Unsaturated /3-lactone

Review Problem 7 a-p-Unsaturated lactones are nsefhl intermediates in syntliesis as they take part in Diels-Alder reactions to buhd larger molecules with more complex functionahty. How would you make tliis one ... 

The reaction can be applied to the synthesis of q, /3-unsaturated esters and lactones by treatment of the ketene silyl acetal 551 with an allyl carbonate in boiling MeCN[356]. The preparation of the q,, 3-unsaturated lactone 552 by this method has been used in the total synthesis of lauthisan[357]. 

PdCb, and the allylated lactone 232 is formed. Regeneration ofPdCl2 as shown by 231 makes the reaction catalytic. In this reaction, use of the Li salt 227 of 4-pentynoic acid (223) is recommended. Reaction of lithium 3-octynoate (233) with allyl chloride affords the unsaturated lactone 234, which is converted into the 7-keto acid 235 by hydrolysis[126]. 

Telomerization Reactions. Butadiene can react readily with a number of chain-transfer agents to undergo telomerization reactions. The more often studied reagents are carbon dioxide (167—178), water (179—181), ammonia (182), alcohols (183—185), amines (186), acetic acid (187), water and CO2 (188), ammonia and CO2 (189), epoxide and CO2 (190), mercaptans (191), and other systems (171). These reactions have been widely studied and used in making unsaturated lactones, alcohols, amines, ethers, esters, and many other compounds. 

Additional applications are exemplified by the well-known Meystre-Miescher degradation of the bile acid side chain and, more recently, in the preparation of a-pyrones from a,iS-unsaturated lactones. ... 

An important side reaction observed during methylenation of 17a-acetoxy 20-ketones (4) is the formation of the unsaturated lactones (6) in high yield. These compounds arise by aldol condensation and dehydration. 

Several reviews deal with the chemistry of these unsaturated lactones (64CRV-353 68RCR254 76CRV625 77UK1250 82CSR75). Synthetic approaches to these compounds have recently been reviewed (94COS287 95COS133). 

Unsaturated -lactone 34 adopts a well-defined conformation and provides a suitable platform for the introduction of the stereogenic center at C-24 (monensin numbering). Catalytic hydrogenation of the carbon-carbon double bond in 34 takes place preferentially from the less hindered side of the molecule and provides an 8 1 mixture of stereoisomers in favor of 35 (100% yield). Cleavage of -lactone 35 with concentrated hydriodic acid at 130°C, followed by treatment of the resultant iodide 36 with triphenylphosphine, completes the synthesis of intermediate 19. 

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). 

In this chapter the addition of carbon nucleophiles to simple a,j8-unsaturated sulfoxides, a-sulfinyl-a,/ -unsaturated ketones and a-sulfmyl-a,/ -unsaturated lactones will be discussed separately, in most cases the asymmetric induction arises from the chirality at sulfur. 

Chelidonic acid has been found to exist in the free state in many plants (122). A concentration as high as 10 2 M, calculated on a fresh-weight basis, has been measured. Leopold et al. (89) found that chelidonic acid functioned as a growth inhibitor in the pea straight-growth test. Some inhibition was obtained at 10 5 M and 50% inhibition was measured at 10 4 M. Growth was promoted in the presence of IAA. This action is similar to that noted for coumarin and other unsaturated lactones. As with lactones, the inhibitory effect of chelidonic acid could be relieved by pretreatment of the tissue with BAL. 

Various phenolic acids have been reported to inhibit IAA oxidase (9, 52,120), and other phenols may act as cofactors of IAA oxidase (144). In general, the cofactors of IAA oxidase are monophenols, whereas the inhibitors of the system are polyphenols, with o-dihy-droxyphenols being the most inhibitory (52, 65). Unsaturated lactones have also been reported to inhibit IAA oxidase (2, 52). 

