Bridgehead Carbon Research Articles

Stereocontrolled formation of oxacephams from carbohydrates

The [2+2] cycloaddition of chlorosulfonyl isocyanate to ( Z)-4- O-propenyl ethers 16, 17, 29 and 30 proceeds with an excellent stereoselectivity in the case of ether 16 and with moderate stereoselectivity in remaining cases. Adducts were transformed into corresponding oxacephams: 37 in the first case, a mixture of 37/ 40 in the second and third case, and a mixture of 50/ 51 in the last case. In all instances addition to the si– re side of the olefin dominates. Oxacephams 41 and 52 with opposite R-configuration at the bridgehead carbon C-5a can be obtained by the alternate methodology based on the alkylation of nitrogen in 4-vinyloxyazetidin-2-one by protected 6- O-triflate 24 or 25, followed by cyclization via intramolecular displacement of the vinyloxy group. Compounds 37, 40, 41, 50, 51 and 52 constitute a convenient entry leading to polyfunctionalized oxacephams.

ChemInform Abstract: Preparation and Kinetic Stabilization of Highly Strained Paracyclophanes

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Synthesis of [2,2‘-Methylenebis(1,3-dimethylcyclopentadienyl)]zirconium Dichloride and Its Reactivity in Ethylene−Norbornene Copolymerization

An ansa-zirconocene compound, [2,2'-methylenebis(1,3-dimethylcyclopentadienyl)]zirconium dichloride (5), bearing methyl substituents on the carbons adjacent to a bridgehead carbon, was synthesized by key steps of the catalytic Pauson-Khand reaction and the retro-Diels-Alder reaction. The crystal structure of 5 was determined. The small angle (117.15°) between the two centroids of the cyclopentadienyls and a zirconium atom and the absence of any substituents on the positions β with respect to the bridgehead carbon indicate that the coordination site for catalysis is widely opened. Compound 5, when activated with MAO, showed good performance for copolymerization of ethylene with a bulky monomer such as norbornene. The activity and norbornene incorporation ability are much better than those of [Ph 2 C(Fluo)(Cp)]ZrCl 2 .

Preparation and Kinetic Stabilization of Highly Strained Paracyclophanes

Abstract In this Account we describe the preparation, structures, and properties of the most highly strained paracyclophanes known to date, i.e. [4]- and [1.1]paracyclophanes and their derivatives. The preparation of these cyclophanes has been accomplished through the photochemical valence isomerization of corresponding 1,4-bridged Dewar benzene derivatives. These strained paracyclophanes are prone to polymerize and are not stable enough to isolate: [4]paracyclophane is rapidly consumed even below -100 °C in fluid solution, though it remains intact indefinitely in a frozen organic glass at 77 K, while [1.1]paracyclophane is stable only below -20 °C in solution. By introducing substituents which sterically hinder access to the bridgehead carbon atoms by other reagents, however, one can remarkably stabilize these species kinetically so as to allow the measurement of 1H NMR spectrum of the former and the isolation of the latter as crystals. The 1H NMR spectrum of the [4]paracyclophane strongly support, in conjunction with theoretical calculations, the sustenance of considerable aromaticity despite the extreme bending of its benzene ring. [4]Paracyclophane is so strained that it is thermodynamically less stable than the corresponding Dewar isomer and the thermal conversion of the benzene form to the Dewar form is observed for the first time. A fully unsaturated derivative of [4]paracyclophane is also generated and confirmed to prefer the structure of 1,2,3,4-tetradehydro[4]paracyclophane rather than that of π-bond isomer, bicyclo[4.2.2]deca-1,3,5,7,9-pentaene. The stabilized [1.1]paracyclophane is found to undergo efficient photochemical transformation into a benzene p,p′-dimer structure, from which the former is thermally regenerated upon mild heating. Structural characteristic features of the [1.1]paracyclophane and the benzene p,p′-dimer are revealed by X-ray crystallography. Limits for experimentally accessible strained paracyclophane are also discussed.

