Cyclic trapping illustration

As cyclic amines are at the heart of medicinal chemistry, there is always interest in new methods for their preparation. Marco Ciufoiini of the Universitc Claude Bernard in Lyon reports (Organic. Lett. 5 4943, 2003) the preparation of a series of dihydro indole derivatives, exemplified here by 3, 6, and 9, by free radical cyclization of an N-O precursor. The N-O precursor can be prepared from the corresponding bromide, as illustrated by the conversion of 1 to 2 and of 4 to 5. Alternatively, a radical precursor such as 8 can be prepared separately. The generated radical is then trapped by 7 to make a new radical, that cyclizcs to 9. 

This trapping technique can also be used to form networks with no cross-links. Mixing the same types of linear chain with large amounts of the cyclics and then functionally end-linking them could give sufficient cyclic interlinking to yield an Olympic or chain-mail network [3, 193, 200, 203], as is illustrated in Figure 5 [193], Attempts have been made to prepare and characterize such materials, because they could well have unusual elastomeric properties [204],... 

Even though radical intermediates are involved in many reductive metallations, cyclizations of alkyl radicals by reductive trapping methods are relatively uncommon. When protonated products are formed, the overall transformations are similar to a tin hydride reductions however, reductive methods may facilitate purification of the cyclic product because tin by-products are absent Two examples of simple reductive cyclizations are shown in Scheme 35. The first example illustrates that Sheffold s procedure, which uses catalytic quantities of vitamin B12 with a chemical or electrochemical coreductant, is attrac-... 

Cyclic allenes have been obtained in high yields, as illustrated by the synthesis of 1,2-cyclononadiene from the dibromocarbene adduct of the readily available cyclooctene (equation 51).138 The smallest stable cyclic allene known to date is (14) it was prepared from the dibromocyclopropane (13) in high yield.139 A small amount of the tricyclic compound (15) was also obtained (equation 52). The cyclic allene (14) did not undergo dimerization even on prolonged standing at ambient temperatures. In contrast, the unsubstituted analog was detected only at -60 °C by H NMR. It should also be noted that cyclohexa-1,2-diene was generated by the reaction of methyllithium on dibromobicyclo[3.1.0]hexane and trapped as the Diels-Alder adduct.160... 

Useful chemical reactions have been carried out in the nano-sized cavity, as illustrated by the in situ isolation of a labile cyclic siloxane trimer (Fig. 20.3.19). In the first step, three to four molecules of phenyltrimethoxysilane enter the cage and are hydrolyzed to siloxane molecules. Next, condensation takes place in the confined environment to generate the cyclic trimer SiPh(0H)0- 3, which is trapped and stabilized in a pure form. The overall reaction yields an inclusion complex [ SiPh(0H)0- 3 c Pt(bipy) 6L4](N03)i2-7H20, which can be crystallized from aqueous solution in 92% yield. The all-cis configuration of the cyclic siloxane trimer and the structure of the inclusion complex have been determined by NMR and ESI-MS. 

Electrochemically generated Co(I) species from vitamin B12 has been used as a catalyst in the radical cyclization reactions. The stereochemistry of the product contrasts with that obtained by using Bu3SnH/AIBN, and complements its synthetic usefulness139. The radical type intermediates generated in these reactions can also be trapped by neighboring multiple bonds to form cyclic products140. These processes are illustrated in Scheme 13. 

Pyrazinecarbonitrile Oxides are unstable but they can be generated from pyrazinecarbaldehyde oximes with TV-chlorosuccinimide and then trapped immediately by appropriate dipolarophiles to afford cyclic adducts, as illustrated in the following examples ... 

The method has found some use in the generation and trapping of strained cyclo-alkynes (equation 72) . Stable cycloalkynes are also obtained, but the rearrangement is accompanied by competing side-reactions, which drastically reduce the yields of the cyclic acetylenes, as illustrated for bromomethylenecyclooctane... 

Alkenylsilanes and -stannanes, and arylsilanes and -stannanes are useful reagents for transfer of an sp -carbon unit to electrophiles under titanium catalysis. Epoxides are opened by TiCE to generate cationic carbon, which is successfully trapped with bis(trimethylsilyl)propene as an aUcenylsilane (Eq. 122) [305]. Other Lewis acids, for example ZnCla, SnCU, and BF3 OEt2, proved less satisfactory. Cyclic epoxides such as cyclopentene and cyclohexene oxides gave poorer yields. An intramolecular version of this reaction proceeded differently (Eq. 123) [305]. Eqs (124) and (125) illustrate diastereoselective alkenylation and arylation of (A,0)-acetals that take advantage of the intramolecular delivery of alkenyl and aryl groups [306], Cyclic ethers... 

