Acetylenic lactones

Medium-ring acetylenic lactones,2 Cyclization to medium size acetylenic lactones is difficult because of geometric constraint imposed by the triple bond, and has been considered practicable only for at least fifteen-membered rings. Surprisingly, the acetylenic w-hydroxy acid 1 when complexed with Co2(CO), is cyclized in 28% yield to the seven-membered complexed acetylenic lactone 2 by Mukai-yama s reagent, 2-chloro-l-methylpyridinium chloride (8, 95-96). The yield is essentially the same as that observed in lactonizaton to a complexed 10-membered... 

The same paper reports another route to 11-membered acetylenic lactones via an intramolecular retro-Dieckmann reaction (equation I). Thus treatment of 3 with... 

A simple, high yielding (65-90%) procedure has been described for the preparation of medium ring and macrocyclic acetylenic lactones which is mechanistically related to the well known Eschenmoser fragmentation reaction, and the following example is representative. Bromination of the tosylhydrazone of 1 was carried out with NBS at -10°C in a water/t-butanol/acetone mixture. The reaction mixture was then treated with aqueous NaHSC>3 solution and the resulting mixture heated at 50-60°C for one hour, which gave the acetylenic lactone 2. 

In a chemical investigation of B. paniculata from Northern Chile, two isomer acetylenic lactones were isolated [30], while the aerial parts of B. salicifolia yielded two prenyl derivatives, Fig. (54) [21],... 

A large number of compounds, which are typical constituents of the Baccharis genus, were isolated from these species and might be partly or wholly responsible for the antimicrobial effects exhibited by the plants. For example, four compounds, including a flavone, an acetylenic lactone, a... 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

The reaction of o-iodophenol, norbornadiene and CO proceeds via alkene and CO insertions to afford the lactone 562, which is converted into coumarin (563) by the retro-Diels-Alder reaction. In this coumarin synthesis, norbona-diene behaves as a masked acetylene[4)3],... 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

The third synthetic scheme is employed when the phenylthio substituent is in the a-position of the lactone function, which interferes with the cyclization (90JOC5894). Acetylenic ketone 194 (95% yield) is readily transformed to the acetal 195 (with potassium carbonate in methanol) however, under the above conditions neither its hydrolysis nor cyclization to the spiroketal occurs. The spirocyclic pyrone 197 is formed in quantitative yield on treatment of 195 with p-toluenesulfonic acid in a 4 1 THF-H2O mixture at reflux for 12 h. 

Shao reported the microwave-assisted hetero-Diels-Alder cycloaddition reaction of a series of acetylenic pyrimidines to introduce a fused lactone/lactam ring, with no degradation of either reactants or products typical for the harsh thermal conditions (150-190°C, 15-144h) [131]. In contrast to the results reported when conventional heating was applied, the Diels-Alder cycloaddition under microwave irradiation gave a high yield of the desired fused lactones or lactams [132]. This reaction provided a practical and general method for the preparation of fused bicyclic pyridines 205 (Scheme 74). 

Chiral lactones were also obtained by cyclocarbonylation of chiral acetylenic alcohols with Pd and thiourea (H2NCSNH2) (Scheme 32). No loss in chirality was observed, but large amounts of Pd and thiourea were used (10 mol %) since the catalyst deactivates by forming metal particles. The catalytic precursor (Pdl2 > PdCl2) and the ratio of thiourea to Pd were very important, thiourea being necessary for this reaction. The active species was supposed to be [Pd(thiourea)3l]I, which forms in situ from [Pd(thiourea)4]l2 and [Pd(thiourea)2]l2. It had to be a partially dissociated species since [Pd(thiourea)4](Bp4)2 was inactive [121]. 

The lactone (59) is made by the method described on page T 96. Addition of the protected acetylene (61) gives the hemlacetal (62) which can be hydrogenated directly to (63). Cyclisation occurs as soon as the protecting group is removed. 

Using propargyl alcohols and propargylamine derivatives as acetylenic compounds, the silylformylation reaction affords, in the presence of a base, a-silylmethylene-P-lactones, I, and P-lactams, II, respectively (Scheme 3) [13]. 

