Medium-sized carbocycles

Mascarenas developed a synthetic method to 1,5-oxygen-bridged medium-sized carbocycles through a sequential ruthenium-catalyzed alkyne-alkene coupling and a Lewis-acid-catalyzed Prins-type reaction (Eq. 3.45). The ruthenium-catalyzed reaction can be carried out in aqueous media (DMF/H20 = 10 1).181... 

Medium sized carbocycle synthesis Ring contracting [1,2]-Wittig rearrangement Yadav and Ravishankar have demonstrated that the Wittig rearrangement of the cyclic substrate 32 is useful for the construction of the taxane skeleton 33, albeit in low yield (equation 17). ... 

An equivalent reaction has been achieved via the treatment of hydroborated bisalkenes with alkaline silver nitrate solution (Table 1.4).22,23 This method has been used to synthesize a number of small and medium-size carbocyclic rings in moderate to good yield. The selectivity for terminal cyclization observed for 1,6-heptadiene and 1,7-octadiene indicates that, in these cases, hydroboration of each of the alkenes occurs independently to yield acyclic boranes. It has, however, been found that both cyclic and acyclic boranes react under these conditions to yield the ring-closed products (Scheme 1.3). 

Preparation of highly functionalized medium-sized carbocycles (210) and (212), derived from carbohydrates, can also be carried out with the same procedure via 8-endo-trig and 1-exo-trig manners, as shown below (eqs. 3.81, 3.82). Moreover, preparation of (3-C-disaccharide (214) proceeds selectively via 8-endo-trig radical cyclization of two temporarily tethered monosaccharide (213), by means of the addition of a carbohydrate-... 

Even though medium-sized carbocycles are structural motifs often encountered in naturally occurring organic substances, richly hydroxylated structures reminiscent of the carbohydrate counterparts are rare, and efforts made to obtain these derivatives via synthesis have not been particularly intense. 

It should be noted at this point, that the delicate issue of constructing medium-sized carbocycles found an elegant solution in this synthesis, based on an unprecedented silylative cycloaldolization protocol. 

Quite recently, Marco-Contelles [73] has made use of free radical cyclization and ring-closing metathesis in order to develop useful synthetic protocols to access a number of chiral non-racemic, densely oxygenated medium-sized carbocycles from carbohydrate precursors. 

Molander has developed a Sml2-mediated Barbier cyclisation-Grob fragmentation sequence for the synthesis of medium-sized carbocycles.134 For example, treatment of mesylate 115 with Sml2 and catalytic Nil2 gave cyclo-decenone 116 in excellent yield (Scheme 5.82). 

The intramolecular Michael reaction is a convenient means for the synthesis of small-to medium-size carbocycles. ... 

Molander, G. A., Le Huerou, Y., Brown, G. A. Sequenced Reactions with Samarium(ll) Iodide. Sequential Intramolecular Barbier Cyclization/Grob Fragmentation for the Synthesis of Medium-Sized Carbocycles. J. Org. Chem. 2001,66,4511-4516. 

The first examples of radical cyclizations to afford medium-sized carbocycles via radical-initiated oxirane cleavage have been described <93JOCi2i5>. Rawal and co-workers have made contributions to this area in a series of synthetically useful examples featuring intramolecular cyclizations <90JOC5181, 92TL3439, 92TL4687, 93TL2899) (Scheme 36). 

Corey and Hamanaka - employed intramolecular allylic coupling in a novel synthesis of medium-size carbocyclic systems. The doubly allylic o.ai-dihulidc (I) on cyclization with nickel carbonyl gave as the chief product the ull-trum-dimethyl-cyclododecatriene (2). eccompenled by an liomar, probably fh, iran.s.tmns. 

Functionalized medium-sized carbocyclic rings (especially seven- and eight-membered rings) can be accessed by this route through the use of the appropriate [3.2.1], [3.3.1], or [4.2.1] oxabicydic substrates. This approach avoids otherwise entropically disfavored cyclization approaches to these rings, and therefore has proven particularly valuable for the syntheses of certain families of natural products. 

Lopez, F., Castedo, L. and Mascarenas, J.L. (2002) Atom-efficient assembly of 1,5-oxygen-bridged medium-sized carbocycles by sequential combination of a Ru-catalyzed alkyne-alkene coupling and a Prins-type cyclization. Journal of the American Chemical Society, 124, 4218-4219 Lopez, F., Castedo, L. and Mascarenas, J.L. (2005) Practical asymmetric approach to medium-sized carbocycles based on the combination of two Ru-catalyzed transformations and a Lewis add-induced cydization. Organic Letters, 7, 287—290. 

The plan for the synthesis of 1 could be formulated in earnest after the successful methodological development of the tandem RCM/cross-coupling protocol. The intramolecular silicon-assisted cross-coupling reaction provides good generality in the synthesis of medium-sized carbocycles that contain a geometrically defined 1,3-diene (Scheme 2). 

The synthesis of medium-sized carbocyclic and heterocyclic rings by ring expansion reactions has been reviewed by Roxburgh <93TI0749>. In general, this section covers work not discussed by Roxburgh, except where particularly important or illustrative reactions are featured. 

Martin and co-workers applied a ring-closing metathesis strategy in the synthesis of medium-size carbocycles fused to butyrolactones/ Fused butyrolactones are ubiquitous in nature and play an important role in the... 

Polythiophens and Related Systems.— Two groups have prepared compounds containing two thiophen rings fused to medium-sized carbocycles. At the University... 

Faustino, H., Alonso, L, Mascarenas, J. L., Lopez, F. (2013). Gold(I)-catalyzed cascade cycloadditions between allenamides and carbonyl-tethered alkenes an enantioselective approach to oxa-bridged medium-sized carbocycles. Angewandte Chemie International Edition, 52, 6526-6530. 

The most prominent and most successful compound classes in this respect are arguably VCPs and MCPs. The ring-expanding annulations of these substrates provide an opportunity for the synthesis of various medium-sized carbocyclic ring systems. However, the number of examples of asymmetric reactions remains relatively low. Their application in asymmetric catalytic processes is the next challenge to render cyclopropane ring opening more useful and fruitful. 

Grubb s ruthenium carbene catalyst to afford medium-sized carbocycles (Equation (10))." Iron tricarbonyl systems containing diazoketones tethered to the terminal position of the acyclic coordinated diene have been utilized to effect ring formation, via inter- and intramolecular carbene reactions, affording new cyclohexa-2,4-dienone and cyclopent-2-enone tricarbonyl iron complexes. ... 

Amann, C.M., Fisher, P.V., Pugh, M.L., and West, EG., Medium-sized carbocycles and ethers from 4-pyrones a photocycHzation-ffagmentation approach, /. Org. Chem., 63, 2806, 1998. 

Synthesis of Natural Products Containing Medium-size Carbocycles by Ring-closing Alkene Metathesis... 

This chapter deals with the synthesis of naturally occurring molecules (or related models) and focuses on the construction of medium size carbocycles by ring-closing metathesis (RCM). We have arbitrarily chosen to organize this chapter by increasing ring size. Strategic aspects and potential problems are discussed. 

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