Esters transformation into alcohols

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

Sodium bromite, NaBr02 H20, a crystalline compound, oxidizes secondary alcohols to ketones [739] and sulfides to sulfoxides [739]. Primary alcohols are transformed into esters [739]. 

The unusual reactivity of dioxiranes is impressively exhibited in their ability to insert into C — H bonds (Scheme 7) [28]. Thus, tertiary alkanes are oxidized to their respective alcohols [29]. In the example shown, the insertion took place with complete retention of configuration at the chirality center. 1,3-Dicarbonyl derivatives [30] are hydroxylated with high efficiency, but more than likely the intermediary enol is being oxyfunctionalized. Secondary alcohols are transformed into ketones, a specific example is the oxidation of the epoxy alcohol in the rosette [31], In an attempt to epoxidize the hydroxy acrylic ester [22], the epoxy 1,3-dicarbonyl product was obtained, although in low yield in accord with its rather reluctant nature towards oxidation. 

Chloromethylation of 2-alkyl-1,3,2-dioxaborinancs with dichloromethyllithium followed by reduction with potassium triisopropoxyborohydride yields one-carbon-homologated boronic esters. The homologation can be repeated and the homologated esters transformed into the corresponding at-, j7- or -/-chiral alcohols, aldehydes and acids13. 

The compounds 26 and 30 were also used for his methynolide synthesis. The aldehyde derived from 26 reacted with crotyltributylstannane to give stereoselectively 121, which was selectively protected to the alcohol 122. This alcohol was transformed into the ketophosphonate carboxylic acid 123. Yamaguchi esterification of 30 with 123 gave the corresponding ester, which was cyclized by Nicolaou method to give the 14-membered enone 124. Selective deprotection of the DMPM group with DDQ followed by Swem s oxidation... 

A possible synthesis is shown below. When analyzing the starting material, 1, and the product, 2, it can be seen that the alcohol is transformed into an ether and that the ester is converted to a different ester. So first determine a method to make an ether the Williamson ether synthesis (base + RX) is a convenient method for ether formation. 

Alcohols occupy a central position in organic chemistry. They can be prepared from many other kinds of compounds (alkenes.. alkyl halides, ketones, esters, and aldehydes, among others), and they can be transformed into an equally wide assortment of compounds (Figure 17.3). 

Compounds in which the —OH of an acid is transformed into —OR (such as —OCH3) are called esters. They can be prepared by the direct reaction between an alcohol and the acid. For example,... 

Oxo-4,5-dihydro-l//-l,2,4-benzotriazepine-3-carboxylates8can be transformed into the acid chlorides 10 with phosphorus pentachloride and the crude products converted into various amides and esters 11 by treatment with amines and alcohols, respectively. Selected examples are given.347... 

The procedure is outlined in Scheme 8.33, starting from the generic allylic alcohol 125. SAE on 125 would provide epoxide 126, which could easily be transformed into the unsaturated epoxy ester 127 by oxidation/Horner-Emmonds olefmation (two-carbon extension). This operation makes the oxirane carbon adjacent to the double bond more susceptible to nucleophilic attack by a hydride, so reductive opening (DIBAL) of 127 provides, with concomitant ester reduction, diol 128. Pro-... 

Carboxamides and esters of arenecarboxylic acids are obtainable directly by reacting arenediazosulfones (Ar — N2 —S02 —Ar ) with CO and amines or alcohols, respectively, in the presence of Pd catalysts (Kamigata et al., 1989). Aromatic aldehydes are formed if the reaction is carried out in the presence of triethylsilane (Kikukawa et al., 1984). In an analogous way, arenediazonium salts can be transformed into ketones (ArCO —R R = CH3, C2H5, or C6H5) in the presence of stan-nanes, R4Sn (Kikukawa et al., 1982). 

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

The TSIL used in this study has an ester moiety in its structure, which enables it to react in enzyme-catalyzed transesterification reaction. In the first part of the cycle, one of the enantiomers of the racemic alcohol is preferentially transformed into an ester of the IL-coupled acid. The other, unreacted enantiomer of the alcohol is then extracted, while the newly formed IL ester is treated with an excess of ethanol in the presence of the same enzyme. This process is accompanied by the regeneration of TSIL in the active form. The main advantage of the presented... 

Secondary alcohols such as cyclohexanol or 2-butanol also react on heating for 20-120 min at 80 °C with TCS 14 in the presence of BiCl3 to give the chloro compounds cyclohexyl chloride 784 and 2-chlorobutane in 93 and 90% yield, respectively, HCl, and HMDSO 7 [11, 12]. Benzyl alcohol is transformed likewise by Me3SiCl 14 after 120 min. at 80 °C into benzyl chloride in quantitative yield. Analogously, esters such as 2-acetoxypropane 785 are also converted by TCS 14 in 100% yield into chloro compounds such as 786 and trimethylsilyl acetate 142. The yS-lactone 787 gives rise to 788... 

Hydrogenolysis of esters to aldehydes or alcohols needs high temperatures and high pressures. Moreover, it leads to the formation of acids, alcohols, and hydrocarbons. In contrast, bimetallic M-Sn alloys (M = Rh, Ru, Ni) supported on sihca are very selective for the hydrogenolysis of ethyl acetate into ethanol [181]. For example while the selectivity to ethanol is 12% with Ru/Si02, it increases up to 90% for a Ru-Sn/Si02 catalyst with a Sn/Ru ratio of 2.5 [182]. In addition, the reaction proceeds at lower temperatures than with the classical catalysts (550 K instead of temperatures higher than 700 K). The first step is the coordination of the ester to the alloy (Scheme 46), and most probably onto the tin atoms. After insertion into the M - H bond, the acetal intermediate decomposes into acetaldehyde and an ethoxide intermediate, which are both transformed into ethanol under H2. 

