Rings, intramolecularly formed

Many examples of intramolecular reactions leading to ring closure have served to establish a correlation between the rate of a reaction and tiie size of the ring being formed. "... 

In a similar manner, ketones can react with alcohols to form hemiketals. The analogous intramolecular reaction of a ketose sugar such as fructose yields a cyclic hemiketal (Figure 7.6). The five-membered ring thus formed is reminiscent of furan and is referred to as a furanose. The cyclic pyranose and fura-nose forms are the preferred structures for monosaccharides in aqueous solution. At equilibrium, the linear aldehyde or ketone structure is only a minor component of the mixture (generally much less than 1%). 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

In intramoleculdf Diels-Alder reacdons, two rings are formed in one step The reacdon has been used to synthesize a number of interesting ring systems" The intramolecular cyckzadon of fE -l-nitrodeca-l,6,8-triene at 80 C affords an endo cycioaddnct with the irons ring fusion preferendally, as shown in Eq 8 18 In contrasr, fZ -nitroalkenes produce a nearly I T mixture of cis- and rrruii -hised cycioaddncts ... 

In the first example of an intramolecular Sakurai reaction, a six-membered ring was formed in the presence of boron trifluoride-diethyl ether complex starting from an acyclic enone36. 

There are some reactions in which an aryl radical reacts with an sp2-carbon atom of an aliphatic side chain. In such reactions a carbo- or heteroalicyclic ring fused with a benzene ring is formed (Scheme 10-80). They may be called intramolecular Meerwein reactions. Techniques for these syntheses were developed by Beckwith s group in the 1980s. The majority of Beckwith s investigations were made with 2-(2 -propenyloxy)- and 2[(2 -methyl-2 -propenyl)oxy]benzenediazonium tetrafluoro-... 

In addition to the synthesis of industrially important azo dyes using heteroaromatic diazo components, intramolecular azo coupling reactions of heterocyclic diazonium ions also have interesting synthetic uses, because they lead to new fused-ring heterocycles, as shown by the diazotization of 2-amino-3-arylbenzimidazoles (12.7) in which, without isolation of the diazonium ion, a 1,2,4-triazine ring is formed (Kolodyazhnaya et al., 1973). Further examples of intramolecular azo couplings were reviewed by Tisler and Stanovnik (1980), and very extensively (403 references ) by Kishimoto et al. (1990). 

Although the intramolecular cyclopropanation of simple alkenes easily occurs in those cases where a five- or six-membered ring is formed in addition to the three-membered ring [13], the intermolecular version of this process was described by Barluenga et al. in 1997 [ 14c]. Thus, this reaction has shown a high... 

Since five-membered rings are formed faster than four or six-membered rings, an otherwise electronically Symmetrical double bond (35) or (36) will be captured intramolecularly to give a y-lactone (37) in acid. 

The steric and configurational factors discussed above would suggest that five-membered rings should form somewhat more readily than rings of six or seven members, but they offer no explanation for the total exclusion of intermolecular condensation, nor do they explain the much greater rate of intramolecular reaction of five-membered units as compared with the rates of intermolecular reaction of larger units. A possible partial explanation for these peculiarities of five-membered... 

Rhodium carboxylates have been found to be effective catalysts for intramolecular C—H insertion reactions of a-diazo ketones and esters.215 In flexible systems, five-membered rings are formed in preference to six-membered ones. Insertion into methine hydrogen is preferred to a methylene hydrogen. Intramolecular insertion can be competitive with intramolecular addition. Product ratios can to some extent be controlled by the specific rhodium catalyst that is used.216 In the example shown, insertion is the exclusive reaction with Rh2(02CC4F9)4, whereas only addition occurs with Rh2(caprolactamate)4, which indicates that the more electrophilic carbenoids favor insertion. 

Friedel-Crafts alkylation can occur intramolecularly to form a fused ring. Intramolecular Friedel-Crafts reactions provide an important method for constructing polycyclic hydrocarbon frameworks. It is somewhat easier to form six-membered than five-membered rings in such reactions. Thus, whereas 4-phenyl-1-butanol gives a 50% yield of a cyclized product in phosphoric acid, 3-phenyl-1-propanol is mainly dehydrated to alkenes.43... 

An enantiospecific synthesis of longifolene was done starting with camphor, a natural product available in enantiomerically pure form (Scheme 13.31) The tricyclic ring was formed in Step C by an intramolecular Mukaiyama reaction. The dimethyl Multistep Syntheses substituents were formed in Step E-l by hydrogenolysis of the cyclopropane ring. 

