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A convenient asymmetric synthesis of methyl (2S,3S,6R)-6-(4-fluorophenyl)-2-(4-hydroxyphenyl)-piperidine-3-carboxylate is described, starting from Baylis–Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland–Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent chemoselective transformation of one of the side-chain groups allows an effective cyclization leading to biologically interesting polysubstituted piperidines in which the 2,6-aryl groups could be attached sequentially.

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl β-lactam is described starting from Baylis–Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland–Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.

The asymmetric synthesis of methyl (E)-4-((1R,2S,3R)-3-amino-2-((E)-2-methoxycarbonyl-eten-1-yl)cyclohexyl)but-2-enoate 14 has been achieved from dimethyl (2E,7E)-nona-2,7-dienedioate 2. A key step is the asymmetric synthesis of 1-hydroxyoctahydro-1H-isochromene derivative 5 whose X-ray analysis corroborated the stereochemistry of the new stereocenters. The asymmetric synthesis of the isochromenyl acetate derivative 11 shows the potential of this methodology for fused cyclohexanic system heterocyclic synthesis.

The title compound, C22H25NO5, was prepared by CAN [cerium(IV) ammonium nitrate] oxidation of the corresponding β-lactam. The dihedral angle between the benzene rings is 13.3 (4)° and the C—N—C(=O)—C torsion angle is 176.1 (6)°. In the crystal, amide-C(4) N—H...O and reinforcing C—H...O hydrogen bonds link the molecules into infinite [010] chains. Further C—H...O hydrogen bonds cross-link the chains in thec-axis direction.

The title compound, C12H15NO3S, was prepared by 1,3-dipolar cycloaddition of 3,4-dihydro-2H-pyrrole 1-oxide and phenyl vinyl sulfone. In the molecule, both fused five-membered rings display a twisted conformation. In the crystal, C—H...O hydrogen bonds link neighbouring molecules, forming chains running parallel to thebaxis.

The 1,3-dipolar cycloaddition of a chiral nitrone with α,β-unsaturated lactones was carried out to give the corresponding isoxazolidines. Tetrahydro-1,3-oxazines with an oxa-tropane skeleton were obtained in one step by alkylation. The structures of several of these compounds were corroborated by X-ray diffraction and molecular modelling studies confirmed the results and proposed a mechanism for their formation.

Different synthetic procedures are described in the rapid elaboration of flexible PNA monomers based on the 6-amino-8-base-octanoate and 5-amino-7-base-heptanoate scaffolds. Asymmetric Aza-Michael monoaddition is successfully applied to starting materials derived from sebacic/azelaic long-chain diacids and 6-membered oxacyclohexane commercial derivatives. Chain length, orthogonality of the ester functionalities, and Z/E isomerism of these prime substrates yielded high-valuable multifunctional intermediates through this asymmetric conjugate addition. Key features are the diversity toward PNA monomer synthesis, orthogonal chemoselective transformations, and Mitsunobu nucleobase substitution as an exceptional approach to introduce nucleobases in the final step.

A convenient asymmetric synthesis of (1R,5R,9R)-2-aza­bicyclo[3.3.1]nonane-9-carboxylic acid is described, starting from (2E,7E)-dimethyl nonadienedioate. The route involves a stereo­selective domino Michael–Dieckman process that furnishes a 1,2,3-trisubstituted cyclohexane derivative bearing three adjacent stereocenters with full stereochemical control. A subsequent chemoselective transformation of one of the side-chain ester groups allows an effective second cyclization leading to the morphan motif. The versatility of this novel amino acid for the generation of molecular complexity was tested by elaborating a tripeptide in homogeneous phase.

