Bicyclo hexane derivatives

Based on his previous work on the catalytic double addition of diazo compounds to alkynes173 using Cp RuCl(COD),174 Dixneuf has developed an efficient one-step synthesis of alkenyl bicyclo[3.1.0]-hexane derivatives of type 163 from enyne precursors 162 (Scheme 43). The catalytic cycle starts with the formation of an Ru=CHR species. It then adds to an alkyne to form ruthenacyclobutene 166, which evolves into vinylcarbene 167. [2 + 2]-Cycloaddition of 167 gives ruthenacyclobutane 168. The novelty in this transformation is the subsequent reductive elimination to give 170 without leading to the formation of diene 169. This can be attributed to the steric hindrance of the CsMes-Ru group. 

Nickel(0)-catalyzed [2-1-2] cycloaddition of cyclobutene to bicyclopropylidene (1) gave rise to the bis(spirocyclopropane)-annelated bicyclo [2.2.0]hexane derivative 232, the main product was 1,5-cyclooctadiene (233), formed by dimerization of cyclobutene with subsequent rearrangement (Scheme 54) [8,144]. 

Kinetic studies for the thermolysis of the three 2,2,3,3-tetra-substituted bicyclo[2.2.0]hexane derivatives (see Table 7) also support a nonconcerted route via 1,4-diradical intermediates with slightly different conformations.173... 

A few natural products which contain the cyclopropyl ring have been synthesized through metal catalysed cyclopropanation using dicarbonyl diazomethanes. ( )-Cycloeudesmol 63, isolated from marine alga Chondria oppositiclada, was synthesized via a sequence involving a copper catalysed cyclopropanation of a-diazo-/8-ketoester 61 to give the key intermediate 62 (equation 73)1 7,108. Similarly, the bicyclo[3.1.0]hexane derivative 65 was synthesized from the corresponding a-diazo-/8-ketoester 64 via the catalytic method and was converted into ( )-trinoranastreptene 66 (equation 74)109. Intramolecular cyclopropanation of -diazo-/i-ketoesters 67 results in lactones 68 which are precursors to 1-aminocyclopropane-l-carboxylic acids 69 (equation 75)110. 

Table 1 Synthesis of 1 -phenyl-2-thia-6-aza-bicyclo[2.2.0]hexane derivatives...

Based on his previous work describing the catalytic double addition of di-azo compounds to alkynes [59], Dixneuf used Cp RuCl(cod) and worked out a simple synthesis of alkenyl bicyclo[3.1.0]hexane derivatives 75 from enyne precursors 74 (Scheme 33). The catalytic cycle starts with the formation of... 

CuCl-catalyzed decomposition of iodonium ylides prepared from -keto esters and diacetoxyiodobenzene, has been developed (equation 151). 1-Methylbenzvalene is obtained in a good yield by treating a mixture of lithium cyclopentadienide and 1,1-dichloroethane with butyllithium l The tandem cyclization substitution in l-selenyl-5-hexenyllithiums derived from corresponding selenacetals via selenium/lithium exchange produces bicyclo[3.1.0]hexane derivatives ... 

Oxidation of polyalkyl-substituted 1,2,5-hexatrienes with m-chloroperbenzoic acid produces bicyclo[3.1.0]hexan-2-one derivatives . Certain 1,4-dienes undergo homo-conjugative addition of phosphorus reagents to give 3-phosphabicyclo[3.1.0]hexane derivatives (equation 36) ... 

Klumpp, G. W., Schakel, M. Diradicals in the vinylcyclopropane rearrangement of bicyclo[3.1.0]hexane derivatives. Tetrahedron Lett. 1983, 24, 4595 598. 

The chemoselectivity of the reaction also depends on the nature of the amino group of the a-chloroenamine 9. Thus, compared to 9d with a pyrrolidino moiety, 9a with phenylmagnesium bromide gave preferentially the bicyclo[3.1.0]hexane derivative... 

Reductive dehalogenation with tin hydrides can be carried out without interference of a number of functional groups. However, a C-C double bond in a 1,5 relationship to the intermediate cyelopropyl radical can function as a trap and result in formation of bicyclo[3.1.0]hexane derivatives. Thus, treatment of l,l-dibromo-2-(but-3-enyl)cyclopropane with tributyltin hydride afforded a 15 85 mixture of l-bromo-2-(but-3-enyl)cyclopropane (13) and 1-bromo-2-methyl-bicyclo[3.1.0]hexane (12). Under similar conditions l-bromo-2,8,8-trimethyltricyclo-[3.2.1.0 ]octan-3-one (15) was obtained in 6% yield from an isomeric mixture of 7,7-dibromo-4-isopropenyl-l-methylbicyclo[4.1.0]hept-2-one the main product, isolated in 86% yield, was an isomerie mixture of 7-bromo-4-isopropenyl-l-methylbicyclo[4.1.0]hept-2-one (14). ... 

