Trans Ring Junction Research Articles

Total synthesis of (R,R)-crinan via regiospecific and stereoselective palladium catalysed cyclisation.

The synthesis of (R,R)-crinan from (S)-1-cyclohexenylethan-1-ol is described. The key palladium catalysed step involves a regiospecific 6-exo trig cyclisation which proceeds with 20:1 stereoselectivity for the trans-ring junction over the cis-ring fusion. The ring junction stereochemistry is sensitive to solvent, phosphine and small amounts of water.

Stereocontrolled formation of cis and trans ring junctions in hydrindane, decalin, and steroid systems by palladium-catalyzed regioselective and stereospecific hydrogenolysis of allylic formates

Both the cis and trans ring junctions can be generated selectively in hydrindane, decalin and steroid systems by the palladium-catalyzed regioselective and stereospecific decarboxylation-hydrogenolysis of allylic formates. The trans junctions were formed from 3β allylic formates of decalin and steroid and 5β allylic formates of hydrindane. The corresponding 3α and 5α formates generate the cis ring junction.

X‐RAY STRUCTURES OF 11,11‐DIMETHOXY‐2‐OXO‐9‐PHENYLSULFONYL‐ BICYCLO[6.3.0]UNDECANE AND ITS DIOXOLANE DERIVATIVE

The structure of the title compounds were determined by X‐ray diffraction. A trans ring junction was observed in both molecules and the phenylsulfonyl substituent was directed anti regarding that junction. The conformation of the polycyclic skeletons are compared.

Stereocontrolled formation of cis and trans ring junctions in hydrindane and decalin systems by palladium-catalyzed regioselective and stereospecific hydrogenolysis of allylic formates

Both cis and trans ring junctions can be generated selectively in hydrindane, decalin, and-steroid systems by the palladium-catalyzed regioselective and stereospecific hydrogenolysis of allylic formates

Cross‐reaction in allergic contact dermatitis from α‐methylene‐γ‐butyrolactones: importance of the cis or trans ring junction

Cross-reaction in allergic contact dermatitis (ACD) is a highly stereoselective process. The importance of the cis or trans ring junction in alpha-methylene-gamma-butyrolactones in cross-reactivity was investigated by reacting Helenin (mostly a mixture of natural allergenic sesquiterpene lactones alantolactone 1 and isoalantolactone 2, which present a cis ring junction) in guinea pigs sensitized to model allergenic alpha-methylene-gamma-butyrolactones: cis-bicyclic lactone 3 and trans-bicyclic lactone 4.

X-ray study of the hetero ring flexibility in trans-5,6- trimethylene- and tetramethylene-5,6-dihydro 2-phenyl-[4 H]-1,3-thiazines

The structures to two 1,3-thiazine derivatives differing only in the number of CH 2 groups in their trans fused hydrocarbon ring ( n  3 for I and n  4 for II) have been established by X-ray crystallography from diffractometer data. Crystals of I ( trans-5,6- trimethylene-5,6-dihydro-2-phenyl-[4 H] - 1,3-thiazine) are triclinic, space group P 1 with a = 7.661(1), b = 8.282(1), c = 9.566(2) Å, α = 91.75(1), β = 100.72(1), γ  105.45(1)° Z = 2, D c = 1.260 g cm -3. Crystals of II ( trans-5,6-tetramethylene-5,6-dihydro-2-phenyl [4 H]-1,3-thiazine) are monoclinic, space group P2 1/ c with a = 7.914(2), b = 19.362(13), c = 8.440(1) Å, β = 109.16(2)°C Z = 4, D c = 1.258 g cm -3. The structures determined by Patterson ( I) and direct ( II) methods were refined to R = 0.050 for 1330 reflections of I and R = 0.082 for 1012 reflections of II. The proper treatment of the positional disorder of the carbon atoms (C(5) and C(6)) forming the trans ring junction in I discovered two discrete conformations with a ratio of 1:2. The opposite chirality of atoms C(51) and C(52), and C(61) and C(62), indicates a simultaneous configurational disorder with a pattern of total disorder: AB̄B̄AB̄B̄. The puckering parameters of the hetero rings in the same enantiomers of molecules IA, IB and II indicate a connection between the conformers: 5 E( II)→ 5 H 6( IB)→ E 6 IA) via pseudorotation. Their relationship is discussed and compared with the conformational freedom of the analogous 1,3-oxazine derivatives.

