Bridgehead Methyl Research Articles

Synthesis of chiral bicyclo[2.2.2]oct-5-en-2-ones via an intramolecular alkylation reaction

Generation of the thermodynamic dienolate of 9-bromocarvone derivatives 5,7 and 11 furnished the chiral bicyclo[2.2.2]octenones 6, 8 and 9 and 12 and 13 containing a bridgehead methyl group via an intramolecular alkylation reaction. In an analogous manner intramolecular alkylation reaction of the bromo enones 15a–e, obtained from carvone 2 by 1,3-alkylative enone transposition (→14) followed by a regiospecific bromoetherification reaction, furnished the bicyclo[2.2.2]oct-5-en-2-ones 16a–e and 17a–e.

Chemistry of Fenchonesulfonic Acid Derivatives

(1 S) - (+)-Fenchone is sulfonated by SO3 or H2SO4/acetic anhydride in the bridgehead methyl group. This could be confirmed by NMR techniques (INADEQUATE). The fenchonesulfonic acid obtained is converted (SOCl2/NH3) to the cyclic fenchonesulfonimide, which can be oxidized to the corresponding oxaziridine, in close analogy to 10-camphorsulfonimide. Improved procedures for this reaction sequences are given. During the treatment of the sulfonic acid with thionyl chloride, a byproduct with a rearranged bicyclic skeleton is observed whose structure has been determined by ozonolytic degradation and NMR techniques. A possible mechanism for this rearrangement is suggested, based on MNDO calculations of the intermediate carbocations. The fenchonesulfonyloxaziridine oxidizes sulfides to chiral sulfoxides with appreciable enantiomeric excess, but very low reaction rate. A comparison with camphor-derived oxaziridines having similar steric requirements is made.

Synthesis of camphor based chiral crown ethers and their interactions with amino acid derivatives

Three camphor based crown ethers have been prepared, starting from (–)-(1R)-camphorquinone, in which 2- and 3-endo-substituents are used to regulate the availability of the endo-l8-crown-6 face for binding organic guests and the bridge head methyl group is available to impart enantioselectivity at the exo-face. The stereochemistry of the key intermediate 2-endo-3-endo-dimethyl bornane-2,3-diol (6) has been confirmed by a single crystal X-ray structure determination. Interactions between these crowns and antipodal phenylglycine salts have been probed using NMR and modelling techniques.

Total synthesis of the novel sesquiterpenes of Eremophila georgei Diels

The first stereoselective total synthesis of the natural sesquiterpenes 4 and 5, having the tricyclo[6.2.1.01,5]undecane skeleton with a bridgehead methyl group, is reported via the intermediate 9, which was obtained by the acid catalysed rearrangement of the alcohols 7 and 8.

Synthesis based on cyclohexadienes. Part 8. Synthesis of 1-methylbicyclo[2.2.2]oct-2-enecarboxylate derivatives

The 1,4-dihydrotoluic acids, obtained by the Birch reduction of 2-methyl- and 3-methyl-benzoic acids are isomerised to 2-methylcyclohexa-1,5-diene-1-carboxylic acid 10 and 5-methylcyclohexa-1,5-diene-1-carboxylic acid 15, respectively. These conjugated diene acids undergo facile cycloaddition with dienophiles resulting in bicyclo[2.2.2]octene derivatives having a bridgehead methyl group. While the cycloaddition of 10 with dienophiles produces regioisomeric mixture of adducts, the acid 15 affords regiospecific products.

Stereochemically controlled intramolecular Diels–Alder reactions: synthesis of substituted trans-fused octahydronaphthalenes possessing a bridgehead methyl group

Stereochemically controlled intramolecular Diels–Alder reactions: synthesis of substituted trans-fused octahydronaphthalenes possessing a bridgehead methyl group

ChemInform Abstract: Crystal Structure of 1,4,9,10‐Tetramethyltriptycene (Ia) and Barriers to Rotation of Bridgehead‐Methyl Groups in 1,4,9,10‐Tetramethyl‐ and 1,4‐Dichloro‐9,10‐dimethyl‐triptycene

