Interesting Esters and Amides

Many low molecular weight esters have pleasant and very characteristic odors. 

Several lactones have important biological activities. 

Ginkgo biloba has existed on earth for over 280 million years. The fossil record indicates that it has undergone little significant evolutionary change for eons. Extracts of the ginkgo tree have long been used in China, India, and Japan in medicine and cooking. 

Vitamin C (or ascorbic acid) is a water-soluble vitamin containing a five-membered lactone that we first discussed in Section 3.5B. Although vitamin C is synthesized in plants, humans do not have the necessaiy enzymes to make it, and so they must obtain it from then-diet. 

Ginkgolide B is one of the active components of ginkgo extract, which has been used for centuries in traditional Chinese medicine. Ginkgo extracts are obtained from the ginkgo tree, an ancient tree native to the Orient, now introduced in Europe and the Americas as well. 

The characteristic odor of many fruits is due to low molecular weight esters. 

The coca plant, Erytfiroxylon coca, is the source of the addictive dmg cocaine. 

---

The reactions of fluorinated esters and amides to form, respectively, enol ethers [47] and enamines [4S] give high yields and are interesting synthetic transformations (equations 34 and 35) (Table 12)... 

Figure 5.7, (a) Widely used biological probes of the TICT type. 4, s4 s7> (b) TICT compounds with dual fluorescence and interesting properties amenable to tailor-making of fluorescence probes. Functionalization and inclusion in larger molecular assemblies is easily possible, e.g., at the positions indicated by R. This holds especially for esters and amides which have been used as probes in large polymers 97-1011 or in TICT-labeled cyclodextrins.(l49)... 

Electrophilic additions to 7t-deficient heterocycles are less common than those to 7t-excessive heterocycles. However, intramolecular electrophilic cyclizations have been used to access the heterocycles of interest in this chapter <1996CHEC-II(7)49>. Recent examples include the preparation of a pyrrolo[2,3-f]pyrazole 165 by acid-catalyzed condensation of 163 and 164 (Equation 37) <1999SC311> and the reaction of 3-(4-pyrazolyl)acrylic acids 166 with excess thionyl chloride in the presence of benzyltriethylammonium chloride (BTEAC) to afford 4-chlorothieno[2,3-f]pyrazole-5-carbonyl chlorides 167 (Equation 38) <2003RJ0893, 2003ZOK942>. In the latter case, the reaction products were readily manipulated to prepare corresponding carboxylic acids, esters, and amides using standard procedures. 

Lehn and Wipff (72) and Gorenstein and co-workers (73-80) have proposed on the basis of molecular orbital calculations that stereoelectronic effects similar to those observed in esters and amides play also an important role in the hydrolysis of phosphate esters. For instance, calculations suggest that the axial P — OR bond in the trigonal bipyramid conformation 120 is weaker than that in the conformation 121 because in the former, the oxygen atom of the equatorial OR group has an electron pair anti peri planar to the axial P — OR bond. Experimental results tend to support this interesting proposal but additional experiments are needed before unambiguous conclusions can be reached (81). 

Introduction of chiral auxiliaries in the starting materials is very attract for applications to organic synthesis. However, to be of synthetic interest, chiral auxiliaries have to be inexpensive, readily introduced on the starting ma rial, inert in the conditions of irradiation, and readily removed from the photo ducts. Even if the first requirements can be easily satisfied with chiral ket esters, and amides, it is often difficult to avoid side reactions involving auxiliary [63]. In order to control all the asymmetric centers created in the in molecular photocycloadditions of cyclic enones with alkenes, esters of c alcohols were first considered. Although menthyl and bomyl derivatives ga only low de, 8-phenylmenthyl esters produced a far better asymmetric inducti [64]. The facial selectivity was found to depend on the syn/anti nature of t cycloadducts and the structure and location of the chiral auxiliary on either tl enone or the alkenyl moiety. More surprisingly the selectivity also depe strongly on the nature of the solvent (Scheme 21). 

The synthetic interest of the reaction is even broader since several functional groups in the substrate, such as C=C double bond, ether, halogen, ester, and amide groups (entries 6-10) can be present in the carbon skeleton. Chemose-lective cyclopropanation reactions involved the enone functionality in the presence of a saturated ketone group (Scheme 9). Recently, the reaction was applied to the conversion of 1,3-dicarbonyl compounds into 2-alkoxyalkenyl cyclopropanes (Scheme 10) [15]. These molecules having both vinylcyclopropane and enol ether moieties are supposed to be versatile synthetic intermediates. 

Once again, the drive for improved performance in transition metal ion-catalysed processes has continued to stimulate the synthesis of new types of organophosphine and tervalent phosphorus-ester and -amide ligands. Activity in the chemistry of heteroaromatic phosphorus ring systems and low-coordination number p -bonded systems has also remained at a high level. New mechanistic insights into the Mitsunobu reaction have been reported, and interest in synthetic applications of Staudinger/Mitsunobu procedures has continued to develop. 

Once again, there has been considerable interest in tervalent ester and amide chemistry that relates to the preparation of new, often chiral, ligand systems for use in metal-catalysed homogeneous catalysis. 

Hydrolases catalyze the addition of water to a substrate by means of a nucleophilic substitution reaction. Hydrolases (hydrolytic enzymes) are the biocatalysts most commonly used in organic synthesis. They have been used to produce intermediates for pharmaceuticals and pesticides, and chiral synthons for asymmetric synthesis. Of particular interest among hydrolases are amidases, proteases, esterases, and lipases. These enzymes catalyze the hydrolysis and formation of ester and amide bonds. 

As in recent years, the synthesis of new chiral phosphines and related chiral tervalent phosphorus esters and amides continues to be a major preoccupation, being driven by the need for improved performance in metal-catalysed processes. It is very pleasing to note that two of the recipients of the 2001 Nobel Prize for Chemistry, William S. Knowles, and Ryoji Noyori, are honoured for their work in the synthesis and application in catalysis of chiral phosphine ligands. Interest in the structures of metallo-organophosphide systems, noted in the previous volume, has continued to develop. The chemistry of heteroaromatic ring systems, notably that of phospholes, and of low coordination number p -bonded compounds, also remain active areas. 

An interesting application to the synthesis of a-diketones, a-ketoesters and a-ketoa-mides, starting from ketones, esters and amides, was achieved by Wasserman and Ives . The method involves conversion of the starting carbonyl compound to the corresponding enamino carbonyl compound, followed by oxidative cleavage of the enamine double bond by singlet oxygen (Scheme 7). 

In the interest of asymmetric synthesis, there has been a considerable effort to develop chiral ketones, esters and amides that will undergo aldol reactions with high diastereofacial preference. One such reagent is ketone (181), available in three steps from (S)-f-butylglycine. [For a discussion of the use of the racemic version of ketone (181) for aldol reactions, see ref. 57d, pp. 181-184.] Aldol reactions of several different enolates of (181) have been studied with benzaldehyde (Scheme 11 Table 20).The... 

I, 5-dicarbonyl compounds and their interesting and varied chemistry, e.g., the formation of cyclohexenones from aldol condensation of the products. As an extension of the de Mayo reaction (the photocycloaddition of enolated /i-diketones to double bonds) enol esters, enol ethers, vinylogous esters and amides, and dioxinone have been employed as the enone components. Some intermolecular examples have already been discussed in Section 1.6.1.4.2.1.6. (cf. Table 4, entries 2 and 3) and some intramolecular systems are collected in Table 5, entries 10,... 

---