Thermodynamically Controlled Photo- cycloaddition of 5-Fluoro-1,3-dimethyl- uracil to Naphthalenes

UV-Irradiation of 5-fluoro-1,3-dimethyluracil (5-FDMU) and 1-acetonaphthone (1a) afforded trans-1,4-adduct, ethenobenzoquinazoline, (2) having an acetyl group at the C-10 bridgehead carbon, together with the cis-isomer (3). The cis-adduct (3) is more fragile than 2 in the dark at ambient temperature, and is more quickly converted back to the starting 1a and 5-FDMU through cycloreversion. Thus, the trans-adduct (2) comes to the predominant product when irradiation is prolonged. Similar irradiation of 1-naphthonitrile afforded cis-ethenobenzoquinazoline-10-carbonitrile (6) and the trans-isomer (7) as the kinetically controlled cycloadducts together with cis-ethenobenzoquinazoline with a CN group on the benzene moiety (5) as thermodynamically controlled product.

Photoinduced electron-transfer substitution reactions via unusual charge-transfer intermediates.

The photoinduced substitution reactions of halogenated alkanes (1-haloadamantanes, 1-haloronorbornanes, menthyl chloride) with a homologous series of amines or alcohols (methylamine, 2-methyl-2-aminopropane, methanol, or 2-methyl-2-propanol) to form the corresponding alkane-substituted amines or ethers and HCl were investigated. The geometry of the bridgehead carbons made S(N)2 reactions impossible. Nonpolar reaction conditions were employed which made classical and nonclassical carbocation S(N)1 reaction pathways unlikely. The reaction rates were measured. Trapping experiments indicated that free radical reactions were uninvolved in the substitution product formation. A novel, photoinduced electron-transfer reaction mechanism involving a charge-transfer intermediate is proposed to explain the observed production of secondary amines and ethers. The excitation wavelength dependence (action spectrum) was measured and found to be comparable to the ultraviolet absorption spectra of the charge-transfer complexes. The stereochemical implications of the reaction mechanism were investigated. The formation of the methyl ether of (1R,2S,5R)-menthol was the only organic reaction product observed in the photoreaction between (1R,2S,5R)-menthyl chloride and methanol.

Synthesis and transformation of a novel methano[60]fullerene having a formyl group

The reaction of [60]fullerene with a dimethylsulfonium α-formylalkylide gave a novel methano[60]fullerene having a formyl group at the bridge-head carbon. This 2,2-[60]fulleroalkanal was readily converted into a variety of N-aryl-2,2-[60]fulleroaldimines by condensation with aromatic amines; one of them showed efficient quenching of the fluorescence of the [60]fullerene core, due to a photoinduced intramolecular electron transfer.

Stereocontrolled formation of cephams from 1,3- O-ethylidene- l-erythritol

[2+2]Cycloaddition of chlorosulfonyl isocyanate to ( Z)-1,3- O-ethylidene-2- O-propenyl-4- O-trityl- l-erythritol proceeds with excellent stereoselectivity to afford the corresponding ( R)-4′-alkoxy-azetidin-2-one which can be transformed into 5-oxa-cepham by intramolecular alkylation of the β-lactam nitrogen atom. Cepham having the alternative ( S) configuration at the bridgehead carbon atom can be achieved by another methodology based on alkylation of the nitrogen atom in 4-vinyloxy-azetidin-2-one by the suitably protected 1,3-ethylidene- l-erythritol followed by intramolecular displacement of the vinyloxy group.

Chiral Ansa metallocenes with Cp ring-fused to thiophenes and pyrroles: syntheses, crystal structures, and isotactic polypropylene catalysts.

