Umamidierungsreaktionen an cyclischen Amino-amid-Systemen. 3. Mitteilung über Umamidierungsreaktionen

Transamidation Reactions with Cyclic Amino-amides Lactames which are substituted at the nitrogen atom by a 3-aminopropyl residue are transformed under base catalysis to cyclic amino-amides enlarged by 4 ring atoms. The formed ring must be at minimum 12-membered. Scheme 2 illustrates this result: the 8-membered 7 is transamidated in 96% yield to the 12-membered ring 8 (in the presence of potassium 3-aminopropylamid in 1, 3-propanediamine), the 9-membered 10 to the 13-membered ring 11 (97%) and the 11-membered 14 to the 15-membered ring 15 . Furthermore, the 13-membered ring 27 (Scheme 5) is transformed to the 17-membered 28 . In the case of the 15-membered lactame 15 it is demonstrated that 14 is not formed back under the conditions of the transamidation. Large ring lactames which are substituted at the nitrogen atom by a 3-(alkylamino) propyl group lead under base catalysis to an equilibrium mixture, e.g. the 17-membered 26 is in equilibrium with the 21-membered 29 . This result is similar to the behavior of the corresponding open-chain amino-amides [2]. Because of transannular interactions, the 11-membered ring 2 is not stable: transamidation of the 7-membered 1 (Scheme 1) doesn't give the expected 2 , but its water elimination product 3 in small yield. The N-tosyl derivative of 2 , namely 20 , is synthesized by an independent route (Scheme 3). Detosylation of 20 yields the 7-membered 1 instead of 2 . Concerning the mechanism of this interesting reaction see Scheme 4.     

Synthesen und Ringerweiterungsreaktionen von 2-(4-Hydroxyalkyl)-2-nitrocycloalkanonen

Syntheses and Ring-Enlargement Reactions of 2-(4-Hydroxyalkyl)-2-nitrocycloalkanones Syntheses of the title compounds were achieved by [Pd{P(C₆H₅)₃}₄]-catalyzed reaction of 2-nitrocycloalkanones 3 with vinyloxirane followed by catalytic hydrogenation. By another route, the known methyl 4-(1-nitro-2-oxocycloalkyl)butanoates 6 were reduced to the corresponding aldehydes 7 which by NaBH₄ reduction or methylation with (CH₃)₂Ti(i-Pr)₂ were transformed to the alcohols 5 and 8 , respectively (Saheme 1). Treatment of 5 and/or 8 with KH/THF under reflux gave, via a 7-membered intermediate, the nitrolactones 12 and oxolactones 13 (Scheme 3). Compared with similar reactions running via 5- or 6-membered intermediates (see 1 and 2 ), the yields are distinctly lower. The natural occurring 12-tridecanolid ( 14 ) was synthesized.     

Umwandlung der diastereomeren 12- und 6-gliedrigen 1-Acetyl-2-methyl-1-cycloalkanole in 1-Äthinyl-2-methyl-1-cycloalkene

Conversion of the Diastereoisomeric 12-and 6-membered 1-Acetyl-2-methyl-1-cycloalkanols to 1-Ethynyl-2-methyl-1-cycloalkenes This paper is concerned primarily with a derivation of the E-configuration of 1-ethynyl-2-methyl-1-cyclododecene ( 10 ), which plays a role in mechanistic considerations on a method for ring expansion by 3 carbon atoms described in apreceding paper [1]. The derivation is based on an argument using the results of the dehydration of trans-1-acetyl-1-2-methyl-1-cyclododecanol ( 4 ) to 10 with phosphorus oxychloride and pyridine. That this dehydration is stereospecific can be concluded from its regiospecificity since the cis-hydroxyketone 3 dehydrates mainly to 1-ethynyl-12-methyl-1-cyclododecene (mixture of stereoisomers 11 and 12 ). An x-ray analysis shows the indicated configurations of the two hydroxyketones 3 and 4 . The direction (anti) of the stereospecificity of the double bond introduction during the 4 → 10 conversion is deduced from the similarity of the behaviour of the two stereoisomeric 1-acetyl-2-methyl-1-cyclohexanols 8 and 9 under the same conditions and from mechanistic considerations, which make it likeley that the anti-elimination behaviour observed in the 6-membered system has not changed over to a syn-elimination behaviour in the 12-membered system. The configurations of the two 6-membered hydroxyketones 8 and 9 correspond to those of the precursor1-ethynyl-2-methyl-1-cyclohexanols 6 and 7 , which were clarified with the help of ¹³C-NMR.-spectral coupling observations. It is of interest that the hydroxyketones 3, 4, 8 and 9 react with phosphorus oxychloride and pyridine so as to introduce both a double and a triple bond. It is probable that the double bond is introduced first, inasmuch as the triple bond is not introduced in the absence of activation of the hydroxyl group, as for instance in acetylcyclohexane. This can be used as an argument that the conversion of the acetyl to an ethynyl group in 3, 4, 8 and 9 does not affect the stereospecificity of the dehydration which introduces the ring double bond. 1-Acetyl-2-methyl-1-cyclododecene ( 24 ), a previously isolated compound with pleasant odor, was synthesized by hydration of 10 . This furnishes an argument for the E-configuration of 24 .     

