Rings four-membered

Four-membered and three-membered rings. Four-membered ring ketones are uncommon. Cyc/obutanone itself absorbs at 1789 cm . This further rise above the value for cyc/opentanone is to be expected and is consistent with the further closure of the bond angle. Cyc/obutane-1 3-dione has been studied by Miller et al. [188]. This shows two very strongly coupled frequencies at 1754 (antisymmetric) and 1809 cm (symmetric), although only the first of these is allowed in the infra-red due to symmetry. 

Cyc/o propanone [189] absorbs at 1813 cm and its 2 3-dichloro derivative [190] at 1822 cm Much interest has been aroused by cyc/o propenone which has been studied by a number of workers. Two bands are shown by all derivatives. The 2 3-dichloro derivative [191] absorbs at 1886 and 1615 cm , and the diphenyl derivative [192, 193] at 1850 and 1640 cm Both the C=C and the CO frequencies would be expected to be high in these compounds, so that they are difficult to identify in terms of individual group frequencies. Attempts have been made to do so using solvent shift techniques, and these suggest that the lower frequency band has more carbonyl character. 

However there is little doubt from isotopic-substitution [194, 195] studies that the bands are strongly coupled and are more correctly described as symmetric and antisymmetric modes. 

Although the frequencies vary in this way the absorption coefficient falls steadily up to about n = 9 before reaching a stable value, whilst the half-band width shows an alternative rise and fall as the ring size increases. 

Parallel results, in so far as the frequency is concerned, have been obtained in very large ring systems derived from benzoyl cyclo-anones [107, 150]. 

Electrocyclic reactions in the chemistry of 4-membered heterocycles 93KGS1155. 

Alkylation of ambident nucleophilic hydroxamates by 4-substituted 2-azetidinones 93H(35)1205. 

3-Dihydroazete 1-oxides, synthesis and reactivity 90BSF704. Four-component condensation in the synthesis of /3-lactams 91MI19. /3-Lactam ring formation 92YGK112. 

Synthesis of homochiral /3-lactams from N-protected a-aminoimines using an asymmetric [2 + 2]-cycloaddition reaction 92BSB541. 

Synthesis of /3-lactams from carbohydrate precursors 92WCH821. 

Thioureas are useful in the preparation of two four-membered ring systems thietanes and l,3-thiazetidin-4-ones. Thietanes (3) can be 

Campbell8 indicated that 2-oxa-6-thiaspiro[3.3]hcptane (4) was formed from 3,3-bis(chloromethyl)oxctane and thiourea however, no experimental details were given. 

The reaction between l,3-diaryl-2-thioureas and phosgene or thio-phosgene has been reported to yield 2-arylimino-3-aryl-l,3-thiazetidin-4-ones (5)9 or thiones (6).10 Recent studies on the reaction between 

Fromm12 proposed that l,3-diazetidine-2-thiones were the products of the reaction between dithiobiurets and aldehydes or ketones, which he called aldurets and keturets, respectively. These structures were subsequently shown to be hexahydrotriazines by Fairfull and Peak.13 Kurzer,3 in his review of dithiobiurets, summarized the structural work on aldurets and keturets. Dixon and Taylor14 claimed that 1,3-diazeti-dine-2-thiones wrere the products of the acid-catalyzed treatment of 

Foerster15 reported that 2-phenylimino-3-phenyl-l,3-thiazetidine was formed by reaction of l,3-diphenyl-2-thiourea with methylene iodide. Underwood and Dains16 repeated this reaction and obtained only a gummy product however, they obtained crystalline 1,3-thiazeti-dines from l,3-di- )-tolyl-2-thiourea and also from l,5-diphenyl-2-methyl-2,4-dithiopseudobiuret. Recently, Ried et a/.17 observed the formation in low yields of 1,3-thiazetidines from unsymmetrically disubstituted thioureas in the presence of triethylamine. They reported that l-(4-quinazolyl)-2-thioureas (7), which have an intramolecular hydrogen bond, react rapidly with methylene iodide in the presence of triethylamine to give the 1,3-thiazetidines (8) in high yields.17 

Derivatives of azete are only known as unstable reaction intermediates. Oxetane and azetidine are considerably less reactive than their three-membered connterparts (oxetane reacts with hydroxide anion 10 times more slowly than does oxirane), but nonetheless do undergo similar ring-opening reactions, for example oxetane reacts with organolithium reagents in the presence of boron triflnoride, or with cuprates, and azetidine is opened on heating with concentrated hydrochloric acid. Azetidininm ions react mnch more easily with nucleophiles.  

