Unsaturated methyl esters

G-20 Dicarboxylic Acids. These acids have been prepared from cyclohexanone via conversion to cyclohexanone peroxide foUowed by decomposition by ferrous ions in the presence of butadiene (84—87). Okamura Oil Mill (Japan) produces a series of commercial acids based on a modification of this reaction. For example, Okamura s modifications of the reaction results in the foUowing composition of the reaction product C-16 (Linear) 4—9%, C-16 (branched) 2—4%, C-20 (linear) 35—52%, and C-20 (branched) 30—40%. Unsaturated methyl esters are first formed that are hydrogenated and then hydrolyzed to obtain the mixed acids. Relatively pure fractions of C-16 and C-20, both linear and branched, are obtained after... 

The proposed mechanism for the conversion of the furanone 118 to the spiro-cyclic lactones 119 and 120 involves electron transfer to the a -unsaturated methyl ester electrophore to generate an anion radical 118 which cyclizes on the /3-carbon of the furanone. The resulting radical anion 121 acquires a proton, giving rise to the neutral radical 122, which undergoes successive electron transfer and protonation to afford the lactones 119 and 120 (Scheme 38) (91T383). 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

Figure 10.7 Melting points of different saturated and unsaturated methyl esters.

Inexpensive and readily available Grignard reagents and stable dinuclear Cu complexes have been used for the first time in catalytic enantioselective conjugate addition reactions to simple acyclic a -unsaturated methyl esters.95 These reactions have provided access to highly valuable -substituted chiral esters in good yields and with excellent enantioselectivities (up to 99% ee). 

The now classic Farmer-type hydrogen-abstraction Initiation of free radical autoxldatlon accounts for a large portion of the nonenzymlc oxidations of n-3 fatty acids (45). Because fish lipids contain substantial concentrations of EPA and DHA (47-48), they provide many allowed sites (18, 22, 45, 46, 49) of hydroperoxide formations, and thus can account for a large array of decomposition products. Oxidizing model systems of unsaturated methyl esters of fatty acids yielded monohydroperoxides, but also produce dlhydroperoxldes that are formed by cycllzatlon of Intermediate hydroperoxy radicals when suitable H-donatlng antioxidants are not present to quench the free radical reaction (45, 50, 51). Decomposition of monohydroperoxides of fatty acids In model systems yields a very different profile of lower molecular weight products than observed for similar decompositions of dlhydroperoxldes of the same fatty acids (45, 46). 

Structurally, cystothiazole B (2) consists of two linked thiazoles of which one is substituted by a simple alcohol residue, while the other bears a longer aliphatic chain comprising two adjacent stereogenic centers and an -configured a,P-unsaturated methyl ester moiety. This side chain is probably a product of the polyketide pathway. 

The selective hydrolysis of acetyl groups, led in methanol in presence of concentrated sulphuric acid, gives the a,P unsaturated methyl ester 13e. Therefore the two hydroxyls at C-3 and at C-4, in sin position each other, are protected by means of formation of isopropylidene function, doing react the methyl ester 13e with 2,2-dimetiioxypropane in acetone in presence of catalj tic quantity of strongly acidic resin, so obtain the 3,4-O-isopropylidene derivative 13f. 

RCOOH + BF3 Et20 -t- MeOH. This procedure has been used for the preparation of unsaturated methyl esters. ... 

In the laboratory of S.V. Ley, the total synthesis of the 3-lactone cholesterol synthase inhibitor 1233A was achieved by using the oxidative decompiexation of a (jt-allyl)tricarbonyliron lactone as the key step. " The (Z)-alkene present in the target was introduced using the S-G modified HWE olefination of an aldehyde with b/s(2,2,2-trifluoroethyl) (methoxycarbonylmethyl)phosphonate to give the desired a, 3-unsaturated methyl ester in excellent yield. 

Ortho ester Claisen rearrangements using trimethyl mcthoxyorthoacetate gave y,<5-unsaturaled methyl esters 24 in moderate yields (20-55%). With respect to internal asymmetric induction, the reaction is unselective501. 

Juvabione, the compound responsible for this activity, was isolated from the balsam fir, Abies balsamea (L.) Miller, and identified as the methyl ester of todomatuic acid, (+)-4(i )-[ 1 R)-S -dimethyl-3 -oxohexyl]-1-cyclohexene-1-carboxylic acid [87]. This compound is a sesquiterpenoid (Fig. (6)) with a cyclohexene group and an a,(3-unsaturated methyl ester group the chemical data for this compound are summarized in Appendix II, Table 1. The IR spectrum suggests that there is a carbonyl ester group present in conjunction with a double bond (1722 and 1645 cm 1) and also an isolated carbonyl group (1712 cm 1) [87]. Mass spectroscopy confirms... 

To improve understanding of mechanistic aspects of Raney nickel s selectivity and activity, a series of seven variously substituted a, 3-unsaturated methyl esters were hydrogenated either under deuterium (deuteriumated) or under nitrogen over deuterated Raney nickel. For comparison, some of the molecules were deuteriumated over Pd/C, and in some instances the Raney nickel was modified with L-glutamic acid. 

The three-step synthesis of 75c from 76a and 77a is characterized by the lack of any need for onerous protecting-group manipulation. From the starting phenol comes a dienone, from that a dieneketene, from that a doubly unsaturated methyl ester. The C,C-bis-alkylated components 80a and rac-81a, formed in the introductory synthetic step, already contain the complete set of C-atoms needed for crocetin (75b), albeit still arranged differently constitutionally. In the second step, the photochemical ring opening takes place, af-... 

The same chemical procedure was followed to synthesize mefliyl 12-hydroxy 9, 10-monoepoxystearate (Fig. 6) from castor oil [80% ricinoleic acid, 12-OH 18 1 (9c)] (40). Methyl ricinoleate contains a polar hydroxy group, making it easily separable from the unsaturated methyl esters present in minor amounts in the FAME... 

Copper-catalysed enantioselective conjugate addition of Grignard reagents to a,p-unsaturated methyl esters is sueeessfully carried out to provide p-substituted chiral esters in good yields and with excellent enantioselec-tivities (Scheme 15.24). A combination of copper iodide and commercially available chiral (R)-2,2 -bis(di-p-tolyl-phosphino)-l,l -binaphthyl (Tol-BINAP) is also effective. ... 

Scheme 15.24 Copper-catalysed asymmetric conjugated addition of Grignard reagents to a,p-unsaturated methyl esters.

A.E. Sherry s paper [55] raises the concern of the potential formation of a,P-unsaturated-y-sultones (lUS). Sherry s paper cites a paper by D.S. Conner et al. [56] that identified l-dodecene-l,3-sultone and l-tetradecene-l,3-sultone as sensitizers in guinea pigs. Sherry suggests that unsaturated methyl esters used as feedstock for SMEs could also result in lUSs. Figure 19 shows the hypothetical lUS that could result from the unsaturated methylesters versus the lUS mentioned in Conner s paper. The two are substantially different from one another. No data were provided by Sherry that l-aIkyl-3-(a-sulfoaIkylester)-1,3-sultone causes skin sensitization. It is also unlikely any lUS that could be formed would survive the harsh peroxide conditions used during the manufacturing of SMEs. 

Another feature which differentiates methyl ester ethoxylates from alcohol ethoxylates is unsaturation. Methyl esters, particularly those in the tallow range, are relatively highly unsaturated, generally >50%. Alcohols, in contrast, are typically fully saturated. The impact of unsaturation on performance can be significant, and is addressed in the last section of this chapter. 

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