Deprotonations group-selective

The treatment of thiazole with n-butyl- or phenyllithium leads to exclusive deprotonation at C-2. When the 2-position is blocked, deprotonation occurs selectively at C-5. However, if the substituent at C-2 is an alkyl group, the kinetic acidities of the protons at the a-position and at the 5-position are similar. The reaction of 2,4-dimethylthiazole with butyllithium at -78°C yields the 5-lithio derivative (289) as the major product but if the reaction is carried out at higher temperature the thermodynamically more stable 2-lithiomethyl derivative (290) is obtained (Scheme 37). The metallation at these two positions is also dependent on the strength and bulk of the base employed (74JOC1192) lithium diisopropylamide is preferred for selective deprotonations at the 5-position. 

The advantage of the LMs is integrating extraction and back-extraction of the desired analyte(s) into one step. Using protonation and deprotonation reactions, selected hydrophobic carriers with carboxyl groups have been shown effective in the separation of amino acids, if the carboxyl functionality was ionized [123]. Optimum values of the stability constants of the complexes between particular amino acids and carrier(s) can be found to increase extraction efficiencies. However, the kinetics of mass transfer often has a more pronounced impact on the efficiency of extraction [118]. 

Interligand asymmetric induction. Group-selective reactions are ones in which heterotopic ligands (as opposed to heterotopic faces) are distinguished. Recall from the discussion at the beginning of this chapter that secondary amines form complexes with lithium enolates (pp 76-77) and that lithium amides form complexes with carbonyl compounds (Section 3.1.1). So if the ligands on a carbonyl are enantiotopic, they become diastereotopic on complexation with chiral lithium amides. Thus, deprotonation of certain ketones can be rendered enantioselective by using a chiral lithium amide base [122], as shown in Scheme 3.23 for the deprotonation of cyclohexanones [123-128]. 2,6-Dimethyl cyclohexanone (Scheme 3.23a) is meso, whereas 4-tertbutylcyclohexanone (Scheme 3.23b) has no stereocenters. Nevertheless, the enolates of these ketones are chiral. Alkylation of the enolates affords nonracemic products and O-silylation affords a chiral enol ether which can... 

When the C-3 position is substituted (e.g., with Me), deprotonation is selective for C-7 even in the presence of a proton at C-2. At the same time, a large blocking group at the indole N (60) generates steric hindrance to deprotonation of both C-2 and C-7 selective lithiation at C-4 results [29, 45, 52, 57]. The N-(tri(isopropyl)-silyl)indole complex (60) can be deprotonated with 2 mol-eq. of n-BuLi at -78 °C for 3 h, and then trapped with a variety of electrophiles to give... 

Another interesting feature of Bowden s system is its ability to act as an active membrane to carry out functional group-selective reactions. The PDMS matrix is hydrophobic, which allows organic molecules to diffuse in, but prevents ionic substances from doing so. In two separate experiments shown in Scheme 5.11, incorporated catalyst 4 was added to a mixture of methanol and water (90 10) containing two different diene substrates (135-136) that readily undergo RCM. In the first reaction, sodium hydroxide was added to deprotonate substrate 135, while in the second, /)-toluenesulfonic acid (PTSA) was added to help facilitate the diffusion of 135 into the PDMS matrix. Under the basic conditions of the first reaction, no formation of 137 was observed, whereas substrate 136 reacted to... 

The bulky triphenylmethyl group has been used to protect a variety of amines such as amino acids, penicillins, and cephalosporins. Esters of N-trityl a-amino acids are shielded from hydrolysis and require forcing conditions for cleavage. The a-proton s also shielded from deprotonation, which means that esters elsewhere in the molecule can be selectively deprotonated. 

In ( )-[2-(l-propenyl)-l, 3-dithian-2-yl]lithium, no problem of EjZ selectivity arises. It is easily prepared by deprotonation of the allylic dithiane87,88 with butyllithium in THF, whereas deprotonation of the 2-propylidene-l, 3-dithiane requires the assistance of HMPA. The addition to saturated aldehydes proceeds with excellent y-regioseleetivity and anti selectivity88,89. As often observed in similar cases, aldehydes which bear an, p2-carbon atom adjacent to the carbonyl group give lower selectivities. The stereoselectivity decreases with ketones (2-bu-tanone y/a 84 16, antiisyn 77 23)88. The reaction with ethyl 2-oxopropanoate is merely nonstereoselective90, but addition of zinc chloride improved the syn/anti ratio to 96 4, leading to an efficient synthesis of ( )-crobarbatic acid. 

The preparation of cyclopentadienes with up to four trimethylsilyl groups can be performed easily on a large scale starting with monomeric cyclopentadiene by repeated metalation with n-butyllithium and treating the resulting anion with chlorotrimethylsilane [84], Any complication caused by formation of regioisomers does not occur, since all trimethylsilyl-substituted cyclopentadienes are fluxional by virtue of proto- and silatropic shifts [85], Upon deprotonation with n-butyllithium the thermodynamically most favorable anion is formed selectively (Eqs. 20, 21). Thus, metalation of bis(trimethylsilyl)cyclopentadiene 74, which exists preferentially as the 5,5-isomer, selectively affords the 1,3-substituted anion 75. Similarly, tris(trimethylsilyl)cyclopentadiene 76, which is found to be mainly as the 2,5,5-isomer, affords the 1,2,4-substituted anion 77. 

It has been found that the tris(tert-butyloxycarbonyl) protected hydantoin of 4-piperidone 2, selectively hydrolyses in alkali to yield the N-tert-butyloxycarbonylated piperidine amino acid 3. The hydrolysis, which is performed in a biphasic mixture of THF and 2.0M KOH at room temperature, cleanly partitions the deprotonated 4-amino-N -(tert-butyloxycarbonyl)piperidine-4-carboxylic acid into the aqueous phase of the reaction with minimal contamination of the hydrolysis product, di-tert-butyl iminodicarboxylate, which partitions into the THF layer. Upon neutralization of the aqueous phase with aqueous hydrochloric acid, the zwitterion of the amino acid is isolated. The Bolin procedure to introduce the 9-fluorenylmethyloxycarbonyl protecting group efficiently produces 4.8 This synthesis is a significant improvement over the previously described method9 where the final protection step was complicated by contamination of the hydrolysis side-product, di-tert-butyl iminodicarboxylate, which is very difficult to separate from 4, even by chromatographic means. 

A novel C-3 functionalization of methylene aziridines has also been reported <06T8447>. Selective deprotonation of 98 to form 99 and the reaction 99 with an electrophile yielded 100 in good yields. In this way, a variety of alkyl groups could be selectively placed on the aziridine. These researchers also found that (S)-a-methylbenzyl substituted methylene aziridines, 101, when deprotonated and reacted with a variety of electrophiles gave 102 in moderate yields and with good diastereoselectivity. 

---