Four-membered ring synthesis

L3 Four-membered ring synthesis and rean angements of bis(homoallyl)... 

Four-membered ring synthesis and rearrangements of bis(homoallyl)metals... 

Schenck, G. O., Hartmann, W., and Steinmetz, R., Four-membered ring synthesis by the photosensitized cycloaddition of dimethyl maleic anhydride to olefins, Chem. Ber., 96, 498,1963. 

Intramolecular amination with allylic acetates is used for the synthesis of cyclic alkaloids 175]. Cyclization of 293 affords the six-membered ring compound 294 rather than a four-membered ring. The reaction is particularly... 

P-Hydroxy acids lose water, especially in the presence of an acid catalyst, to give a,P-unsaturated acids, and frequendy P,y-unsaturated acids. P-Hydroxy acids do not form lactones readily because of the difficulty of four-membered ring formation. The simplest P-lactone, P-propiolactone, can be made from ketene and formaldehyde in the presence of methyl borate but not from P-hydroxypropionic acid. P-Propiolactone [57-57-8] is a usehil intermediate for organic synthesis but caution should be exercised when handling this lactone because it is a known carcinogen. 

There are very few totally synthetic antibiotics presently on the market. One of these is the 1-oxacephem, moxalactam (96). One may speculate that the enhanced potency of moxa-1actam stems in part from the substitution of the smaller oxygen atom for the sulfur normally present in the six-membered ring of cephalosporins thereby enhancing the reactivity of the adjoining four-membered ring. It is also partly a measure of the present stage of development of chemical synthesis and of the relative economics of production of 7-aminocephalosporanic acid that such an involved synthesis apparently is economically competitive. 

In this synthesis, we have witnessed the dramatic productivity of the intramolecular enone-olefin [2+2] photocycloaddition reaction. This single reaction creates three contiguous and fully substituted stereocenters and a strained four-membered ring that eventually provides the driving force for a skeletal rearrangement to give isocomene. 

D. The Synthesis of Four-membered Ring Sulfoxides and Sulfones. . . 444... 

Synthesis of the propellane (4) requires FGA. With two four-membered rings probably to be made by photochemical reactions, a carbonyl group on the six-membered ring is best, allowing a 2 + 2 disconnection. 

The synthesis takes advantage of the well-documented sulfoxide - sulfenate rearrangement , as well as of its retro-process, leading to cyclization and formation of the desired four-membered ring sulfoxide system (i.e. 211, 212). A closely related ring enlargement is based on the reversibility of this rearrangement and has found wide use in penicillin chemistry . 

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