Synthese der Phoracantholide K,O und M

Synthesis of Phoracantholide K, O and M Two 14membered ring lactones 3 and 4 and a 12membered ring lactone 5 isolated from the metasternal secretion of the eucalypt longicorn Phoracantha synonyma have been synthesized as racemic mixtures by the following method. Reaction of the dilithium derivative of 5-hexynoic acid (6) with threo-8-bromo-2,4-isopropylidenedioxyoctane (7) , followed by removal of the protecting group and esterification with diazomethane gave methyl-threo-11, 13-dihydroxy-5-tetradecy-noate (8) (s. Scheme 2). Partial hydrogenation of the triple bond in 8 with Lindlar Pd-catalyst, followed by saponification lead to (threo, Z)-11, 13-dihydroxy-5-tetra-decenoic acid (10) . The dihydroxy acid 10 was converted into the S-(2-pyridyl) thioate and cyclized in diluted benzene solution under the influence of silver ions to yield the corresponding 12- and 14-membered lactones in approximately equal amounts. Isomerization of the mixture with p-toluenesulfonic acid in methylene chloride yielded the 14-membered lactone (cis-11, 13–5Z)-11-hydroxy-5-tetradecen-13-olide almost exclusively. It proved to be identical in its properties with natural phoracantholide K (3). With 5-hexynoic acid and 7-tetrahydropyranyloxy-octyl bromide or 5-tetrahydropyranyloxy-hexyl bromide as starting materials (±)-phoracantholide O (4) and M (5) have been synthesized in an analogous manner.     

Synthesen makrocyclischer Lactone durch Ringerweiterung Herstellung von (±)-Phoracantholid I, (±)-Dihydrorecifeiolid und (±)-15-Hexadecanolid

Syntheses of Macrocyclic Lactones by Ring Enlargement Reaction Reaction. Preparation of (±)-Phoracantholide I, (±)-Dihydrorecifeiolide and (±)-15-Hexadecanolide A general procedure for the synthesis of macrocyclic lactones is described. The Michael adducts of 2-nitrocycloalkanones and acrylaldehyde were regiospecifically methylated with CH₃Ti[OCH(CH₃)₂]₃ or (CH₃)₂Ti[OCH(CH₃)₂]₂ at the aldehyde carbonyl group. Treatment of the so-formed alkohols with tetrabutylammonium fluoride gave the lactones enlarged by four ring members. This method was used to synthesize the 10-membered (±)-phoracantolide I ( 11 ), the 12-membered (±)-dihydrorecifeiolide ( 17 ), and (±)-15-hexadecanolide ( 24 ) in 52%, 26.5%, and 58.7% respectively.     

Temperature dependent NMR spectra of oxazepines,thiazepines, oxazocines and thiazocines

The temperature dependence of several 7-membered 5-substituted-5,11-dihydrodibenz[b,e] [1,4]oxazepines (Z = O) and thiazepines (Z = S), as well as of 8-membered 12-substituted -6,11-dihydro-12H-dibenz[b,f] [1,4]oxazocines (Z = O) and thiazocines (Z = S), has been studied by NMR spectroscopy. The average ΔF* (kcal/mol) values at coalescence temperatures are 14·0 (M = CHO), 18·2 (M = COCH₃) for oxazepines, 17·3 (M = CHO), >21 (COCH₃) for thiazepines, and 13·0 for oxazocines and 13·3 for thiazocines, respectively. These data show that replacement of oxygen by a sulfur atom raises the barrier height of ring inversion, but that this effect is greater with the 7-membered than with 8-membered heterocycles. Thus the 8-membered rings have a greater degree of flexibility than do the 7-membered ones. With the oxazepines and the thiazepines, it was also possible to measure the thermodynamics (ΔF*, ΔH* and ΔS*) of the hindered rotation around the N? CO bond by studying the temperature dependence of the formyl and acetyl proton resonances. The results suggest that the processes of conformational inversion and hindered rotation in the same molecule are independent of each other. The rate of hindered rotation is slower than the rate of conformational inversion. The conformational preferences of the compounds are also discussed.     

