Amides sterically crowded

For the preparation of sterically crowded amides amino magnesium salts have been recommended for the reaction with imidazolides in order to increase the nucleophilicity of the amine moiety. Amino magnesium salts are prepared from the appropriate amines and ethyl magnesium bromide in tetrahydrofuran [90]... 

However, although the accuracy of these predictions is impressive one must remember that they apply to a very closely defined series. We are still unable to predict the specific effects of substituents and have no answer to the intriguing question of why does the introduction of the OCH2 unit into the phenylethanolamines give such good (3-blockers, or why the addition of a polar group (amide or ether) to a para-alkyl substituent to some extent relieves the steric crowding (cf ICI 66082 (15) and metoprolol (id)) table 2. 

Monomeric amide, alkoxide and thiolate derivatives of germanium(II), tin(II) and lead(II) are only obtained with very sterically crowded ligands. Thus, bis(2,2,6,6-... 

Rotaxane 80e can even be dimerized by reaction with l,3,5-tris(4-methyl-phenyl)benzene (105) [42]. Considering the steric crowding, it is remarkable that the resulting wheel-tris[2]rotaxane ([4]rotaxane) 106 is formed in 35% yield (Figure 42). Extension of the strategy of coupling rotaxanes to multifunctional units should enable easy access to amide-linked dendritic rotaxane structures. 

Dichlorodimethylsilane was used for the synthesis of amides from unprotected amino acids by a simultaneous protection-activation strategy <2002TL9203>. However, sterically crowded di- 7-butyldichlorosilane reacted with phenylalanine in the presence of Et3N to give 5-aza-l,3-dioxa-2,4-disilacycloheptan-7-one 214 in 40% yield (Equation 42), whose structure was confirmed by MS, H, and 13C NMR spectral data. 

On the other hand, on increasing the steric crowding on the amide, total diastcrcosclcction is obtained in the cyclization48. 

Amines and Phosphines. As in reactions of alcohols and acids with oiganosilanes, reaction of the Si—H bond with amines and phosphines proceeds only under catalysis. Alkali metal amides or phosphines are the catalysts of choice and effect replacement of the Si—H bond with Si—N or Si—P bonds, respectively. Catalytic activity of the alkali metals for these reactions is K > Na > Li (113). Reactions of thoiganosilanes with ammonia (qv) and amines have been the most widely studied. Ammonia affords the disubstituted nitrogen compounds or disilazanes with no trisubstitution being observed. This presumably occurs because of steric crowding at nitrogen. For example, reactions for the formation of triethjidisilazane [2117-18-2] and triphenyldisilazane [4158-64-9] are as follows ... 

In alkaline solution, A-substituted benzamides undergo cathodic cleavage to form benzyl alcohol and an amine [127,128]. In acidic solution A-substituted 2-pyridinecarbox-amides are reduced to the corresponding aldehyde and alcohol unless severe steric crowding is present, which results in the corresponding methylene amine being formed [129]. 

The four-electron reduction of derivatives of 3-methoxypicolinic acid may follow different routes, depending on the substitution in the ester or amide. Amides may, after uptake of two electrons, lose an amino or a hydroxyl group, and then be further reduced to a pyridinemethanol or an aminomethylpyridine, or the compound may be reduced in the pyridine ring steric crowding favors the formation of aminomethylpyridines or tetra-hydropyridines [452]. 

The reaction of (EBI)H2 [EBI = ethylene-1,2-bis(indenyl)] and titanium amides did not give the expected ansa-titanocene products. Even with the azetidine complex, Ti(NC3H6)4 reacts with only a single amine elimination to give the mono(indenyl) derivative (C9H6CH2CH2C9H7)Ti(NC3H6)3. By contrast, -zirconocene and hafnocene are easily obtained by the amine elimination process. It is likely that increased steric crowding around the smaller Ti disfavors the second amine elimination.674... 

Amination of 110 takes place exclusively in the 2-position, despite steric crowding and lower electron density in the 6-position. This may be due to coordination of the tightly bound sodium amide with the dimethylamino group (Scheme 44). The geometry of the coordination complex (113) makes addition of the amide ion at C-2 attractive. 

Very sterically crowded group 4 metal complexes bearing three or four amidate ligands can be synthesized via protonolysis (Figure 11). [34] The tris(amidate)... 

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