Returning to a reaction we met right at the start of this chapter will illustrate that the regio-and stereochemistry of many different electrophilic reactions with alkenes can be controlled by intramolecular nucleophiles. The mercuration of the cis alkene Z-184 leads to a 6 1 ratio of diastereoisomers of a cyclic ether 185 by a related trapping of the intermediate by the internal OH group. 

The procedure illustrated here is representative of a general and versatile method for the preparation of 2-substituted tetrahydrofurans and tetrahydropyrans from cyclic ether sulfones and the appropriate alkynyl, vinyl, or aryl Grignard reagent. From the examples shown in the Table and others previously reported,3-7 a selectivity for the trans-product is observed with 6-substituted tetrahydropyrans irrespective of the initial geometry of the sulfone. This implies the presence of a common reaction intermediate such as an oxonium ion which is trapped by preferred axial bond... 

Supported reagents were further applied to achieve post-cleavage purification of products obtained by solid-phase synthesis. This is illustrated by an example from Ellman s laboratory Scheme 1.6.22). The p-tum mimetic precursor 43 was released from solid support by TCEP (41) mediated cleavage of a disulfid linkage. The polymeric guanidine 44 was used to remove excess of 41 and of the phosphinoxide 42, to promote formation of the cyclic sulfide 45, and to trap the byproduct HBr from solution. 

Another carbon dioxide insertion reaction is observed with Al (TPP)(OMe) This compound readily and reversibly traps carbon dioxide at room temperature in the presence of 1-methylimidazole. The trapped carbon dioxide is sufficiently activated to react with an epoxide at room temperature, thus producing the corresponding alkylcarbonate. As illustrated in Scheme 11, the cyclic carbonate is considered to be formed - at least partly - by nucleophilic attack on a linear intermediate. Thus the alkoxide aluminum porphyrin-methylimidazole system would be a good catalyst for synthesis of alkylene carbonates from carbon dioxide and epoxides under mild conditions. 

The idea that a polymer support could help to isolate polymer-bound reactive species from one another was suggested and illustrated sh y after the flrst solid phase peptide syntheses. Cyclic tetrapeptides were obtained in higher yields from polymer-bound 2-nitrophenyl esters than from analogous micromolecular active esters (Scheme 1) (X). Polymer-bound ester enolates were formed at 0 °C and trapped with alkyl bromides and carboxylic acid chlorides with no competing selfcondensation (Scheme 2) (Z). Soluble analogs gave primarily self-condensation. 

Further chemistry with the methoxylated products leads to the facile production of polycyclic molecules. Methoxylation of more substituted substrates is well covered in the review by Moeller [34], who has also described a number of reactions where the cation radical generated by the oxidation of an olefin is trapped by an alcohol group in an intramolecular reaction [35-37] to form a cyclic product. Recently, Moeller has applied such reactions to the synthesis of sugar derivatives an illustrative example is the oxidation of tetramethoxy-furanose derivative ... 

Nevertheless, we were not able to carry out TOP measurements with calamitic monomers, because the dark currents in the liquid crystalline phases were too high. As mentioned before, such measurements are possible with the cyclic tetramers. The transient photocurrents of the tetrasiloxanes 19, 21, 22 illustrate that the carrier transport is totally dispersive, i. e. dominated by deep traps in which the charge carriers are captured. This is a typical behaviour of amorphous polymers. No transit time could be detected and no statements about the carrier mobility can be made for the rod-like mesogens. 

In subsequent studies, the scope of the Heck reaction/ anion-trapping cascade was further extended using soft car-banionic nucleophiles as illustrated in the asymmetric synthesis of (—)-D -capnellene 17. Treatment of prochiral vinyl triflate 15 with Pd(OAc>2, (5)-BINAP, and NaBr, as weU as the sodium enolate of diethyl (2-((rert-butyldiphe-nylsilyl)oxy)ethyl)malonate, gave the cyclic product 16 in 87% ee and 77% yield as the sole product. The use of NaBr as an additive improved the optical yields and was critical in preventing counteranion exchange between the triflate anion and the enolate anion by complexing with sodium enolate (Scheme 13.6). Compound 16 was then advanced through several steps to complete the total synthesis (—)-D -capnellene 17. 

The preparation of (5)-[3- C]aspartic acid illustrates the preparation and use of this cyclic glycinate. (5)-[ C]197 was prepared by alkylation of 2-phenylglycinol with phenyl bromo[2- C]acetate, readily available in two steps from sodium [2- C]acetate, and heating of the resultant reaction mixture with B0C2O. The overall yield from sodium [ CJacetate was 35-40% Deprotonation of (5)-[ C]197 with LiHMDS and trapping of the enolate with ethyl bromoacetate gave 222 in 87% yield. In general, nonactivated alkyl... 

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