The broken curves in Figure 9 are the expected values of Mc/Mc for trifunctional and tetrafunctional networks, assuming that all the ring structures formed are of the smallest size (v bonds), and that only the ring structures formed pre-gel give elastically ineffective loops(29,32). They show that intramolecular... 

Amides and sulfonamides undergo intramolecular chemistry to form aryl amides and aryl sulfonamides (Equations (17)—(19)) in the presence of palladium catalysts ligated by arylphos-phines.35,89 Initially, complexes of P(furyl)3 and P(o-tol)3 were most effective catalysts, but complexes of Hayashi s MOP and van Leeuwen s DPEphos and xantphos have lately been shown to be more active.90 In the presence of catalysts containing one of these ligand systems, five-, six-, and seven-membered rings were formed from halogenated benzamides or from substrates containing an acetamide, an A-carbobenzyloxy, or a t-butylcarbamate substituent tethered to the aryl halide (Equations (18) and (19)) ... 

A pyran ring is formed in the intramolecular Diels-Alder cycloaddition of alkene-tethered enantiopure (lS,2R)-l,2-dihydroxycyclohexa-3,5-diene-l-carboxylic acid derivatives (derived from the biodihydroxylation of benzoic acid). For the three cases illustrated in Scheme 6.246, Mihovilovic and colleagues found that moderate to high yields of the desired cycloadducts could be obtained by exposing a solution of the precursor to microwave irradiation at 135-210 °C for extended periods of time... 

Further variations of the general scenario described in Scheme 4 consist in trapping adduct radical 48 before oxidation occurs7. This can be achieved if intramolecular radical additions are possible, as is the case in radical 62. Oxidation of 62 to the corresponding allyl cation is slower than 6-ew-cyclization to the chlorobenzene ring to form radical 63, which subsequently is oxidized to yield tetrahydronaphthalene 64 as the main product (equation 27). This sequence does not work well for other dienes such as 2,3-dimethyl-1,3-butadiene, for which oxidation of the intermediate allyl radical is too rapid to allow radical cyclization onto the aromatic TT-system. 

Another idea, which was originally put forward by Ruzicka (1935) and has ever since provided a common basis for many discussions of reactivity in intramolecular reactions, is that the ring-shaped transition state should be affected by a significant fraction of the strain-energy of the ring being formed. The simplest way to express this idea is by use of (62), where the weighting... 

This hydroxycyclopropanation of a terminal double bond also works perfectly well in an intramolecular situation, e. g. with terminally alkenyl-substituted esters, to yield substituted l-hydroxybicyclo[n.l.O]alkanols [85a,85b,100], aminobicyclo[n.l.O]alkanols [85c], and heterocyclic analogues [99a,99b,100], in which five- and six-membered rings are formed (Table 11.7). 

Grigg s group synthesized a unique bicyclic P-lactam 108 via an intramolecular Heck reaction from 107 [87, 88]. The 7-membered ring was formed via an unusual insertion at C(3) of furan, an aromatic rc-system. 

An intramolecular cyclization of a tetrazole-containing nucleoside 64 has been observed by Chu and co-workers <1997JOC7267> (cf. other properties of this compound in Table 3). These authors reported that the 3-OH group on the arabinofuranose ring participates in an addition reaction at position 7 of the tetrazolo[l,5-c]pyrimidine ring to form 65 which is a dihydro derivative of the parent heterocycle. The final structure elucidation has been carried out with the help of the tricyclic tandem mass spectrometry (MS/MS) fragment 66. 

Intramolecular Michael addition.1 Cesium carbonate catalyzes the intramolecular Michael addition of a cyclic (3-keto ester to an a,(3-ynone to form a cyclic enone after protonation. This reaction proceeds readily when a five- or six-mem-bered ring is formed higher rings can be formed, but in low yield.1... 

One aspect, besides the size of the ring that forms upon intramolecular glycosylation, governing the stereoselective outcome using this concept has been shown to be... 

As early as in 1973 it was shown [1089] that the C-H insertion of acceptor-substituted carbene complexes can take place with retention of configuration (e.g. Table 4.5, Entry 3) [953,1090,1091]. In the case of intramolecular C-H insertions into methylene groups high diastereoselectivities are often observed when 4-6-membered rings are formed (see examples in Tables 4.4-4.S). 

If secondary AAs are heated in the presence of aldehydes containing a proximate terminal double or triple bond and then condensed, decarboxylation and intramolecular cycloaddition tri-, tetra-, penta-, or hexa-cyclic cycloadducts with a condensed pyrrole ring are formed. An example is the reaction with sarcosine (Scheme 55) (88T4953). 

---