The product distribution upon conjugate addition of homochiral lithium N-benzyl-N-alpha-methylbenzylamide to dimethyl-(E,E)-nona-2,7-dienedioate can be controlled to give either the cyclic 1,2-anti-1,6-anti-beta-amino ester (derived from conjugate addition and intramolecular enolate cyclisation) or the acyclic bis-beta-amino ester derivative (derived from double conjugate addition) in high de. The introduction of a protected nitrogen functionality into the diester skeleton facilitates, after conjugate addition and intramolecular enolate cyclisation, the asymmetric construction of piperidines in high de; variation in the N-protecting group indicates that the highest stereoselectivity is observed with alpha-branched N-substituents. Tandem conjugate addition-aldol reactions can also be achieved stereoselectively, with lithium amide conjugate addition to epsilon- and zeta-oxo-alpha,beta-unsaturated esters giving the corresponding five and six membered cyclic beta-amino esters in high de. N-deprotection by hydrogenolysis of the products arising from these reactions furnishes a range of polyfunctionalised transpentacin and transhexacin derivatives in high de and ee.

An enantioselective synthesis of (2 S ,3 R )-piperidine-2,3-dicarboxylic acid and (2 S ,3 S )-piperidine-2,3-dicarboxylic acid is described. This synthesis was mainly based on a δ-amino acid formation via a domino reaction: allylic acetate rearrangement, stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition protocol from a Baylis–Hillman adduct, in which the cinnamaldehyde double bond is a masked carboxylic functionality, and a cerium(IV) ammonium nitrate promoted monodebenzylation.

This paper describes an anomalous behaviour of the Sharpless dihydroxylation of a terminal olefin. The synthesis of a new chiral pyrrolidine and its application as an organocatalyst in the Michael addition of cyclohexanone into nitrostyrenes are described.

[EN] A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different β-disubstituted-α,β-unsaturated aldehydes with a chiral α,β-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner.

An efficient asymmetric synthesis of (+)-L-733,060, (―)-(2S,3R)-1 and (+)-CP-99,994, starting from a Baylis―Hillman adduct, is described. The key steps include a novel domino reaction: stereoselective Ireland―Claisen rearrangement, asymmetric Michael addition, and piperidone ring formation through a one-pot reaction hydrogenolysis/lactamization and a stereoselective inversion of a hydroxy group.

A highly efficient asymmetric synthesis of (1S,2R)-2-aminocyclooctanecarboxylic acid has been completed. This asymmetric synthesis using cycloocta-1,5-diene as the starting material is achieved in 77% yield via a four-step sequence from tert-butyl cycloocta-1,7-dienecarboxylate 10 where the extra double bond adjacent to the unsaturated ester is essential to improve the yield. Furthermore, the Michael adduct intermediate (1S,2R,αR)-14 could be used towards the synthesis of the natural product tashiromine.

A novel domino reaction--stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition--is described. A protocol starting from Baylis-Hillman adducts 3a-f using chiral lithium amide affords optically active gamma-substituted delta-amino acids 4a-f with high diastereoselectivities and enantioselectivities. The acid can be isolated easily from large-scale reactions and transformed to 2,3-disubstituted piperidines 11 or 2-substituted nipecotic acid derivates 12.

A new chiral organocatalyst is described in this paper. A new mechanism for the overall Michael condensation of ketones with nitroolefins using our catalyst is suggested based on molecular modelling studies.

An expeditious asymmetric synthesis of pent-3-yl (R)-6-methyl-cyclohex-1-enecarboxylate has been achieved in four steps in 42% overall yield employing as the key step a domino reaction initiated by a highly diastereoselective lithium amide 1,4-conjugate addition to a nona-2,7-diendioic diester followed by a 6-exo-trig cyclisation of the thus formed enolate. Cope elimination protocol of the cyclic adduct affords, depending on the lithium amide used, the corresponding nitro-compound or the expected cyclohexene derivative. The methyl group attached to the cyclohexane ring is achieved by selective ester hydrolysis and subsequent Barton decarboxylation. © 2006 Elsevier Ltd. All rights reserved.

A new synthesis of chiral alkyl pyrroles and pyrrolines has been achieved in an easy straightforward way, using the addition of organometallics to chiral imines.

A study of the addition of vinylsulfones versus alkylsufones has been done, and applied to the synthesis of N -( tert -butoxycarbonyl)- l -homophenylalanine.