Stereoelectronic effects in the conformation and hydrolysis of epimeric(4aα, 8aβ)-hexahydrobenzo-2-( [formula omitted]-Nitrophenoxy)-2-Oxo-1,3,2λ 5 dioxaphosphorinanes and 4aα-methyl-8aβ-pentahydrobenzo-2- ( [formula omitted]-Nitrophenoxy) -2- oxo-1, 3,2λ 5 -dioxaphosphorinanes

The epimeric (4aα, 8aβ)-hexahydrobenzo-2-( p -nitrophenoxy)-2-oxo- 1,3,2 λ 5-dioxaphosphorinanes 1a , 1b (axial and pseudo-equatorial p -nitrophenoxy group) and 4aα-methyl-8aβ-pentahydrobenzo-2-( p -nitrophenoxy)-2-oxo-1,3,2λ 5-dioxaphosphorinanes 2a , 2b (axial and equatorial p -nitrophenoxy group) were hydrolyzed in 12% methanol/water. For axial isomers 1a and 2a , the methyl group at the trans-ring junction did not affect the rate of hydrolysis. The methyl substitution of the equatorial isomer 2b , on the other hand, decreased the hydrolysis rate by 30% as compared to 1b . For both epimers, the equatorial compounds (as viewed in a chair conformation) hydrolyzed faster than the corresponding axial isomer. These results are consistent with the idea that the axial isomers react via a chair conformation and the equatorial isomer 1b reacts via a twistboat conformation with the leavinq group in a pseudo-axial position.

Studies of chromenes. Part 4. Oxidation of hexahydro-5H-chromeno[3,4-c]-pyridazines and conformational isomerism in tetra-and hexa-hydro-N,N′-dialkoxycarbonyl-5H-chromeno[3,4-c]pyridazines

3,4-Bis(t-butoxycarbonyl)- and 3,4-bis(methoxycarbpnyl)-8-methoxy-5,5-dimethyl-2,3,4,4a-tetra-hydro-5H-chromeno[3,4-c]pyridazines and their 2,2-dimethyl analogues were hydrogenated to give hexahydrochromenopyridazines possessing only a trans-ring junction. Removal of the t-butoxy-carbonyl groups from the trans-products afforded the corresponding 1,2,3,4,4a,10b-hexahydro-5H-chromeno[3,4-c]pyridazines which were oxidised first to 1,2,3,10b-tetrahydro- and then 1,2-dihydro-5H-chromenopyridazines. The last-named dihydro compounds possess an unusual [3,4]pyridazine hydrogenation pattern. The dialkoxycarbonyl derivatives of both the tetra- and hexahydrochromenopyridazines exist as pairs of conformational isomers whose interconversion is acid catalysed. The isomerism is considered to be due to restricted rotation about the less hindered N(3)–CO bond, the N(4)–CO bond being locked in one conformation by 1,3 interactions.

Stereoelectronic control of the hydrolysis of a conformationally locked acetal

The hydrolysis of the nitrophenyltetrahydropyranyl acetal (3e; Y = H), with leaving group fixed equatorial by the trans-ring junction, is substantially slower than expected for a comparable conformationally flexible acetal. It is also slower than the hydrolysis of the axial isomer, by a factor of 60 in acid, but only 2 for the spontaneous reaction. It is suggested that both reactions of (3e) are slow because there is a stereoelectronic barrier to the departure of an equatorial leaving group, not readily overcome in a system where the conformation at the acetal centre is fixed by a trans-ring junction. The spontaneous hydrolysis of (3a) appears to be slow for a different reason: rapid internal return from the initial product of C–O cleavage enforces a change in rate-determining step, to hydration of the oxocarbonium ion, as shown by the solvent deuterium isotope effect for this reaction.

Selectivite de la reduction de l'androsten-4 dione-3,17 et de la progesterone par divers borohydrures: role de l'assistance electrophile par le cation ou un solvant hydroxyle

The reduction of Δ 4-androsten-3, 17 dione 1 and of progesterone 2 by nBu 4NBH 4 is highly chemioselective: in THF only the a-enone moiety is reduced, the saturated C 17 or C 20 keto group being kept unchanged. When TMEDA is added, saturated alcohols are obtained, without any allylic alcohol when the reaction goes to completion. However this reduction is poorly stereoselective as 70:30 mixtures of A/B cis and trans ring junction compounds are obtained. In MeOH, the saturated keto group is more than 90% selectively reduced. However, the reduction of 1 and 2 by LiBH 4 and Zn(BH 4) 2 is poorly chemioselective. These results are interpreted in terms of competition between electrophilic assistance and steric effects.

Stereochemical studies, 47, saturated heterocycles, 25 a simple stereospecific synthesis of oxazasteroids

8-Aza-12-oxasteroids have been synthesized in a simple three-step process. As a consequence of two stareocontrolled reactions, the product is a stereospecifically homogeneous isomer with all- trans ring junctions; its structure has been determined by 1H and 13C NMR spectroscopy and X-ray diffraction.

Stéréosélectivité de l'addition de réactifs nucléophiles sur des cétones polycycliques à jonction trans

The nucleophilic additions of hindered organometallic compounds to polycyclic ketones with trans ring junctions involve predominant axial attack when flattening of the ring containing the carbonyl group occurs. The influence of nucleophile structure (O-Por C-metallated character) on equatorial or axial attack is discussed.

