Double umpolung

What is more striking is how frequently such entities are generated by the application of two umpoled synthons double umpolung), such as in the reaction of a dithiane anion with an epoxide [85]. The advantage is clear if one of the functional groups must remain protected over many of the subsequent synthesis operations. In the case shown in Scheme 2.49, the keto function is converted into a dithiane at the outset, and therefore needs no extra protection step. 

Scheme 2.49 Double umpolung during generation of a 7,3-difunctionalized skeleton...

The strategy of double umpolung appears suspect at first sight, but it has proven to be effective [86, 87] in the context of many demanding syntheses [88] (Scheme 2.50). 

Aside from the standard use of natural synthons and the routes via double umpolung, there is the possibility of enlisting 1,3-dipolar cycloadditions to form 7,5-difunctionalized molecular skeletons. Typical examples include the addition of nitrones, silyl nitronates [94], or nitrile oxides to alkenes. The initial products of the latter cycloaddition are isoxazolines, which may be refunctionalized in various ways (Scheme 2.52). When this generates sensitive functionalities, refunctionalization may be postponed until later in the synthesis sequence [95]. 

Recently, a further unique domino methodology has been reported by Lu and coworkers (Scheme 2.74) [173]. Herein, a triphenyl phosphine-catalyzed umpolung addition/cyclization of allenes and alkynes containing an electron-withdrawing group 2-316-2-318 followed by reaction with a double nucleophile 2-319 is assumed to account for the production of a broad palette of various heterocycles 2-321 and 2-323 via 2-320 and 2-322, respectively. Dihydrofurans, piperazines, morpholines and diazepanes were obtained during the process. 

Reactive donors can be generated ca-thodically by reductive cleavage of hahdes to carbanions or by reduction of double bonds to radical anions. Using these methods, two acceptors can be dimerized in one step by reductive Umpolung , for example, two molecules of acrylonitrile to adipodini-trile - a reaction, which normally needs two or more steps. 

HP-3 FGI, in order to introduce a C=0 group, modify a double bond or to proceed to a "reactivity inversion" operation Umpolung) in dissonant bifunctional relationships (see below iii-a). 

Hetero-substituted allyl compounds obtained by electrophilic attack in the 1-position can be reduced to give the heteroalkyl compounds carrying the new substituent on the a-carbon atom ( ). In this case, the double bond was used as an activating substituent only, to achieve easier deprotonation and higher nucleophilicity. In both cases the synthetically important umpolung of reactivity was achieved20. 

Such additions of nucleophiles to non-activated double bonds mediated by hypervalent iodine compounds are also possible in other cases (Section 3.5). This umpolung of reactivity is due to the formation of an adduct with hypervalent iodine which renders this intermediate highly electrophilic. In this way 6-propionylflavo-nols gave 1,2-dimethoxy-adducts in methanol-perchloric acid [10] ... 

The side chain R in these enals contained functionalities such as a double bond, or an acetoxy group, which were unaffected. The reaction proceeds again through a vinyl iodonium intermediate which serves as a reactive allyl cation. In this way the umpolung of allylsilanes is achieved and, indirectly, the reactivity of allyl halides is considerably increased. 

Overall the reaction achieves an anti-Michael addition across the double bond of 42, an umpolung reactivity pattern also observed in some unsaturated amides (see below).31... 

A way out may be found if the cycloaddition of diazomethane to 1 occurs in the reverse direction as represented in XVII. Now the newly introduced methylene will be in the appropriate position for ring expansion to a six-mem-bered ring. This requires that the first new C-C bond of I with diazomethane be formed at the /3 carbon of the cyano aciylate group as opposed to V. This is possible thanks to the inversion of polarity or umpolung of the double bond due to its conjugation with the nitrile. This effect along with the influence of the ester overrules the polarization pull of the lactam ring. 

Abstract The possible utilization of room temperature ionic liquids (RTILs), instead of volatile organic compounds (VOCs), in the electrochemical procedures of organic synthesis has been discussed. The synthesis of p-lactams, the activation of carbon dioxide and its utilization as renewable carbon source and the carbon-carbon bond formation reactions via umpolung of aldehydes (benzoin condensation and Stetter reaction) and via Henry reaction have been selected as typical electrochani-cal methodologies. The results, related to procedures performed in RTILs, have been compared with those performed in VOCs. The double role of RTILs, as green solvents and parents of electrogenerated reactive intermediates or catalysts, has been emphasized. 

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