3- Phenyl-4-pentenoic acid

A. 3-Phenyl-4-pentenoic acid. A mixture of 33.7 g (0.25 mol) of cinnamyl alcohol (Note 1), 46.1 mL (0.25 mol] of triethyl orthoacetate (Note 1), and 0.19 mL (1.5 mmol) of hexanoic acid (Note 2) is placed in a 250-mL, round-bottomed flask equipped with a thermometer, Claisen head, and condenser. The solution is heated in an oil hath with distillation of ethanol. After 3 hr, distillation of ethanol slows and another 0.1-mL portion of hexanoic acid is added. Additional portions (0.1 mL) of the catalyst are added again at 3.5 and 4.5 hr. After 6 hr, a total of 27 mL of ethanol, out of a theoretical 29.2 mL, has been collected, and GC analysis (Note 3)... 

The solution is allowed to cool, and 19.7 g (0.35 mol) of potassium hydroxide 1n 25 mL of water and 75 mL of methanol is added. The mixture is heated under reflux for 1 hr under nitrogen. After the alkaline solution is allowed to cool to room temperature, It is washed with ether and acidified with coned HC1. The acidic solution is extracted with three 50-mL portions of ether, and the organic layer is dried over MgS04, filtered, and concentrated under reduced pressure. The yield of crude 3-phenyl-4-pentenoic acid is 38-39 g (86-88%). This material is essentially pure by NNR analysis and can be used directly as starting material for the following iodolactonization reactions. The acid can be further purified by crystallization from hexane (86% recovery in two crops) to give product melting at 44-46°C. 

Stereocontrolled iodolactonization (8, 257 9, 248). Iodolactonization of 3-phenyl-4-pentenoic acid (1, I2, CH3CN, 0°, 12 hours) gives the more stable fra/w-iodolactone 2 as the major product. In the presence of NaHC03 (kinetic control), the cis-iodolactone 3 is the major product. The contrast between the thermodynamically controlled and the kinetically controlled reactions observed in this case is fairly general, but usually not so marked. Thus when the phenyl group of 1 is replaced by methyl the ratio of trans- to ds-iodolactonization obtained under thermodynamic control is only 11 1 however, the... 

In a similar way, 3-phenyl-4-pentenoic acid (3) is lactonized in almost quantitative yield and a cis/trans ratio of 94 6 when treated with iodine in water/chloroform in the presence of sodium hydrogen carbonate183. 

A mixture of 10 g (0.057 mol) of 3-phenyl-4-pentenoic acid (3), 9.1 g (0.11 mol) of NaHCOj and 200 mL of H,0 is stirred until a homogeneous solution is obtained. 200 mL of CHC13 arc added, the mixture is cooled in an ice bath, and 28.4 g (0.112 mol) of iodine are added. The mixture is stirred at OX for 6 h, and the organic phase is washed with 10% aq sodium thiosulfate until colorless, then with H,0 and brine. The organic layer is dried and the solvent is removed under reduced pressure. The crude cw-iodolactone is obtained as a semisolid yield 15.5-16.3 g (91-95%) d.r. (cis/trans) 77 23 (determined by H NMR) mp 75-90X. Direct recrystallization of this material (diisopropyl ether) affords 9.0-9.5 g (52-55%) of material with a cis/trans ratio of 98 2 mp 103-104X. Further recrystallization from diisopropyl ether gives (in two crops) 8.3-8.9 g (48-52%) of product with a purity of 98% mp 104 105 X. Additional product can be obtained from the mother liquors. 

Phenyl-4-pentenoic acid (3) is converted to the corresponding mercury derivative 7 by treatment with mercury(II) acetate in methanol26. After demercuration with sodium borohydride in sodium hydroxide, dihydro-5-methyl-4-phenyl-2(3//)-furanone (8) is obtained as an 85 15 mixture of trans/cis-isomers in 45 % yield. 

Both diorganotellurium(IV) and diorganoselenium(IV) dibromides are known, stable compounds, which permits a direct comparison of the selenium(IV) and tellurium(IV) compounds. Di-4-chlorophenyltellurium(IV) dibromide (36) and one equivalent of pyridine were essentially unreactive with respect to bromination of either 4-pentenoic acid or 4-pentenol. With either substrate, 36 gives only 2-3% conversion to brominated products after several days of reaction (Fig. 17). In contrast, diphenylselenium(IV) dibromide (1, Fig. 1) and 2-(dimethylaminomethyl)-phenyl phenyl bromoselenonium bromide (37) gave essentially complete bromination of either 4-pentenoic acid or 4-pentenol in 1 h in the presence of one equivalent of pyridine as shown in Fig. 17. 

Fig. 17 Bromination of 4-pentenoic acid and 4-penten-l-ol with bromine/pyridine and with di-4-chlorophenyltellurium(IV) dibromide (36), diphenylselenium(IV) dibromide (1), and A, A -dimethyl-2-(aminomethyl)phenyl phenyl bromoselenonium bromide (37) and one equivalent of pyridine.

