Base-promoted acyloin rearrangement of 1,8-di-tert-butyldimethylsilyloxybicyclo[2.2.2]oct-5-en-2-ones

Treatment of 1,8-di-tert-butyldimethylsilyloxybicyclo[2.2.2]oct-5-en-2-ones having an electron-withdrawing group such as a nitro, formyl, cyano, and imido group at C-7 with a strong base (potassium hydride, or potassium bistrimethylsilylamide, etc.), resulted in an acyloin rearrangement reaction accompanied by retention of two silyloxy groups to afford 1,8-disilyloxybicyclo[3.2.1]oct-3-en-2-ones.     

Die Synthese von 4-substituierten Bicyclo[2.2.2]oct-1-yl-p-nitrobenzolsulfonaten

Synthesis of 4-Substituted Bicyclo[2.2.2]oct-1-yl-p-Nitrobenzenesulfonates The syntheses of the 4-substituted bicyclo[2.2.2]oct-1-yl-p-nitrobenzenesulfonates 1a–2s are described.     

Alkoxide-Accelerated [1,3] Sigmatropic Shift of Bicyclo[3.2.1]oct-6-en-2-ols to 8-endo-Hydroxybicyclo[3.3.0]oct-2-en-4-ones

Bicyclo[3.2.1]oct-6-en-2-ols 6 are shown to undergo [1,3] sigmatropic shift to afford 8-endo-hydroxy-bicyclo[3.3.0]oct-2-en-4-ones 8 under the influence of potassium hydride.     

β-Cleavage of Potassium Bicyclo[2.2.2]oct-5-en-2-olates. Stereoselective synthesis of (±)-trichodiene

The transformations of 12 bicyclo[2.2.2]oct-5-en-2-ols ( V or VI ) to 3-(cyclohex-3-enyl)-2-alkanones ( III or IV ), via β-cleavage of their potassium alkoxides in HMPA, has been investigated (cf. Table 1). As an illustration of this synthetic methodology, a stereoselective synthesis of (±)-trichodiene ((±)- 1 ) is described which involves the β-cleavage of the tricyclic potassium alkoxides 46a and 47a to cyclopentanone 4 (cf. Scheme 7).     

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.     

Fragmentation of Homoallylic Alkoxides. Thermolysis of potassium 2-substituted bicyclo [2.2.2]oct-5-en-2-alkoxides

Thermolysis of the potassium 2-substituted bicyclo [2.2.2]oct-5-en-2-alkoxides derived from alcohols 2–17 at 90–120° in hexamethylphosphoric triamide affords unsaturated ketones resulting from allylic bond cleavage. The mechanistic and synthetic aspects of this anionic fragmentation are discussed with reference to the formation of 1-(3′-cyclohexenyl)-2-alkanones 18–28 via initial heterolytic C(1), C(2)-bond cleavage in the substrate alkoxide and regioselective, intramolecular protonation of the resultant transient allylic anion.     

The Non-planarity of the Bicyclo[2.2.1]hept-2-ene Double bond. Crystal Structures of Bicyclo[2.2.2]oct-2-ene,Bicyclo[2.2.1]hept-2-ene,and Bicyclo[2.1.1]hex-2-ene Systems

The crystal structures of (1R,4R,5S,8S)-9,10-dimethylidentricyclo[6.2.1.0^2,7]undec2(7)-ene-4,5-dicarboxylic anhydride ( 3 ), (1R,4R,5S,8S)11-isopropylidene-9,10-dimethylidenetricyclo[6.2.1.m^2,7]undec-2(7)-ene-4,5-dicarboxylic anhydride ( 6 ), (1R,4R,5S8S)-9,10-dimethylidenetricyclo[6.2.2.0^2,7]dodec-2(7)-ene-4,5-dicarboxylic anhydride ( 9 ), (1R4R5S8S)-TRICYCLO[6.2.2.0^2,7]dodeca-2(7), 9-diene-4,5-dicarboxylic anhydride ( 12 ) and (4R,5S)-tricyclo[6.1.1.0^2.7]dec-2(7)-ene-4,5-dicarboxylic acid ( 16 ) were established by X-ray diffraction. The alkyl substituents onto the endocyclic bicyclo[2.2.1]hept-2-ene double bond deviate from the C(1), C(2), C(3), C(4), plane by 13.5°4 in 3 and by 13.9° in 6 , leaning toward the endo-face. No such out-of-plane deformations were observed with the bicyclo[2.2.2]oct-2-ene derivatives 9 and 12 . The exocyclic s-cis-butadiene moieties in 3, 6 and 9 do not deviate significantly from planarity. The deviation from planarity of the double bond n bicyclo[2.2.1]hept-2-ene derivatives and planarity in bicyclo[2.2.2]oct-2-ene analogues is shown to be general by analysis of all known structures in the Cambridge Crystallographic Data File. The non-planarity of the bicyclo[2.2.1]hept-2-ene double bond cannot be attributed only to bond-angle deformations which would favour rehybridizatoin of the olefinic C-atoms since the double bond in the more strained bicyclo[2.1.1]hex-2-ene drivative 16 deviates from planarity by less than 4°.     

