A -Butenolide synthesis

Aldehyde (8) was needed for a butenolide synthesis. How would (8) be made ... 

Catalyst 2 can also be used in a butenolide synthesis on the basis of a ruthenium catalyzed Alder ene type reaction. [6-9] In the course of a reaction sequence directed to the synthesis of acetogenins, Trost et al. coupled alkene 16 with propargyl alcohol 17 in the presence of 2 to give butentolide 18 in up to 82 % yield (Scheme 6). 

In preparation for scale-up of the strigol synthesis described by Sih (8), efforts were made to improve the yield of some of the seven steps involved in the scheme. Of these steps, nine are satisfactory from the standpoint of yield and experimental conditions. For three of the steps, we have improved the yield and/or experimental conditions such that the yield of (+ )-strigol would be raised to 2.85% overall from citral rather than 1.53% based on Sih s procedure and reported yields. Improvements were developed preparation of a-cyclocitral (III), the oxidation of the hydroxyaldehyde (V) to the ketoacid (VII), and for the preparation of the hydroxybutenolide (XVII). For the remaining five steps, our attempts to change experimental conditions have failed to improve, and in most cases to even obtain, the yields reported in the literature (8). We have considered the preparation of strigol analogs and determined the conditions and limitations for the preparation of a series of alkoxybutenolides (XVI) and a butenolide dimer (XVIII). Modification of the literature procedure (11) to eliminate the use of the mesylate (XX) and the use of polar aprotic solvents gave better yields of the 2-RAS (XXI). 

Stille coupling (12, 56).1 The key step in a synthesis of (E)-neomanoalide (4) involves palladium-catalyzed coupling of an allyl halide with an a-stannylfuran. Thus 1 and 2 couple in the presence of Pd(dba)2 and P(C6H5), to form 3 as a 1 1 mixture of (E)- and (Z)-isomers in 66% yield. Conversion of 3 to 4 involves reduction (DIBAH) and selective singlet oxygen oxidation of a 2-silylfuran to a butenolide. 

A total synthesis of (35, 4/ )-(+)-eldanolide (246), a sex attractant pheromone, has been reported (243). Compound 246 was synthesized by two different routes, both involving the butenolide 245 as the key precursor. The higher-yielding sequence is described here. Treatment of the tosylate acetal 242 with methanolic sodium methoxide led, as previously described by Hoffman and Ladner (244), to the epoxide 243. Addition of lithium diiso-butenylcuprate to 243 afforded 244, which after successive hydrolysis of the isopropylidene group, treatment with triethyl orthoformate, and pyrolysis,... 

N-Bromoiraides, 46, 88 />-Bromophenyl isothiocyanate, 46, 21 Butadiene, 46, 106 Butadiyne, diphenyl, 46, 39 A -Butenolide, 46, 22 i-Butyl alcohol in synthesis of phenyl 1-butyl ether, 46, 89 1-Butyl azidoacetate, 46, 47 hydrogenation of, 46, 47 1-Butyl chloroacetate, reaction with sodium azide, 45, 47 i-Butyl hypochlorite, reaction with cy-clohexylamine, 46,17 1-Butylthiourea, 46, 72 1-Butylurea, 46, 72... 

Beck B, Magnin-Lachaux M, Herdtweck E, Domling A (2001) A novel three-component butenolide synthesis. Org Lett 3 2875-2787... 

The Diels-Alder cycloadduct of furan and maleic anhydride has played a key role in a new synthesis of butenolides (79S607). Treatment of the cycloadduct (24) with methanol affords a half acid ester which is reacted in turn with an excess of a Grignard reagent to produce the lactone (25) on acidic work-up. On heating this lactone at 150-180 °C, thermal fragmentation takes place to yield the 4,4-dialkylbutenolide (26) in high overall yield (Scheme 5). 