A totally different approach to conformationally restricted glutamic acid analogues is described, in which one of the acid functions is replaced by a cyclopropanol. The reactivity of cyclopropanol vinyl sulfones toward addition of lithiated Schollkopf bislactim ether provides a facile synthesis of α-amino acid diastereoisomers. Conformational analysis of these analogues, incorporating solvation effects, and docking to a glutamate receptor model, are used to show the relevance of the conformational restrictions employed.

The asymmetric synthesis of the orthogonally funtionalised compounds tert -butyl 2- N -benzyl- N -α-methylbenzylamino-5-methoxycarbonylmethylcyclopentane-1-carboxylate and methyl 2- N -benzyl- N -α-methylbenzylamino-5–carboxymethylcyclo-pentane-1-carboxylate by a domino reaction of tert -butyl methyl ( E , E )-octa-2,6-diendioate with lithium N -α-methylbenzyl- N -benzylamide initiated by a Michael addition, subsequent 5- exo -trig intramolecular cyclisation and posterior selective hydrolysis with trifluoroacetic acid is reported. Keywords: Asymmetric synthesis, chiral lithium amide, β-amino acids, domino reaction, β-aminocyclopentane carboxilate, aminodiester orthogonal protection. Introduction The asymmetric synthesis of polyfunctionalised cyclopentane derivatives has been widely pursued in organic synthesis, with much recent interest focusing around strategies for the asymmetric synthesis of cis -pentacin ( 1 ) and trans -pentacin ( 2 ), respectively. The cis -diastereoisomer shows potent

The stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate may be prepared stereoselectively from diester derivatives of (E,E)-octa-2,6-diendioc acid, with the key step utilising the conjugate addition of homochiral lithium N-benzyl-N- alpha-methylbenzylamide. The trans-C(1)-C(2)-stereoisomers are readily prepared via a diastereoselective tandem conjugate addition cyclisation protocol with lithium (R)-N-benzyl-N- alpha-methylbenzylamide, with subsequent hydrogenolysis and ester hydrolysis giving the (1R,2R,5R)- and (1R,2R,5S)- beta-amino diacids in good yields. The preparation of the cis-C(1)-C(2)-stereoisomers utilises a protocol involving N-oxidation and Cope elimination of the major diastereoisomeric product arising from conjugate addition and cyclisation, giving homochiral (R)-5-carboxymethyl-cyclopentene-1-carboxylate. Conjugate addition of either lithium (R)- or (S)-N-benzyl-N- alpha-methylbenzylamide to (R)-5-carboxymethyl-cyclopentene-1-carboxylate, and diastereoselective protonation with 2,6-di-tert-butyl phenol gives, after hydrogenolysis and ester hydrolysis, the (1S,2R,5R)- and (1R,2S,5R)- beta-amino diacids in good yield. The use of (S)-N-benzyl-N- alpha-methylbenzylamide in the initial conjugate addition and cyclisation reaction, and subsequent repetition of the elimination and conjugate addition strategy allows stereoselective access to all stereoisomers of 2-amino-5-carboxymethyl-cyclopentane-1-carboxylate.

By using the appropriate protecting groups, the opening of (2S,3S,4E)-5-benzenesulfonyl-2,3-epoxy-pent-4-en-1-ol (−)-2 could be controlled and used for the synthesis of the enantiomeric pyrrolidines (+)- and (−)-18 and the tetrahydrofuran analogs (+)- and (−)-19.

This paper describes a full conformational and stereochemical study of bicylo[3.3.1]nonanes, obtained from the reaction between cinnamaldehyde and 1-morpholine 1-cyclohexene. NMR data and stereochemistry were unequivocally established and assigned by two-dimensional experiments and single-crystal X-ray analysis. The crystal structure of a minor compound, 4, is reported. Cyclooctenes, which are present in natural products with biological activities, were synthesized from the bicyclononanes via the Wharton fragmentation.

