Chemo- and Stereoselective Coordination of 5,6-Dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene by d8- and d6-Metal Carbonyls. Diels-Alder reactivity of Dienes Perturbed by Remote Olefin Complexation

The endocyclic double bond C(2), C(3) in 5,6-dimethylidene-7-oxabicyclo[2.2.1]-hept-2-ene ( 1 ) can he coordinated selectively on its exo-face before complexation of the exocyclic s-cis-butadiene moiety. Irradiation of Ru₃(CO)₁₂ or Os₃(CO)₁₂ in the presence of 1 gave tetracarbonyl [(1R,2R, 3S,4S)-2,3-η-(5,6-dimethylidene-7-oxabicyclo[2.2.1]-hept-2-ene)]ruthenium ( 6 ) or -osmium ( 8 ). Similarly, irradiation of Cr(CO)₆ or W(CO)₆ in the presence of 1 gave pentacarbonyl[(1R, 2R, 3S,4S)-2,3-η-(5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene)]chromium (10) or -tungsten (11) . Irradiation of complexes 6 and 11 in the presence of 1 led to further CO substitution giving bed-tricarbonyl-ae-bis[(1R,2R,3S,4S)-2,3-η-(5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene)]ruthenium ( 7 ) and trans-tetracarbonyl[(1R,2R,3S,4S)-2,3-η-(5,6-dimethylidene-7-oxabicyclo-[2.2.1]hept-2-ene)]tungsten (12) , respectively. The diosmacyclobutane derivative cis-m?-[(1R,3R,3S,4S)-(5,6-dimethylidene-7-oxabicyclo[2.2.1]hepta-2,3-diyl)]bis(tetracarbonyl-osmium) (Os-Os) (9) wa also obtained. The Diels-Alder reactivity of the exocyclic s-cis-butadiene moiety in complexs 7 and 8 was found to be significantly higher than that of the free triene 1 .     

Diels-Alder Regioselectivity Controlled by Remote Substituents. The Cycloadditions of 1-(Dimethoxymethyl)-2,3-dimethylidene- and -2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptanes

The syntheses of 2,3-dimethylidene- and 2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptanes substituted in position C(1) are reported. The 1-dimethoxymethyl group in derivatives 2 and 6 controls the regioselectivity of the Lewis-acid-catalyzed Diels-Alder additions with methyl vinyl ketone and butynone. For the EtAlCl₂-catalyzed addition of methyl vinyl ketone to 6 , the regioselectivity can be reversed by a small solvent modification. The tetraene 2 is a versatile reagent for regioselective ‘tandem’ cycloadditions.     

Crystal and Molecular Structure of Tricarbonyl-[(1R*, 4S*, 4aS*, 9aR*)-1,4-epoxy-2, 3-dimethylidene-1,2,3,4,4a,9,9a,10-octahydroanthracene]iron

The thermal cyclodimerization of 5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene assisted by Fe₂ (CO)₉ gives the title complex 1 , a precursor for the synthesis of antitumoral anthracyclinones. The crystal structure of 1 has been determined by X-ray diffraction: a = 11.188 (1); c = 26.968 (3) Å; space group tetragonal, P4₁2₁2, Z = 8; R = 0.041; R_W = 0.033. The tricarbonyliron group is in the exo-position and the coordination polyhedron is tetragonal pyramidal. The NMR coupling constants are well-related to the observed dihedral angles between the non-aromatic protons and now give a reliable criterion for assigning the stereochemistry of the metal in d⁸-complexes of 2,3-dimethylidene-7-oxanorbornane derivatives.     