In the course of a total synthesis of aphidicolin (107), the conjugate addition of the dienoiate (104) to the chiral butenolide derivative (105) serves as a key step. A 7.4 1 mixture of diasteieomeric products is obtained, from which the major isomer (106) can be isolated in pure form after recrystaliization (Scheme 41).121 The selectivity of this remarkable reaction, in which two quaternary stereogenic centers are simultaneously generated in a highly selective manner, can be explained by the assumption that the reactants approach each other in the chelate-mode indicated in (108). 

In certain other systems, there is compelling evidence for the insertion into a metal-caiboxylate complex (equation 37). For example, in the synthesis of a-methylene-y-lactones from alkynic alcohols,70,71 no double bond rearrangement to a butenolide occurs, a reaction shown to take place in the presence of transition metal hydrides. The source of the vinyl proton (deuterium) on the a-methylene group is indeed the alcohol function. Finally, palladium carboxylate complexes containing alkynic (equation 40) or vinyl tails (equation 41) can be isolated and the corresponding insertion reaction can be observed. 

Butenottdes. A synthesis of the isodehydroabietenolide (5) used a new method for preparation of a butenolide (2) which was then transformed into the benzenoid ring of 5. Thus, reaction of the ketene dithioketal 1 with dimethylsulfonium methylide followed by acid hydrolysis produced the butenolide 2 in high yield. This product was then converted via the furane 3 into the salicyclic ester 4 via a Diels-Alder reaction.1... 

The efficiency of this method was demonstrated in a total synthesis of the antibiotic (-r)-tetrahy-drocerulenin 28 (Scheme 8) and (-h)-cerulenin [11]. Irradiation of complex 22 in the presence of the chiral iV-vinyl-oxazolidinone 24, which is easily prepared from the amino carbene complex 23 [12], leads to the cyclobutanone 25 with high diastereoselectivity. Regioselective Baeyer-Villiger oxidation followed by base-induced elimination of the chiral carbamate yields the butenolide 26 in high enantiomeric purity. This is finally converted, using Nozoe s protocol [13], to the target molecule 28 by diastereo-selective epoxidation (- 27) and subsequent aminolysis. 

A concise synthesis of highly substituted furans, pyrroles, butenolides, and 2-butene-4-lactam esters starts from alkynyl adducts of a Fischer carbene complex 21 (Scheme 27) < 1998JOC3164>. Incorporation of an aldehyde yields a reactive vinyl tungstencarbonyl complex 22 that can be oxidatively transformed to an ester group, furnishing the furan carboxylic ester 23. 

A synthesis of a-l,l,l trifluoroethyl A -butenolides starting from 7-ketothioesters by deprotonation with Hiinig s base has been reported (Equation 45) <2006S1050>. 

In a Mn(OAc)3-mediated oxidative radical reaction of allenes with dimethyl malonate or ethyl cyanoacetate, an efficient synthesis of A -butenolides is realized (Equation 59) <2007S45>. 

A regioselective synthesis of 3-substituted A -butenolides by palladium-catalyzed reductive carbonylation can be carried out with a simple terminal alkyne as starting material (Equation 68) <1999TL989>. 

A few other examples are listed in Scheme 49 intramolecular addition of amine giving a good synthesis of (/ )-(-P)-camegine, synthesis of chiral butenolides by carbonation of vinylic carbanions and conjugate additions of cuprates yielding chiral chromans. ... 

Thermolysis of 2-(diazoacetyl)cyclobutanones 338 furnishes 5-spirocyclo-propyl-A -butenolides via intermediate a-ketenylcyclobutanones. The method is acceptable for the synthesis of various spiropolycyclic compounds 340, 341 in moderate to high yields (91JOC1453). Diazo compound 342 was pyrolyzed (350°C/0.1 mm) to give 343 in 40% yield (86TL2447). 

Minami, T., Watanabe, K., Chikugo, T., and Kitajima, Y., A new synthesis of y-lactones with a,P-fused ring systems using a-diethoxyphosphinyl-A P-butenolides, Chem. Lett., 2369, 1987. 

Tanyeli, C., and Caliskan, AIL.. A facile synthesis of various butenolides. Synth. Commun., 30, 2855, 2000. 

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