Bicyclo nonanes synthesis

The potential of Fischer carbene complexes in the construction of complex structures from simple starting materials is nicely reflected in the next example. Thus, the reaction of alkenylcarbene complexes of chromium and tungsten with cyclopentanone and cyclohexanone enamines allows the di-astereo- and enantioselective synthesis of functionalised bicyclo[3.2.1]octane and bicyclo[3.3.1]nonane derivatives [12] (Scheme 44). The mechanism of this transformation is initiated by a 1,4-addition of the C -enamine to the alkenylcarbene complex. Further 1,2-addition of the of the newly formed enamine to the carbene carbon leads to a metalate intermediate which can... 

Two types of synthesis of this skeleton are reported depending on the positions of the sulfur introduced either at the bridge or at the bridgehead the former has been studied by Stetter s research group189-191 and the latter by Klages and Schmidt192 starting from bicyclo[3.3.1]nonane derivatives and cyclohexane derivatives, respectively. 

The mercuration-demercuration reaction of cw,cw-l,5-cyclooctadiene (3) has been widely studied in order to get some insight into the synthesis of 9-oxa and 9-azabicyclo-nonane derivatives. However, the results of the reaction have often been the subject of some controversy since the ratio of the two isomeric bicyclo[3.3.1]- [199 and 201] and [4.2.1]- [198 and 200] nonanes, after reduction (equation 166), strongly depended on the reaction conditions of the mercuration step168,169. 

Synthesis of twistane from a bicyclo[3.3.1]nonane precursor... 

The synthesis of twistane involving an intermediate of type D was reported in 1976 by Hamon and Young [2]. This synthetic approach constitutes a violation of Corey s rule number 4 (which refers to "perimeter" and "core bonds") and involves a bicyclo[3.3.1]nonane precursor in which the relative configuration of the C(6) side-chain is crucial if cyclisation is to occur. The cost of such a "violation" was relatively high and a great number of drawbacks are found in the original article. 

Graindorge and co-workers" reported the synthesis of 2,5,7,9-tetranitro-2,5,7,9-tetraaza-bicyclo[4.3.0]nonane-8-one (113) (K-56, TNABN) from the nitration of 2,5,7,9-tetraazabi-cyclo[4.3.0]nonane-8-one dihydrochloride (112) with dinitrogen pentoxide in absolute nitric acid, the latter obtained from the condensation of urea with l,4-diformyl-2,3-dihydroxy-piperazine (111) in hydrochloric acid. Treatment of (112) with nitronium tetrafluoroborate in nitromethane results in the nitration of the piperazine ring nitrogens only and the isolation of (114) in 86 % yield (Table 5.2). 

The direct synthesis of the fused ring compound (55) from the reaction of phosphorus trichloride with ethylamine hydrochloride has already been described (Scheme 16). Its N-methyl analogue (67) can be obtained from the reaction of (MeNPX)3 (X = Cl or Br) with heptamethyldisilazane (Scheme 19). The identification of the structures of these fused-ring compounds, which are structurally related to the bicyclo(3.3.1)nonane carbocycles, pose difficult problems. An example of their... 

Studies by the submitters have indicated that the procedure reported here is the preferred method for the preparation of bicyclo[3.2.1]octan-3-one. It employs readily available, inexpensive reagents, and the overall yield is good. In addition, the method can be used for the synthesis of the difficultly accessible next higher homologues of bicyclo[2.2.2]oct-2-ene as well as for derivatives of norbornene. Bicyclo[3.2.2]nonan-3-one and l-methylbicyclo[3.2.1]octan-3-one have been prepared by a similar route6 in 60% and 47% yields, respectively (based on adduct). However, the preferred procedure for the formation of the dichlorocarbene adduct of bicyclo[2.2.2]oct-2-ene is that of Seyferth using phenyltrichloromethylmercury. Even in this case the overall yield is moderate (37%). 