For maximum selectivity, low temperatures are essential under such conditions, simple alcohols, even allylic, are unaffected, and with unsaturated lactones as substrates, the double-bond position stays unchanged. 

Lactams 618 <5-Lactols 627 Lactones 617 reactions of 636 synthesis of 632, 737, 815 a,fl-unsaturated - see a,/J-Unsaturated lactones... 

The high chemoselectivity for the Baeyer-Villiger process was utilized in the synthetic elaboration of another hetero-bicyclic substrate. The biooxidation only provides the expected unsaturated lactone in a desymmetrization reaction without compromising the olefin functionality. The biotransformation product was then converted to pivotal intermediates for C-nucleosides like showdomycin, tetrahydro-furan natural products like kumausyne, and goniofufurone analogs in subsequent chemical operations (Scheme 9.17) [161]. 

In 1,4-conjugate additions toward cyclic unsaturated lactones, facial selectivity... 

A recent synthesis of P-D lactone (Scheme 13.51) used an enantioselective catalytic approach. A conjugate addition of a silyl ketene acetal derived from an unsaturated ester gave an unsaturated lactone intermediate. The catalyst is CuF-(S )-tol-BINAP.30 The catalytic cycle for the reaction is shown below. 

Chapman, O. L. McIntosh, C. L. Photochemical decarbonylation of unsaturated lactones and carbonates. J. Chem. Soc., Chem. Commun. 1971, 383-384. 

The compounds implicated in allelopathy have been divided into chemical classes by recent reviewers (4, 20). They can be arbitrarily classed as (A) hydrocarbons, (B) organic acids and aldehydes, (C) aromatic acids, (D) simple unsaturated lactones,... 

The classic seed burial studies of W. J. Beal and his successors have shown seeds of at least one weed species, Moth Mullein (Verbascum blattaria L.) can remain viable in soil for a peiod of 100 years, whereas three species continued to germinate after 80 years of burial (30). Weed seeds not only resist decay by soil microbes, but they vary in dormancy characteristics. There is considerable evidence that chemical inhibitors are responsible for both phenomena. Unsaturated lactones and phenolic compounds in particular, are potent antimicrobial compounds present in many seeds (4J. Fruits and seeds are also known to contain diverse germination inhibitors including phenolic compounds, flavonoids and/or their glycosides and tannins. Unique methods to destroy inhibitors could provide an excellent weed management strategy. 

Table 1. Unsaturated Lactones with Plant Growth Inhibiting Activity...

Recently, the hydroxy derivatives of furan, thiophene, and selenophene have been studied with regard to their physical properties and reactions. These compounds are tautomeric and if the oxygen function is placed in the 2-position they exist as unsaturated lactones and undergo carbon-carbon rearrangement, whereas the 3-hydroxy derivatives form oxo-enol tautomeric systems. By NMR the structures of the different tautomeric forms have been determined as well as the position of the tautomeric equilibrium and the rate of isomerization. 

The ionization potentials, using mass spectrometry, for both 2-hydroxy-and 3-hydroxythiophenes have been compared with data for compounds derived from either tautomeric form in order to analyze the tautomeric composition.124 125 In the 2-hydroxy-substituted system the enol isomer could not be detected. Of the two possible unsaturated lactones the oc,/l-unsaturated form was the major isomer. In the 3-hydroxy-substituted case both the oxo form and the enol form are important. The position of the equilibrium was compared with those of the corresponding furan and sele-nophene systems for both isomers. 

A. P. Rauter, J. A. Figueiredo, I. Ismael, T. Canda, J. Font, and M. Figueiredo, Efficient synthesis of a,/ -unsaturated /-lactones linked to sugars, Tetrahedron Asym., 12(2001) 1131-1146. 

Intramolecular cycloadditions of a,p-unsaturated lactones to alkenes have been used as key step in the synthesis of a precursor of the terpene reserpine 480) (4.68) and of fused cyclooctanes (4.69) 481 ... 

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