Inductive effects, silyl groups

Silicon protection is also commonly used to direct lithiation chemistry in five-membered heterocycles. For example, oxazoles , thiazoles and Ai-alkylimidazoles ° ° lithiate preferentially at C-2, where the inductive effect of the heteroatoms is greatest. If C-2 is blocked, lithiation occurs at C-5, where there is no adjacent lone pair to destabilize the organolithium. Functionalization of these heterocycles at C-5 can therefore be achieved by first silylating C-2, reacting at C-5 and then removing the silyl group. The synthesis of 666 illustrates this sort of sequence (Scheme 258) °. ... 

The determination of the crystal structures of a series of silyl(amino)boranes shows that the B-Si bond is significantly shortened by the introduction of chlorine substituent at boron and is even Shorter in the presence of a Q atom at the silyl group. This definitely shows that the Cl atoms have a noticeable inductive effect on the length (and strength) of the B-Si single bond. 

An interesting result of control of acyclic stereochemistry is reported by Nagano et al. [57], who showed that efficient 1,2-asymmetric induction can be achieved in radical-mediated allylation of diethyl (25,35)-3-bromo-2-oxo-succinates stereoselectively. In the Eu(fod)3 (1.1 equivalent) photocatalyzed reaction of bromohydroxy compound (4) diastereoselectivity is reversed with respect to the simple photoreaction. On the other hand, substitution with silyl groups tends to enhance diastereoselectivity up to 8.6 1. The effect is still operative to a lesser extent with catalytic amounts of the lanthanide reagent (0.1 equivalents, threo/erythro [5/6] = 3 1) (eq. (2)) [57]. 

Aldol reactions. The Mukaiyama aldol reaction employing 1-triisopropoxy-l-r-butylthioethene as donor displays exceptional Cram-type selectivity, thus the bulk of the silyl group has a crucial effect on the level of 1,2-asymmetric induction. Bicyclic lactones are formed by treatment of a hydroxyalkylalkyne substituted with tungsten and also carrying an acetal side chain. ... 

The cause of this phenomenon can undoubtedly be attributed, at least in part, to inductive effects due to the low electronegativity of the silyl group (10), but it has been suggested, based also on ultraviolet (42) and NMR data, that intramolecular interaction between the nonbonding electrons of the ketone oxygen and the d orbitals of silicon occur in the compounds" (43), i.e., o(p-d) bonding. 

The a-TMS group has a large inductive effect which leads to a slight cathodic shift in the oxidation potential of the oligomer. A rise in the 7t HOMO level of a-silylated n systems has been observed from electronic spectroscopy experiments [34],... 

The assumed transition state for this reaction is shown in Scheme 5.5. The two bulky t-butoxy groups are expected to locate at the two apical positions. One of the 3,3 -phenyl groups would effectively shield one face of an imine, and consequently, a diene attacks from the opposite side. Judging from this model, similar selectivities were expected in the Mannich-type reactions of imines with silyl eno-lates. Actually, when ligand 10 was used in the reaction of imine la with S-ethyl-thio-l-trimethylsiloxyethene, the corresponding / -amino thioester was obtained in 84% ee (Scheme 5.6). As expected, the sense of the chiral induction in this case was the reverse of that observed when using catalyst 6 [12, 25]. 

The influence of the alcohol on the reaction was evaluated (Scheme 26). The results of a competition experiment between the alcohols are shown in Table 7. Both alcohols were treated with mono-alkoxysilane le using 10 % Pd/C as the catalyst. The silyl ketals of both alcohols were isolated as a mixture and the area under the methine protons, from the (+)-ethyl lactate moiety of both silyl ketals, was compared by NMR analysis. The difference in reactivity of primary, versus secondary, versus tertiary alcohol was small. The differences in reactivity range from 1.5 1 for 1° vs 2°, to 3 1 for 1° vs 3°. The reactivity of a benzyl alcohol is slower than the aliphatic alcohol as shown in entries 4 to 6. Entries 4 and 5 show an increase in the ratio of 1° 2° alcohol and a decrease in ratio for the 2° 3° for the secondary benzyl alcohol. Entries 6 and 7 confirm that benzyl alcohols are less reactive than aliphatic alcohols. The inductive electron withdrawing effect of the aryl group in the benzyl alcohol renders it less nucleophillic and this may affect the rate of reaction with the silane. Although the difference in reactivity is small, this trend may be informative. The influence of the alcohol s nucleophilicity on the reaction mechanism will be addressed in a later section. 

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