ChemInformVolume 19, Issue 49 Physical Organic Chemistry ChemInform Abstract: Crystal Structure of 1,4,9,10-Tetramethyltriptycene (Ia) and Barriers to Rotation of Bridgehead-Methyl Groups in 1,4,9,10-Tetramethyl- and 1,4-Dichloro-9,10-dimethyl-triptycene F. IMASHIRO, F. IMASHIRO Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorK. HIRAYAMA, K. HIRAYAMA Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorK. TAKEGOSHI, K. TAKEGOSHI Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorT. TERAO, T. TERAO Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorA. SAIKA, A. SAIKA Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorZ. TAIRA, Z. TAIRA Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this author F. IMASHIRO, F. IMASHIRO Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorK. HIRAYAMA, K. HIRAYAMA Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorK. TAKEGOSHI, K. TAKEGOSHI Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorT. TERAO, T. TERAO Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorA. SAIKA, A. SAIKA Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this authorZ. TAIRA, Z. TAIRA Dep. Chem., Kyoto Univ., Kyoto 606, Jap.Search for more papers by this author First published: December 6, 1988 https://doi.org/10.1002/chin.198849052Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue49December 6, 1988 RelatedInformation

Crystal structure of 1,4,9,10-tetramethyltriptycene and barriers to rotation of bridgehead-methyl groups in 1,4,9,10-tetramethyl- and 1,4-dichloro-9,10-di-methyl-triptycene

Barriers to rotation of the bridgehead-methyl groups in 1,4,9,10-tetramethyl-(1) and 1,4-dichloro-9,10-dimethyl-triptycene (2) are investigated both in solution and in the solid. The barrier is larger for (2) than for (1) not only in the solid state but also in solution, the barriers in solution being somewhat higher than those in the solid for both (1) and (2). X-Ray crystallography for (1)[monoclinic, space group P21/n, Z= 4, a= 20.525(5), b= 9.776(2), c= 8.499(2)A, and β= 99.31 (2)°, R= 0.0417 and Rw= 0.0467 (w= 1.0) for 2 181 reflections] reveals planar benzene rings in the triptycene skeleton of (1). Remarkable upfield 13C n.m.r. chemical shifts of the methyl carbon atoms for (1) in solution compared with those in the solid suggest deformation of the benzene rings and an increase of the methyl barrier in solution. Molecular mechanics calculations of features of the molecular structure of (1) are critically evaluated.

NMDA receptor channels: Labeling of MK-801 with iodine-125 and fluorine-18

Methods for labeling the glutamate channel blocking agent MK-801 with iodine-125 ( 125I) and fluorine-18 ( 18F) are described. Radioiodine was incorporated in the 1- or 3-positions of the aromatic ring of (±)MK-801 by solid-state halogen exchange techniques. Attachment of the [ 18F]fluoromethyl group to the bridgehead methyl position was achieved by reaction of [ 18F]fluoride with the triflamide alcohol 8 or the novel cyclic sulfamate 9 recently reported by Merck chemists. Radiochemical yields of (±)13-[ 18 F]- fluoromethyl- MK-801 were >72%, EOB; radiochemical purity >99%. In competitive binding studies using rat brain homogenates, (±)3-bromo-MK-801 showed greater affinity than (±)MK-801 for the glutamate-linked channel. The experimental log P (2.1 ± 0.1) of MK-801 is optimal for transit of the blood-brain barrier. These preliminary findings support further testing of 3-[ 123I]iodo-MK-801 and (±)13-[ 18 F] fluoromethyl- MK-801 as possible agents for in vivo mapping of the glutamate receptor complex.

Conformational control of photochemical reactions of tetrahydro-1,4-naphthoquinones

The crystal structures of two asymmetrically substituted tetrahydro-l,4-naphthoquinones have been determined and correlated with their photochemical behaviour. T=295 K, Mo Kal, h =0.70930~. (I): 6,7-Benzo-2,4a-dimethyl-cis-4a,5,8,8a-tetrahydro- 1,4-naphthoquinone (2,4a-dimethyl-cis-4a,9a,9,10-tetrahydro-l,4-anthracenedione), C16Hi602, M r = 240.30, triclinic, P1, a=6.834(3), b=9.817(4), c=10.071(4) A, a=85.46(2), /3=73.48(3), 3,= 76-71 (3) °, V = 630.4 (5) A3,Z= 2,Dx = 1.266 gcm -3, F(000) = 256,/z = 0.73 cm -1, R = 0.042 for 2130 observed reflections. (II): 6,7-Benzo-2,3,4a-trimethylcis-4a,5 ,8,8a-tetrahydro- l ,4-naphthoquinone (2,3,4atrimethyl - cis - 4a, 9a, 9,10 - tetrahydro - 1,4-anthracenedione), C17H1802 Mr=25433, monoclinic, P2~/a, a =9.8329(17), b=8.0652(8), c= 17-3772 (32),~,, /3 = 102.69 (1)°, V = 1344.4 (4)/~3, Z = 4, Dx = 1.256 g cm -3, F(000) = 544, p. = 0.75 cm -~, R = 0.052 for 1330 observed reflections. Bond lengths and angles are close to normal values for both molecules (I) and (II). In each structure the two fused non-aromatic six-membered rings are twisted with respect to each other; however, while the solid-state conformation of compound (I) is such that the bridgehead methyl group is pseudo-axial to the cyclohexenone moiety, in compound (II) the methyl group is pseudoequatorial. Molecular-energy calculations are used to determine the energy difference between the two molecular conformations for each compound, and the different photochemical behaviour of (I) and (II) in the solid state and in solution is interpreted; the solid-state reactions are topochemically controlled, while reactions in solution are governed by the amounts and reactivities of the two conformers.

