal cause for linear products from nonfunctional olefins. 

In MeOH the hydride reacts with higher a-olefins, propene, 1-hexene and 1-hexadecene with formation of only the linear insertion product, probably for steric reasons. In all the insertion products, the alkyl ligand presents the /f-agoslic interaction. At room temperature, the insertion of ethene is quantitative whereas with propene an appreciable amount of the hydride is present, with 1-hexene the hydride prevails, with 1-hexadecene only the hydride is present. The fact that the position of the insertion equilibrium strongly depends on the chain length of the alkyl substituent is probably connected with the high steric hindrance of the ligand [115]. 

The structure of the cyclic ketone is of utmost importance. Reduction of cyclic ketone by complex hydrides is started by a nucleophilic attack at the carbonyl function by a complex hydride anion. The approach of the nucleophile takes place from the less crowded side of the molecule (steric approach or steric strain control) leading usually to the less stable alcohol. In ketones with no steric hindrance (no substituents flanking the carbonyl group or bound in position 3 of the ring) usually the more stable (equatorial) hydroxyl is generated (product development or product stability control) [850, 851, 852, 555]. The contribution of the latter effect to the stereochemical outcome of... 

The effect of steric hindrance can be nicely demonstrated in the reduction of two bicyclic ketones, norcamphor and camphor. The relatively accessible norcamphor yielded on reduction with complex hydrides predominantly (the less stable) endo norborneol while sterically crowded camphor was reduced by the same reagents predominantly to the less stable exo compound, isobor-neol [837], From the numerous examples shown it can be deduced that the stereoselectivity increases with increasing bulkiness (with some exceptions), and that it is affected by the nucleophilicity of the reagent and by the solvent. 

Fig. 2.9 Template structures for the intermediate in catalytic asymmetric hydroboration with alkene, ligand, catechoborane and hydride coordinated, (a) R-BINAP and (b) R-QUINAP. E-propenylbenzene is illustrated to show the increased steric hindrance to the alkene in the BINAP case.

Barton-McCombie deoxygenation is not always stereoselective the diastereo-meric ratios strongly depends on the nature of the protecting groups and of the ester moiety. However, in 2-C-trifluoromethyl-2-deoxyfuranose, the a compound is the major product of the reaction, due to steric hindrance of this a side. In 3-C-trifluoromethyl-3-deoxyfuranose, deoxygenation by tributyltin hydride yields only the a product, if it is performed with oxalate instead of thiocarbonate. Another possibility to obtain this selectivity is to perform the reaction with 1,2,5,6-di-O-isopropylidene-a-D-glucofuranose (Figure 6.34). ... 

Acyl halides can be reduced to aldehydes1206 by treatment with lithium tri-f-butoxyaluminum hydride in diglyme at -78°C,1207 R may be alkyl or aryl and may contain many types of substituents, including N02, CN, and EtOOC groups. The reaction stops at the aldehyde stage because steric hindrance prevents further reduction under these conditions. Acyl halides can also be reduced to aldehydes by hydrogenolysis with palladium-on-barium sulfate... 

In complexes (16) and (26), the situation is rather different, because there is now steric hindrance from the diene terminal substituent. As a result, the electronically less favorable products are predominant. However, when steric effects at both methylene groups are balanced, as in complex (19), the hydride abstraction proceeds with electronic control to give (30 equation 13). 

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