Intramolecular addition can occur when nucleophilic substituents are suitably positioned as in Eq. 14 [88]. When the latter electrolysis is conducted in CH2CI2/BU4 NCI, 75% of the chloro-y-lactone are obtained. Electrolysis of ( )-5-phenyl-4-pentenoic acid affords a 4-(phenyl-methoxymethyl) -4-butanolide [89]. 

A more useful way of reducing esters to ethers is a two-step procedure applied to the reduction of lactones to cyclic ethers. First the lactone is treated with diisobutylaluminum hydride in toluene at —78°, and the product - a lactol - is subjected to the action of triethylsilane and boron trifluoride etherate at —20° to —70°. y-Phenyl-y-butyrolactone was thus transformed to 2-phenyltetrahydrofuran in 75% yield, and 5-lactone of 3-methyl-5-phenyl-5-hydroxy-2-pentenoic acid to 4-methyl-2-phenyl-2,3-dihydropyran in 72% yield [1034]. 

Pentenoic Acid 2-Fluoro-3-mcthyl-5-phenyl- E10b2. 204f. (F - OH)... 

Pentenoic Acide 2-(tert.-Butyloxy-carbonylainino)-3.3-difluoro-4-(methoxy-methoxy)-5-phenyl-E10b2. 220 [F2C = C(OR)... 

Hydrogenolysis of 2-pyrone derivatives to give open-chain products occurs especially readily when phenyl group is substituted in the 6 position.237,238 4-Ethoxy- and 4-hy-droxy-6-phenyl-5,6-dihydro-2-pyrones were hydrogenated to give 3-ethoxy-5-phenyl-2-pentenoic acid and 3-hydroxy-5-phenylvaleric acid, respectively, over Raney Ni at room temperature and 0.3 MPa H2 (eq. 12.126).237... 

Trimethylacetyl chloride (0.065 mol) was added to 4-methyl-2-pentenoic acid (0.06 mol) and triethylamine (0.187 mol) dissolved in 200 ml THF at —20°C. After 1 hour the mixture was treated with LiCl (0.55 mol) and (R)-(-)-4-phenyl-2-oxazolidinone (0.05 mol) and a thick suspension formed, which was stirred 20 hours at ambient temperature. The suspension was filtered and the filtrate concentrated. The residue was recrystallized using hexane/EtOAc, 5 1, and the product isolated in 68% yield as a white solid. 

Olefinic acids have been reduced to saturated acids in excellent yields by a variety of methods. Catalytic hydrogenation at room temperature over platinum oxide catalyst is described for 4-phenyl-3-pentenoic acid (98%). Behenic and undecanoic acids are prepared from the naturally occurring erucic and undecylenic acids with this catalyst. New and "aged platinum oxide catalysts have been compared, Reduction by nickel-aluminum alloy has been preferred to catalytic hydrogenation over platinum catalyst in the preparation of y-isopropylvaleric acid. ... 

Activation of organolithium compounds. n-Butyllithium and phenyllithium react very slowly with diphenylacetylene. However, the 1 1 complex of either lithium compound and TMEDA reacts with diphenylacetylene at room temperature. For example, the reaction of /-butyllithium under these conditions followed by carbonation gives cis-4,4-dimethyl-2,3-diphenyl-2-pentenoic acid (1) and a trace of 2-phenyl-3-f-butylindone (2). Thus addition takes place as well as metallation.1... 

The lactonization of 4-phenyl-4-pentenoic acid (345) upon treatment with PhI(OAc)2 has been reported (Scheme 3.137) [432]. The mechanism of this reaction includes electrophilic lactonization induced by the addition of the iodine(III) electrophile to the double bond of substrate 345 followed by 1,2-phenyl migration leading to the final rearranged lactone 346. 

Methyl-2-pentenoic acid Methyl phenylacetate 3-Methyl-4-phenyl-3-buten-2-one 2-Methyl-4-phenyl-2-butyl acetate 2-Methyl-4-phenyl-2-butyl isobutyrate... 

The palladium-catalyzed aqueous hydrocarboxylation reaction of styrene, 1-octene, 3-buten-l-ol, and 4-pentenoic acid was studied in acidic solutions. The catalyst employing N3P as ligand (N3P = N-bis(N, N -diethyl-2-aminoethyl)-4-aminomethyl-phenyl-diphenylphosphane) was found to show an inverted regioselectivity compared to the TPPTS system. Noncoordinating anions gave the best results in terms of activity and stability of the catalyst [143]. 

ASYMMETRIC CATALYTIC GLYOXYLATE-ENE REACTION METHYL (2R)>2 HYDROXY-4-PHENYL-4 PENTENOATE (Benzenabutanoic acid, a-hydroxy-y-methylene, methyl ester, (R)-)... 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

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