Carbocycles, structures

Ipc)2BH adopts a conformation that minimizes steric interactions. This conformation can be represented schematically as in H and I, where the S, M, and L substituents are, respectively, the 3-H, 4-CH2, and 2-CHCH3 groups of the carbocyclic structure. The steric environment at boron in this conformation is such that Z-alkenes encounter less steric encumbrance in TS I than in H. 

The matter was settled in 1994 in back-to-back communications by Gould [12] and Dmitrienko [13]. Gould showed that treatment of natural prekinamycin with dirhodium tetraacetate in methanol yielded the fluorene 16 (Scheme 3.1). The vinyl proton formed in this reaction (H-l) provided a critical spectroscopic handle and allowed unambiguous determination of the carbocyclic structure, excluding the presence of an indole heterocycle. In parallel, his research group obtained a high-quality crystal structure of a kinamycin derivative. The refined data set was shown to best accommodate a diazo rather than cyanamide (or isonitrile) function. 

The asymmetric synthesis of (+)-Codeine 432 devised by White and colleagues included a Beckmann rearrangement to introduce the nitrogen atom in the carbocyclic structure (equation 182). Even though two isomeric lactams 430 and 431 were obtained as a result of the rearrangement, the preferential migration of the bridgehead carbon atom produced 430 as the predominant isomer. The synthesis of the non-natural enantiomer of Codeine was completed after oxidation, olefin formation and reduction. 

Recently, racemic 2-azabicyclo[3.2.2]nonanes 437 were synthesized to be tested as /3-glycoside inhibitors (equation 185). Once again the Beckmann rearrangement was selected as the method to introduce selectively the nitrogen atom into the carbocyclic structure. 

A number of intramolecular cycloadditions of alkene-tethered nitrile oxides, where the double bond forms part of a ring, have been used for the synthesis of fused carbocyclic structures (18,74,266-271). The cycloadditions afford the cis-fused bicyclic products, and this stereochemical outcome does not depend on the substituents on the alkene or on the carbon chain. When cyclic olefins were used, the configuration of the products found could be rationalized in terms of the transition states described in Scheme 6.49 (18,74,266-271). In the transition state leading to the cis-fused heterocycle, the dipole is more easily aligned with the dipolarophile if the nitrile oxide adds to the face of the cycloolefin in which the tethering chain resides. In the trans transition state, considerable nonbonded interactions and strain would have to be overcome in order to achieve good parallel alignment of the dipole and dipolarophile (74,266). 

ANTIBIOTICS TETRACYCLINES. The tetracyclines are a group of antibiotics having an identical 4-ring carbocyclic structure as a basic skeleton and differing from each other chemically only by substituent variation. Figure 1 shows die principal tetracycline derivatives now used commercially. 

Gibberellic acid is tetracarbocyclic and the ready transformation to allogibberic acid suggests that it possesses the same carbocyclic structure as allogibberic acid and differs only in ring A which can be readily aromatized. This view is supported by many facts (5,10), only one of which is mentioned here. 

The implementation of this methodology for a synthesis of advanced macro-cyclic precursors of antitumor antibiotics lankacidins, which posses a carbocyclic structure, has been reported by Thomas [77]. In such a route, Scheme 13, one of the key steps is the ring opening of the (3-lactam nucleus in 30 by methanol, assisted by KCN, to give the corresponding (3-amino ester intermediate 31. The latter, upon cyclization and protecting group manipulation, renders 32, which on subsequent elaboration affords lankacidin C. 

The sum of the hydrogens and bromines is 4, not 6. Therefore there must be a carbon-carbon double bond Br2C=CH2 or BrCH=CHBr. No carbocyclic structure is possible because there are only two carbon atoms. (In Chapter 3, Sec. 3.5, we will see that the relative orientations of the Br in the latter structure can lead to additional isomers.)... 

This forms the basis of an attractive synthetic method for converting polyenes into carbocyclic structures (Equation B3.13). 

Cyclic fatty acids with a carbon ring alone or at the end of the alkyl chain occur naturally in plants, especially in certain seed oils and in microorganisms. Cyclopropane fatty acids are reported occasionally from marine animals and may be synthesized by symbiotic bacteria. In addition, a variety of carbocyclic structures are formed from methylene-intermpted polyenes during food processing. 

DA reactions are the largest family of cycloaddition processes. In a DA reaction, an ethylene derivative, named the dienophile, adds to a 1,3-diene to afford a six-membered carbocyclic product. By varying the nature of the diene and dienophile, many different types of carbocyclic structures can be built up. However, not all possibilities take place easily. For instance, the simplest cycloaddition reaction is the DA reaction between butadiene and ethylene. However, this reaction must be forced to take place after 17 hours at 165° C and 900 atmospheres, it does give a yield of 78%.28 29 An interesting alternative is that the presence of electron-releasing substituents in the diene and electron-withdrawing (EW) substituents in the dienophile or vice versa can drastically accelerate the process. 

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