Carbocyclic substrates

An advantage of the metal-catalyzed conversion of styrenyl ethers to chromenes is that control of relative stereochemistry on the carbocyclic substrate before catalytic synthesis of chromenes can lead to the formation of various functionalized heterocycles that are diastereomerically pure (Table 1). 

The chemistry described in this review article demonstrates the impressive positive influence that catalytic RCM has had on our research in connection to the development of other catalytic and enantioselective C-C bond forming reactions. There is no doubt that in the absence of pioneering work by Schrock and Grubbs, the Zr-catalyzed alkylation and kinetic resolution would be of less utility in synthesis. The number of unsaturated heterocyclic and carbocyclic substrates available for Zr-catalyzed asymmetric carbomagnesation would be far more limited without catalytic RCM. 

Most of the primary syntheses from aliphatic or carbocyclic substrates fall into this category, which is subdivided successively according to the number and the type of ring atoms supplied by each synthon. 

The action of the nitrating mixture on 1-alkylimidazoles gives the 4-and 5-nitro derivatives with a preference for the former [130-132], The sizes of the substituent have practically no effect on the ratio of the isomers [132], At the same time this effect is quite noticeable in the series of carbocyclic substrates (Scheme 13). 

Good yields are obtained by this method only with rigid carbocyclic substrates such as steroids. The following procedure is an adaptation from steroid chemistry. ... 

Small carbocyclic substrates are also challenging, often giving low stereoselectivities. Some selected examples of alkylations of these substrates using P-stereogenic ligands are shown in Scheme 8.8. 

Substrates for Diene Photooxygenation Carbocyclic Substrates Heterocyclic Substrates . . 25-3... 

These halogenoquinoxalines undergo all the reactions that would be expected of a carbocyclic analog (e.g., 2-chloromethylnaphthalene) and at comparable rates unless the activity of an individual substrate is affected appreciably by an adjacent passenger group. 

The carba-trehaloses are carbocyclic analogs of trehalose, in which one or both of the D-glucopyranose units is (are) replaced with D-carba-glucopy-ranose, and may be expected to act as a substrate analog or an inhibitor of... 

There is clearly enormous potential using other cis dihydrodiols produced from benzocyclo-alkenes, or from the numerous dihydrodiols produced from polycyclic carbocyclic and heterocyclic substrates. 

In a similar way as described for the hydroformylation, the rhodium-catalyzed silaformylation can also be used in a domino process. The elementary step is the formation of an alkenyl-rhodium species by insertion of an alkyne into a Rh-Si bond (silylrhodation), which provides the trigger for a carbocyclization, followed by an insertion of CO. Thus, when Matsuda and coworkers [216] treated a solution of the 1,6-enyne 6/2-87 in benzene with the dimethylphenylsilane under CO pressure (36 kg cm"2) in the presence of catalytic amounts of Rh4(CO)12, the cyclopentane derivative 6/2-88 was obtained in 85 % yield. The procedure is not restricted to the formation of carbocycles rather, heterocycles can also be synthesized using 1,6-enynes as 6/2-89 and 6/2-90 with a heteroatom in the tether (Scheme 6/2.19). Interestingly, 6/2-91 did not lead to the domino product neither could 1,7-enynes be used as substrates, while the Thorpe-Ingold effect (geminal substitution) seems important in achieving good yields. 

In addition to terpenes (as described above), carbohydrates have also been used as substrates in domino metathesis reactions, the aim being to synthesize enan-tiopure polyhydroxylated carbocyclic rings. These structures are components of several biologically active compounds such as aminoglycoside antibiotics [254], inositol phosphates [255], and carbanucleosides [256]. An efficient entry to this skeleton was developed by Madsen s group using a domino RCM/CM of the carbohy-... 

The resulting derivatives (269) can be considered as strategically important intermediates in the synthesis of glycosidase inhibitors and carbocyclic nucleosides (150). A new approach to the stereoselective synthesis of the piperidine ring with the use of [4+ 2] [3+ 2]-cycloaddition from specially prepared substrates is also very interesting (431)b, c. In the context of this problem, the conditions for the formation of systems containing quaternary vicinal stereocenters were found. 

In this review, an attempt is made to exhaustively catalog the rapidly growing subset of metal-catalyzed reductive C-C bond formations comprising the hydrometallative and hydrogenative carbocyclization of 7t-unsaturated substrates, and application of these methods in target-oriented synthesis. Content is organized on the basis of reaction... 

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