Cyclodimerization of 1-(Dimethoxyniethyl)-5,6-dimethylidene-7-oxa-bicyclo[2.2.1]hept-2-ene Induced by Nonacarbonyldiiron. Crystal Structure of (1RS, 2SR, 3RS, 4RS, 4aRS, 9aSR)- Tricarbonyl[C, 2,3, C-η-(1,4-epoxy-1,5-bis(dimethoxymethyl)-2,3-dimethylidene-1,2,3,4,4a,9,9a,10-octahydroanthracene)]iron

The transition-metal-carbonyl-induced cyclodimerization of 5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene is strongly affected by substitution at C(1) While 5,6-dimethylidene-7-oxabicyclo[2.2.1]hept–2-ene-l-methanol ( 7 ) refused to undergo [4 + 2]-cyclodimerization in the presence of [Fe₂(CO)⁹] in MeOH, 1-(dimethoxymethyl)-5,6-di-methylidene-7-oxabicyclo[2.2.1]hept-2-ene ( 8 ) led to the formation of a 1.7:1 mixture of ‘trans’ ( 19, 21, 22 ) vs. ‘cis’ ( 20, 23, 24 ) products of cyclodimerization together with tricarbonyl[C, 5,6, C-η-(l-(dimethoxymethyl)-5,6-di-methylidenecyclohexa-1,3-diene)]iron ( 25 ) and tricarbonyl[C,3,4, C-η-(methyl 5-(dimethoxymethyl)-3,4-di-methylidenecyclohexa-1,5-diene-l-carboxylate)]iron ( 26 ). The structures of products 19 and of its exo ( 21 ) and endo ( 22 ) [Fe(CO)₃(1,3-diene)]complexes) and 20 (and of its exo ( 23 ) and endo (24) (Fe(CO)₃(1,3-diene)complexes) were confirmed by X-ray diffraction studies of crystalline (1RS, 2SR, 3RS, 4RS, 4aRS, 9aSR)-tricarbonyl[C, 2,3, C-η-(1,4-epoxy-1,5-bis(dimethoxymethyl])-2,3-dimethylidene-1,2,3,4,4a,9,9a,10-octahydroanthracene)iron ( 21 ). In the latter, the Fe(CO)₃(1,3-diene) moiety deviates significantly from the usual local C_s symmetry. Complex 21 corresponds to a ‘frozen equilibrium’ of rotamers with η-alkyl, η³-allyl bonding mode due to the acetal unit at the bridgehead centre C(1).     

Stereoselective Synthesis of 2,4,6-Trimethylcyclohex-4-ene-1,3-diol Derivatives and of polypropionate fragments with four contiguous stereogenic centers

The Diels-Alder adduct (±)- 3 of 2,4-dimethylfuran and 1-cyanovinyl acetate was converted stereoselectively into benzyl 6-(4-chlorophenylsulfonyl)-1,3-exo,5-trimethyl-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl ( 26 ) and -2-endo-yl ether ( 36 ). Addition of LiAlH₄ to the latter led to the 3-O-benzyl derivatives 28 and 37 of (1RS,2SR,3SR,6SR)- and (1RS,2SR,3RS,6SR)-5-(4-chlorophenylsulfonyl)-2,4,6-trimethylcyclohex-4-ene-1,3-diol, respectively. Methylenation of 6-exo-(4-chlorophenylthio)-1-methyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-one ( 16 ), obtained by reaction of (±)- 3 with 4-Cl-C₆H₄SCl and saponification gave, 6-exo-(4-chlorophenylthio)-1-methyl-3,5-dimethylidene-7-oxabicyclo [2.2.1]heptan-2-one ( 43 ), the reduction of which with K-Selectride afforded 6-exo-(4-chlorophenylthio)-1,3-endo-dimethyl-5-methylidene-7-oxabicyclo[2.2.1]heptan-2-endo-ol ( 44 ). The 3-O-benzyl derivative 48 of (1RS,2RS,3RS,6SR)-5-(4-chlorophenylsulfonyl)- 2,4,6-trimethylcyclohex-4-ene-1,3-diol was derived from 44 via based-induced oxa-ring opening of benzyl 6-endo-(4-chlorophenylsulfonyl)-1,3-endo-5-endo-trimethyl-7-oxabicyclo[2.2.1]hept-2-endo-yl ether ( 49 ). Benzylation of 28 , followed by reductive desulfonylation and oxidative cleavage of the cyclohexene moiety afforded (2RS,3SR,4RS,5RS)-3,5-bis(benzyloxy)-2,4-dimethyl-6-oxoheptanal ( 32 ).     