Bildung von 4-, 5- und 6gliedrigen Heterocyclen durch ambidoselektive Ringschlüsse von Enolat-Ionen

Formation of 4-, 5- and 6-membered heterocycles by ambidoselective cyclization of enolate anions N-Acylmethyl-N-chloracetyl-2,6-dimethylanilines 4 were cyclized with base to 4-, 5- or 6-membered ring compounds, depending on the substituent R² (Scheme 2). All products can be rationalized as derived from the intermediate enolate anions a and b . The enolate anion a reacts by intramolecular alkylation to yield either 1, 4-oxazines 5 or azetidines 6 (Schemes 1, 3 and 7). The regioselectivity observed is expected on the basis of the allopolarization principle. The enolate anion b reacts only with formation of a new C? C bond (Scheme 5). Comparison with the behaviour of the 2, 6-unsubstituted anilines 9, 1a and 12 , shows a strong dependence not only on electronic but also on steric factors (Scheme 4 and 6).     

Synthesis of new crown ethers and their metal complexes: 1H and 13C NMR study

A new type of crown ethers containing a diphenyl ether unit has been prepared, the ring size ranging from 12 to 36. ¹H and ¹³C NMR spectra of both free ligands and their metal-ion complexes have been recorded. For 18- and 21-membered compounds a general downfield shift was observed for both methylene and aromatic proton resonances on metal-ion complexation. The stoichiometry of K⁺ and Na⁺ complexes was deduced from chemical shift dependence on metal-ion concentration. The K⁺ and Na⁺ complexes of 18- and 21-membered rings have a guest to host ratio of 1:1, whereas the K⁺ salt of the 15-membered ring exists as a 1:2 complex in solution. The ¹H shift observed on salt formation was attributed to electric-field and conformational effects. The ¹³C resonances for the aryl carbons, C-1, C-2 and C-3, and the α-methylene carbon in 15- and 18-membered rings were shifted upfield when an equivalent amount of KSCN was added in CDCI_3?DMSO-d₆. The shift changes were independent of the anion, and similar results were obtained for SCN^?, Br^?, and I^? salts. The upfield shift is explained by conformational factors. The spectral changes were slight for 12- and 36-membered rings. In 15- and 18-membered rings, complexation induces conformational changes which force the C-α carbon into the plane of the benzene ring. The solution conformation of these molecules is discussed.     

The synthesis of medium-sized cyclic lactams by the intramolecular friedel-crafts cyclization of isocyanates. Formation of novel pyrazolo[3,4-c]benzolactams

A series of 4-ω-phenylalkyl substituted-1H-pyrazol-5-amines has been synthesized from the corresponding α-acetylphenylalkanenitriles and methylhydrazine. They were converted into the corresponding 5-isocyanates and cyclized under Friedel-Crafts conditions to medium-sized cyclic lactams. The reaction was shown to give the 7-, 8-, 9-, and 10-membered lactams but failed to yield the 11-membered lactam. Rings synthesized were: pyrazolo[3,4-c][2]benzazepin-2(1H)-one; 10H-pyrazolo[3,4-c][2]benzazocin-10-one; pyrazolo[3,4-c][2]benzazonin-11(1H)-one; 12H-pyrazolo[3,4-c][2]benzazocin-12-one.     

8 and 16-Membered ring phosphorus compounds. Ring size dependence of the NMR parameters

The ¹H NMR spectral analysis of four 8-membered rings, 2-thioxo- (or 2-oxo-) 2-R-1,3,6,2- trithiaphocane, is reported. The stereochemistry of the 8-membered ring is discussed. The ³¹P NMR spectral parameters [δ³¹P, ¹J(PC)] obtained on several cyclic 1,3,2-dithiaphospha compounds of variable size (5, 6, 8, 12 and 16-membered rings) are discussed as a function of the ring size and of the geometry of the molecule.     