Syntheses, crystal structures, and polymerization data for new isospecific metallocenes (heterocenes) having cyclopentenyl ligands b-fused to substituted thiophenes (Tp) and pyrroles (Pyr) are reported. The C2- and C1-symmetric heterocenes are dimethylsilyl bridged, have methyl groups adjacent to the bridgehead carbon atoms, and have aryl substituents protruding in the front. rac-Me2Si(2,5-Me2-3-Ph-6-Cp[b]Tp)2ZrCl2/MAO (MAO = methyl alumoxanes) is the most active metallocene catalyst for polypropylene reported to date. rac-Me2Si(2,5-Me2-3-Ph-6-Cp[b]Tp)2ZrCl2 and rac-Me2Si(2,5-Me2-1-Ph-4-Cp[b]Pyr)2ZrCl2 have the same structure, and the former is 6 times more active, produces half the total enantiofacial errors, and is 3.5 times less regiospecific in propylene polymerizations at the same conditions. rac-Me2Si(2-Me-4-Ph-1-Ind)2ZrCl2/MAO is 3.5 times lower in activity than rac-Me2Si(2,5-Me2-3-Ph-6-Cp[b]Tp)2ZrCl2 catalyst, and while the former is the more stereospecific and the less regiospecific, the sum of these two enantioface errors is the same for both species. Fine-tuning the heterocene sterics by changing selected hydrogen atoms on the ligands to methyl groups influenced their catalyst activities, stereospecificites, regiospecificites, and isotactic polypropylene (IPP) Mw. Thus, both substituting a hydrogen atom adjacent to the phenyl ring with a methyl group on an azapentalenyl ligand system and replacing one and then two hydrogens on the phenyl ring with methyls on thiopentalenyl ligands provided increased polymer Tm and Mw with increasing ligand bulk. Polymer molecular weights are sensitive to and inversely proportional to MAO concentration, and the catalyst activities increase when hydrogen is added for molecular weight control. The polymer Tm values with the thiopentalenyls as TIBAL/[Ph3C][B(C6F5)4] systems were higher than with MAO as catalyst activator. A racemic C1, pseudo-meso complex with a hybrid dimethylsilyl-bridged 2-Me-4-Ph-1-Ind/2,5-Me2-4-Ph-1-Cp[b]Pyr ligand produced the first sample of IPP with all the steric pentad intensities fitting the enantiomorphic site control model. Speculative mechanistic considerations are offered regarding electronic effects of the heteroatoms and steric effects of the ligand structures, the preferred phenyl torsion angles, and anion effects.

Synthesis, Spectral Characterisation and Crystal Structure of (1,24-Bicyclophthalocyaninato)bismuth(III)

A new orange bicyclophthalocyanine complex of bismuth(III), [Bi(C48H24N13)], has been synthesised by means of the template reaction of bismuth(III) acetate with phthalodinitrile. The ligand consists of the phthalocyanine skeleton, which is bridged by two additional isoindole units. The conjugation of the phthalocyanine ring is interrupted by the two bridgehead sp3-hybridised carbon atoms. The main difference between this new bicyclophthalocyanine and those previously reported in the literature lies in the position of the bridgehead carbon atoms. In order to differentiate between these bicyclophthalocyaninato complexes, we propose a nomenclature: [Bi(C48H24N13)] is named Bi(1,24-Pcc), and the other bicyclic ligands already reported in the literature are named (1,16-Pcc) and (1,17-Pcc). The molecular structure of Bi(1,24-Pcc) shows the coordination polyhedron around the bismuth atom, made up of the six isoindole nitrogen atoms of the macrocycle, as a strongly distorted trigonal prism. The two Bi−Niso bonds of the bridge and two of the four Bi−Niso bonds of the (Pc) ring have bond lengths between 2.40 and 2.47 A. One of the remaining bonds is longer (2.55 A), and the sixth has a very short length of 2.20 A. This new complex was fully characterised by UV/Vis and IR spectroscopy, also reported here.

Ab initio calculations of the NMR spectra of [1.1.1]propellane and bicyclo[1.1.1]pentane

New high-level ab initio values of all the NMR shielding and spin–spin coupling constants in [1.1.1]propellane and bicyclo[1.1.1]pentane are obtained and compared with previous theoretical results and available experimental data. Electron correlation effects are taken into account and large basis sets suitable for NMR studies are applied. The results for the shielding constants depend primarily on the basis set, while the spin–spin coupling constants, in particular for the carbon–carbon coupling, are very sensitive to electron correlation effects. The computed NMR parameters agree well with the known experimental values, with the exception of the bridgehead–bridgehead carbon coupling constant in [1.1.1]propellane. Our best estimates of this constant differ from the experimental value for a substituted [1.1.1]propellane, and possible explanations of this discrepancy are discussed.

An octapositive cation incorporating multiple redox centres: Cage amine complexes of cobalt(III) linked by a 2,2 '-bis(pyridinium) unit

The methyl substituents of diquaternized 4,4′−dimethyl-2,2′-bipyridine are suff iciently acidic to be used as the source of a bridgehead carbon in the formation of cage amine derivatives from [Co(sen)]3+ [sen = 4,4′,4′′-ethylidynetris(3-azabutan-1-amine)]. The resulting octapositive bis(cage)-bipyridinium species can be obtained in both meso and optically active forms, the latter showing readily detectable potential shifts in the presence of enantiomeric anions.

