Tandem electrophile/nucleophile

Scheme 55. Tandem electrophile/nucleophile addition to the y -benzene ligand of TpRe(CO) (MeIm)(f/ -benzene) (MMTP = l-methoxy-2-methyl-l-(trimethylsiloxy)propene).

This synthesis of 1 is noteworthy for its seminal demonstration of the utility of tandem electrophilic hydrazination-nucleophilic cyclisation9 for preparing functionalised homochiral cyclic a hydrazino acids.10 It highlights, yet again, the great utility of functionalised glyceraldehyde synthons for the installation of remote hydroxy stereocentres in natural product target molecules. 

Another example for gem-functionalization is demonstrated in the reaction with disulfides. The tandem sulfenylation and carbonylation to 1-alkylthiocy-clopropanecarbothioates 168 are realized, indicating that disulfides can serve both as nucleophiles and electrophiles [81], (Scheme 63)... 

Among all tandem hydroformylation sequences the ones involving additional C,C-bond formations are the most synthetically valuable tandem hydroformylation sequences. These C,C-bonds can be formed by adding nucleophiles, which attack the carbonyl carbon, or by adding electrophiles, which attack the a-position. Furthermore, tandem reactions in which the aldehyde or an aldehyde derivative is involved in sigmatropic rearrangement are described. 

In almost the same manner, tandem hydroformylation/aldol condensation aldol condensation of ketoolefins, such as p,y-unsaturated ketones, gives a single cyclization product under acid catalysis. Similar to the stepwise reaction, the in situ generated aldehyde preferentially acts as the electrophilic carbonyl component, while the ketone acts as the nucleophilic enol to form the five-membered ring product. Subsequent dehydration and hydrogenation of the resulting enone readily occurs under the reductive reaction conditions used (Scheme 30) [84],... 

Electrophiles that have been used for the second alkylation of this tandem Michael addition -alkylation sequence are limited to primary iodoalkanes, (bromomethyl)benzenes and 3-bromo-propenes. Tables 9 and 10 provide details of the alkylations of enolate species prepared by 1,4-additions of -a,/j-unsaturated iron-acyl complexes by anionic carbon nucleophiles and anionic nitrogen nucleophiles, respectively. 

Derivatives of trifluoroethanethiol have limited though interesting chemistry. Unfortunately, metallated difluorothioenol chemistry has not been reported, because rapid nucleophilic attack occurs even by hindered bases such as LDA. Nakai et al. exploited this high electrophilicity in a tandem addition/elimina-tion-rearrangement sequence [146], but more recent applications have concerned free radical chemistry (Eq. 46). Chlorination of trifluoroethyl phenyl sulfide followed by exposure to tin hydride in the presence of an allylstannane resulted in C-C bond formation with a reasonable level of stereocontrol [147]. 

Dihydrooxazoles are also effective ortho directors for nucleophilic addition to naphthalene and some heteroaromatic derivatives. Tandem additions result if the reaction mixtures are quenched with electrophiles (Scheme 72). 

A consideration in a tandem strategy is the choice of two pairs of nucleophiles and electrophiles to achieve the reaction sequences of cyclization and convergent ligation. One entire pair essential for the cyclization reaction is placed in the peptide precursor, while the other pair for the convergent ligation is split between the peptide and the core. Although various combinations of these pairs can be exploited for the sequential reactions in thiol and... 

The general reaction sequence has been named more specifically as tandem vicinal dialkylation, nucleophilic-electrophilic carbacondensation,11 dicarbacondensation1213 or conjugate addition-enolate trapping,14 usually in reference to the fact that most of the reaction examples available create two new vicinal carbon-carbon bonds. Many noncarbon nucleophiles and electrophiles also are known, resulting... 

The two distinct bond-forming steps in tandem vicinal difunctionalization have been studied extensively. The first step consists of a nucleophilic addition to a ir-system the nucleophile is almost invariably an organometal. 1,4-Addition to an a, -unsaturated carbonyl substrate concomitantly generates a new cr-bond at the (3-carbon and an enolate ion. The second step constitutes C-functionalization of the enolate intermediate, forming a new o -bond between the nucleophilic a-carbon of the enolate and an electrophilic reagent. 

In conclusion, it should be noted that the Barton-Zard condensation formally might be considered as a tandem SnH-Sn ipso process (see Section III.B.3). However, the corresponding crH-complcx is stabilized here not via elimination of any auxiliary leaving group or oxidation but by means of an intramolecular nucleophilic attack on an isonitrile fragment. This is due to the amphoteric nature of isocyanoacetate ion acting at first as a nucleophile and then as an electrophile. 

Benzynes generated from silylaryl triflates 803 react with ortho-hydroxy benzoates via a tandem nucleophilic coupling-electrophilic cyclization process to afford xanthones in good yield (Scheme 224) <2005OL4273>. 

---