Structure-Activity Relationship (SAR) is a current approach in the design of new pharmacological agents. We previously reported the synthesis of a novel analogue of morphine, a 2-azabicyclo[3.3.1]nonane, which contains a β-amino acid. This bicyclic core exhibits two distinctive chemical handles for further elaboration, which allowed us to create a library of morphan-containing compounds by in silico molecular docking on the μ opioid receptor. Lead candidates were synthesized and biological tests were performed to evaluate their ability to bind to opioid receptors. The four top compounds, three phenyl esters and an N-phenylethyl morphan derivative, were selected for Molecular Dynamics simulations to get topological and thermodynamic information. Aromatic morphan derivatives displayed an interacting domain which fits into a hydrophobic cleft and the effect of the substituents in their affinity was explained by the differences in the calculated binding free energies. Our results indicate that the 3D arrangement of the aromatic ring in the morphine derivatives is not a key issue for a specific ligand – μ receptor interaction. Thus, these morphan derivatives represent a new class of opioid receptor ligands which may be of great use in the clinical practice.

Strategies for obtaining either the products from tandem conjugate addition–cyclisation or from double addition in the highly stereoselective addition of lithium ( R )-(α-methylbenzyl)benzylamide to (α,β)(α′,β′)-diendioate esters are demonstrated.

[EN] Isatin and its derivatives have been widely studied due to their biological activities. Recently there has been a renewed interest in the synthesis of new derivatives by use of organocatalysts. This review deals with this area., The authors gratefully acknowledge FSE, MICINN CTQ2009-11172BQU, Junta de Castilla and León (SA162A12-1) for financial support. MFF is grateful to the JCyL-ESF for her FPI fellowship. JP is grateful to MINECO for a FPU fellowship. P.G-G. is grateful for a JAE-DOC contract from CSIC co-funded by the European Social Fund (ESF)

The reaction of bicyclic diterpenes either with an allylic grouping or an equivalent function on ring B afforded a simple and rapid synthesis of tetrahydronaphthalenic diterpenes of the isofregenedane type.

The synthesis of (±) 10-epi-tormesol, 27, has been achieved from (±) 1-acetyl-3a,6 dimethylhexahydroazulene 1, by coupling of 5, a dehydroderivative of 1, with 23. The same synthetic procedure afforded a series of diterpenes 24–26 and 28 with the same biannular system. Direct reduction of 1 with different methods does not give the desired spatial relationship (trans/cis) between Me-C7/H-6/H-10 on the substrate, affording instead trans/trans (compounds 5 and 18) and cis/cis (compound 9). Indirect reduction: epoxydation followed by catalytic hydrogenation afforded the desired stereochemistry on the intermediate but deoxygenation caused epimerization at C-10. This synthetic achievement confirmed the original structure assigned to tormesol some years ago.

The right hand fragment, 36, of Usneoidone E, 1, a powerful antiviral and antitumoural agent has been synthesized from the β-pyrone 32. Using linalool as starting material, a 2,2,6,6-tetrasubstituted dihydropyrane 20, precursor of 32 and 33, was prepared. 20 was also synthesized from geranyl acetate through selenide 7, and is a versatile precursor for the synthesis of tetraprenyltoluquinols. Unambiguous 13C NMR assignment has been done by 2D correlations.

Three new diterpenoid acids isolated from the aerial parts of Halimium viscosum were identified as 15-acetoxy-7, 13 E -labdadien-17-oic acid, 15-hydroxy-7,13 E -labdadien-17-oic acid and 14,15-dinor-13-oxo-7-labden-17-oic acid by spectroscopic and chemical correlation methods. They share the novel feature of containing a C- 17 carboxyl group.

The study of the chemical components of the neutral part of the extract of Halimium viscosum, chemotype Valparaiso, has been completed. Twelve labdanes have been isolated, nine are new natural compounds (two of them are tetranor-derivatives). Their structures were determined by spectroscopic methods and by chemical transformations from the major components present in this extract.

The components of the neutral part of the extract of Halimium viscosum , chemotype Villarino de los Aires, have been studied and the study of the co

The unsaponificable part of the hexane extract of Halimium viscosum chemotype (Valparaiso, Zamora, Spain) afforded three hydrocarbons, an epoxide, a ketone (valparone), five allylic alcohols and a seco derivative with valparane skeleton and an α,β-unsaturated ketone with valparolane skeleton. The majority of them have been correlated chemically. Chemical correlation between valparanes and valparolanes, absolute stereochemistry determined by means of CD for valparone and the confirmation of the absolute stereochemistry of valparanic and valparolanic compounds have been done by CD curve of the cyclohexanone obtained from valparolone.