Interaction between Exocyclic s-cis-Butadiene and Homoconjugated Functions. Preparation and Diels-Alder Reactivity of Remotely Substituted 2,3-Dimethylidenebicyclo[2.2.2]octanes

The preparations of 5,6-dimethylidene-2exo-bicyclo[2.2.2]octanol ( 8 ), its endo isomer 9 , 5,6-dimethylidene-2-bicyclo[2.2.2]octanone ( 10 ) and 2 exo, 3 exo-epoxy-5,6dimethylidenebicyclo[2.2.2]octane ( 11 ) are described. The kinetics of their cycloaddition to tetracyanoethylene has been measured in toluene at 25° together with those of 2,3-dimethylidenebicyclo[2.2.2]octane ( 7 ) and 5,6-dimethylidenebicyclo[2.2.2]oct-2-ene (12). The effects of remote substitution on the Diels-Alder reactivity of 2,3-dimethyl idenebicyclo[2.2.2]octanes are compared with those observed in the 2,3-dimethylidenenorbornane series ( 1–6 ).     

Exo- und endo-Tricarbonyleisenkomplexe von bicyclischen 2,3-Dimethylidenverbindungen

Exo- and endo-Tricarbonyliron Complexes of Bicyclic 2,3-Dimethylidene Compounds. The preparation of exo- and endo-tricarbonyliron complexes (exo- and endo- 5 , -6 , -8 , and 9 ) of 2,3-dimethylidene-5-bicyclo[2.2.1]heptene( 1 ), -bicyclo[2.2.1]-heptane ( 2 ), -5-bicyclo[2.2.2]octene ( 3 ) and -bicyclo[2.2.2]octane ( 4 ) is described. The complexes are obtained by thermal reaction of the bicyclic butadienes with di-ironenneacarbonyl in hexane solution. exo- and endo- 5 are also formed photochemically from ironpentacarbonyl and 1 in pentane solution at ?35°. The structural assignment of exo- and endo -5 and -6 is based on their mass-spectra and on coordination shifts in ¹H- and ¹³C-NMR.-spectra exo- and endo -6 are correlated with exo- and endo -5 , respectively, by hydrogenation. Hydrogenation of the uncomplexed double bond in exo- and endo -5 occurs in both complexes from the exo side as shown by deuteration experiments. The free ligand 1 reacts in the same stereospecific manner.     

Conformational Analysis of Endoperoxides Grafted onto Bicyclo[2.2.n]alkanes as a Test of the Rigidity of the Bicyclic Skeleton. Photo-oxidation of [2.2.2] Hericene and 2,3,5,6-Tetramethylidenebicyclo[2.2.n]alkanes

The photo-oxidation of [2.2.2]hericene ( 6 ) gave successively the endoperoxides 11 (9,10,11,12-tetramethylidene-4,5-dioxatricyclo[6.2.2.0^2,7]dodec-2(7)-ene), the bis-endoperoxide 16 (15,16-dimethylidene-4,5,11,12-tetraoxatetracyclo[6.6.2.0^2,7.o^9,14]hexadeca-2(7),9(14)-diene), and the tris-endoperoxide 19 (4,5,11,12,17,18-hexaoxapentacyclo[6.6.6.0^2,7.0^9,14.0^15,20]icosa-2(7),9(14),15(20)-triene). The endoperoxides 11, 16 , and 19 were formed in the presence or in the absence of a dye sensitizer. The sensitized photo-oxidations of 2,3,5,6-tetramethylidenebicyclo[2.2.2]octane ( 4 ), 5,6,7,8-tetramethylidenebicyclo[2.2.2]oct-2-ene ( 5 ), 2,3,5,6-tetramethylidenebicyclo[2.2.1]-heptane ( 7 ), and 2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane ( 8 ) gave successively the corresponding mono-endoperoxides 9, 10, 12 , and 13 and the bis-endoperoxides 14, 15, 17 , and 18 , respectively. Low-temperature NMR spectra of the bis-endoperoxides 14 and 16 indicated that their C₂ and C_s conformers have the same stability. Similarly, there was no difference in the enthalpy of the D₃ and C₂ conformers of the tris-endoperoxide 19 . The following reactivity sequence was observed for the sensitized photo-oxidations of 6–8 and 5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene ( 23 ): 6 + ¹O₂→ 11 > 7 + ¹O₂→ 12 > 8 + ¹O₂→ 13 > 23 + ¹O₂→ 24 , a trend parallel with that reported for the ethylenetetracarbonitrile (TCNE) cycloadditions to the same polyenes. The rate-constant ratios k₁/k₂ and k₂/k₃ for the three successive photo-oxidations of [2.2.2]hericene ( 6 ) did not differ significantly from unity, in contrast with the Diels-Alder additions of 6 . Similarly, the rate-constant ratios k₁/k₂ for the two successive photo-oxidations of tetraenes 7 and 8 were significantly smaller than those reported for the successive TCNE cycloadditions to 7 to 8 . The endoperoxide formations are not sensitive to the change in the exothermicity of the reactions but they are sensitive to the electronic properties (IP's) of the polyenes.     