P-Lactones (propiolactones) too are readily attacked at the carbonyl carbon, for example they are particularly easily hydrolysed, but a second mode of nucleophilic attack - Sn2 displacement of carboxylate via attack at C-4 - occurs with many nucleophiles. The example shows the use of a homochiral P-lactone, available from serine. 

4-Dihydro-2H-pyran and 2,3-dihydrofuran can be metallated in the same way as their acyclic analogues, 

Three-membered rings have not been metaUated directly in the absence of anion-stabilising substituents but simple lithio derivatives of aziridines can be prepared by exchange from the corresponding stannane. iV-f-Butylsulfonyl-aziridines can be substituted, via non-stabiUsed lithio intermediates, by reaction with LiTMP, usually in the presence of the electrophile.  

2-Trifluoromethyloxirane can be lithiated at C-2 using n-butyllithium at -102 °C, the product after reaction with electrophiles retaining configuration.  

Saturated and mono-unsaturated 5- and 6-membered rings can be metallated in the same way as their acyclic analogues. In the case of tetrahydrofuran however, warming with n-butyllithium produces a lithio-derivative which undergoes a 

The conformationally restrained, cyclic nature of dihydrofuran (and dihydro-pyran) leads to an abnormal sequence during a Heck reaction. The addition of the arylpalladium halide occurs normally but rotation cannot occur so instead of syn / -hydride elimination towards the aryl substituent, elimination takes place towards C-4. In some cases, particularly at higher temperatures, further migration of the double bond occurs. 

Related cyclisations involving hetero atom attachment to an alkene via tt-complexes with cations such as Br, I, Hg, and Pd , are useful methods because they give products with functionalised side-chains for further transformations. 

Liebmann and Greenberg s survey of strained molecules is a valuable source of information on molecules containing four-membered rings. 

The spiro [3,4]octane-2-carboxylic acids (1—4) have been prepared and used in experiments designed to test the applicability of either the field or inductive models for the effects of polar substituents. The experimentally determined ApK, values of these acids have been compared with values calculated using either spherical or ellipsoidal cavities in a modified Kirkwood-Westheimer expression. 

spectra of a series of benzocycloalkanes and their 3- and 4-fluoro-derivatives have been obtained, including benzycyclobutane. Aromatic carbon assignments were confirmed, in the case of the hydrocarbons, by use of appropriately deuteriated substrates. The variation of the chemical shifts with the size of the fused ring has been discussed. The n.m.r. spectra of these compounds were also examined, 

The low temperature, single crystal, polarized absorption spectrum of tetra-methyl-l,3-cyclobutanedione shows four different electronic singlet n n transitions. Analysis of the vibrational structure, polarization behaviour, and intensities, of the bands has allowed their assignments to UuCMj), B2 ( Bi),and Mu(M J 

Both bicyclo[3,l,l]heptenones and bicyclo[3,l,0]hexenones show bathochromic hypochromic u.v. spectral shifts relative to the corresponding bicyclo[3,2,l]octenone and monocyclic models. These shifts have been accounted for in terms of extension of the chromophore by the small ring, rather than by any distortion of the enone geometry induced by the presence of the small ring. 

Details have appeared of the preparation and variable-temperature n.m.r. of the difluorophosphoranes (27), (29), and (30).29 Only with (27) was the conformer (28), with a diequatorial four-membered ring, detected at low temperatures. Interconversion of the cis- and trans-isomers of (30) was slow on the n.m.r. time-scale at —90 °C. 

The variable-temperature 19F and 31P n.m.r. spectra of the diazadiphosphetidines (31)30 and (32)31 have been recorded. Analysis32 of the n.m.r. spectra of the phos-phorane (33) indicates that the lone fluorine is basically equatorial rather than apical. 