The right hand fragment, 36, of Usneoidone E, 1, a powerful antiviral and antitumoural agent has been synthesized from the β-pyrone 32. Using linalool as starting material, a 2,2,6,6-tetrasubstituted dihydropyrane 20, precursor of 32 and 33, was prepared. 20 was also synthesized from geranyl acetate through selenide 7, and is a versatile precursor for the synthesis of tetraprenyltoluquinols. Unambiguous 13C NMR assignment has been done by 2D correlations.

The synthesis of (±) 10-epi-tormesol, 27, has been achieved from (±) 1-acetyl-3a,6 dimethylhexahydroazulene 1, by coupling of 5, a dehydroderivative of 1, with 23. The same synthetic procedure afforded a series of diterpenes 24–26 and 28 with the same biannular system. Direct reduction of 1 with different methods does not give the desired spatial relationship (trans/cis) between Me-C7/H-6/H-10 on the substrate, affording instead trans/trans (compounds 5 and 18) and cis/cis (compound 9). Indirect reduction: epoxydation followed by catalytic hydrogenation afforded the desired stereochemistry on the intermediate but deoxygenation caused epimerization at C-10. This synthetic achievement confirmed the original structure assigned to tormesol some years ago.

One of the chemotypes of Halimium viscosum—La Fregeneda—provided a new natural product with a rearranged skeleton. The new bicyclic diol possesses an aromatic ring B and its structure has been determined on the basis of 1H, 13C and 2D NMR (1H13C HETCOR and 1H13C long range inverse detected HMBC) studies.