Potassium fluoride in a two-phase system was also efficient when 18-crown-6 was present as a phase-transfer catalyst. The desilylation by fluoride produced a 7-0x0 enolate which could be reacted with various electrophiles. Appropriately substituted bicyclo[3.1.0]hexane derivatives 42 and 44 have been used to study this reaction.a,/l-Unsaturated carbonyl compounds gave rise to the formation of Michael adducts, while treatment with triphenylvinylphos-phonium salts gave bicyclo[3.3.0]octenes 46 as the result of a subsequent intramolecular Wittig reaction. 

Lochynski, S., and Walkowicz, M., Stereochemishy of bicyclo[3.1.0]hexane derivatives. Part 14. Wittig reactions. Rearrangmcnent of bicyclo[3.1.0]hexane system to cyclohexane system, Pol. J. Chem., 56, 1333, 1982. 

Treating l-(morpholin-4-yl)cyclohexene with CBT in the presence of triethylamine yields bicyclo[3.1.0]hexane derivative 100 in 70% yield [94H(38)319], Reaction proceeds through the formation of an intermediate chlorinated enamine and subsequent elimination of chlorine followed by the addition of benzotriazole (Scheme 78). 

Summary The reactivity of some trichlorosilane-derived silazanes has been studied. Treatment of 2-amino-l,3-bis(trimethylsilyl)-l,3-diaza-2-silacyclopentane (2) with two equivalents of n-butyllithium results in the formation of its hexameric W,A-dilithium derivative 3, the structure skeleton of which is best described as a singly truncated but lithium-centered rhombic dodecahedron of eight lithium and five nitrogen atoms. Reduction of Si-Cl-containing silazanes with lithium alanate opens a straightforward access to aminoalanes. Bis[(tert-butylamino)chloroalane] (8), bis[(tert-butyl-amino)alane] (9), and l,3-di-/er/-butyl-lC7 , 3CT -diaza-2o , 60 -dialumina[2.1.1]bicyclo-hexane (10) have been synthesized and structurally characterized. 

Photolytic. Dehydrochlorination will occur after prolonged exposure to sunlight releasing hydrochloric acid (U.S. Department of Health and Human Services, 1989). Two compounds isolated from toxaphene, 2- xo,3- xo,5,5,6- (io,8,9,10,10-nonachloroborane and 2- xo,3- X(9,5,5,6- <7(9,8,10,10-octachloroborane were irradiated with UV light X >290 nm) in a neutral aqueous solution and on a silica gel surface. Both compounds underwent reductive dechlorination, dehydrochlorination and/or oxidation to yield numerous products including bicyclo[2.1.1]hexane derivatives (Parlar, 1988). 

Intramolecular photochemical cyclization of N-substituted-3-alIyloxy-5,5-di-methylcyclohexenones (312) gives 2-aza- or 2-oxa-bicyclo[2,l,l]hexane derivatives (313). The reaction is sensitized by benzophenone and quenched by piperylene or phenanthrene. The products of parallel addition (bicyclo[2,2,0]hexane derivatives) are not found. 

The 4-cyclohexenyl ion provides an example of the dependence of the extent of rearrangement on reaction conditions. Acetolysis of the tosylate gives considerable hydride shift to the more stable allylic ion as well as a little cyclization to a bicyclo[3.1.0]hexane derivative... 

Monnier, R, Castillo, D., Derien, S., Toupet, L., Dixneuf, R H. (2003). Addition of diazoaUcanes to enynes promoted by a ruthenium catalyst simple synthesis of alkenyl bicyclo[3.1.0]hexane derivatives. Angewandte Chemie — International Edition, 42, 5474-5477. 

Ikeda, H., Takasaki, T., Takahashi, Y, Konno, A., Matsumoto, M., Hoshi, Y, Aoki, T., Suzuki, T, Goodman, J., and Miyashi, T, Photoinduced electron-transfer Cope rearrangements of 3,6-diaryl-2,6-octadienes and 2,5-diaryl-3,4-dimethyl-l,5-hexadienes stereospecificity and an unexpected formation of the bicyclo[2.2.0]hexane derivatives,/. Org. Chem., 64,1640, 1999. 

Based on initial studies of Mazur, method B for the production of vitamin D metabolites and analogs has been nicely developed by several groups. In the Mazur approach, the vitamin D isomerized to the i-steroid 191, which can be modified at carbon C-1 and then subsequently back-isomerized under solvolytic conditions to afford la,25-dihydro-xyvitamin D3 or analogs. The studies presented here led to the separate production of bicyclo[3.1.0]hexane derivatives 192 in a chemoenzymatic synthetic approach to 191. 

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