Ring-fusion carbons

Magnus was the first to develop extensive synthetic applications of the Pauson-Khand preparation of the bicyclo[3.3.0]oct-l-en-3-one system. His efforts amply demonstrate the degree to which the high level of functionality in the Pauson-Khand products can be directly utilized in building more complex structures. A formal synthesis of the antitumor sesquiterpene coriolin illustrates a very efficient sequence for construction of the third ring in the linearly fused triquinane series in the presence of considerable functionality (Schemes 10 and 18). A synthesis of the related triquinane hirsutic acid utilizes the observation that the proper stereochemical relationship between the substituents at C-7 and the ring-fusion carbon (C-5) of the bicyclo[3.3.0]oct-l-en-3-one system, while not controllable in the cycloaddition reaction itself, may be readily established by acid- or base-catalyzed equilibration (equation 54 and Scheme 19). ... 

The Lewis acid catalyzed expansion with ethyl diazoacetate also gives good regioselectivity, with a preference for migration of the non-ring-fusion carbon (equations 11-16). The use of SbCb as die Lewis acid at -78 C was reported to improve the regioselectivity in one case (equation 14). ... 

Bonds 1 and 2 (which are part of ring B) are equatorial substituents with respect to ring A. Bonds 3 and 4 (which are part of ring A) are equatorial substituents with respect to ring B. Both hydrogen atoms on the ring fusion carbons are axial with respect to both rings. 

Notice that making all-chair cyclodecane is essentially the same as removing the ring-fusion bond from /rans-decalin and replacing it with two hydrogens—one on each former ring-fusion carbon ... 

The pattern of atoms or groups along the points of ring fusion (carbons 5 to 10, 10 to 9, 9 to 8, 8 to 14, and 14 to 13) is nearly always trans-znti—trans-znti—trans. 

Extension of aromaticity. The extension of the aromatic ring system through fusion (as in naphthalene) or direct substitution (as in biphenyl) appears to increase log P, especially if the heteroaromatic atom is next to the juncture. If the ring-joining carbons are attached only to other aromatic carbons, electron delocalization is minimal the correction is -rO.lO for each 1C. If the ICs are also attached... 

It is interesting to note that all previous attempts to utilize the Claisen rearrangement within the carbon framework of the fenestrane system as well as all efforts to prepare a fenestrane in which one of the ring fusions is trans, had not been successful. In Eq. 12.74, a facile rearrangement of fenestrene took place in aqueous pyridine to form a... 

Methyl deoxypodocarpate 127 (Scheme 1) 129) represents a simple problem since the ketone 132 is well-known and readily available from Hagemann s ester in three steps. The problem of geminal alkylation of this ketone stems from its existence as an EjZ mixture of ring fusion isomers. Recognizing that decarbonylation of aldehydes occurs readily with Wilkinson s catalyst creates a structural equivalence of an acetaldehyde chain and a methyl group as in 128. This simple relationship immediately establishes several options, a simple one uses a thioacetal such as 129 as a synthon for the aldehyde. The presence of a carbonyl group three carbons away... 

The [5,5] (2Nl)-fused heterocyclic system contains four ring-carbon atoms, the fusion carbon atom and two and one carbon atom in the respective five-membered rings. 

The (5,5) (2N2)-fused heterocyclic system contains three ring carbon atoms, one fusion carbon atom, and one additional nonfusion carbon atom in each five-membered ring. Only scattered H and 13C nuclear magnetic resonance (NMR) data are available for these systems. 

The nucleophilic attack on the bridging carbon results in two different reactivities. Usually ring opening occurs. Malononitrile under hydrolytic solid-liquid phase-transfer conditions attacks the methiodides 26 at the fusion carbon atom, thereby inducing ring opening and the formation of 4-(Ar-aryl-3 -methylisothioureido)-5-(dicyanomethylcnc)-l-... 

A concave and a convex diastereoface may be distinguished, and it is apparent from ketone 7 that steric crowding is much more pronounced on the concave face. Thus, attack occurs from the convex face with high selectivity33. A variation of this principle is when the reagent adds to an unsaturated carbon at the ring fusion. 

E. J. Corey recently described (Organic Lett. 2005, 7,2699, 2703) an even more elegant approach to the y-lactam. Exposure of 5 to the Kulinkovich conditions followed by iodination delivered 18, presumably by way of the titanacycle 17. Although all-carbon trans-5,5 systems are strained, the trans ring fusion is the expected stereochemical outcome with (RO),Ti in the ring. Complexation of the ester to the Ti may explain the observed facial selectivity. Brief exposure of 18 to Et,N followed by silylation converted it to 6. The preparation of several more analogues in this series is also reported in these two articles. 

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