Synthesis of analogues of isosorbide in one pot from 1-hydroxymethyl-4-phenylsulfonylbutadienes has been achieved. In the previous paper, we have described a simple way to obtain 1-sulfonyl-1,3-dienes with adequate functionalization. These compounds have been the object of numerous studies in the last years, above all as dienes or dienophiles.1 Furthermore, it should be noted that there are more examples with sulfoxides rather than sulfones due to the potential chirality that these substrates2 can possess. In our case, having developed a very easy way to get 1-sulfonyl-1,3dienes with an allylic alcohol, we wanted to exploit this feature to produce chiral compounds by way of the Sharpless enantioselective epoxidation.3 In this way, we planned to develop a short synthesis of analogues of isosorbide 1. Amino derivatives of 1 are being used as chiral auxiliaries4 in asymmetric synthesis while the dinitro derivative 2 and the piperazine derivative 3 possess antianginal activity5. 1, has been used recently as the starting material for the synthesis of novel bicyclic dideoxynucleosides as potential antiviral agents 4.6 All different routes to isosorbide analogues start from isosorbide 1 as the starting material. In this context, we have found a new and versatile method to obtain analogues with different stereochemistry and functionalization, which allows not only the use of SN2 type reactions but also the use electrophilic reagents. Results and discussion Compound 6 was easily obtained as described in the previous paper by treatment of sulfone 5 with n-BuLi/THF at -78° C (Scheme I). Treatment of 6 with n-BuLi/THF followed by addition of acetone as the electrophile gives compound 7 in excellent yields (90%). When 7 reacts with m-CPBA it afford compound 8 directly (77%). The second cyclization proved to be difficult, with bases such as NaH or KH giving inconsistant results. However, use of Craig s conditions7 (tBuOH/ tBuOK 5:1) gave satisfactory yields of 9 (83%). When 7 reacts under Sharpless conditions with L-(+)-DET, after the usual work up of the reaction only homochiral (-)-98 is isolated. The stereochemistry was established by study of N.M.R. spectra and n.O.e. studies. The CIS relationship between H-4 and H-5 (mechanism) was confirmed by the n.O.e observed (Scheme I) and the same relationship of H-5 and H-1 was established for the existence of another n.O.e. between them. The stereochemistry of H-8 was based on its coupling constant with H-1 ( J = 5.8 Hz ), the other stereochemistry would give a nearly zero coupling constant, (see ref 4). This was confirmed by the existence of n.O.e between H-1 and H-8 in the bencil derivative. So, in conclusion we have developed a short, and stereocontrolled way to obtain analogues of isosorbide. At the moment, we are trying to introduce further functionalization at C-8, and a range of electrophiles are being used in the addition step. Acknowledgement: This work was supported by Junta de Castilla y Leon (SA 44-96); M.E.C. and CICYT. References and Notes (1) a) Backwall, J.E.; Lofstrom, C.; Maffesal, M.; Lauger, V. Tetrahedron Lett. 1992, 33, 2417. b) Padwa, A.; Gareau, Y.; Harrison, B.; Norman, B.H. J. Org. Chem. 1991, 56, 2713. (2) a) Aversa, M. C.; Baratucci, A.; Bonaccorsi, P.; Gianneto, P. Tetrahedron Asymm. 1997, 9, 1339. b) Carreno, M. C. Chem. Rev. 1995, 95, 1717. (3) Gao, Y.; Hauson, R.M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765 (4) Tamion, R.; Marsais, F.; Ribereau, P.; Queguiner, G.; Abenhaim, D.; Loupy, A.; Munnier, L. Tetrahedron Asymm. 1993, 8, 1879. (5) Hayashi, H.; Keolo, J. I.; Kubo, K.; Mokiyama, J.; Karasama, A.; Suzuki, F. Chem. Pharm. Bull. 1993, 41, 1100 (6) Chao, Q.; Zhang, J.; Pickening, T. S.; Jahande, M.; Nair, V. Tetrahedron 1998, 54, 3113. (7) a) Craig, D.; Ikin, M. J.; Mathews, N.; Smith, A. M. Tetrahedron Lett. 1995, 41, 7531. b) Padwa, A.; Gareau, Y.; Harrison, B.; Norman, B. H. J. Org. Chem. 1991, 56, 2713. Scheme 1 D ow nl oa de d by : D on al d C ra ig . C op yr ig ht ed m at er ia l. December 1998 SYNLETT 1365 (8) Spectral data for 9: (-)-9: [α]D= -39.9 (c=1.0, CHCl3).; IR (cm-1): 2930, 2857, 1719, 1290, 1152, 1084.; 1H NMR (400MHz, CDCl3): δ 1.60 (3H, s, Me-C7), 1.61 (3H, s, Me-C7), 3.29 (1H, d, J=5.8Hz, H-8), 3.46 (1H, dd, J=9.5 and 6.6Hz, HB-3), 3.79 (1H, dd, J=9.5 and 5.5Hz, HA-3), 4.08 (1H, m, H-4), 4.60 (1H, t, J=5.8Hz, H-5), 5.22 (1H, t, J=5.8Hz, H-1), 7.60 (2H, m, Ar), 7.66 (1H, m, Ar), 7.91 (2H, m, Ar); 13C NMR (100Mhz, CDCl3): δ 23.1 (Me-C7), 28.6 (Me-C7), 70.5 (C8), 71.9 (C-3), 76.6 (C-4), 78.3 (C-5), 85.0 (C-1), 86.8 (C-7), 128.2 (2CHortho, Ar), 129.2 (2CHmeta, Ar), 133.9 (CHpara, Ar), 134.0 (Cipso, Ar). Anal. Calcd for C14H18O5S: C, 56.36; H, 6.08; Found: C, 56.35; H, 5.99. D ow nl oa de d by : D on al d C ra ig . C op yr ig ht ed m at er ia l.

This paper describes a full conformational and stereochemical study of bicylo[3.3.1]nonanes, obtained from the reaction between cinnamaldehyde and 1-morpholine 1-cyclohexene. NMR data and stereochemistry were unequivocally established and assigned by two-dimensional experiments and single-crystal X-ray analysis. The crystal structure of a minor compound, 4, is reported. Cyclooctenes, which are present in natural products with biological activities, were synthesized from the bicyclononanes via the Wharton fragmentation.