Facial selectivity in the nucleophilic additions of vinylmagnesium bromide to bicyclo[2.2.2]oct-5-en-2-one derivatives

The levels of diastereoselection attainable by addition of vinylmagnesium bromide to a selection of bicyclo[2.2.2]octenone derivatives 1-6 in the presence of various Lewis acids such as LiBr, CeCl3, TiCl4, ZnBr2, MgBr2, and Et2AlCl have been determined. The 1,2-addition of ketone 1 with vinylmagnesium bromide in THF provided a mixture of anti- and syn-isomers. The reactions of 2 with vinylmagnesium bromide at room temperature afforded anti- and syn-isomers with preference to anti-isomers in most cases. These reactions in the presence of Lewis acids afforded anti-isomers as the major product with an excellent stereoselectivity or as single isomers in some cases. The ketones 3 gave surprisingly different results providing anti-isomers predominantly even in the presence of Lewis acids. The bicyclic ketones 4 and 5 and all-carbon tricyclic ketone 6 furnished the syn-isomer as the main product. There is no significant effect of Lewis acid catalysis in the nucleophilic addition reactions of 1, 4, 5, and 6. The use of a preformed vinylmagnesium bromide-CeCl3 reagent for the addition reactions of 2d-f and 3d-f provided almost exclusively syn-isomers. The substituents and reaction conditions can influence facial selectivity in the nucleophilic additions to the bicyclo[2.2.2]oct-5-en-2-one derivatives.     

Stereochemical dependence of13C-shift and31P-13C-coupling in 3-substituted bicyclo[2.2.1]hept-5-en-2-yl- and bicyclo[2.2.2]oct-5-en-2-yl-phosphonates

Steric influences operating on¹³C-shifts and³¹P-¹³C-coupling constants have been investigated on phosphonates with a rigid framework.

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Stereochemische Abhängigkeit von¹³C-Verschiebungen und³¹P-¹³C-Kopplungskonstanten in 3-substituierten Bicyclo[2.2.1]hept-5-en-2-yl- und Bicyclo[2.2.2]oct-5-en-2-yl-phosphonaten

Zusammenfassung Der sterische Einfluß auf¹³C-Verschiebungen und³¹P-¹³C Kopplungskonstanten wurde an Phosphonaten mit starrer Struktur untersucht.

     

Polar Effects. Part 14. Inductive Charge Dispersal in Bicyclo[2.2.2]oct-1-yl Cations

The rate constants (log k) for solvolysis of 2-, 3-, and 4-substituted bicyclo[2.2.2]octyl p-nitrobenzenesulfonates 10, 11 and 12 , respectively, correlate linearly with the corresponding inductive substituent constants s?. The formation of the ion pairs 9 is, therefore, controlled by the I effect of neighboring substituents. It follows from the corresponding reaction constants ρ₁ of ?1.54, ?1.12, and ?1.22 that inductivity is highest at the positions α to C(1). It is lower and practically equal at the β- and γ-positions. Therefore, charge dispersal is similar to that previously observed in the quinuclidinium ion 7 .     

The Carbonyl Group as Homoconjugated Electron-Releasing Substituent. Regioselective electrophilic additions at bicyclo[2.2.1]hept-5-en-2-one,bicyclo[2.2.2]oct-5-en-2-one,and derivatives