Data on the relative apicophilicities of groups have been obtained from a study of the variable-temperature F n.m.r. spectra of the hexafluoro-acetone adducts of 1-substituted phosphetans. The pseudorotation that can be followed is that which places the four-membered ring diequatorial, i.e. (10) (11). The results (Table 1) were discussed in terms of apico-philicity being a balance between electronegativity, increase in which 

The phosphetan (12) with bis(trifiuoromethyl) peroxide or bis(trifluoro-methyl) disulphide at — 78 °C gave the difluorophosphorane (13). The and n.m.r. spectra at — 100 °C show clearly that the phosphorane is a 2.3 1 equilibrium mixture of (13a) and (13c), equilibration via the high energy phosphorane (13b) being slow at this temperature. The apicophilicity of fluorine is balancing the increased strain involved in placing the four-membered ring diequatorial. 

The same phosphetan (12) with the dithieten (14) gave the stable adduct (15) whose n.m.r. did not change from — 50 to -I- 147 °C. The formation of 1,3,2-dithiaphospholens from (14) and tervalent phosphorus compounds is a general reaction they appear to be less stable than the corresponding 1,3,2-dioxaphospholens. 

An X-Tay structirre determination has been reported for the 1,2-oxaphosphetan (18), obtained from ethyldiphenylphosphine and hexafluoroacetone. Oxaphosphetans are probably formed from hexa-fluoroacetone and phosphines containing an a-hydrogen via the ylides (20), formed by proton transfer in the initial 1 1 adducts (19). 

The exchange of alkoxy-groups when oxyphosphoranes are treated with alcohols is base catalysed.When the oxaphosphetan (21) is treated with CD3OD in the presence of tertiary base, CH3OD is liberated before 

Boyd and B. J. Walker, Aliphatic, Alicyclic, Saturated Heterocycl. Chem. 1, Pt. 2, 445-500(1973). 

Coffey (ed.), Rodd s Chemistry of Carbon Compounds, Part 4A. Elsevier, Amsterdam, 1973. 

Muller and J. Hamer, 1,2-Cyclo-addition Reactions. Wiley (Interscience), New York, 1967. 

Previous extended Hiickel calculations on the bis(trifluoromethyl) derivative 6 show the favored isomer to be 6b, while the CNDO/2 method favors 6a [75JCS(P2)559]. More recent ab initio calculations for different R substituents show that electron-releasing substituents favor the ring-opened dithione (6b), whereas electron-withdrawing substituents favor the cyclic structure (6a) (80JA6687). These conclusions are supported by electron diffraction (ED) (76JA899) and photoelectron (PE) spectral data 

Derivatives of azetidine were prepared from a-, /3-, or y-AA. L-Threonine was transformed in eight steps into 4 

A derivative of a fused three- and four-membered ring 5 (aza-l-bicyclo-[2.1.0]pentane) was obtained from Ala after alkylation with methyl a-bromoacrylate (85T2707). 

The nucleophilic 7V,ALdiethyI-l-propynamine adds across the C=C bond of 31 at 20° C to yield the adduct 187, whereas the electrophilic diphenyl-ketene adds across the N=N bond at -8°C to give 188 (97%).167 This difference in behavior finds a parallel in the Diels-AIder reactions (Section IV.E.l). 

Weedon in Synthetic Organic Photochemistry, Ed. W. M. Horspool, Plenum, New York 

Houben-Weyl, Methods of Organic Chemistry, 4th ed, Vol E21c, C. Thieme, Stuttgart-New York (1995). p 3085 

Review Comprehensive Organic Synthesis, Eds. B. M. Trost and I. Fleming, Pergamon, Oxford (1991), Vol 5, Part Zl, p 63 

For photochemical ring closure, see page 413, Section 2.2, and for Lewis acid-catalyzed ring closures, see page 410, Section 2.1. 

Tetramethyldiphosphine and hexafluoroacetone gave the phosphoranes (29), (30), and (31) in which the chiral centres at phosphorus led to doubling of resonances in their n.m.r. spectra.  

A number of phosphoranes have been prepared in which the phosphorus is part of a diazadiphosphetidine ring. Among them are (19), (20), (32), (34) and (35),  

Details have appeared of the preparation and variable-temperature F n.m.r. spectra of the phosphetan-hexafluoroacetone adducts (18). The trans-dimethylaminophosphorane (18 R = Me2N) on dissolving in hexa-fluoropropan-2-ol gave the hexafluoroisopropox3q)hosphorane [18  

R = (CF3)aCHO] as a pure isomer but it was not possible to determine the stereochemistry of this substitution. The spirophosphorane (20) was the only product from the reaction of the tm j-l-benzylphosphetan (19) with hexafluoroacetone. In chloroform solution in the presence of hexafluoropropan-2-ol, equilibrium was established between (20) and its isomer (21). 

