Photochemical rearrangement of 8-oxabicyclo[3.2.1]oct-6-en-2-ones

Irradiation of 8-oxabicyclo[3.2.1]oct-6-en-2-ones results in a 1,3-acyl rearrangement. The initial photoproduct undergoes a subsequent reaction involving hydrogen transfer followed by intramolecular cycloaddition of a ketene intermediate.     

Stereoselective carbonyl reductions of chloro-substituted 8-oxabicyclo[3.2.1]oct-6-en-3-ones

The lithium aluminium hydride reduction of 2,2,4,4-tetrachloro-8-oxabicyclo[3.2.1]oct-6-en-3-one (8) was reinvestigated. In contrast to most halogeno-substituted oxabicyclic ketones, which give predominantly the corresponding endo alcohols, the expected (3endo)-2,2,4,4-tetrachloro-8-oxabicyclo[3.2.1]oct-6-en-3-ol (9n) is formed in a minute proportion. An X-ray structure analysis of the dominating product gave proof of the exo-alcohol, i.e., (3exo)-2,2,4,4-tetrachloro-8-oxabicyclo[3.2.1]oct-6-en-3-ol (9x). On the other hand, reduction of trichloroketone 11, 2,2,endo-4-trichloro-8-oxabicyclo[3.2.1]oct-6-en-3-one, and the methoxy-substituted chloroketones 13 and 14 provided the corresponding endo alcohols (12 and 15).     

Synthesis of the 5-hydroxymethyl-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one natural products descurainin and cartorimine

Reaction of pyranulose 6 with styrenes 12c or 13 and Et₃N in CH₂Cl₂ at 25 °C afforded the [5+2] cycloadducts 14c and 15, which were hydrolyzed to give the natural products 1 and descurainin (2) in 24 and 27% overall yield, respectively. Heating pyranulose 6 with cinnamate ester 21 in the presence of 2,6-di-t-butylpyridine in CH₃CN at 175 °C afforded the [5+2] cycloadduct, which was hydrolyzed to give cartorimine (3) in 13% yield.     

Conformations and reactions of bicyclo[3.2.1]oct-6-en-8-ylidene

Bicyclo[3.2.1]oct-6-en-8-ylidene (1) can assume either the conformation of "classical" carbene 1a or that of foiled carbene 1b in which the divalent carbon bends toward the double bond. Oxadiazoline precursors for the generation of 1 were prepared, followed by photochemical and thermal decomposition as well as flash vacuum pyrolysis (FVP) of a tosyl hydrazone sodium salt precursor, to give a number of rearrangement products. Matrix isolation experiments demonstrate the presence of a diazo intermediate and methyl acetate in all photochemical and thermal precursor reactions. The major product from rearrangements of "classical" bridged carbene 1a is bicyclo[3.3.0]octa-1,3-diene as a result of an alkyl shift, while dihydrosemibullvalene formed from a 1,3-C-H insertion. In contrast, thus far unknown strained bicyclo[4.2.0]octa-1,7-diene formed by a vinyl shift in foiled carbene 1b. The experimental results are corroborated by density functional theory (DFT), MP2, and G4 computations.     

Chiral Allyl Cations in Cycloadditions to Furan: Synthesis of 2-(1′-Phenylethoxy)-8-oxabicyclo[3.2.1]oct-6-en-3-one in High Enantiomeric Purity

Efficient shielding of the π face is offered by the phenyl group of the chiral auxiliary (TES=triethylsilyl) to the allyl cation generated at low temperature from 1 . This protection induces high π-facial selectivity and allows high chemical yield on the capture of the cation by furan to afford the title cycloadduct 2 .     

Highly Diastereoselective Aldol Reaction of Bicyclo[3.2.1]oct-6-en-3-ones and 8-Oxabicyclo[3.2.1]oct-6-en-3-ones. (E)-Selective conversion into α-alkylidene ketones

The bicyclic ketones 1–6 entered into diastereoselective (> 95% d.e.) aldol reactions with a variety of aldehydes (Scheme 1 and Table 1). A representative series of aldols was converted (E)-selectively into α,β-unsaturated ketones by (i) spontaneous base-promoted dehydration (Scheme 1 and Table 2) and also by (ii) conversion into brosylate and base-mediated elimination with lithium diisopropylamide/N,N,N′,N′-tetramethylethylenediamine (LDA/TMEDA; Scheme 2). The simple α-methylidene ketones 17a and 18a were obtained via oxidation of the phenylselenides 19 and 20 , respectively (Scheme 4). The tertiary aldol 27 was synthesized best by treatment of 1,3-diketone 26 with Me₄Zr (Table 4). In this fashion, the facile retro-aldol reaction of 27 was suppressed effectively.     