Structure of 2,3,6,7-dibenzo-4aβ,8aβ-dimethyl-4a,5,8,8a-tetrahydro-1,4-naphthoquinone

C20H1802, Mr=29036, triclinic, P1, a= 9.907(3), b=12.094(4), c=13.049(4) A, ~= 80.54 (2), fl= 85.03 (2), ?= 89.73 (2) °, v= 1536.3 (8)A 3, z= 4 (two molecules per asymmetric unit), D x = 1.255 g cm -3, 2(Mo Kay) = 0.70926 A, /~ =0.71cm -~, F(000)=616, T=295K, final R= 0.046 for 4388 observed reflections. The crystal- lographically independent molecules are related by roughly P2Jbll symmetry, and adopt a similar conformation, with a half-chair cyclohexene ring eis-fused to a half-chair cyclohexene-1,4-dione moiety; each molecule is twisted so that the bridgehead methyl groups are staggered with torsion angles of 63 and 65 o. The solution and solid-state photochemistry are inter- pretable in terms of molecular conformation and packing.

Perhydroazulenes. 6. 4-Keto derivatives with bridgehead methyl substituents

Perhydroazulenes. 6. 4-Keto derivatives with bridgehead methyl substituents

Heterolysis of N-chloro-1,2,3,4-tetrahydro-1,4-iminonaphthalenes and related systems; effects of structure and of solvent on reaction pathways

Replacement of hydrogen by methyl at the 1,4-positions of 1,2,3,4-tetrahydro-1,4-iminonaphthalenes substantially modifies the Ag(I)-catalysed solvolytic behaviour of this system giving tetrahydrobenzazepine derivatives; small amounts of methanol in non-polar solvents have a profound effect favouring heterolytic, rather than homolytic, NCl cleavage. Methanoquinolines are produced via secondary rearrangement. Bridgehead methyl substituents also divert the reactions of N-chloro-1,4-dihydro-1,4-iminonaphthalenes, leading to quinoline derivatives.

Facile H–D exchange of the bridgehead methyls of bicyclo[2.2.2]octan-2,5-diones. Evidence for a carbon analogue of the acyloin rearrangement

Hexamethyltwistyl-2,5-dione 4 has been synthesized and its H–D exchange studied in t-BuOK/t-BuOD at 125 °C. We find that the bridgehead methyl at C-3 undergoes exchange 7 × 105 times faster than the bridgehead methyl of bicyclo[2.2.1]heptan-2-one (fenchone). This result, along with a previous study, establishes the first examples of the carbon analogue of the acyloin rearrangement of alicyclic systems.

The photoinduced addition of acetone to 1,7-dimethyltricyclo[4.1.0.02,7]Heptane. Hydrogen atom abstraction from an activated methyl group

Activation of a bridgehead methyl group by the bicyclo[1.1.0]butyl moiety resulted in hydrogen abstraction by a photogenerated acetonyl radical, followed by a radical chain addition process.

Homoenolization of 1,3,3-trimethylbicyclo[2.2.2]octane-2,5-dione. Unusually rapid H–D exchange of a bridgehead methyl

The title compound 2a undergoes unusually rapid H–D exchange at the bridgehead methyl at a rate 5300 times faster than exchange of the bridgehead methyl of 1,3,3-trimethylbicyclo[2.2.1]heptan-2-one (fenchone). From the isotopic composition of partially deuterated 2a, we deduce that exchange occurs via an isomer, in equilibrium with 2a, which contains an active methylene derived from the bridgehead methyl.

Synthesis of 6-Hydroxyfulvenes. II. Isomerization of 7-Oxanorbornadienes and 3-Oxaquadricyclanes

Substituted 7-oxanorbornadienes (1a–e) isomerize in good yield in the presence of iodine to 6-hydroxyfulvenes (2a–e): the reaction is catalyzed by light. Oxaquadricyclanes having bridgehead methyl substituents (3b, c) also undergo slow photoisomerization (2537 Å) to the same fulvenes. Irradiation of the oxanorbornadienes with bridgehead phenyl substituents (1d, e) resulted in oxepines (7d, e). Phenyl substituted oxaquadricyclanes could not be isolated.