Sensitive alcohol substrates

The addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

A very effective and mild procedure for the silyl protection (using TBDMSCl and TBDPSCl) of a wide variety of OH-containing substrates (including primary, secondary, allyUc, propargylic, benzylic, hindered secondary, tertiary, add-sensitive and base-sensitive alcohols, and also hindered phenols) involves the use of lb as the catalyst, Eq. (23). The reactions are carried out in acetonitrile as a solvent from 24 to 40°C, and on rare occasions in DMF from 24 to SOX. 

Devine et al. (2010) have presented a methodology for htanium catalyzed es-terificahon and transesterificahon using microwave irradiahon. It was observed that the reachons were completed within 1 h of heating at 160 °C. It was found feasible to use aromahc, aliphahc and heteroaromahc acids in esterification. Some acid sensitive alcohols like fmfuiyl alcohol were also found as suitable substrates. Transesterification reachons are also possible in presence of microwaves. 

The catalyst is sensitive to pre-existing chirality in the substrate the expoxidation of racemic secondary allylic alcohols often proceeds tepidly with only one of the enantiomers ... 

Reactions of alcohols with sulfur tetrafluoride, because of decomposition and/or polymerization, usually do not give fluorinated products However, in the presence of a hydrogen fluoride scavenger like triethylamine or pyridine, even such sensitive substrates as benzylic alcohols [555], 2-phenylethanol, and 2-furylmethanol [554] can be fluorinated to give the expected fluoro derivatives (equation 73)... 

Since the imidazolide method proceeds almost quantitatively, it has been used for the synthesis of isotopically labeled esters (see also Section 3.2), and it is always useful for the esterification of sensitive carboxylic acids, alcohols, and phenols under mild conditions. This advantage has been utilized in biochemistry for the study of transacylating enzymes. A number of enzymatic transacylations (e.g., those catalyzed by oc-chymo-trypsin) have been shown to proceed in two steps an acyl group is first transferred from the substrate to the enzyme to form an acyl enzyme, which is then deacylated in a second step. In this context it has been shown[21] that oc-chymotrypsin is rapidly and quantitatively acylated by Af-fraw.s-cinnamoylimidazole to give /ra/w-cinnamoyl-a-chymotrypsin, which can be isolated in preparative quantities and retains its enzymatic activity (see also Chapter 6). 

The approach by Brennan with collaborators led to notable improvement in the biocompatibility of sol-gel processing. However, there are some disadvantages. Their approach does not exclude the hydrolytic separation of alcohol. Its presence is detrimental for sensitive biopolymers. Furthermore, the two-stage synthesis is accompanied by the significant shrinkage of sol-gel derived nanocomposites. This leads to a decrease in the pore size that sometimes can restrict the accessibility of enzymes to substrates. 

They offer the advantage that reductions can be effected under conditions that permit the conversion of substrates that may be adversely sensitive to the presence of strong Brpnsted acids. For example, in the presence of a 10% excess of triethylsilane, addition of one-half equivalent of boron trifluoride etherate to octanal results, within one hour, in the formation of a 66% yield of dioctyl ether after a basic hydrolytic workup. Benzaldehyde provides a 75% yield of dibenzyl ether under the same reaction conditions. The remainder of the mass is found as the respective alcohol.70 Zinc chloride is also capable of catalyzing this reaction. With its use, simple alkyl aldehydes are converted into the symmetrical ethers in about 50% yields.330... 

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