On the conformation of 8-substituted bicyclo [3.2.1] oct-6-en-3-ones

A series of 8-substituted bicyclo [3.2.1] oct-6-en-3-ones (of type i) possessing various R₁ and R₂ groups were prepared and characterized. The conformations of the possible isomers of 1-4 were assigned according to the following three methods: (a) NMR spectrum, (b) time averaged precise metal ion location within the Eu (dpm)₃-carbonylic compound complex, (c) UV spectra. Comparison of the chair and boat conformers by UV spectra showed that interactions between the double bonds and the carbonyl occurred in both cases, although to different extents, the ε being dependent on R₁ and R₂. The fore-mentioned interaction exists even in both series of the C₆C₇ dihydro derivatives.     

Synthesis and reactions of 2-aryl-8-oxabicycloc[3.2.1]oct-6-en-3-ones

A number of 1-aryl-1-bromopropanones have been prepared and converted into the corresponding oxyallyl carbocations. These were reacted with furan to produce the expected 2-aryl-8-oxabioyclo[3.2.1]oct-6-en-3-ones, as well as a number of interesting side-products. These included 3-aryl-propanoic acid esters produced via Favorskii rearrangements. Attempts to cleave the ether linkage in the cycloadducts using bromotrimethylsilane produced instead 1-aryl-3-furylpropanones in excellent yield.     

3-exo,3′-exo-(1R,1′R)-Bithiocamphor — a versatile source for functionally different 3,3′-bibornane derivatives, II. 1 An access to 3-exo,3′-exo-(1r,1′r)-bicamphor and related compounds

3-exo,3′-exo-(1R,1′R)-bicamphor (12) is obtained from 3-exo,3′-exo-(1R,1′R)-bithtiocamphor (3) by condensation with hydrazine hydrate followed by hydrolysis of the resulting dihydropyridazine 11. Deprotonation of 12 with NaH and subsequent treatment with potassium hexacyanoferrate (III) furnishes the 2,2′-dioxo-3,3′-bibornanylidene 13, whilst reduction of 12 with L1AlH₄ affords the 3,3′-biisoborneol 16. Further related transformations to various 2,2′-difunctional 3,3′-bibornane derivatives are described, which are could be of interest as chiral ligands     

3-exo,3′-exo-(1R,1′R)-Bithiocamphor — a versatile source for functionally different 3,3′-bibornane derivatives — I. Ring-closure reactions and prototropic rearrangements

The title compound 3, derived from (+)-camphor, allows preparatively useful conversions to be carried out at the 3,3′-bibornane skeleton. The reactions are characterized by steric factors. Despite the increasing steric strain in the bicyclic units, ring-closure reactions of 3 to born-2-ene anellated sulfur-heterocycles are possible, including the formation of the 1,2-dithiine (6), thiophene (11), and 1,2,3-trithiepine system (13), respectively. Compound 6 is distinguished by several unusual properties. In contrast to the normal behaviour of aliphatic thioketones, 3 cannot exist as enthiol. The latter and related intermediates are immediately stabilized by 1,5-prototropic rearrangements leading to bornylidene units e.g. in 16 and consecutive products.     

13C NMR spectra of 8-aryl-8-azabicyclo[3.2.1]oct-3-en-2-ones and related compounds

Carbon-13 NMR spectra of various 8-aryl-8-azabicyclo[3.2.1]oct-3-en-2-ones and other related compounds, including tropinone, were determined, and the predominant conformation at the bridgehead nitrogen was established. The full assignment of resonances from proton decoupled and coupled spectra was based on the analysis of the splitting pattern and characteristic chemical shifts. The use of the determined ¹³C NMR spectra in the assignment of ¹³C NMR data in related but more complicated structures is also proposed.     

Concise entry to both enantiomers of 8-oxabicyclo[3.2.1]oct-3-en-2-one based on novel oxidative etherification: formal synthesis of (+)-sundiversifolide

Both enantiomers of 8-oxabicyclo[3.2.1]oct-3-en-2-one (6) have been synthesized from 4-hydroxycyclohept-2-enone (3) on the basis of a novel oxidative cyclo-etherification using PhI(OH)OTs (Koser's reagent). (-)-(1S,5R)-8-Oxabicyclo[3.2.1]oct-3-en-2-one [(-)-6, 95% ee] was expeditiously transformed to (+)-sundiversifolide (1).