The Circular Dichroism of 5,6-Dimethylidene-2-bicyclo[2.2.n]alky Esters. Chiral Exciton Coupling between Benzoate and Exocyclic s-cis-Butadiene Chromophores

The optically pure aryl-substituted 5,6-dimethylidene-2-bicyclo[2.2.1]heptyl benzoates 12–21 were prepared; their UV absorption and CD spectra are reported. The (?)-(1S,2S)-esters 17–21 with carbonyl groups in endo-position exhibit typical excitonsplit Cotton effects whereas the corresponding (?)-(1S,2R)-esters 12 - 16 with carbonyl groups in exo-position do not present such effects. The chiral exciton coupling between the exocyclic diene and a remote p-substituted benzoate chromophore can be used for unambiguous assignment of the absolute configuration of 5,6-dimethylidene-2-endo-bicyclo[2.2.1]heptyl derivatives. The method is applied to establish the absolute configuration of 5,6-dimethylidene-2-exo and -2-endo-bicyclo[2.2.2.]octyl p-bromobenzoates (?)- 24 and (?)- 25 .     

New Dienophiles: 1-Acetylvinyl Arenecarboxylates. Reactivity toward cyclopentadiene and exocyclic dienes

The preparations of 1-acetylvinyl arenecarboxylates H₂C=C(COCH₃)OCOR with R = phenyl, p-nitrophenyl, 2,4-dinitrophenyl, α- and β-naphthyl are described (3) . The Diels-Alder reactivity of these dienophiles toward cyclopentadiene is evaluated and compared with that of methyl vinylketone, 3-trimethylsilyloxy-, 3-ethoxy- and 3-acetoxy-3-buten-2-ones. The stereoselectivity of the cycloadditions of these dienophiles with 2,3,5,6-tetramethylidene-7-oxanorbornane (1) and 5,8-dimethoxy-1,4-epoxy-2,3-dimethylidene-1,2,3,4-tetrahydroanthracene (2) is studied. In principle, the dienophiles 3 allow direct functionalization of the position C(9) of the A-ring of daunomycinone analogs by Diels-Alder additions to exocyclic dienes such as 1 and 2 .     

Inductive and Polarizability Effects of an Exocyclic Diene-Iron Tricarbonyl Group. The acetolyses of exo- and endo-irontricarbonyl complexes of 5,6-dimethylidene-2-exo-norbornyl and 2,3-dimethylidene-7-anti-norbornyl parabromobenzenesulfonates