In CHCl₃, CH₃CN, or AcOH, benzeneselenenyl chloride (PhSeCl), bromide (PhSeBr), and acetate (PhSeOAc), 2-nitrobenzenesulfenyl chloride (NO₂C₆H₄SCl), and 2,4-dinitrobenzenesulfenyl chloride ((NO₂)₂C₆H₃SCl) added to bicyclo[2.2.1]hept-5-en-2-one ( 5 ) in an. anti fashion with complete stereo- and regioselectivity, giving adducts 20–24 in which the chloride, bromide, or acetoxy substituent (X) occupies the endo position at C(6) and the Se- or S-substituent (E) the exo position at C(5), The addition 5 + (NO₂)₂C₆H₃SCl→ 24 was accompanied by the formation of (1RS, 2RS)-2-(2,4-dinitrophenylthio)cyclopent-3-ene-l-acetic acid ( 25 ). The latter was the major product in AcOH containing LiClO₄. The additions of PhSeCl and PhSeBr to bicyclo[2.2.2]oct-5-en-2-one ( 6 ) were less stereoselective (proportion of exo vs. endo mode of electrophilic attack was ca. 3:1) but highly regioselective gazing adducts 27/28 and 29/30 , respectively, the regioselectivity being the same as that of the electrophilic additions of 5 . The reaction of PhSeCl with a 4:1 mixture of 2-exo-chloro- and 2-endo-chlorobicyclo[2.2.1]hept-5-ene-2-carbonitriles ( 12 ) was slower than addition 5 + PhSeCl; it gave adducts 31/32 (4:1) in which the PhSe moiety occupies the exo position at C(6) and the Cl atom the endo position at C(5). The addition of PhSeCl to 2-chlorobicyclo[2.2.1]oct-5-ene-2-carbonitriles ( 13 ) was very slow and gave adducts with the same regioselectivity as 12 + PhSeCl, but opposite with that of reactions of the corresponding enones 5 and 6 . PhSeX (X = Cl, Br, OAc) added to 2-cyanobicyclo[2.2.1]hept-5-en-2-yl acetates ( 14 ) with the same regioselectivity as 12 + PhSeCl. The additions of PhSeCl, PhSeBr, NO₂C₆H₄SCl, and (NO₂)₂C₆H₃SCl to 2-(bicyclo[2.2.1]hept-5-en-2-ylidene)propanedinitrile ( 49 ) were not regioselective, showing that a dicyanomethylidene function is not like a carbonyl function when homoconjugated with a π system. The results are in agreement with predictions based on MO calculations suggesting that a carbonyl group homoconjugated with an electron-deficient centre can behave as an electron-donating, remote substituent because of favourable n(CO)?σC(1), C(2)?p(C(6) hyperconjugative interaction.     

Thermal rearrangement of 2-oxabicyclo[2.2.2]oct-5-eno-3-carboxylic acids

The decarboxylation of 2-oxabicyclo[2.2.2]oct-5-eno-3,3-dicarboxylic acid, obtained by hydrolysis of the Diels-Alder adduct of diethyl mesoxalate with cyclohexa-1,3-diene, gave two stereoisomeric γ-lactones of 2-hydroxy-1,2,5,6-tetrahydromandelic acid.     

Stereoselectivity of the reaction of mercuric acetate with dimethyl bicyclo[2.2.2]oct-2-en-5,6-cis-endo-dicarboxylate

The stereoselelectivity of the reaction of mercuric acetate with dimethyl bicyclo[2.2.2]oct-2-en-5, 6-cis-endo-carboxylate in acetic acid was studied. One of the reaction products is formed when the reagent attacks the double bond from the sterically less accessible side. The nature of the orientation effect of the carboxylate groups is discussed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1646–1648, September, 1993.     

Photochemical reaction of 5-dicyanomethylenebicyclo[2.2.2]oct-2-ene as a model for a light-energy conversion and storage system

Upon irradiation, 5-dicyanomethylenebicyclo[2.2.2]octene ($\text{3}$) gives a highly strained compound, 2,2-dicyanotricyclo[4.2.1.0^1,3]nonene ($\text{6}$) in good yield. Of additional interest is the observation that the starting material $\text{3}$ can be quantitatively regenerated from the photo-product $\text{6}$ with release of 28.8 kcal/mol.     

Rearrangements initiated by trimethylsilyl iodide: ready deoxygenative rearrangement of bicyclo[4.2.0]octane-2,5-diones to bicyclo[3.3.0]oct-1(5)-en-2-ones

Reaction of bicyclo[4.2.0]octane-2,5-diones with trimethylsilyl iodide gave bicyclo[3.3.0]oct-1(5)-en-2-ones by a clean reductive rearrangement in good yields, providing a simple and effecient synthetic method for the enones.     

Synthese von Bicyclo[3.3.o]oct-1(5)en-2-on aus Cyclohexanon

Synthesis of Bicyclo[3.3.0]oct-1(5)en-2-one from Cyclohexanone Treatment of 2-nitrocyclohexanone ( 2 ) with acrylaldehyde yielded in the presence of tetrabutylammonium fluoride the bicyclic product 5 , which was oxidized to the nitro-diketone 3 . The conversion of 3 to the title compound 1 was achieved in the nearly quantitative yield under unusual conditions: K₂CO₃/H₂O and H₂SO₄. Compound 3 , was also converted to 1 (stepwise and one-pot reaction, respectively) by treatment with 1. NaOCH₃, 2. TiCl₃, and 3. H₂SO₄ (Scheme).     

Synthesis and Crystal Structure of 5-Amino-4-cyano-8-isobutyl-7-isopropyl-6-thiocarbamoyl-2-azabicyclo[2.2.2]oct-5-en-3-thione

5-Amino-4-cyano-8-isobutyl-7-isopropyl-6-thiocarbamoyl-2-azabicyclo[2.2.2]oct-5-en-3-thione was synthesized by the condensation of isovaleryl aldehyde with cyanothioacetamide. The structure of the product was established by X-ray crystallography.