Ynolate anions as equivalents of ketenyl anions and their transformations into /Mactones and /1-lactams 00YZ1233. 

Development of catalytic approach to the enantioselective synthesis of /3-lactams 01AG(E)4377. 

4-Oxoazetidine-2-carbaldehydes as useful building blocks in stereocontrolled synthesis 01CSR226. 

Recent progress in the synthesis and reactivity of azetidine-2,3-diones 01OPP315. 

Progress in the stereoselective syntheses of /1-lactams mediated by oxazoline N-oxides 00PAC1721. 

Syntheses of 3-lactams, 3-lactones, and 1,3- and 1,4-diazetidinediones by pho-tochemically induced cycloaddition reactions of chromium carbene complexes with imines, aldehydes, and azo compounds 97T4105. 

Asymmetric S5mtheses of 3-lactams by Staudinger ketene-imine cycloaddition reaction 98KGS1448, 99EJ03223. 

The azomethine ylide strategy for 3-lactam synthesis 99JHC1365. 

Methods for the synthesis of optically active 3-lactones (2-oxetanones) 99T6403. 

Patemo-Biichi reaction in preparation and transformations of 3-oxetanols and 3-aminooxetanes 97LA1627. 

Addition of the butyl group to sulfur generates the sulfurane and initiates the decomposition process. Least motion collapse expels M-butyl- 

Cyclobutanes can be synthesized from 1,4-dicarbonyl precursors via a reaction in which a metallated dithiane-acetal [viz. (28)] displaces its own acetal function intramolecularly.  

This area is dominated by [2+2] cycloadditions in their various guises. Thus a new, and useful route to cyclobutane-1,3-dione involves the dimerization of t-butoxyethyne (9), which is thought to go via formation of ketene from (9) followed by a [2+2] cycle- 

The conformations and relative stabilities of the cis- and trans-isomers of 1,3-difluorocyclobutane and 1,3-dimethylcyclobutane have been investigated by ab initio methods using the STO-3G basis set. The cis-isomers are found to be the more stable, by 1.39 kcalmolfor the fluorinated cyclobutanes and by 1.48 kcalmol for the methylated cyclobutanes. These values are within the range of known experimental values. The ring puckering angles in the cis-isomers were calculated to be 19.9° and 23.7° respectively. The trans-isomers were foimd to be less puckered and more flexible than the cis-isomers. 

The C-H coupling constants in tricyclo[3,1,0,0 ]hexane have been measured and compared with values derived from a semi-empirical relationship between /( C-H) and the calculated percent of s-character of the C-atom hybrid orbital in a 

The microwave spectrum of 1,2-dimethylenecyclobutane in the 26.5—40 GHz range has been investigated, and rigid-rotor constants have been derived for the ground state. A dipole moment fi = 0.457 + 0.002 D has been found. The infrared and Raman spectra of perfluorocyclobutane in the gas and solid states have been discussed. The spectra are assigned on the basis of 2 symmetry in the gas phase. The barrier to methyl rotation in methylcyclobutane has been found to be 2.47 kcal mol-.  

The electronic and N(ls) X-ray photoelectron (p.e.) spectra of the 1,2- and 1,3-dianilides (la) and (2a) both show a considerable red shift of the n- n band relative to derivatives (lb) and (2b), indicating participation of the nitrogen atoms in the conjugation. The N(ls) binding energies are the same (399.5 and 399.6 eV) in both isomers, and reflect the high imminium character of the nitrogen atoms. 

The enthalpy of combustion of cyclobutylamine has been determined by oxygen bomb calorimetry to be AH (298.15 K) = —684.96 + 0.13 kcal mol in the liquid state. The enthalpy of formation was also derived, and gaseous cyclobutylamine appears to be co. 2 kcal mol more stable than would be predicted from thermodynamic data on other amines and hydrocarbons. 

Full details have been reported for the conversion of cyclopropylmethanol into cyclobutanone (27) in 31-35% overall yield together with an improved route to the useful o-phenylthio derivative (28).  