The exo- and endo-irontricarbonyl complexes of 5,6-dimethylidene-2-exo-norbornyl alcohols 10x, 10n , p-bromobenzenesulfonates 11x, 11n , acetate 12x and of the 2,3-dimethylidene-7-anti-norbornyl alcohols 17x, 17n , p-bromobenzenesulfonates 19x, 19n and acetates 20x, 20n have been prepared. The S_N1 buffered acetolyses of 11x, 19x and 19n gave 12x, 20x and 20n , respectively (retention of configuration). The first-order rate constants of the acetolyses have been evaluated and compared with those of the acetolyses of the uncomplexed 5,6-dimethylidene-2-exo-norbornyl ( 14 ) and 2,3-dimethylidene-7-anti-norbornyl p-bromobenzenesulfonates ( 18 ). A rate retardation effect of ca. 1.5 · 10⁵ was measured for 11x → 12x (65°) compared with the acetolysis of 14 . The retardation effect is larger (> 5 · 10⁷) with 11n . Contrastingly, the acetolysis 19x → 20x was slightly accelerated with respect to that of the uncomplexed p-bromobenzenesulfonate 18 . An unsignificant rate-retardation effect was measured for the acetolysis 19n → 20n . The results are interpreted in terms of competitive inductive destabilization and charge-induced dipole stabilizing interaction by the exocyclic diene-iron tricarbonyl fragment. PMO. arguments give a rationale for the difference in polarizability between the diene-Fe(CO)₃ group in 19 and that in the endo-7-norbornadienyl-iron tricarbonyl system.     

Stereochemical studies. 58. Saturated heterocycles. 39. Preparation and steric structures of dihydro-1,3-oxazines, 1,3-oxazin-2-ones and 1,3-oxazine-2-thiones fused with norbornane and norbornene

3-endo-Aminobicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid ( 1 ), prepared from endo-norborn-5-ene-2,3-dicarboxylic acid anhydride, and the analogous saturated cis-exo-amino acid ( 3 ) were reduced with lithium aluminum hydride to the aminoalcohols 2 and 4 ; the latter were cyclized by means of arylimino ethers to methylene-bridged tetrahydro- ( 6a-c ) and hexahydro-3,1-benzoxazines ( 7b-d ), respectively. The endo ( 2 ) and exo ( 4 ) aminoalcohols were converted to methylene-bridged tetrahydro-3,1-benzoxazin-2-one ( 9 ) and hexahydro-3,1-benzoxazin-2-one ( 12 ) with ethyl chloroformate and sodium methoxide; treatment of the alcohols with carbon disulfide gave, via the dithiocarbamates, the corresponding 2-thiones ( 11, 13 ). The structures were confirmed by ir and nmr spectroscopy.     

Reactions of p-Nitrophenyloxirane with Amines Containing Fragments with Bicyclic Skeleton

Reactions of p-nitrophenyloxirane with amines containing fragments with bicyclic skeleton of norbornene, norbornane, epoxynorbornane (stereoisomeric exo- and endo-5-aminomethylbicyclo[2.2.1]hept-2-enes, N-benzyl-endo-5-aminomethylbicyclo[2.2.1]hept-2-ene, endo-5-(2-aminoethyl)bicyclo[2.2.1]hept-2-ene, stereoisomeric exo- and endo-2-aminomethylbicyclo[2.2.1]heptanes, 2-(1-aminoethyl)bicyclo[2.2.1]heptane, exo-5-aminomethyl-exo-2,3-epoxybicyclo[2.2.1]heptane) were investigated. The aminolysis of p-nitrophenyloxirane occurred regioselectively according to Krasusky rule as was proved by ¹H and ¹³C NMR data. As shown by ¹H and ¹³C NMR spectroscopy the oxyalkylation product obtained from N-benzyl-endo-5-aminomethylbicyclo[2.2.1]hept-2-ene was composed of two diastereomers originating from the presence of a chiral nitrogen atom in the rear part of the rigid bicyclic skeleton. New products of amino groups transformation in the molecules of hydroxyamines were obtained by reaction with p-methylbenzoyl chloride and p-nitrophenylsulfonyl chloride. Regioselectivity of the attack of electrophilic reagents on the nitrogen in the hydroxyamines was confirmed by IR and ¹H NMR spectra of the products. The data on pharmacological activity tests of N-2-hydroxyethyl(p-nitrophenyl)-5-aminomethylbicyclo[2.2.1]hept-2-ene are reported.     

Synthesis and Dehydration of endo-2-(3-R-Isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ols

endo-2-Ethynyl-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ol reacts with nitrile oxides, yielding endo-2-(3-R-isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ols. Treatment of the latter with methanesulfonyl chloride in pyridine leads to dehydration and formation of mixtures of the corresponding 1-(3-R-isoxazol-5-yl)-3,3-dimethyl-2-methylenebicyclo[2.2.1]heptanes and 2-(3-R-isoxazol-5-yl)-1,7,7-trimethylbicyclo[2.2.1]hept-2-enes at a ratio of 2:1.     