Kinetic Stabilization of the [1.1]Paracyclophane System: Isolation and X-ray Structural Analysis of a [1.1]Paracyclophane Derivative and Its Interconversion with the Transannular Adduct

Intentionally designed kinetic stabilization of the [1.1]paracyclophane skeleton has been achieved by multiple substitution of the aromatic rings with trimethylsilylmethyl and N,N-dimethylcarbamoyl groups, which serve to shield the proximate bridgehead carbon atoms sterically from access by other reagents. The bis(Dewar benzene) precursor (1 a) has been prepared in essentially the same manner as previous derivatives—starting from the photocycloaddition of 1,4-bis(trimethylsilyl)-2-butyne to octahydroindacene-1,5-dione—except for a few critical modifications described in the text. Substituted [1.1]paracyclophane (2 a), photochemically generated from the precursor, is indefinitely stable at 50 °C and suffers decomposition only by 8 % after 2 h at 100 °C in degassed n-decane, demonstrating its greatly improved kinetic stability compared to previous [1.1]paracyclophanes. Since 2 a undergoes efficient photochemical transformation into the transannular addition product 3 a, irradiation of 1 a tends to produce a mixture of products consisting mainly of 3 a. Compound 3 a, however, reverts thermally to 2 a in a process of half life 40 min at 55 °C; the activation parameters for this process are ΔH≠=21.1±0.8 kcal mol−1 and ΔS≠=−10.5±2.6 cal K−1 mol−1. Thus, on heating 3 a in benzene and cooling the resultant solution, 2 a is obtained as orange-red crystals. X-ray crystallographic analysis of 2 a reveals benzene rings bent to the highest degree ever reported for a paracyclophane, with their face-to-face arrangement in unusually close proximity. The shortest nonbonding interatomic distance is 2.376 Å; less than the sum of the van der Waals radii by more than 1.0 Å. The generation of related substituted [1.1]paracyclophanes and their kinetic stabilities are also reported.

Kinetic stabilization of the [1.1]paracyclophane system: isolation and X-ray structural analysis of a [1.1]paracyclophane derivative and its interconversion with the transannular adduct.

Intentionally designed kinetic stabilization of the [1.1]paracyclophane skeleton has been achieved by multiple substitution of the aromatic rings with trimethylsilylmethyl and N,N-dimethyl-carbamoyl groups, which serve to shield the proximate bridgehead carbon atoms sterically from access by other reagents. The bis(Dewar benzene) precursor (1a) has been prepared in essentially the same manner as previous derivatives--starting from the photocycloaddition of 1,4-bis(trimethylsilyl)-2-butyne to octa-hydroindacene-1,5-dione--except for a few critical modifications described in the text. Substituted [1.1]paracyclophane (2a), photochemically generated from the precursor, is indefinitely stable at 50 degrees C and suffers decomposition only by 8 % after 2 h at 100 degrees C in degassed n-decane, demonstrating its greatly improved kinetic stability compared to previous [1.1]paracyclophanes. Since 2a undergoes efficient photochemical transformation into the transannular addition product 3a, irradiation of la tends to produce a mixture of products consisting mainly of 3a. Compound 3a, however, reverts thermally to 2a in a process of half life 40 min at 55 degrees C; the activation parameters for this process are deltaH(not equal to)= 21.1 +/- 0.8 kcalmol(-1) and deltaS(not equal to) = -10.5 +/- 2.6 cal K(-1)mol(-1). Thus, on heating 3a in benzene and cooling the resultant solution, 2a is obtained as orange-red crystals. X-ray crystallographic analysis of 2a reveals benzene rings bent to the highest degree ever reported for a paracyclophane, with their face-to-face arrangement in unusually close proximity. The shortest nonbonding interatomic distance is 2.376 A; less than the sum of the van der Waals radii by more than 1.0A. The generation of related substituted [1.1]paracyclophanes and their kinetic stabilities are also reported.

