Four-membered heterocycle-derived

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)... 

The diazaphosphane or aminoiminophosphane ligands with a NPN framework are another subclass of cyclophosphazenes. These compounds with both phosphorus in oxidation state (111) [104-110] and (V) [111-112] have been employed in the synthesis of four membered heterocycles and coordination chemistry with group 13 derivatives. Several complexes of trivalent phosphorus derivatives with both aluminum halide and alkyls are known as illustrated for 48 in Scheme 21 [113-119]. The structure determination of 48 confirms the formation of a four membered metallacycle [116, 117],... 

The most common structural motif of aluminum and gallium hydrazides is the centrosymmetric four-membered heterocycle with two exocyclic N—N bonds. The N-N distances of all these compounds fall in a very narrow range of about 145.5 pm on average with the most significant deviation (143.7 pm) detected for the diphenylhydrazido gallium derivative 14. The E2N2 heterocycles are planar with almost ideally equidistant E-N separations. As expected, the Al—N bonds of these compounds (196 to 199 pm) are shorter than the Ga—bonds (199 to 207 pm). 

Formal substitution of two benzene double bonds by sulfur atoms leads to the four-membered heterocycle 1,2-dithiete (37). This compound has not been synthesized, although derivative 38 is known,59,80 and dicyano-l,2-dithiete (39) is very probably an intermediate in some reactions of thiacyanocarbons (see below). Models of both compounds have been studied theoretically,23,91 but the calculations are... 

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>. 

An important group of four-membered heterocyclic compounds are the derivatives of the /i-lactam [azetidin-2-one (15)] system. Many of the compounds are biologically active, for example, the monocyclic nocardicins [e.g. (16)] and the bicyclic penicillin and cephalosporin antibiotics [e.g. (17) and (18) respectively], and the -lactamase inhibitors of the clavam group (19). 

Unlike cyclobutane and its derivatives, many of the four-membered heterocycles usually have planar structures. However, diazetidines are slightly nonplanar or puckered. Earlier, Ruben and co-workers <1974AXB1631> and Loeppky et al. <1991JA2308> have reported X-ray crystallography of a few 1,2-diazetidines. Beckert and co-workers <2002H(57)1257>, while carrying out cyclization of amidrazone with bis-imidoyl chloride, isolated a new crystalline compound which was not the expected triazine but A2-l,2-diazetine or 1/7,4/7-diazetine derivative 22 as established by X-ray analysis. 

All four-membered heterocycles with three heteroatoms can be classified into four types compounds with three similar heteroatoms 1 symmetrical 2, and unsymmetrical 3 heterocycles with two different heteroatoms and derivatives with three different heteroatoms 4 <1996CHEC-II(1B)1189>. 

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. 

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. 

Table 2 shows dimensions that have been determined using X-ray crystallography for a range of four-membered heterocycles. The dimensions for the 1,2-thiazetine ring were obtained for the derivative 41. 

With methyllithium in 1,2-dimethoxyethane tris(trimethylsilyl)phosphane and -arsane are quantitatively converted to their related lithium derivatives (Eq. 2). These highly sensitive compounds crystallize as dimers building up four-membered heterocycles with dme-coordinate lithium and bis(trimethylsilyl)phosphanyl [8] or -arsanyl fragments alternately arranged [9]. 

Compounds of type 77, passing through the seleniranium intermediates 78, give rise to the four-membered cyclic compounds 79 which, according to Baldwin s rules [61], are the result of a 4-exo-trig cyclization, or to the five-membered derivatives 80 as the result of a 5-endo-trig cyclization. Only very few cases are known in which the cyclization affords a four-membered heterocyclic... 

Starting from (silyl)(phosphino)diazomethane derivatives, stable pseudo-diazoalkenes and carbenes have been obtained. The diazomethylenephosphoranes are very reactive dipolarophiles but are also synthetic equivalents of naked carbon C . The stable carbenes react in a similar manner to their transient analogues, but also exhibit new reactions the synthesis of unsaturated three-membered heterocycles is particularly noteworthy. Ring expansion reactions involving the latter are of special interest since they afford novel non-antiaromatic four-7t-electron four-membered heterocycles. 

The immense amount of information available induced us to divide it into separate chapters. This first chapter draws the attention to/zurz-fused heterocyclic naphthalene derivatives with a four-membered heterocyclic ring. 

Few reactions of alkynes with C=X bonds are valuable for the preparation of four-membered heterocycles. Ynamines - react with aldehydes and ketones in the presence of Lewis acids to give unstable oxetene derivatives which undergo electrocyclic opening (Scheme 43). Open-chain products are also obtained with thiocarbonyl compounds,Schiff bases and iminium salts. Reactions of ynamines with carbon dioxide, ketenes. - ketenimines - and isocyanates often give mixtures of products and are of little preparative value. 

Azetidines are an interesting class of four-membered heterocyclic compounds, with various biological activities. These derivatives are difficult to synthetize due to ring strain. The allenylidene complex 43 has shown to be a useful substrate to generate this skeleton and to study its evolution into hexahydroquinoline [41]. Treatment of dichloromethane solutions of 43 with 1 equiv of dicyclohexylcarbodiimide at room temperature affords the iminiumazetidinylidenemethyl complex 111, which is isolated as a 4 1 mixture of the isomers Z and E shown in Eq. 5. 

The study of the chemistry and biology of strained four-membered heterocycles has become an extremely active field of research in 2014. In this chapter, the reader will find a brief discussion of new contributions focused on fields such as organic synthesis and medicinal chemistry. For the sake of clarity, contributions are separated in sections depending on the nature of the heteroatom. Although oxa- and azaheterocycle derivatives dominate the field in terms of the number of scientific pubheations, the chemistry of sulfur-, silicon-, and phosphorus-based heterocycles is also of great relevance.The aim here is not to provide an in-depth analysis of all the vast scientific Hterature concerning four-membered heterocycles during the calendar year 2014. Consequently, there are many examples that are cited but not covered in detail. 

FOUR-MEMBERED HETEROCYCLIC RINGS AND THEIR FUSED DERIVATIVES... 

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