Repetierbare Ringerweiterungen durch [2,3]-sigmatropische Umlagerungen in cyclischen Allylsulfonium-allyliden; Synthese von mittleren und grossen Thiacyclen. Vorläufige Mitteilung

Repeatable ring expansions by [2,3]-sigmatropic shifts in cyclic allylsulfonium allylides; synthesis of medium- and large-sized thiacycles Allylation of a 2-vinyl thiacyclus with allyl bromide in 2,2,2-trifluoroethanol followed by ylide generation by use of aqueous potassium hydroxide results in a [2,3]-sigmatropic rearrangement with formation of a new 2-vinyl thiacyclus enlarged by three carbon atoms (Scheme 1). In this way, starting from the 5-membered ring 1 , a series of four ring enlargement sequences leads to the 17-membered thiacycles 9 and 10 via the 8-, 11- and 14-membered rings 4 , 7 and 8 (Scheme 2).     

Precision enzymatic polymerization to polyesters with lipase catalysts

Ring-opening polymerization of lactones with different ring-size has been achieved via lipase catalysis. Small-size (4-membered) and medium-size lactones (6- and 7-membered) as well as macrolides (12-, 13-, 16-, and 17-membered) were subjected to the lipase-catalyzed polymerization. The polymerization behaviors strongly depended on the lipase origin and the ring-size of the lactones. In using Pseudomonas family lipases as catalyst, the polymerization of macrolides showing much lower anionic polymerizability proceeded much faster than that of ϵ-caprolactone. The enzymatic polymerizability of the lactones was evaluated by Michaelis-Menten kinetics. V_max increased as a function of the ring-size, whereas K_m values were not so different with each other. The granular immobilized lipase derived from Candida antarctica. showed the extremely efficient catalysis in the polymerization of ϵ-caprolactone. Single-step synthesis of methacryl- and ω-alkenyl-type polyester macromonomers was achieved by the lipase-catalyzed polymerization of 13-membered lactone in the presence of vinyl esters acting as terminator. Lipase also catalyzed a polycondensation of dicarboxylic acid and glycol in the aqueous medium, in which the dehydration took place in water.     

Synthesen und Thermolysen von 1-Alkinyl-2-methyl-1,2-epoxy-cycloalkanen. - Versuche zur Ringerweiterung um drei Kohlenstoffatome

Syntheses and Thermolyses of 1-Alkynyl-2-methyl-1,2-epoxy-cycloalkanes. - Attempts at Ring Enlargement by Three Carbon Atoms The 1-alkynyl-2-methyl-1,2-epoxy-alkene 2 and -cycloalkenes 9, 28 and 29 were obtained by epoxidation of the conjugated en-ynes 1, 7, 26 and 27 . The 12-membered ring en-ynes 26 and 27 were synthesized by ethynylation or propynylation of 2-methylcyclododecanone ( 19 ) to the 1-ethynyl- or 1-(1′-propynyl)-cyclododecanols 20 A/B and 21 A/B , respectively, followed by dehydration to give separable mixtures of the regio- and stereoisomeric en-ynes 22, 24, 26 and 23, 25, 27 , respectively. Gas-phase thermolyses of the epoxides 2, 9, 28 and 29 were carried out under reduced pressure through a quartz tube at 550–600°. The formation of 5-hexine-2-one ( 3 ) and 4,5-hexadien-2-one ( 4 ) from 2 can be explained by [1, 5]- and [1, 3]- hydrogen shifts, respectively, and subsequent Claisen-type rearrangements. Thermolysis of the six-membered carbocyclic epoxide 9 induced the expected ring expansion by three carbon atoms to give 14% 4-cyclononynone ( 12 ), along with the ketones 13, 14 and 15 as by-products, which probably arose from surface induced heterolytic C, O-bond fission and Wagner-Meerwein-type rearrangement processes. Preliminary experiments with the thermolysis of the 12-membered carbocyclic ethynyl-epoxide 28 , yielded a mixture, which contained 4-cyclopentadecynone ( 30 ) and afforded, after hydrogenation, cyclopentadecanone ( 31 , exaltone®) in 36% yield as the semicarbazone. Traces of 3-methylcyclopentadecanone ( 32 , rac, -muscone) were identified after thermolysis and hydrogenation of the propynyl-epoxide 29 .     