Preparation of the quaternary anticholinergic agent benzilonium bromide (47) is begun by conjugate addition of ethylamine to methylacrylate, giving aminoester 42. Alkylation of 42 with methyl bromo-acetate leads to diester 43, which is transformed into pyrrolidone 44 by Dieckmann cyclization, followed by decarboxylation. Reduction of 44 by lithium aluminum hydride leads to the corresponding amino-alcohol (45). Transesterification of alcohol 45 with methyl benzilate leads to 46. Benzilonium bromide (47) is obtained by alkylation of ester 46 with ethyl bromide. 2... 

Selective reduction of the ester function in products (37), step (2), affords nitro alcohols (38), which are either transformed into halo-containing compounds... 

In addition to their transformation into linear alcohols by hydrogenation, methyl esters obtained in the transesterification of fats and oils can also be used as raw materials for sulfonation, yielding a family of derivatives known as methyl ester sulfonates (MES). These products are only significant in some southeast Asian markets, Japan and to a much lesser extent in other markets such as the US. 

Transformation of carboxylic acids, esters, alcohols, or ethers into nitriles [28] or other nitrogen containing derivatives [29]... 

Recently, Settambolo et al. [194] reported a formal synthesis of (S)-myrmi-carin 217 (206) using a sequence of reactions slightly modified from the one described in Scheme 4. Indeed, rather than to cyclize directly the diester (S)-207, the latter was first transformed into the aldehyde 219 (Scheme 7) that was further intramolecularly cyclodehydrated into ester 220. The latter can be converted into (S)-myrmicarin 217 (206) via the alcohol (S)-209 as described previously by Sayah et al. [192] (see Scheme 5). 

Imidazolidinium salts can also be transformed into the corresponding diamino ortho-esters by alkaline alkoxylate, and upon alcohol elimination at elevated temperature the imidazolidin-2-ylidenes can be trapped. The reaction of tria-zolium salts with sodium methanolate in methanol yields 5-methoxy-4,5-dihydro-IH-triazole which also eliminates methanol upon heating in vacuo. The resulting triazolin-5-ylidenes can either be isolated or trapped by an appropriate metal precursor [Eq. (19)]. Benzimidazolin-2-ylidenes are similarly accessible by this route. 

Olefination of the Aldehyde 178 using a stabilized Wittig reagent followed by protecting group chemistry at the lower branch and reduction of the a,p-unsaturated ester afforded the allylic alcohol 179 (Scheme 29). The allylic alcohol 179 was then converted into an allylic chloride and the hydroxyl function at the lower branch was deprotected and subsequently oxidized to provide the corresponding aldehyde 161 [42]. The aldehyde 161 was treated with trimethylsilyl cyanide to afford the cyanohydrin that was transformed into the cyano acetal 180. The decisive intramolecular alkylation was realized by treatment of the cyano acetal 180 with sodium bis(trimethylsi-lyl)amide. Subsequent treatment of the alkylated cyano acetal 182 with acid (to 183) and base afforded the bicyclo[9.3.0]tetradecane 184. 

Much more conveniently, even a,)S-unsaturated esters can he transformed into a,)S-unsaturated alcohols by very careful treatment with lithium aluminum hydride [1073], sodium bis(2-methoxyethoxy)aluminum hydride [544] or diiso-butylalane [1151] (Procedure 18, p. 208). An excess of the reducing agent must be avoided. Therefore the inverse technique (addition of the hydride to the ester) is used and the reaction is usually carried out at low temperature. In hydrocarbons as solvents the reduction does not proceed further even at elevated temperatures. Methyl cinnamate was converted to cinnamyl alcohol in 73% yield when an equimolar amount of the ester was added to a suspension of lithium aluminum hydride in benzene and the mixture was heated at 59-60° for 14.5 hours [1073]. Ethyl cinnamate gave 75.5% yield of cinnamyl alcohol on inverse treatment with 1.1 mol of sodium bis(2-methoxy-ethoxy)aluminum hydride at 15-20° for 45 minutes [544]. 

Methyl 2-bromo-2-cyclopropylideneacetate (11a) has never been tested in these reactions, but has been used as a starting material for the stepwise construction of 1,6-heptadienes with methylenecyclopropane units for intramolecular Heck reactions. Thus, bromo ester 11a, after reduction, subsequent conversion of the resulting alcohol to the bromide and coupling with enolates of substituted malonates, was transformed into dienes of the type 254 (Scheme 73) - versatile synthetic blocks for the preparation of functionally substituted spirocyclopropanated bicyclo[4.3.0]nonenes 255a-d by a domino Heck-Diels-Alder reaction [122a]. 

The ester derivative of pyrrolo-benzoxazepine 403 (Scheme 84) has been transformed into ketone 404 with methyl lithium, while ester 406 was synthesized by esterification with acetyl bromide of alcohol 405, prepared by LAH reduction of 403 (1996JMC3435). 

Chorazepate Chorazepate, 7-chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1H-1,4-benzo-diazepin-3-carboxylic acid (5.1.34), which is used in the form of a dipotassium salt, is synthesized by yet another interesting synthetic scheme. 2-Amino-5-chlorobenzonitrile is used as the initial compound, which upon reaction with phenyhnagnesiumbromide is transformed into 2-amino-5-chlorbenzophenone imine (5.1.32). Reacting this with amino-malonic ester gives a heterocyclization product, 7-chloro-l,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one (5.1.33), which upon hydrolysis using an alcoholic solution of potassium hydroxide forms a dipotassium salt (5.1.34), chlorazepate [30-32]. 

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