Tandem addition-trapping

Sibi and Chen [42] reported a related tandem intermolecular nucleophilic free-radical addition-trapping reaction of enoate 168 establishing chirality at both a and /(-centers with control over both absolute and relative stereochemistry (Scheme 9.30) using a Lewis acid catalyst and the bisoxazoline ligand 169. They observed... 

Scheme 9.30. Enantioselective tandem intermolecular free-radical addition-trapping reaction of enoates.

Contrary to what is observed during tandem addition reactions to [Os]-toluene (vide supra), electrophilic additions to [Os]-bound ortho- and meta-xylenes result in regioselective attack at C6 (Table 3). A coordination isomer having the metal across C4-C5 (19) is the only isomer observed for both ortho- and meta-xylene. Electrophilic addition of HOTf (entry 1) or dime-thoxymethane (entries 2 and 3) at C6 generates the complexed allyl cation 20, which can be trapped with MMTP to form the complexed diene 21. Demetalation using AgOTf releases the free diene 22, which potentially possesses two adjacent quaternary centers (entry 3) [15]. 

Miyabe et al. developed a tandem addition/cycUzation reaction featuring an unprecedented addition of alkoxycarbonyl-stabihzed radicals on oxime ethers [117], and leading to the diastereoselective formation of /1-amino-y-lactone derivatives [118,119]. The reaction proceeds smoothly in the absence of toxic tin hydride and heavy metals via a route involving a triethylborane-mediated iodine atom-transfer process (Scheme 37). Decisive points for the success of this reaction are (1) the differentiation of the two electrophilic radical acceptors (the acrylate and the aldoxime ether moieties) towards the nucleophilic alkyl radical and (2) the high reactivity of triethylborane as a trapping reagent toward a key intermediate aminyl radical 125. The presence of the bulky substituent R proved to be important not only for the... 

Watanabe et al. examined a similar addition/trapping tandem involving vinylic sulfones [178]. Acceptable ee s were obtained when bidentate chelation was made possible, as was the case when benzimidazolyl moities were attached to the sulfur atom (the ligand was again a box derivative). Yet only one stereogenic center was created during the reaction. 

Finally, a novel three-component radical cascade reaction involving isonitriles has just been published [6]. In this paper, aromatic disulfides, alkynes, and isonitriles have been reported to react under photolytic conditions to afford -arylthio-substituted acrylamides 49 or acrylonitriles 50 in fair yields as mixtures of the E and Z geometric isomers (Scheme 21). The procedure entails addition of a sulfanyl radical to the alkyne followed by attack of the resulting vinyl radical on the isonitrile. A fast reaction, for example, scavenging by a nitro-derivative (route a) or f-fragmentation (route b), is necessary in order to trap the final imidoyl radical, since addition of vinyl radicals to isonitriles seems to be a reversible process. The reaction provides very easy access to potentially useful poly-functionalized alkenes through a very selective tandem addition sequence. 

Irradiation of cyclohexenone 32 with the tertiary a-silylamine EtjNCHjSiMej in methanol solution in the presence of the electron acceptor 9,10-dicyanoanthracene (DCA) yields predominantly the desi-lylated adduct 32b. The product ratios depend on amine concentration. " The mechanism proposed for adduct formation is outlined in Scheme 24. Oxidation of the tertiary amine by singlet DCA yields the amine cation radical, which undergoes desilylation upon nucleophilic reaction with the solvent. Addition of the a-aminoalkyl radical to the neutral enone affords the radical adduct, which is reduced by DCA and protonated by solvent. " Intramolecular trapping of the radical adduct can compete with reduction by DCA"-, as seen in the reaction of 32 with an a-silylanihne, which yields the tandem addition product 32c (Scheme 24). ... 

Tliis beaelicial effect of additions has been observed in tliat tlie yields in tlie tandem vet in situ trapping of tlie reactive ei tlie addition of Et2Zn to 44 wbet Higli enantioselectivities 183-... 

Carbonyl ylides continue to be targets of opportunity because of their suitability for trapping by dipolar addition. High enantiocontrol has been achieved in the process described by Eq. 16 [109], but such high enantioselectivity is not general [110] and is dependent on those factors suggested by Scheme 11. Using achiral dirhodium(II) catalysts, Padwa and coworkers have developed a broad selection of tandem reactions of which that in Eq. 17 is illustrative [111] these... 

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). 

In the case of nitronates possessing ester or nitrile moieties as terminal olefin substituents, tandem Michael addition to produce substituted furans 174,175 occurred faster than trapping of the nitronate anion by TMSCl (Eq. 17). 

Several examples of conjugate addition of carbanions carried out under aprotic conditions are given in Scheme 2.24. The reactions are typically quenched by addition of a proton source to neutralize the enolate. It is also possible to trap the adduct by silylation or, as we will see in Section 2.6.2, to carry out a tandem alkylation. Lithium enolates preformed by reaction with LDA in THF react with enones to give 1,4-diketones (Entries 1 and 2). Entries 3 and 4 involve addition of ester enolates to enones. The reaction in Entry 3 gives the 1,2-addition product at —78°C but isomerizes to the 1,4-product at 25° C. Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,(3-unsaturated esters (Entry 5). Entries 6 to 8 show cases of... 

The main MS/MS techniques are precursor ion, product ion, and neutral loss. In addition, it is possible to carry out MSn experiments using an ion trap (Kang and others 2007). In this context, de Rijke and others (2003) carried out a study with 15 flavonoids, comparing different ionization sources and different analyzers. Among the results, the authors showed that the main fragmentations observed in the MS spectra on the ion trap, or the tandem MS spectra on the triple-quadrupole, were generally the same. 

Low Mass Region. All spectra shown in the examples were acquired using the quadmpole ion trap mass spectrometer. As noted previously, this widely used and relatively cheap mass analyzer suffers the low-mass cut-off phenomena. In addition to techniques used in the examples shown above, other mass analyzers applied for tandem mass spectrometers may cover the low mass region of the fragmentation spectmm that can be information rich. 

Several attempts to take advantage of the intermediate boron enolate to achieve tandem conjugate addition-aldol reaction have been proposed [71]. Recently, Chandrasekhar [72] reported the addition of triethylborane to methyl vinyl ketone followed by the in situ trapping of the enolate by aromatic aldehyde (Scheme 26). 

Tandem procedures under hydroformylation conditions cannot only make use of the intrinsic reactivity of the aldehyde carbonyl group and its acidic a-position but they also include conversions of the metal alkyl and metal acyl systems which are intermediates in the catalytic cycle of hydroformylation. Metal alkyls can undergo -elimination leading to olefin isomerization, or couplings, respectively, insertion of unsaturated units enlarging the carbon skeleton. Similarly, metal acyls can be trapped by addition of nucleophiles or undergo insertion of unsaturated units to form synthetically useful ketones (Scheme 1). 

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