When the platinum-catalyzed hydrothiolation was performed for acetylenic alcohols, intramolecular cyclization took place to afford a-methylene lactone 25 in up to 67% yield (Eq. 7.19) [30]. 

W=X is N=N or C=N, never if it is C=C. The ring stability of 3-furyl-carbenes conforms with this rule. Ring opening is again the main reaction in a biradical which is generated by extruding carbon dioxide from a lactone at 675°C and which then collapses to an acetylenic ketone.277... 

The mechanism of the reactions of 3-hexyne and acetylene-cobalt hexacarbonyl in toluene solution is similar to reactions (1) and (2) of the lactone decomposition. These reactions are followed by some disproportionation of the monophosphine... 

Ethynyl compounds react with sugar lactones to give acetylenic lactols (16,63). Reaction of 2,3-O-isopropylidene-D-ribonolactone (16a) with lithium acetylenic derivatives gave l-(2-substituted ethynyl)-2,3-0-isopropyli-dene-D-ribofuranoses. Similarly, treatment of 2,3 5,6-di-O-isopropylidene-L-gulono-1,4-lactone (9b) with various lithium acetylenic reagents gave... 

The a-acetylenic alcohols were used in a synthesis of optically active 4-alkyl- y-lactones (80) (90), as shown in Scheme 11. Lactones with optical purity >... 

As part of a study of the reactions of metallacyclic y-ketovinyl complexes of molybdenum and tungsten with acetylenes, directed toward the synthesis of complexed -/-lactones, Stone has reported92 the isolation of several vinyl-ketene complexes. When complex 72 was heated with 2-butyne, one molecule of the alkyne was incorporated into the complex with concomitant carbonylation. X-ray analysis of the product (73) has shown unequivocally that the C-l to C-4 vinylketene fragment is bonded in a planar, rj4-configu-ration. In contrast to the thermal reaction, ultraviolet irradiation of 72 or 74 in the presence of 2-butyne affords the complexes 75 and 76, respectively, where the lone carbonyl remaining after alkyne insertion had been replaced by a third molecule of the alkyne. 

The sequential addition method also allows the synthesis of many different block copolymers in which the two monomers have different functional groups, such as epoxide with lactone, lactide or cyclic anhydride, cyclic ether with 2-methyl-2-oxazoline, imine or episul-Hde, lactone with lactide or cyclic carbonate, cycloalkene with acetylene, and ferrocenophane with cyclosiloxane [Aida et al., 1985 Barakat et al., 2001 Dreyfuss and Dreyfuss, 1989 Farren et al., 1989 Inoue and Aida, 1989 Keul et al., 1988 Kobayashi et al., 1990a,b,c Massey et al., 1998 Yasuda et al., 1984]. 

A second approach (472) to 512 started with trans-2-buitnc epoxide (524) (Scheme 67). Opening of the epoxide ring of 524 with lithium acetylide gave an acetylenic alcohol, which was converted to the acetylenic acid (525) by carbox-ylation with gaseous carbon dioxide. Partial hydrogenation of 525 followed by lactonization afforded the a,3-unsaturated lactone (526) which was transformed to the nitrolactone (527) by a Michael addition reaction of nitromethane. The Nef reaction of 527 gave the tetrahydrofuranyl acetal (528) which was converted to... 

The utility of the creation of a y-lactone enolate through 1,4-addition of a carbanion and its interception by an electrophile has also been demonstrated in other classes of natural products, e.g., in the enantioselective synthesis of 10-oxa-l 1-methyl PGE2 analogues22. This synthesis starts with 1,4-addition of the sulfone-stabilized anion from 27 to ( + )-(S )-4-methyl-2-buteno-lide which has been prepared in three steps from (—)-(S)-l,2-epoxypropane. The intermediate enolate 28 is reacted with the acetylenic iodide to give the trisubstituted diastereomeric mixture of lactones 29, which is eventually converted into the pure compound 30, both reactions occurring with high diastereoselectivity. 

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