Of carbocycles

Rudisill and Stille developed a two-step procedure in which 2-bromo-or 2-trifluoromethanesulfonyloxyacetanilides were coupled with tri-n-butyl-stannylacetylenes in the presence of Pd(PPh3)4.[l], Cyclization was then effected with PdCl2(CH3CN)2. The conditions are compatible with a variety of carbocyclic substituents so the procedure can provide 2-substituted indoles with carbocyclic substituents. The reported yield ranges from 40% to 97% for the coupling and from 40% to 82% for cyclization. 

The procedure has been found to be compatible with a variety of carbocyclic substituents. Table 5.1 provides some examples of the reaction. 

The chemistry of dye intermediates maybe conveniendy divided into the chemistry of carbocycles, such as benzene and naphthalene, and the chemistry of heterocycles, such as pyridones and thiophenes. 

Annelation of carbocycle to heterocycle and cyclizations with simultaneous formation of carbo- and heterocyclic fragments 98JCS(P1)983. 

Synthesis of annelated furanoses and their use for preparation of carbocycles 98SL693. 

Miller and coworker report a total syndiesis of carbocyclic polyoxin C from cis-(N- en-butylcarbamoyl cyclopent-2-en-Tol, as shovm in Scheme 5.11. This syndiesis feanires a... 

Trost and co-workers have explored asymmetric transidon metal-catalyzed allylic alkyla-dons. Details on this subject have been well reviewed by Trost and others. With the use of asymmetric palladium-catalyzed desymmetrizadon of meso-2-ene-l,4-diols, cii -l,4-dibenzoy-loxy-2-cyclopentene can be converted to the enandometrically pure cii -4-rfirr-butoxycar-bamoyl-l-methoxycarbonyl-2-cyclopentene. The product is a usefid and general building block for synthesis of carbocyclic analogs of nucleosides as presented in Scheme 5.12. 

The cyclitols are a group of carbocyclic sugar derivatives having the general formulation 1,2,3,4,5,6-cyclohexanehexol. How many stereoisomeric cyclitols are possible Draw them in their chair forms. 

The intramolecular Hiyama reaction is excellently suited for the construction of carbocyclic and heterocyclic ring systems of different size. In most examples, problems of induced diastereoselectivity are involved (Sections 1.3.3.3.9.2.2. and D.2.3.). In the total synthesis of the antitumor germacranolide ( )-costunolide from ( ,.E)-farnesol, the correctly substituted ( , )-cyclodecadiene moiety was constructed by an intramolecular Hiyama reaction22. 

This section describes Michael-analogous processes in which, mostly under electrophilic conditions, ally - or alkynylsilanes undergo addition to enones or dienones (Sakurai reactions). The intramolecular addition of allylsilanes is an extremely useful reaction especially for the construction of carbocyclic ring systems, which occurs in a diastereoselective manner, in many cases with complete asymmetric induction. 

A characteristic property of most diazotizations of aminoazoles is the occurrence of a relatively stable transient intermediate (probably the A-nitrosoamine), in contrast with the diazotization of carbocyclic aromatic amines, where A-nitrosoamines have been considered to be unstable intermediates. This problem will be discussed in the context of the mechanism of diazotization in Section 3.4. 

It is noteworthy that, based on the sulfoxide- sulfenic acid rearrangement, the readily accessible 1,3-dithiolane systems (316) may be utilized (equation 116) as an efficient entry into the 1,4-dithiane series303, including the construction of carbocyclic fused systems304. The oxidation of the dithienes 318 to the corresponding sulfoxides (319 and 320) and sulfones is a simple, straightforward process. 

Good yields and high diastereoselectivities were obtained by using zeolites in combination with Lewis-acid catalyst [21]. Table 4.7 illustrates some examples of Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with methyl acrylate. Na-Y and Ce-Y zeolites gave excellent results for the cycloadditions of carbocyclic dienes, and combining these zeolites with anhydrous ZnBr2 further enhanced the endo diastereoselectivity of the reaction. An exception is the cycloaddition of furan that occurred considerably faster and with better yield, in comparison with the classic procedure [22], when performed in the presence of sole zeolites. 

The majority of sequential radical reactions deal with cyclizations as the key steps. The constructions of carbocycles, oxygen, and nitrogen heterocycles using (TMSlsSiH as a mediator are many and represents the expansion and importance of these synthetic approaches. For example, Nicolaou and coworkers found that (TMSlsSiH serves as a superior reagent in the radical-based approach toward the synthesis of azadirachtin, an antifeedant agent currently used as an insecticide, and in other related systems. ° ° Here below we collected a number of reactions mostly from the recent work in the area of intramolecular reactions. 

In the construction of carbocycles, five-membered ring formation has been used for preparing fused cyclic compounds, such as functionalized diquinanes. ° The reaction of 36 with (TMSlsSiH furnished the expected product 37 in 80% yield and in a or.fi ratio of 82 18, as the result of a kinetic controlled reaction (Reaction 43). 

Kim CU, Lew W, Wilhams MA, Liu H, Zhang L, Swaminathan S, Bischofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC (1997) Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 119 681-690... 

One-pot tandem sequences involving 1,4-addition and ISOC as the key steps have been developed for the construction of N and 0 heterocycles as well as of carbocycles [44]. In this sequence, the nitronate arising from 1,4-addition to an a, -unsaturated nitro alkene is trapped kinetically using trimethyl silyl chloride (TMSCl). The resulting silyl nitronate underwent a facile intramolecular 1,3-dipolar cycloaddition with the unsaturated tether (e.g.. Schemes 20-22). 

It was also of interest to apply such lOOC reactions to formation of carbocyclic rings. Oxime olefins 230 a-e, formed in good yield via reaction of 229 with 0-silyl-a-bromoaldoximes 228 in the presence of F ions, cyclized in a sealed tube at 190 °C to provide 231 a-e (Eq. 24, Table 22) [63]. Reduction of 231a provided amino alcohol 232 a in 68% yield. Amino alcohol 232 e was converted stereo-specifically to the fused -lactam 233. 

In contrast to the synthesis of carbocyclic rings, the Cope rearrangement has been used sparsely for generating azepinones. Recently, the enantioselectivity of the conversion of 2-aza-divinylcyclopropane 286 has been investigated. The synthesis started from the optically active cyclopropanecarboxylic acid (90% ee), which had been converted into the isocyanate 286 by initial azidation to 285 and a consecutive Curtius rearrangement. Furthermore, the conditions of the iso-... 

Other Carbocyclic Aromatic Compounds Reduction of Carbocyclic Rings... 

Another versatile domino process for the synthesis of carbocycles as well as heterocycles is the Pd-catalyzed reaction of organic halides or triflates with alkynes or allenes, which contain a carbo- or heteronucleophile in close vicinity to these functionalities (see Scheme 6/1.75) [133]. 

As demonstrated by Hoffmann and coworkers, hydroformylation can also be combined with an allylboration and a second hydroformylation, which allows the formation of carbocycles and also heterocycles [213]. A good regioselectivity in favor of the linear aldehyde was obtained by use of the biphephos ligand [214]. Reaction of the allylboronate 6/2-76 having an B-configuration with CO/H2 in the presence of catalytic amounts of Rh(CO)2(acac) and biphephos led to the lactol 6/2-80 via 6/2-77-79 (Scheme 6/2.17). In a separate operation, 6/2-80 was oxidized to give the lactone 6/2-81 using tetrabutyl ammonium perruthenate/N-methylmorpholine N-oxide. 

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. 

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