Ironcarbonyl Complexes of 5,6-Dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene Derivatives. Synthesis of Substituted Tricarbonyl(ortho-quinodimethane)iron Complexes and 2-Indanones

The l-dimethoxymethyl-5,6-dimethyldene-7-oxabicyclo[2.2.1]hept-2-ene ( 9 ) has been prepared. On treatment with Fe₂(CO)₉, the endocyclic double bond C(2)?C(3) was coordinated first giving the corresponding exo-Fe(CO)₄ complex 10 . The latter reacted with Fe₂(CO)₉ and afforded cis-heptacarbonyl-μ-[1RS,2SR,3RS,4SR,5RS,6SR-2,3-η: C5,6,C-η-(1-(dimethoxymethyl)-5,6-dimethylidene-7-oxabicyclo[2.2.1]hept-2-ene)]diiron ( 11 ) as a major product. On heating, 11 underwent deoxygenation of the 7-oxabicyclo[2.2.1]heptene moiety yielding tricarbonyl[C,5,6,C-η-(1-(dimethoxymethyl)-5,6-dimethylidenecyclohexa-1,3-diene)]iron ( 13 ). In MeOH, a concurrent, regioselective methoxycarbonylation was observed giving tricarbonyl[C,3,4,C-η-(methyl 5-(dimethoxymethyl)-3,4-dimethylidenecyclohexa-1,5-diene-1-carboxylate)]iron ( 14 ). Oxidative removal of the Fe(CO)₃ moiety in 13 and 14 did not afford the expected ortho-quinodimethane derivatives but led to CO insertions giving 2,3-dihydro-2-oxo-1Hindene-4-carbaldehyde ( 20 ) and methyl 7-formyl-2-3-dihydro-2-oxo-lH-indene-5-carboxylate ( 21 ), respectively.     

Interaction between Oxygen Lone-Pair Orbitals of Ether and α,β-Unsaturated Ketone Functions in 3,5,6-Trimethylidene-7-oxabicyclo[2.2.1]heptan-2-one and 3,6-Dimethylidene-7-oxabicyclo[2.2.1]heptane-2,5-dione: A PE-Spectroscopic Investigation

Controlled ozonolysis of 2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptane ( 1 ) afforded 3,5,6-trimethylidene-7-oxabicyclo[2.2.1]heptan-2-one ( 2 ). Ozonolysis of 2 gave a 1:1 mixture of 3,5-dimethylidene-7-oxa-bicyclo[2.2.1]heptane-2,6-dione ( 3 ) and 3,6-dimethylidene-7-oxabicyclo[2.2.1]heptane-2,5-dione ( 4 ). The He(Iα) photoelectron (PE) spectra of 2 and 4 have been recorded. Comparison with the PE data of related systems, and with the result of ab initio STO-3G calculations, confirm the existence of significant through-bond interactions between the oxygen lone-pair orbitals n(CO) of the carbonyl functions and n(O) of the O(7) ether bridge.     

Stereoselective ring-opening reactions with AcBr and AcCl. A new method for preparation of some haloconduritols

The actions of AcX (X=Br, Cl) on 7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetates and a transoid-epoxide prepared from the acetonide of cyclohexa-3,5-diene-cis-1,2-diol were studied. H₂SO₄-catalyzed cleavage of exo-cis-7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetate with AcCl gave (1α,2α,3α,6β)-6-chloro-4-cyclohexene-1,2,3-triol triacetate, from which the corresponding chloroconduritol was obtained by trans-esterification (MeOH/HCl). A similar reaction of the exo-diacetate with AcBr in the presence of H₂SO₄ resulted in bromine addition. The formation of bromine from the reaction of AcBr and H₂SO₄ was observed by independent experiments. H₂SO₄-catalyzed reaction of endo-cis-7-oxa-bicyclo[2.2.1]hept-5-ene-2,3-diol diacetate with AcX (X=Br, Cl) gave (1α,2α,3β,6β)-6-halo-4-cyclohexene-1,2,3-triol triacetates. The reaction of the transoid-epoxide with AcX (X=Br, Cl) with no catalyst gave also (1α,2α,3β,6β)-6-halo-4-cyclohexene-1,2,3-triol triacetates.     