Jump rope rotation in trans-cycloalkenes

A series of 1,2-bis-methylenecycloalkane monoepoxides(2a-e)was prepared from the related 12-to 16-membered cyclic ketones. Reduction with lithium in ammonia afforded the corresponding trans-and cis-2-methylcycloalkenylmethanols (3a/4a-3e/4e) in ratios of 92:8-78:22. Sharpless epoxidation of these allylic alcohols with 0.6 equivalents of the reagent prepared from titanium isopropoxlde, (+)-diisopropyl tartrate, and t-butylhydroperoxide gave rise to a mixture of the epoxy alcohols 6a-e and recovered allylic alcohols. In the case of the 12- to 14-membered cycloalkenes the recovered alcohols 3a-c were optically active. The 15- and 16-membered cases 3d and e were racemic. Barriers to jump rope rotation were calculated by means of the Still Macro Model program.     

Synthese und Reaktionen 8-gliedriger Heterocyclen aus 3-Dimethylamino-2,2-dimethyl-2H-azirin und Saccharin bzw. Phthalimid

Synthesis and Reactions of 8-membered Heterocycles from 3-Dimethylamino-2,2-dimethyl-2H-azirine and Saccharin or Phthalimide 3-Dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) reacts at 0-20° with the NH-acidic compounds saccharin ( 2 ) and phthalimide ( 8 ) to give the 8-membered heterocycles 3-dimethylamino-4,4-dimethyl-5,6-dihydro-4 H-1,2,5-benzothiadiazocin-6-one-1,1-dioxide ( 3a ) and 4-dimethylamino-3,3-dimethyl-1,2,3,6-tetrahydro-2,5-benzodiazocin-1,6-dione ( 9 ), respectively. The structure of 3a has been established by X-ray (chap. 2). A possible mechanism for the formation of 3a and 9 is given in Schemes 1 and 4. Reduction of 3a with sodium borohydride yields the 2-sulfamoylbenzamide derivative 4 (Scheme 2); in methanolic solution 3a undergoes a rearrangement to give the methyl 2-sulfamoyl-benzoate 5 . The mechanism for this reaction as suggested in Scheme 2 involves a ring contraction/ring opening sequence. Again a ring contraction is postulated to explain the formation of the 4H-imidazole derivative 7 during thermolysis of 3a at 180° (Scheme 3). The 2,5-benzodiazocine derivative 9 rearranges in alcoholic solvents to 2-(5′-dimethylamino-4′,4′-dimethyl-4′H-imidazol-2′-yl) benzoates ( 10 , 11 ), in water to the corresponding benzoic acid 12 , and in alcoholic solutions containing dimethylamine or pyrrolidine to the benzamides 13 and 14 , respectively (Scheme 5). The reaction with amines takes place only in very polar solvents like alcohols or formamide, but not in acetonitrile. Possible mechanisms of these rearrangements are given in Scheme 5. Sodium borohydride reduction of 9 in 2-propanol yields 2-(5′-dimethylamino-4′,4′-dimethyl-4′H-imidazol-2′-yl)benzyl alcohol ( 15 , Scheme 6) which is easily converted to the O-acetate 16 . Hydrolysis of 15 with 3N HCl at 50° leads to an imidazolinone derivative 17a or 17b , whereas hydrolysis with 1N NaOH yields a mixture of phthalide ( 18 ) and 2-hydroxymethyl-benzoic acid ( 19 , Scheme 6). The zwitterionic compound 20 (Scheme 7) results from the hydrolysis of the phthalimide-adduct 9 or the esters 11 and 12 . Interestingly, compound 9 is thermally converted to the amide 13 and N-(1′-carbamoyl-1′-methylethyl)phthalimide ( 21 , Scheme 7) whose structure has been established by an independent synthesis starting with phthalic anhydride and 2-amino-isobutyric acid. However, the reaction mechanism is not clear at this stage.     

