Four-membered ring formation

Examples of four-membered ring formation are rare. The cyclization of the cyclic allylic acetate 42 afforded a 2 1 mixture of the four-membered ring compound 43 and the six-membered ring compound 44[45]. 

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. 

Four-membered ring formation between unsaturated carbon bonds and carbonyl compounds is a photochemical reaction [25], This is an excited-state reaction in the delocalization band (Scheme 6). 

Several relevant papers and review articles have appeared recently. These contain reports on the mechanism and kinetics of the ene reaction of ADC compounds,243-245 examples of four-membered ring formation,246-247 other cycloadditions of ADC compounds,248-252 the synthesis of azoalkanes,253 the use of chiral l,2,4-triazole-3,5-diones,254 and the use of the DEAZD/PI13P reagent in organic synthesis.255... 

The first expeditious solid-phase procedure for the preparation of optically active quaternary r/.v- 3-lactams with an innovative substitution pattern is reported by Gonzalez-Muniz et al. [214]. They describe an operationally simple four-step procedure for the solid-phase synthesis of chiral (3S,4S)-l,3,4,4-tetrasubstituted p-lactams. Taking into account the recurrence of 1,3,4-trisubstituted pattern in bioactive monocyclic (3-lactams, the development of an environment friendly method for the synthesis of this 1,3,4,4-analogues may be of major interest. The key step to the four-member ring formation is the enantioselective phosphazene base-assisted cyclization of the resin-bound /V-(alky 1)-W- [(5)-2-ch Ioropropiony 1 ]... 

Four-membered Ring Formation Using Sml2... 

The thermal [2-1-2] cycloaddition of cumulenes with alkenes, imines or carbonyl compounds is one of the most useful methods of four-membered ring formation. The cycloaddition of ketenes with alkenes to give cyclobutanones represents a reaction of general importance. According to Woodward and Hoffmann, these reactions proceed via a [ttIs+ttIi,] pathway [24]. Dihaloketenes are more reactive than simple ketenes and readily react with electron-rich olefins [25]. 

While 2,2-dimethyImethylenecyclopropane can be cyclodimerized in 80 to 90% yield, tetramethylmethylenecyclopropane gives mainly the ring-opened product 2,3,3-trimethyl-l,4-pentadiene 172>. Control of stereochemistry in these reactions is low. However, the observed regiospecifity of four-membered ring formation is surprising (Eq. 69). 

Although there is some variation among systems, the general order is5>6>3>7> 4 > 8 to 10-membered transition states. In more concentrated solutions intermolecular reactions may be competitive with four-membered ring formation. In summary, any intramolecular process with a 5-, 6-, 3-, or 7-membered transition state is aimost aiways faster than the corresponding intermoiecuiar process. 

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