Exo-methylene lactones

Research Focus Preparation of polymethylmethacrylate derivatives containing pendant sulfonyl or exo-methylene lactone functions. 

Anomeric radicals can be trapped by sugars having an exo-methylene group. This principle has been applied to C-2 exo-methylene lactones, opening the way to the interesting new class of carbon-linked disaccharides [113,114] (Scheme 30). 

If the electrophilic end of the alkene is unsubstituted, it is particularly prone to conjugate additions. Examples include exo-methylene lactones 63, ketones 64 and vinyl ketones 65 that are often used... 

Now a Lewis-acid-catalysed reaction of the allyl silane via a p-silyl cation, gives the lactone. The This silicon chemistry was double bond in these exo-methylene lactones easily moves into the ring in acid or base so the mild devised by A. Haider, Synthesis, conditions for allyl silane reactions are ideal. 19S5, 271. 

The third compound, an exo-methylene lactone, is carcinogenic and might react by conjugate addition with proteins and nucleic acids if glutathione does not react more quickly. Fortunately, thiols are excellent at conjugate addition. 

They even react cleanly with formaldehyde, thus solving the problem that the Mannich reaction is not applicable to esters. The synthesis of the exo-methylene lactone 80 can be accomplished this way. Enone disconnection13 reveals formaldehyde as the electrophilic component in a crossed aldol reaction, realised with a lithium enolate 82.14 The mono-adduct 83 of formaldehyde and the lactone 81 can be isolated and the cautious dehydration step is to avoid migration of the double bond into the ring. 

Similar compounds 56 can be made13 from zinc derivatives of bromoesters 54 and even the simple alcohol14 57 gives the diol 59 and hence another exo-methylene lactone 60 by oxidation. 

In 1977 Still and Schneider used an Ireland-Claisen rearrangement of a 3° allylic ester in the synthesis of ( )-frullanolide (Scheme4.102) [93]. Rearrangement to the j8-pyrrolidinomethyl ester was followed by Cope elimination to the exo-methylene lactone. Stereocontrol of the alkene was of course not an issue in this case since the alkene was confined within a ring. 

As the first example of asymmetric radical addition using chiral aluminum Lewis acid, in 1995, Urabe and Sato reported enantioselective inter molecular radical addition of butyl radical generated from iodobutane to exo-methylene lactone (Scheme 6.172) [202]. In this reaction, chiral Lewis acid (i )-(14) derived from (R)-BINOL and Et2AlCl gave only low enantioselectivity (up to 23% ee). Shortly after this report, Nishida and coworkers reported that in the presence... 

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