Conformational Analysis of Azabicycloalkane Amino Acid Scaffolds as Reverse-Turn Inducer Dipeptide Mimics

In an effort to design structural mimics of protein and peptide reverse-turns, the conformations of 5,5-, 6,5-, and 7,5-fused 1-aza-2-oxobicycloalkane amino acids have been evaluated. The conformational preferences of these proline-derived bicyclic lactams have been studied by Monte Carlo molecular mechanics searches, and the reverse-turn inducing properties of the calculated structures have been quantitatively assessed using various geometrical parameters. All of the four possible diastereoisomers arising from two of the three stereogenic centres [C3 and bridgehead carbon atom; Pro Cα is (S) in all compounds] have been considered for each bicyclic scaffold. These studies have revealed that the (3S)-Pro Cα(S) configuration is an effective turn-inducer, although the torsion angles of the backbone do not always mimic those of classical β-turns. A dependence of the turn-inducing ability on lactam ring size and bridgehead stereochemistry has also been found. Reverse-turn mimetic bicyclic lactams have been shown to exhibit a tendency to form an inverse γ-turn or a type II′ β-turn. Experimental 1H-NMR and FT-IR spectroscopic data of model compounds in chloroform solutions have complemented our computer modelling studies and have confirmed our conclusions.

Conformational Analysis of Azabicycloalkane Amino Acid Scaffolds as Reverse-Turn Inducer Dipeptide Mimics

In an effort to design structural mimics of protein and peptide reverse-turns, the conformations of 5,5-, 6,5-, and 7,5-fused 1-aza-2-oxobicycloalkane amino acids have been evaluated. The conformational preferences of these proline-derived bicyclic lactams have been studied by Monte Carlo molecular mechanics searches, and the reverse-turn inducing properties of the calculated structures have been quantitatively assessed using various geometrical parameters. All of the four possible diastereoisomers arising from two of the three stereogenic centres [C3 and bridgehead carbon atom; Pro Cα is (S) in all compounds] have been considered for each bicyclic scaffold. These studies have revealed that the (3S)-Pro Cα(S) configuration is an effective turn-inducer, although the torsion angles of the backbone do not always mimic those of classical β-turns. A dependence of the turn-inducing ability on lactam ring size and bridgehead stereochemistry has also been found. Reverse-turn mimetic bicyclic lactams have been shown to exhibit a tendency to form an inverse γ-turn or a type II′ β-turn. Experimental 1H-NMR and FT-IR spectroscopic data of model compounds in chloroform solutions have complemented our computer modelling studies and have confirmed our conclusions.

A DFT/GIAO/NBO and experimental study of13C SCSs in 1-X-bicyclo[1.1.1]pentanes

The 13C NMR spectra of 24 members of a series of 1-X-bicyclo[1.1.1]pentanes were measured. SCSs on 13C1 were found to linearly correlated with those on 13C3, although the former correspond to deshielding effects and the latter to shielding effects. Even though the 13C1 SCSs follow the same trend as α-SCSs in other types of substrates, they are significantly smaller. In order to provide an insight into the different intramolecular interactions that define such a trend, theoretical studies that include SCSs calculated at the GIAO B3LYP/6–311G** level, electron delocalization analysis within the NBO approach at the same level and electrostatic interaction effects on chemical shifts were carried out. Important halogen heavy-atom effects on C3 were observed, suggesting that the spin–orbit interaction is transmitted through space between the bridgehead carbon atoms. Additionally, in a few members of the series X = H, F, CH3, NH2, OCH3, CN, COOH, COCH3), theoretical calculations of the substituent chemical shifts, 13C SCSs, were carried out with particular reference to the C1 position. These theoretical calculations included: (a) full geometry optimizations, (b) magnetic shielding constant calculations using the GIAO (gauge-included atomic orbitals) method within the DFT (density functional theory) approach and (c) natural bond orbital (NBO) analysis of intramolecular charge transfer interactions. Copyright © 2000 John Wiley & Sons, Ltd.

Carbon-13 Shift Tensors in Polycyclic Aromatic Compounds. 8. A Low-Temperature NMR Study of Coronene and Corannulene

The principal values of the 13C chemical shift tensors were measured for coronene and corannulene, both at room temperature and at approximately 100 K. At room temperature the molecules are moving, resulting in a motionally averaged powder pattern. A comparison of the principal values between the room temperature motionally averaged pattern and the low-temperature static pattern provides experimental information about the orientation of the principal axis system of the shift tensor for the bridgehead carbons in these molecules. For corannulene, the orientation of δ33 component was determined to lie at an angle of 13° from the rotation axis (the 5-fold symmetry axis of the molecule) for the inner bridgehead carbons and at an angle 26° from this same rotation axis for the outer bridgehead carbons. These orientations are in good agreement with the angles necessary to place the δ33 component along the p orbitals involved in π-bonding at these carbons. In the case of coronene, the differences between the principal values at the two temperatures indicate there is an angle of 14° between the axis of rotation and the δ33 component for both the inner and outer bridgehead carbons. This indicates that the motion is not constrained to simple in-plane rotation, but must also have an out-of-plane component. Quantum chemical calculations of the shielding tensors were also completed using both experimental and optimized molecular geometries. The results of the calculations are in good agreement with the experimental findings.