Esterification and isolation of the carboxylic acid with salicyl-bis-hydrazide via coordination of iron(III) 18-metallacrown-6 complex

The trianionic heptadentate ligand, (Z)-3-(5′-bromosalicylhydrazinocarbonyl) propenoic acid ((Z)-H₄bshcpa), has been synthesized in good yield and reacted with FeCl₃?·?6H₂O to produce [Fe^III ₆(C₁₂H₈N₂O₅Br)₆(H₂O)₂(CH₃OH)₄]?·?8H₂O?·?8CH₃OH. The complex has been characterized by single-crystal X-ray diffraction. In the self-assembly process the ligand was esterified and transferred into (Z)-methyl 3-(5′-bromosalicylhydrazinocarbonyl) propenoate ((Z)-H₃mbshcp). In the crystal structure, the neutral Fe(III) complex contains an 18-membered metallacrown ring consisting of six Fe(III) and six trianionic ligands. The 18-membered metallacrown ring is formed by six structural moieties of the type [Fe(III)–N–N]. Due to the meridional coordination of the ligands to Fe³⁺, the ligands enforce stereochemistry of the Fe³⁺ ions as a propeller configuration with alternating Λ/Δ forms. The metallacrown can be treated with SnCl₂ to obtain purified ester. In addition, we have also obtained reduced esterified ligand, methyl 3-(5′-bromosalicylhydrazinocarbonyl) propanoate (H₃mbshcp), with Zn powder as reductant.     

Aspergillolide,a new 12-membered macrolide from sea cucumber-derived fungus Aspergillus sp. S-3-75

Abstract

A new 12-membered macrolide, aspergillolide (1), along with nine known compounds (2–10), were isolated from the fungus Aspergillus sp. S-3-75 associated with the sea cucumber Holothuria nobilis Selenka. The structure and absolute stereochemistry of 1 were elucidated on the basis of extensive spectroscopic methods and single crystal X-ray diffraction analysis.     

Synthese des (R)-trans-11-Hydroxy-8-dodecensäure-lactons (Recieifeiolid)

Synthesis of Recifeiolide The synthesis of the mould metabolite recifeiolide (VIII), a 12-membered ring lactone, is described. 1,3-Butandiol was resolved with (?)-camphanic acid via (R)-1-iodo-3-butanol (II) into (R)-3-hydroxybutyl triphenyl phosphonium iodide (III). Wittig condensation of the phosphorane derived from III with methyl 8-oxo-octanoate (V) led to the methyl trans-11-hydroxy-8-dodecenoate (VI). The corresponding hydroxy acid VII was transformed into the S-(2-pyridyl) carbothioate which cyclizes under the influence of silver ion to the lactone VIII. With (?)-(R)-1,3-butandiol (I) as starting material the naturally occurring (+)-(R)-recifeiolide (VIII) is produced in 70% yield from VII.     

Metal complexes with macrocyclic ligands. Part XIX. Synthesis and Cu2+-complexes of a series of 12-, 14- and 16-membered cis- and trans-N2S2-macrocycles

A series of 12-, 14-, and 16-membered N₂S₂-macrocycles ( 9–11 and 19–21 ) with cis and trans-arrangement of the heteroatoms have been synthesized by high-dilution cyclization and subsequent reduction of the amides with B₂H₆. With these ligands the corresponding Cu²⁺-complexes were prepared and their UV/VIS spectra, their electrochemistry and their EPR properties have been studied. Generally three absorption bands at 270–320 nm, 330–370 nm and 530–620 nm can be observed in aqueous solution and these have been assigned to the N→Cu²⁺ and S→Cu²⁺ charge-transfer bands and to the d-d* transition, respectively. The cyclic voltammetry in CH₃CN shows in all cases a reversible or quasi-reversible Cu²⁺/Cu⁺-transition at potentials of 10–480 mV against SHE. The values of g_‖ and A_‖ obtained from EPR spectra indicate that the geometry of the Cu²⁺-complex of the 14-membered cis-N₂S₂-macrocycle is less distorted than that of the other complexes.     

1H, 13C, 31P NMR and conformational study of 7-membered ring organophosphorus compounds. 1,3,2-dioxaphosphepanes

The ¹H, ¹³C and ³¹P NMR data of several 2-R-2-thiono-1,3-dioxa organophosphorus molecules with 7-membered rings [R = Cl, OC₆H₅, C₆H₅, CH₃, N(CH₃)₂] are reported. The conformation of the 7-membered ring is discussed by reference to the ³J(POCH) coupling constants which are compared with those observed in 6-membered 1,3,2-dioxaphosphorinanes. It is shown that caution must be exercised in using the ³J(POCH) angular dependence as a stereochemical tool. The ³¹P spin lattice relaxation times of some of these 7-membered rings have been measured and the values are discussed.