Synthesis of (+)-1,3:2,5-dianhydroviburnitol ((+)-(1R,2R,3S,5R,6S)-4,7-dioxatricyclo[3.2.1.03,6]octan-2-ol)

Epoxidation of (?)-(1R,2R,4R)-2-endo-cyano-7-oxabicyclo[2.2.1]hept-5-en-2-exo-yl acetate ((?)-5) followed by saponification afforded (+)-(1R,4R,5R,6R)-5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptan-2-one ((+)-7). Reduction of (+)-7 with diisobutylaluminium hydride (DIBAH) gave (+)-1,3:2,5-dianhydroviburnitol ( = (+)-(1R,2R,3S,4R,6S)-4,7-dioxatricyclo[3.2.1.0^3,6]octan-2-ol; (+)-3). Hydride reductions of (±)-7 were less exo-face selective than reductions of bicyclo[2.2.1]heptan-2-one and its derivatives with NaBH₄, AlH₃, and LiAlH₄ probably because of smaller steric hindrance to endo-face hydride attack when C(5) and C(6) of the bicyclo-[2.2.1]heptan-2-one are part of an exo oxirane ring.     

Bis(trifluoromethyl)-containing 1-azatricycloheptanes

6-Substituted 7-halo-3,3-bis(trifluoromethyl)-2-azabicyclo[2.2.1]heptanes were synthesized by the addition of water, alcohols, and acetic acid to 3-halo-7,7-bis(trifluoromethyl)-1-azatricyclo[2.2.1.0^2,6]heptanes in the presence of H₂SO₄. 5,6-Disubstituted 3,3-bis(trifluoromethyl)-2-azabicyclo[2.2.1]heptanes were prepared by oxymercuration of 3,3-bis(trifluoromethyl)-2-azabicyclo[2.2.1]hept-5-ene.     

Acid-Catalyzed Rearrangements of 5,6-exo-Epoxy-7-oxabicyclo[2.2.1]hept-2-yl Derivatives. Migratory Aptitudes of Acyl vs. Alkyl Groups in Wagner-Meerwein Transpositions

In the presence of HSO₃F/Ac₂O in CH₂CL₂, 2-exo- and 2-endo-cyano-5,6-exo-epoxy-7-oxabicyclo[2.2.1]hept-2-yl acetates ( 6a , b ) gave products derived from the epoxide-ring opening and a 1,2-shift of the unsubstituted alkyl group (σ bond C(3)–C(4)). In contrast, under similar conditions, the 5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptan-2-one ( 6c ) gave 5-oxo-2-oxabicyclo[2.2.1]heptane-3,7-diyl diacetates 20 and 21 arising from the 1,2-shift of the acyl group. Acid treatment of 5,6-exo-epoxy-2,2-dimethoxy-7-oxabicyclo[2.2.1]heptane ( 6d ) and of 5,6-exo-epoxy-2,2-bis(benzyloxy)-7-oxabicyclo[2.2.1]heptane ( 6e ) gave minor products arising from epoxide-ring opening and the 1,2-shift of σ bond C(3)–C(4) and major products ( 25 , 29 ) arising from the 1,3-shift of a methoxy and benzyloxy group, respectively. Under similar conditions, 5,6-exo-epoxy-2,2-ethylenedioxy-7-oxabicyclo[2.2.1]heptane ( 6f ) gave 1,1-(ethylenedioxy)-2-(2-furyl)ethyl acetate ( 32 , major) and a minor product 33 , arising from the 1,2-shift of σ bond C(3)–C(4). The following order of migratory aptitudes for 1,2-shifts toward electron-deficient centers has been established: acyl > alkyl > alkyl α-substituted with inductive electron-withdrawing groups. This order is valid for competitive Wagner-Meerwein rearrangements involving equilibria between carbocation intermediates with similar exothermicities.