Syntheses of polymethylene bridged dinuclear zirconocenes and investigation of their polymerisation activities

The polymethylene bridged dinuclear zirconocenes [(CH 2) n (C 5H 4) 2][(C 9H 7)ZrCl 2] 2 ( n=3 ( 10), 5 ( 11), 7 ( 12), 9 ( 13)) have been synthesised by treating not only the respective disodium salts of the ligands with two equivalents of (C 9H 7)ZrCl 3 in THF, but also the distannylated derivatives of the ligands with two equivalents of (C 9H 7)ZrCl 3 in toluene. All complexes are characterised by 1H- and 13C-NMR and mass spectrometry and elemental analysis. It turned out that the values of Δ δ=[ δ d− δ p], the chemical shift difference between the distal ( δ d) and proximal ( δ p) protons, for the produced dinuclear compounds (0.1 for 10 and 11, and 0.11 for 12 and 13) were smaller than the Δ δ values of the known polysiloxane bridged dinuclear compounds. The chemical shifts of the bridgehead carbons in these complexes are about 135 ppm shifted downfield with respect to the other two resonances at cyclopentadienyl ring (113.7 and 113.7 ppm, respectively). In order to investigate the catalytic properties of the dinuclear complexes and mononuclear metallocenes, ethylene polymerisation has been conducted in the presence of MMAO. The most important feature is that the polymethylene bridged dinuclear metallocenes represent enormously improved activities compared with the activities from the corresponding mononuclear metallocene as well as the polysiloxane bridged dinuclear zirconocenes. In addition, the influence of both the nature and length of the bridging ligand upon the reactivities of the dinuclear metallocenes has also been observed.

The Bicyclo[3.2.0]heptan-endo-2-ol and Bicyclo[3.2.0]hept-3-en-6-one Approaches in the Synthesis of Grandisol: The Evolution of an Idea and Efforts to Improve Versatility and Practicality

In this paper we will disclose a chemistry story that started with a single molecule, the monoterpene grandisol, used in protecting cotton crops from an important pest, Anthonomus grandis Boheman. Initially, efforts were aimed at giving ever more practicality, versatility, and efficiency to a synthetic scheme that was centered on the key role of the 2,5-dimethylbicyclo[3.2.0]heptan-endo-2-ol, available from intermolecular photocyclization and methylation or, better and more conveniently, by an intramolecular copper(I)-catalyzed photobicyclization of the 3,6-dimethylhepta-1,6-dien-3-ol. We have developed an enantiospecific synthesis of both enantiomers of grandisol although some drawbacks would preclude scale up and commercialisation. The major limits of this original single-target synthetic scheme are pointed out along with the changed landscape resulting from recent developments in the fields of bioorganic chemistry and entomology. These changes prompted the elaboration of a new strategy focused on the conception and the development of a practical and efficient preparation bicyclo[3.2.0]hept-2-en-6-ones. The “bicyclo[3.2.0]hept-2-en-6-one approach” stems from a very convenient and general preparation, without photochemical steps, of bicyclo[3.2.0]hept-2-en-6-ones. These compounds proved to be amenable to selective manipulations to prepare not only grandisol but also other important molecules such as lineatin, filifolone, and raikovenal in multitarget and versatile synthetic schemes. Moreover, through resolution of the bicyclo[3.2.0]hept-2-en-6-ones, the procedures can be used to produce enantiomerically pure products. The bismethylation of the carbon atom adiacent to the carbonyl group as well as the conversion into the corresponding unsaturated bicyclic lactones are two important reactions that amplify the potential utility of bicyclo[3.2.0]hept-2-en-6-ones. Their peculiar reactivity, ascribed to the fact that the carbonyl group and the carbon−carbon double bond are attached to the same bridge-head carbon atom, has been demonstrated by the high chemio-, regio-, and stereoselectivity of the NBS-induced lactonization.