Forming four-membered heterocycles

Structures C and D have never been observed for gallium hydrazides, which exclusively form four-membered heterocycles. In contrast, all kinds of structures were observed with aluminum. Quantum-chemical calculations showed that for aluminum the five-membered heterocycle is the most... 

Not many examples of [3 + 1] combinations to form four-membered heterocycles are known, and it is apparently not a general method. 

In reactions of primary alkylamines with internal perfluoroolefins, intramolecular nucleophilic cyclization gives a heterocyclic compound with a perfluoroalkyl group. As mentioned above, primary alkylamines can be binucleophilic reagents with nucleophilic centers on the nitrogen atom. Such compounds having an NH2 group form four-membered heterocycles and many polycyclic heterocycles with one nitrogen atom. 

Sulphenes have been shown to undergo both [2 + 2] and [4 + 2] cycloaddition to dienamines61-63. Other methods of forming four-membered heterocyclic rings, such as 1,2-cycloaddition of isocyanates64 and TV-sulphonylimines65, do not seem to have been applied to dienamines. 

Four-membered heterocycles can be formed by the addition of isocyanides to 1,3-dipoles (80AG(E)45) and by the reaction of carbon monoxide with -haloamines, with the aid of palladium catalysis (Scheme 10) (79CC699). 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Vacuum thermolysis (160°C) of the hemiaminal 11 generates the azaphos-phetane 65 in 85% yield.32 This product clearly results from the intramolecular insertion of the transient (amino) (phosphino)carbene 2h into the C-H bond of a diisopropylamino group bonded to phosphorus. Note that the four-membered heterocycle 65 is formed exclusively in spite of the ratio of six methyl-CH bonds to one methine-CH bond, and that only one of the two possible diastereomers is detected. The same regio- and diastereo-selectivity have already been observed with the di(phosphino)carbene 2g,74 but is in marked contrast to the exclusive formation of five-membered rings... 

A recent review on four-membered heterocycles formed from imino-phosphoranes concentrates on the preparation and the reactivity of 2,4-diimino-l,3-diazetidine and related compounds (93JPR305). As an example, the synthesis via bisiminophosphorane 85 is described in Scheme 42. The bisiminophosphorane has both a heteroaryl and a styryl site. From a mechanistic view, the reaction of the bisiminophosphorane proceeds with aryl isocyanate formation via an aza-Wittig mechanism. Intermediate car-bodiimide formation (86) occurs directly on the iminophosphorane moiety... 

Dimethylbisthiomalonic acid (120), when treated with an acylated enol, produced intermediate 121 thietanediones 122 and 123 then were formed by elimination of thioketone and acetic acid (see Eq. 12). Similarly, cyclobutane-l,l-bisthiolcarboxylic acid gave 123, a previously unknown sulfur analog of malonic anhydride, (Eq. 12). Thermolysis of 120 also results in the formation of the four-membered heterocycles in addition to carbonyl sulfide, hydrogen sulfide, and thiocarbonic acid. ... 

One of the very few examples of a four-membered heterocycle with sulfur atoms substituted 1,2 was reported by Dupont workers (60JA1515,61JA3434). Its synthesis involves the high temperature reaction of fluorinated alkynes and elemental sulfur, probably via a diradical intermediate (Scheme 102). The chemistry of these 1,2-dithietenes has been reviewed (76RCR639). As discussed later, these dithietenes form complexes with a number of transition metals. 

Tandem intermolecular Paterno-Biichi reaction of benzophenone with trimethylsilyl vinylcyclopropyl ether 72 (Scheme 31) leads in its first step to the formation of seven-membered 73 rather than to four-membered heterocycle while its second step proceeds in a normal fashion. With aromatic aldehydes, only tetrahydrooxepine derivatives 74 are formed <1998J(P1)2363>. 

These reagents are usually prepared by treatment of a phosphine with an alkyl halide and successive addition of base, like BuLi or NaHMDS. Reaction with the ketone takes place by attack of the carbanionoid carbon of the ylide form on the electrophilic carbon of the carbonyl group via a four-membered heterocyclic transition state, the oxaphosphetane 35. The driving force for this transformation is provided by formation of the very strong phosphorus-oxygen bond. Subsequent collapse of the oxaphosphetane furnishes the desired exomethylene group under retention of geometry. 

The latter example (reaction 36) already indicates that the Yang cydization can also be used to synthesize four-membered heterocycles. After light absorption, the a,(3-unsaturated carbonyl compound 84 undergoes intramolecular hydrogen abstraction at the a-position of the carbonyl moiety (reaction 37), leading to the 1,4-biradical intermediate XXX [87]. A radical combination then efficiently yields the spirocyclic P-lactam derivative 85, and only one stereoisomer is formed in this case. In this transformation, the a,P-unsaturated carbonyl function can be considered as being vinylogous to a simple ketone. 

The formation of these compounds may be explained by the following transformations. The weakly nucleophilic hexamethyldisilazane initially reacts at the carbon atom of the multiple bond, and fluoride ion elimination takes place in the new zwitterion, forming a terminal double bond. Further catalysis by the fluoride ion generates an active N-nucleophile intramolecular cyclization involving the latter leads to a four-membered heterocycle. 

Intramolecular nucleophilic cyclization is used for the synthesis of four-membered heterocycles. This is a general route for reactions of many perfluoroolefins with primary amines. Thus the interaction between perfhioro-3,4-dimethylhex-3-ene and butylamine in the presence of triethylamine forms N-butyl-perfhioro-2,3,4-trimethyl-2-ethyl-l, 2-dihydro-azete (87ASCC31). In the absence of triethylamine, a mixture of products is obtained, among which are the derivatives of azetidine 15 and azete 16. 

Thus with electron-donor substituents in the benzene ring anilines lead to quinazolines, whereas four-membered heterocycles are formed in the case of electron acceptors or halides in the or /zo-positions. 

This method works well to form three-, five-, and six-membered nitrogen heterocycles, but does not work well to form four-membered rings. In fact, four-membered rings are generally among the... 

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