Variations on the theme of [2 + 2]cycloaddition reactions as a route to cyclobutanes continue to be developed. 1,2-Diynylcyclobutanes (29) can be prepared by triplet-sensitized photochemical dimerization of the corresponding enynes in general, this method cannot be used for the efficient synthesis of more highly substituted cyclobutanes. Similar photochemical methods have also been used to prepare a range of substituted ci5-l,2-diaminocyclobutanes (30), and the tricyclic compounds (31), which can serve as precursors to the tricyclo[4.2.0.0 ]octanes (32) via the Wolff rearrangement.  

Martin, H. Greuter, and D. Bellus, Helv. Chim. Acta., 1981, 64, 64 P. Martin, H. Greater, G. Ribs, T. Winkler, and D. Bellus, ibid., p. 2571 G. Greuter, J. Dingwall, P. Martin, and D. BelluS, ibid., p. 2812. 

Eisenhuth, H. Siegel, and H. Hopf, Chem. Ber., 1981, 114, 3772 for a review of such photosensitized reactions, see A. Albini, Synthesis, 1981, 249. 

Ethyl buta-2,3-dienoate reacts readily with various olefins in the presence of AICI3 to provide cyclobutylideneacetic esters (33), largely as the E-isomers, in a wide range of yields (14-95%).  

The number of illustrations of the use of McMurray s reagent (TiCl3-LiAlH4) in the reductive coupling of carbonyl compounds to alkenes has burgeoned in the 

Irradiation of a mixture of anisole and acrylonitrile in acetonitrile provides a facile synthesis of the cyclobutene derivative (29) by way of the [2 + 2] cycloadduct (28), and Lukas et al. have established that [2 -I- 2] cycloadditions of alkynes to alkenes, leading to cyclobutenes, can be realized in the presence of Lewis acids, e.g. (30) (31). 

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Nevertheless, there are situations where one wants to work with six four-membered rings in cubane (e.g., when considering the symmetry of the ring system). In this situation, one adds a sixth four-membered ring to obtain firom the SSSR the so-called extended set of smallest rings (ESSR). 

Th c values of V I, V2, and V3, in keal/tnol, are listed in mmp-tor.txtfdbf). fhc MM+ force field uses special values for the torsional force constants when the atoms are in a four-member ring. 

The most important disconnection for four-membered rings corresponds to the photochemical 2 + 2 cycloaddition of olefins ... 

Grandisol, with a four-membered ring, is another insect hormone, the male sex hormone of the boll weevil to be precise. It may also be useful as a highly specific pest control. How might it be made ... 

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]. 

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... 

Later, fireflv oxyluciferin was successfully synthesi2ed (403. 408) and has been isolated and identified in firefly lanterns (luciola cruaciata) after the lanterns were treated with pyridine and acetic anhydride to prevent decomposition (409). In 1972, Suzuki and Goto firmly established that oxyluciferin is involved in the bioluminescence of firefly lanterns and in the chemiluminescence of firefly luciferin (403. 410).. A. mechanism involving a four-membered ring cyclic peroxide has been proposed for the reaction (406. 411). However, it was not confirmed by 0 -labelinE experiments (412). 

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. 

Fig. 1. Methods for representing SiO and AlO tetrahedra by means of (a) baH-and-stick model, (b) soHd tetrahedron, (c) skeletal tetrahedron, and (d) spare-filling of packed spheres (1). (e) Linking of four tetrahedra in a four-membered ring, (f) Secondary building unit called tmncated octahedron as...

Because of the high ring strain of the four-membered ring, even substituted oxetanes polymerize readily, ia contrast to substituted tetrahydrofurans, which have tittle tendency to undergo ring-opening homopolymerization (5). 

A. Rosowsky, ia A. Weissberger, ed., Heteroyclic Compounds with Three- and Four-Membered Rings, Part One, Interscience PubHshers, a division of John Wiley Sons, Inc., New York, 1964, pp. 289, 308. 

Cyclic and Polymeric Substances Containing Arsenic—Arsenic Bonds. A number of organoarsenic compounds containing rings of four, five, or six arsenic atoms have been prepared (cycHc polyarsines). The first such four-membered ring compound to be adequately characterized, tetrakis (trifluoromethyl) tetrarsetane [7547-15-17, was obtained by the interaction of a diiodoarsine and mercury (107,108) ... 

Photochemical additions to give four-membered rings are known. Thus the reactions of imidazoles across the 4,5-bond with benzophenone and acrylonitrile are illustrated by (278) (279) and (280) (281), respectively (80AHC(27)24l). Oxazolin-2-one undergoes... 

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