Fi Lactones

Recently, it has been demonstrated by Sweeney and co-workers that fi-lactones can also be prepared by radical 4-exo cychsation methodology [93], The intermediate 0-(alkenoyl)oxyalkyl radicals 101 could be prepared by tin hydride treatment of the corresponding (l-bromopropyl)cinnamate. However, best results were obtained with N-hydroxypyridine thione (PTOC) esters 100. In this case a toluene solution of the PTOC ester and BusSnH was slowly added by syringe pump to a heated flask irradiated with a timgsten lamp (Scheme 22). For precursors containing only one substituent at the terminus of the double bond the direct reduction was the main process. For precursors 100 with two phenyl or two arylthio substituents, 4-exo cyclisation of the intermediate C-centred radicals 101 was efficient and good yields of -lactones 103 were isolated, accompanied in each case by minor amounts of the direct reduction product. The bis-arylthio functionahty was particularly appropriate for further FGI. 

A. N-(Benzyloxycarbonyl)-L-serin9 fi-lactone. A 2-L, three-necked, round-bottomed flask is equipped with a magnetic stirring bar, an argon inlet adaptor, a low temperature thermometer, and a rubber septum (Note 1). The flask is charged with tetrahydrofuran (1.1 L) and triphenylphosphine (42.1 g, 160 mmol. Note 2). The triphenylphosphine is dissolved with stirring and the flask is then cooled to -78°C with a dry ice-acetone bath (Note 3). Distilled dimethyl azodicarboxylate (17.7 mL, 160... 

Synthesis of fi-lactones. Dichloroketene (generated in situ from dichloroacetyl chloride and triethylamine) reacts with aliphatic and aromatic aldehydes in ether at low temperatures (<20°) to give a,a-dichloro-/3-lactones.4 Esters of a-keto-carboxylic acids also undergo the reaction. 

Kim, B. Y., and Kinsella, J. E. (1989). Rheological changes during slow acid induced gelation of milk by D-glucono-fi-lactone. J. Food Sci. 54, 894-898. 

Ketenes are another type of unsaturated molecules of high electron deficiency and structural strains therefore, they are very reactive for the [2+2] cycloaddition. The most common [2+2] cycloaddition involving ketenes are Staudinger [2+2] Cycloadditions to form fi-lactones, initially reported in 1911, and the dimerization of ketenes." Besides the easy cycloaddition with imine, as shown in the Staudinger [2+2] Cycloaddition, ketenes can also react with aldehydes to afford /3-lactones. It has been found that high diastereoselectivity can... 

A focused compound collection of 99 compounds with a fi-lactone core structure was synthesized (Scheme 8.1) [7]. Thirty compounds with a sy -configuration around the P-lactone core were synthesized by syn selective aldol reactions of ethyl esters and aliphatic aldehydes [14]. The syn aldol products were saponified... 

Scheme 8.1 Synthesis of a focused compound collection with a fi-lactone as core structure, (a) (nBu)jBOTf, DIPEA, CH2CI2 (b) LiOH, dioxane, H2O (c) PhS02CI, pyridine (d) (Chx)2BOTf, EtjN, CH2CI2 (e) Pd/C, H2, MeOH (f) carbony-lation using [(salph)Cr(THF)2][Co(CO)4] and CO (salph = N,W-o-bis...

In the second section of this chapter, we turn to a different class of compounds. While ADEPs can be comprehended as large cyclic esters, fi-lactones are among... 

The reaction was shown to proceed in a stereoconvergent manner, as both the Z- and the E-ketene acetal stereoisomers furnished the trans-fS-lactone exclusively. On the other hand, when the same reaction was conducted with SnCl4 as Lewis acid, the ds-fi-lactone 3 was obtained in moderate yield and high stereoselectivity [2]. Here, only a-unbranched aldehydes gave acceptable yields (Scheme 8.1). 

Photolysis at temperatures higher than 8 K in methanol or in ether leads to electrocy-dization of the pyrone-1,3-diene system affording the fi-lactone 9, which yields the enol ether 12 by addition of CH3OH. 

Across C=0 bonds The [2+2] cycloaddition of ketenes across C=0 bonds to give fi-lactones was extensively investigated by Staudinger and his coworkers. The reaction often proceeds without a catalyst, but added catalysts sometimes alter the course of the reaction. The reaction involves the C=C bond of the ketene, which adds across the C=0 bond of the carbonyl compound. At elevated temperatures, the cycloadducts eliminate carbon dioxide to give olefins. Trihaloaldehydes react especially well to produce the four-membered ring cycloadducts The thus obtained /3-lactones can be converted in a one-pot (two steps) reaction into /3-lactames . 

Bloembergen, S., D.A. Holden, T.L. Blubm, G.K. Hamer, R.H. Marcbessault. 1989. Isodimorpbism in synthetic poly(fi-hydroxybutyrate-co-B-hydrox3rvalerate) stereoregular copolyesters from racemic fi-lactones. Macromolecules 22 1663-1669. 

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