Ester directing effect

AH the common monobasic (107) and dibasic esters (108) of tetrahydrofurfuryl alcohol have been prepared by conventional techniques the dibasic esters and some of the mono esters are effective as primary or secondary plasticizers for vinyl polymers. Tetrahydrofurfuryl acrylate [2399-48-6] and methacrjiate [2455-24-5] specialty monomers, have been produced by carbonylation (nickel carbonyl and acetylene) of the alcohol (109) as weU as by direct esterification (110—112) and ester interchange (111). 

Hagemann s ester, synthesis of, 912 Halo group, directing effect of, 567-568... 

The general ordering of aminomethyl > hydroxymethyl > CH=0 > ester suggests that Lewis basicity is the dominant factor in the directive effect. Problem 5.2 involves considering the ordering of the various acyl substituents in more detail. 

The directive effect of allylic hydroxy groups can be used in conjunction with chiral catalysts to achieve enantioselective cyclopropanation. The chiral ligand used is a boronate ester derived from the (VjA jA N -tetramethyl amide of tartaric acid.186 Similar results are obtained using the potassium alkoxide, again indicating the Lewis base character of the directive effect. 

In the hydrogenation of 3-substituted itaconate ester derivatives by rhodium-dipamp, the alkoxycarbonyl group at the stereogenic center also exerts a powerful directing effect, comparable to that induced by OH in the kinetic resolution of (a-hydroxyethyl)acrylate, leading to a high enantiomer-discriminating ability up to feR fes = 16 1 (Table 21.18, entry 5) [64]. 

These cinchona esters also effect asymmetric dihydroxylation of alkenes in reactions with an amine N-oxide as the stoichiometric oxidant and 0s04 as the catalyst. Reactions catalyzed by 1 direct attack to the re-face and those catalyzed by 2 direct attack with almost equal preference for the 5i-face. 

SA node and A-V fibers become dominant. Activation of M2 receptors increases the potassium permeability and reduces cAMP levels, slowing the rate of depolarization and decreasing the excitability of SA node and A-V fiber cells. This results in marked bradycardia and a slowing of A-V conduction that can override the stimulation of the heart by catecholamines released during sympathetic stimulation. In fact, very high doses of a muscarinic agonist can produce lethal bradycardia and A-V block. Choline esters have relatively minor direct effects on ventricular function, but they can produce negative inotropy of the atria. 

Third, acyl-CoA cholesterol acyltransferase (ACAT) [EC 2.3.1.26], an enzyme that works after the formation of cholesterol, was considered a unique target of inhibition [32], ACAT catalyzes the synthesis of cholesteiyl esters from cholesterol and long-chain fatty acyl-CoA. ACAT plays important roles in the body, for example, in the absorption of dietary cholesterol from the intestines, production of lipoprotein in liver and formation of foam cells from macrophages in arterial walls. Therefore, ACAT inhibition is expected not only to lower plasma cholesterol levels but also to have a direct effect at the arterial wall. A number of synthetic ACAT inhibitors such as ureas, imidazoles, and acyl amides have been developed [33], Several groups have searched for novel ACAT inhibitors... 

Stimulation of HA synthesis also occurs following phorbol ester (PMA) and PDGF treatment, although a direct effect on HAS has not been demonstrated. Glucocorticoids induce a nearly total inhibiton of HAS mRNA in dermal fibroblasts and osteoblasts.183 Extracts of dermal fibroblasts indicate that HAS-2 is the predominant HA synthase therein. This may be the molecular basis of the decreased HA in glucocortcoid-treated skin. However, an additional effect on rates of HA degradation has not been examined. 

Syn hydroxyladon is most commonly performed using osmium tetroxide or potassium permanganate, and addition usually occurs hx)mrhe less hindered side of the double bond in the absence of other directing effects. With Aese reagents, the steieospecificity of syn addition results from formation of cyclic ester intermediates. Support for these arises from isolation of solid addition complexes (1) on reaction of... 

Treatment of a -keto ester directly with peracid has been shown in one case (21) to effect quantitative a-hydroxylation. Presumably this arises through epoxidation of the enol. Peracid reactions of this kind will be discussed in more detail in Section 2.3.2.1.3.i. Oxidations of the enols of 3-keto esters to the a-hydroxy derivatives using singlet oxygen in the presence of fluoride ion occurs in moderate yield through an ene process (Section 2.3.2.1.3.ii). 

This worked well [(2,6-(i-Pr)rPh]N=CHPh and (2,6-MerPh)N=CHPh gave 94 and 79% diboration, respectively, but significantly limited the molecular diversity of the resulting alpha-aminoboronate esters. Our third strategy arose from an observation that an ortho-methoxyphenyl substituent on the imine nitrogen yielded no diboration product. We presumed this was due to a substrate directing effect, and use of this substituent on the imine carbon then allowed us to diborate a number of N-alkylaldimines in good yield (Equation 7). 

A second metal-catalyzed route to alpha-thioboronate esters consists of the regiospecific, Markovnikov hydroboration of phenyl vinylsulfide which proceeds in high yield to give 14a,b (Equation 11). We are in the process of extending this unique reaction to other alkenyl sulfides and to alkenyl phosphines in order to determin whether the observed regiochemistry of addition is due to a directing effect of the soft heteroatom donor towards the catalyst center. 

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