Synthesis of 5-Lactone

All of the efficient catalytic systems reported to date have involved the use of palladium species, together with various ligand architectures such as [Pd(r 3-2-Me-C3H4)(OAc)], Pd(acac)2 with P Bu3 and P Pr3, and [Pd(PPh3)2(p-benzoquinone)] [68]. 

In spite of the academic significance of this synthesis, the industrial value of 8-lactone as a versatile starting material has remained low because of the few applications reported to date. Dinjus and coworkers [74] described the synthesis of polymers via the photoinitiated polyaddition of 8-lactone with various dithiols which displayed intact lactone fragments within the polymer backbone. However, the complicated synthesis and the formation of rather statistic polymers with hard-to-tune characteristics hindered their potential industrial applications. 

Behr and coworkers have reported on some promising approaches using 8-lactone as the starting compound for exploitable specialty chemicals. One such strategy involves the three-step synthesis of 2-ethylheptanoic acid, an interesting building block for new alkyd resins (as used in printing inks, baked enamels, and 

It is not only a wide range of applications that is important to insure a significant industrial up-scaling, but also an ingenious process design allowing easy catalyst retrieval. By relying on catalytic systems that functioned in acetonitrile, Behr et al. tested numerous polyalcohols as extraction media to separate the palladium 

2 Nishimura, T., Kamashita, T., Wada, M., Nagata, T., Tanabe, Y., Hasegawa, R., and Nakatsuka, M. (1997) US Patent 5647896, Mitsui Toatsu Chemicals. 

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Although intermolecular additions to a,f5-unsaturated carbonyl compounds have not been used as often, these transformations are also attractive from a synthetic point of view for the synthesis of 5-lactones or 5-hydroxy esters. An example is shown in Scheme 12.11 [5d]. 

Scheme 2.2.7.10 Synthesis of 5-lactone equivalent 20 and application in the synthesis of (S)-argentilactone, (S)-goniothalamin, (-)-callystatin, and (-t)-strictifolione [34-36],...

Colson, P.-J. and Hegedus, L.S. (1994) Synthesis of [5-lactones by the photochemical reactions of chromium alkoxycarbene complexes with aldehydes. Journal of Organic Chemistry, 59, 4972-4976. 

Table 21 Synthesis of /5-lactones. Reproduced with permission from Elsevier...

There is an ongoing interest in catalytic C-C bond-forming reactions of CO2 [3] and much work has been invested in palladium-catalyzed synthesis of 5-lactone 2 from butadiene 1 and CO2 [3 e, 3 f, 4]. Table 1 presents the catalyst development for this catalytic coupling reaction, and the optimum conditions as known up to now are summarized in eq. (1). 

Scheme 7.6. Synthesis of 5-lactones using enantioselective solid-phase allylation reaction.

The use of iodolactonization in the synthesis of 5-lactones is demonstrated in routes to a prostaglandin endoperoxide analogue, and to the antibiotic malyngolide. The latter compound (164) has also been prepared as a mixture of C-2 epimers by lactonization of the epoxide (163). Stereoselective sul-phenyl-lactonization plays an important role in a synthesis of octahy-droleukotrienes, and cyclization of the cyclopropyl acid (165) leads to the lactone (166). A spirocyclic dilactone has been prepared and undergoes... 

Dinjus E, Leitner W (1995) New insights into the palladium-catalysed synthesis of 5-lactones from 1,3-dienes and carbon dioxide. Appl Organomet Chem 9(l) 43-50... 

Scheme 22 Synthesis of 5-lactones present in the white butterfly Idea leuconoe...

Scheme 27 Synthesis of 5-lactones via enantioselective Henry reaction...

Adger et al. have reported an enantioselective method for the synthesis of 5-lactones via application of enzymatic Baeyer-Villiger oxidation [75] (Scheme 32). Oxidation of cyclopentanone derivative 168 using a monooxygenase... 

Scheme 32 Synthesis of 5-lactones via application of enzymic Baeyer-Villiger oxidation...

Scheme 39 Synthesis of 5-lactones via oxidative lactonization of alkenols...

Scheme 41 Synthesis of 5-lactones by ozonolytic cleavage of vinyl phosphonates...

Scheme 49 Synthesis of 5-lactones by desymmetrization of mero-dialdehydes...

Scheme 51 Direct catalytic enantioselective synthesis of 5-lactones...

Described in this section are a couple of reports on the synthesis of 5-lactones wherein the ring closure has been achieved through a radical cyclization. Bachi and Bosch have reported the synthesis of 5-lactones by free-radical annelation of phenylselenyl carbonates [103] (Scheme 58). An intramolecular addition of an alkoxycarbonyl radical, formed by reaction of phenylselenyl carbonates 275 with tri-n-butyltin hydride in the presence of AIBN, to carbon-carbon multiple bonds provided the highly substituted lactone 276. The salient features of this free-radical cyclization include high regioselectivity favoring exo addition and a high ratio of cyclization to reduction products. 

A radical cyclization approach for the synthesis of 5-lactones has also been reported by lhara et al. [104] (Scheme 59). Treatment of bromo ester 277 with tri- -butyltin hydride in the presence of AIBN under dilute conditions facilitated a 6-exo-trig radical cyclization to provide diastereomeric lactone 278 in 92 % yield. However, the reaction was found to be dramatically concentration dependent as it exclusively gave the reduced product 279 under concentrated conditions. Nevertheless, this problem was overcome by using tris(trimethylsilyl)silane, which exclusively led to the desired 5-lactone irrespective of the concentration of the reaction. 

There are few reports in which the 5-lactone ring is constmcted through a samarium iodide-mediated reductive cyclization of 1,5-dicarbonyl compounds. In the first example. Fang, Tsai et al. have reported the synthesis of 5-lactones using samarium... 

Scheme 62 Synthesis of 5-lactones through Pd(II)-assisted oxidative lactonization...

Scheme 76 Synthesis of 5-lactones via one-carbon ring enlargement...

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