Very sterically hindered

It is unlikely that T2R2 compounds can be prepared by the usual hydrolytic routes to siloxanes, but it might be possible to prepare one by dehydration of a very sterically hindered silanetriol, RSi(OH)3 which can readily be isolated, ... 

Nolan and colleagues published in 1999 the first coupling between aryl chlorides, bromides or iodides and aryl Grignards, in which an in situ generated NHC-Pd complex served as catalyst. The reaction proceeded in most cases in excellent yields, however, very sterically hindered products formally derived from aryl halides and aryl Grignards both possessing orf/io-substituents could not be obtained [75] (Scheme 6.16). 

Scheme 6.20 Coupling between very sterically hindered partners using Cazin conditions...

The most widely used method for adding the elements of hydrogen to carbon-carbon double bonds is catalytic hydrogenation. Except for very sterically hindered alkenes, this reaction usually proceeds rapidly and cleanly. The most common catalysts are various forms of transition metals, particularly platinum, palladium, rhodium, ruthenium, and nickel. Both the metals as finely dispersed solids or adsorbed on inert supports such as carbon or alumina (heterogeneous catalysts) and certain soluble complexes of these metals (homogeneous catalysts) exhibit catalytic activity. Depending upon conditions and catalyst, other functional groups are also subject to reduction under these conditions. 

With heterocycles containing an sp--nitrogen atom, a totally different problem can occur, namely nucleophilic addition of the base to the azo-methine (C=N) bond. The use of very sterically hindered bases such as lithium tetramethylpiperidide (LiTMP) can prevent this type of addition in certain cases, but bases of this sort tend to be expensive and not suitable for general use. However, two different approaches to overcoming the problem of azomethine addition have been developed over the years, both relying on the fact that the addition is temperature dependent, and that by enabling metalation reactions to be performed at low temperatures, the desired carbanion formation can often be achieved. 

Direct synthesis of complexes of structure type B from germylenes, stannylenes and plumbylenes is possible in several cases. Many complexes of the very sterically hindered metallenes M[CH-(SiMe3)2]2 (M = Ge, Sn, Pb) have been obtained (Scheme 1).2 27... 

However, under more forcing conditions, high yields of the 2,6-diaryl derivatives 39 can be obtained, and particularly with more reactive aryllead derivatives, such as 2,4,6-trimethoxyphenyllead triacetate 41 (Equation (40)).8 Highly hindered structures of the 2 -hydroxy-1, 3 -terphenyl type can be obtained. For example, 3,5-di-/rrt-butylphenol 40 reacted with 2,4,6-trimethoxyphenyllead triacetate 41 (3 equiv.) and pyridine (10 equiv.) to afford the very sterically hindered 2,6-diarylphenol 42 in 87% yield together with 10% of the monoarylated product (Equation (41)).66... 

As a-azido acids are readily reduced to a-amino acids, the problem of a-amino protection is fully bypassed with the highly reactive a-azido acid chlorides (see also Section 2.1.1.10.2). The quantitative reduction of a-azido acids to the corresponding amino acids is accomplished by treatment with DTT/DIPEA/DMF at 50°C.P Chiral a-azido acid chlorides can be used under solid-phase conditions without loss of configuration, but since the reduction process is slow, the method is not attractive for standard peptide synthesis. Compatibility of the a-azido acids with Fmoc- and Boc-chemistry and acid chloride activation, however, makes a-azido amino acid chlorides highly useful for incorporation of very sterically hindered amino acids such as C -disubstituted glycines. 

Carbonylation of aryl bromides and iodides with carbon monoxide, an alcohol, a base, and a palladium catalyst, give carboxylic esters. Even very sterically hindered... 

Because the effect of an electronegative group diminishes with distance, the carbonyl carbon in this system will have the greatest partial plus and therefore will be harder and attract a hard, negatively charged nucleophile best the 1,2 product or normal addition product will be the kinetic product for hard nucleophiles. Soft nucleophiles therefore prefer conjugate attack. Finally, if one site is very sterically hindered, attack at the more open site will dominate. 

The Sn2 has access problems, for the site of attack is very sterically hindered. The cutoff for a reasonable Sn2 is a secondary site, shown in Figure 4.13, so this tertiary site is just too hindered to proceed by Sn2. 

The addition of diborane and substituted boranes to carbon-carbon double bonds is the basis of a very important method of synthesis of alcohols. The addition process is called hydroboration. This reaction was discovered relatively recently (during the 1950 s) by H. C. Brown. Subsequently, other procedures for the utilization of organoborane intermediates have been developed by Brown. The hydroboration reaction involves addition in a single step. Diborane or substituted boranes can provide the B-H bonds. Except in the case of very sterically hindered... 

If this principle is taken to its ultimate conclusion, there should be halo-cyclohexanes for which an E2 reaction is impossible. 2,6-Dimethyl-l-bromocy-clohexane (34) is such a case. To satisfy the relative stereochemistry of the two methyl groups (cis to each other) and the bromine anti to the two methyl groups), the bromine atom must be axial in one chair conformation with two axial methyl groups (34A), but equatorial in the other chair conformation that has two equatorial methyl groups (34B). Only conformation 34A has an axial bromine atom required for an E2 reaction, but both P-hydrogen atoms (Hg and Hb) are equatorial. No P-hydrogen atoms are trans, diaxial to an axial bromine, so there is no E2 reaction. When 34 is heated with ethanol KOH, there is no E2 reaction. The carbon bearing the bromide in 34 is very sterically hindered, so an Sn2 reaction is very unlikely certainly the substitution will be very slow. 

Very sterically hindered carbenes, such as di-f-butyl and diadamantyl carbene (see margin) can persist long enough to be observed spectroscopically at 40 K. Both are ground state triplets, but their reactions are indicative of both singlet and triplet states. 

Pedersen reported in 1967 that the dicyclohexyl-18-crown-6 complex of potassium hydroxide was soluble in toluene and in this medium could readily hydrolyze the very sterically hindered ester methyl mesitoate [33]. He later reported that this complex could also hydrolyze the tertiary-butyl ester [34]. Similarly, Lehn found that the [2.2.2]-cryptate complex of potassium hydroxide was even more effective in this saponification reaction under directly comparable conditions [35]. The hydrolysis reaction is formulated in equation 9.15. This method has recently been applied in the hydrolysis of C-labelled methyl tetradecanoate [36]. Starks found that tetra-decanoate anion acted as a catalyst poison and impeded further hydrolysis [7]. This is therefore one of the few examples where crown ether catalysis is clearly superior to quaternary ammonium ion catalysis. 

---