Stereoelectronic control of acetal cleavage. Separation of the π-donor and σ-acceptor properties of oxygen

The lone pair electrons of the oxygen atom in ring A assist the fragmentation of the acetal (2ca), but not that of the isomer (2ta), with a trans ring-junction.

Annelated tropones. Part 3. Photochemistry of some cyclohepta[b]-thiophen-4-ones

On irradiation, methanolic solutions of the cyclohepta[b]thiophen-4-ones (5)–(7) give dimers, shown by spectral evidence to be [π 4 +π2] dimers, formed by reaction of the 5,6-bond of one thienotropone molecule with the 5,7-diene system of another. The dimers are of the head-to-head type and have a trans-ring junction. Irradiation of 2,6-dimethylcyclohepta[b]thiophen-4-one (8) leads to an intramolecular electrocyclic disrotatory reaction, giving a tricyclic ketone (14). The syntheses of the parent cycloheptathiophenone (5) and of the 7-methyl derivative (8) are described, and that of 7,8-dihydro-2-methylcyclohepta[b]thiophen-4-one (17).

Elaeocarpus alkaloids. I. The structures of (±)-elaeocarpine, (±)-isoelaeocarpine, and (±)-isoelaeocarpicine, three new indolizidine alkaloids from Elaeocarpus polydactylus

Three new interrelated alkaloids have been isolated from Elaeocarpus poly-dactylus Schltr. (family Elaeocarpaceae). Two of these alkaloids, (�)-elaeocarpine (I) and (�)-isoelaeocarpine (II), are isomeric and the structure and complete stereochemistry of (�)-elaeocarpine have been established from an X-ray crystal structure analysis of (�)- elaeocarpine hydrobromide.1 From a detailed analysis of the spectroscopic properties of (�)-elaeocarpine and (�)-isoelaeocarpine, and in particular of their 100-Mc/s n.m.r. spectra, it has been shown that the alkaloids are epimeric at C7 and that (�)-isoelaeocarpine has a cis ring junction at C7,C8, whereas (�)-elaeocarpine is known to have a C7,C8 trans configuration. In methanolic sodium hydroxide solution (�)-elaeocarpine and (�)-isoelaeocarpine are interconvertible. (�)-Isoelaeocarpicine (VIa) is closely related to (�)-elaeocarpine and (�)-iso-elaeocarpine, and has been so named because the configuration at C7,C8 corresponds to that of (�)-isoelaeocarpine. (+)- Isoelaeocarpicine is phenolic, differs from (�)-elaeocarpine and (�)- isoelaeocarpine in molecular composition by the elements of water, and is converted into a mixture of elaeocarpine and isoelaeocarpine by the action of methanolic sodium hydroxide solution. Study of the 100-Mc/s n.m.r. spectrum of (+)-isoelaeocarpicine has established the complete stereochemistry shown in (VIa). The structures indicated for the three alkaloids (I), (II), and (VIa) depict relative stereochemistry only and are not intended to imply a particular absolute configuration. Study of the reaction between (+)-isoelaeocarpicine (VIa) and acetic anhydride shows that an O-acetyl derivative (VIb) is formed rapidly, but that with longer reaction periods the amide (VIIIa) is obtained. The steric requirements of the borohydride reduction of (I) and (II) have been studied, and it has been found that the n.m.r. spectra of solutions of the alcohol (XIIa) in CD3CO2D or of its hydro- chloride in CD3OD indicate an equilibrium between two deuteronated forms of (XIIa), one of which is considered to have a cis and the other a trans ring junction for the indolizidine ring. A minor alkaloid, C17H21N3, amounts to <1% of the total alkaloids, and a minor non-alkaloidal constituent has been identified as 2- hydroxy-6-methylacetophenone.

The stereochemistry and Hofmann degradation of Lupinine methiodides

Optical rotation studies on the epimers (-)-lupinine and (+)-epilupinine and their methiodides lead to the conclusion that while (+)-epilupinine methiodide has the normal trans-ring junction, (-)-lupinine methiodide has a cis-ring junction. Unlike the quaternary salts of cryptopleurine, canadine, and tetrahydropalmatine, neither of the lupinine methiodides could be racemized by refluxing with alkali.

Configuration of the C/D ring junction in equilenin and other steroids.

THE configuration of the C/D ring fusion in equilenin has been the subject of a number of communications1–3. We consider that the arguments advanced for a trans ring junction leave much to be desired. Shoppee's1 conclusion that the dehydrogenation of equilin to equilenin under mild conditions proves the steric identity of the C/D union in these two substances can no longer be accepted, since isoequilin, which is now known4,5 to be also trans, gives isoequilenin (which has the opposite C/D configuration to equilenin) under the same conditions6.