Thiiranes can be formed directly and stereospecifically from 1,2-disubstituted alkenes by addition of trimethylsilylsulfenyl bromide, formed at -78 C from reaction of bromine with bis(trimethylsilyl) sulfide (Scheme 7).12 A two-step synthesis of thiiranes can be achieved by addition of succinimide-A/-sulfe-nyl chloride or phthalimide-A -sulfenyl chloride to alkenes followed by lithium aluminum hydride cleavage of the adducts (Scheme 8).13 Thiaheterocycles can also be formed by intramolecular electrophilic addition of sulfenyl chlorides to alkenes, e.g. as seen in Schemes 914 and 10.13 Related examples involving sulfur dichloride are shown in Schemes 1116 and 12.17 In the former case addition of sulfur dichloride to 1,5-cyclooctadiene affords a bicyclic dichloro sulfide via regio- and stereo-specific intramolecular addition of an intermediate sulfenyl chloride. Removal of chlorine by lithium aluminum hydride reduction affords 9-thiabicyclo[3.3.1]nonane, which can be further transformed into bicyclo[3.3.0]oct-1,5-ene.16... 

Bicyclic carbosilanes are more difficult to synthesize than compounds of the (me2Si-CH2) type, partly owing to differences in the reactivity of the functional intermediates caused by effects of the substituents. So far synthesis of the l,3,5,7-tetrasila-bicyclo-[3.3.1]nonane system and of the 1,3,5,7,9-penta-siladecaline system has been reported (16). 

Synthesis of 1,3,5,7-Tetrasila-bicyclo-[3.3.1]nonanes Containing Si-functional Groups... 

The PK reaction allows access to complex molecular frameworks. In 2007, Mukai and co-worker reported the synthesis of three related alkaloids by using the PK reaction twice in the same molecule - initially to construct a bicyclo[4.3.0]nonane carbon framework (57 — 58) and then a second time to fuse a bicyclo[3.3.0]octane skeleton onto the initial framework (59—>60 -Scheme 22).70... 

Barboni, L., Gabrielli, S., Pabnieri, A., Femoni, C., and Ballini, R. 2009. Diastereoselective, one-pot synthesis of polyfnnctionahzed bicyclo[3.3.1]nonanes via an anionic domino process. Chemistry-A European Journal, 32 7867-70. 

Butkus, E. 2001. Stereocontrolled synthesis and reactions of bicyclo[3.3.1]nonanes. Synlett, 12 1827-35. 

Scheme (12). Synthesis of furans spirofused to bicyclo 4.3.0 nonane.

A methodically related transformation, the copper(Il)-mediated transfer of a cyano(ethoxycar-bonyl)methylene unit from ethyl cyanoacetate to alkenes, is presented in Section I.2.I.2.4.2.9. The copper-mediated synthesis of cyclopropyl ketones from a,a-dibromo ketones and alkenes seems to be of very limited scope and even less efficient than the corresponding synthesis of cyclopropanecarboxylic acids from o ,a-dibromoacetates (vide supra). The reaction (toluene, 100°C, 93 h) of cyclooctene (4.0 mmol), dibromomethyl phenyl ketone (8.0mmol), and commercial grade copper powder (18 mmol) activated with iodine (0.2 mmol) gave exy-9-benzoyl-bicyclo[6.1.0]nonane (7, 12%) and (2-oxo-2-phenylethyl)cyclooct-l-ene (8, 3%). ° A similar treatment of styrene gave l-benzoyl-2-phenylcyclopropane in only 2% yield [ratio (cisjtrans) 1 l.b]. " ... 

Nishitani, K., Nakamura, Y, Orii, R., Aral, C., and Yamakawa, K., Studies on the terpenoids and related alicyclic compounds. Part 43. Stereoselective intramolecular cyclization of P-alkoxycarbonyl-CO-formylallylsilanes into bicyclic a-methylene-y-lactones, Chem. Pharm. Bull., 41, 822, 1993. Kuroda, C., Ohnishi, Y, and Satoh, J.Y, Intramolecular cyclization of P-(aIkoxycarbonyl)allylsilane with conjugated ketone. A new entry to bicyclo[4.3.0]nonane. Tetrahedron Lett., 34, 2613, 1993. Kuroda, C., Inoue, S., Takemura, R., and Satoh, J.Y, Intramolecular cyclization of allylsilanes in the synthesis of guaian-8,12-olide. Stereoselective formation of trans- and cw-fused methylenelactones, 7. Chem. Soc., Perkin Trans. 1, 521, 1994. 

Kuroda, C., Nogami, H., Ohnishi, Y., Kimura, Y.. and Satoh. J.Y. Stereochemistry of Lewis acid and fluoride promoted intramolecular cychzation of P-(alkoxycarbonyl)allylsilane with enones. Synthesis of bicyclo[4.3.0]nonanes. Tetrahedron. 53, 839, 1997. 

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