Conjugate substitution alkynylation

In addition to Zn, B, and Sn—three metal countercations that were found to be highly satisfactory for alkynylafiorf —the Sonogashira alkynylation protocol (Sect IIL2X1) has also proved to be generally tqtpUcable to this case. Some representative examples of Pd-catalyzed conjugate substitution with alkynylmetals and terminal alkynes are summarized in Table 3. 

Dieter developed a flexible two step synthesis of substituted pyrroles involving initial Beak deprotonation of /ert-butoxycarbonyl (Boc) amines 36 followed by addition of CuX-2LiCl (X = -Cl, -CN) to afford a-aminoalkylcuprates. Such cuprates undergo conjugate addition reactions to a,(3-alkynyl ketones affording a,(3-enones 37, which upon treatment with PhOH/TMSCl undergo carbamate deprotection and intramolecular cyclization to afford the pyrroles 38 . 

As previously mentioned, allenes can only be obtained by 1,6-addition to acceptor-substituted enynes when the intermediate allenyl enolate reacts regioselectively with an electrophile at C-2 (or at the enolate oxygen atom to give an allenyl ketene acetal see Scheme 4.2). The regioselectivity of the simplest trapping reaction, the protonation, depends on the steric and electronic properties of the substrate, as well as the proton source. Whereas the allenyl enolates obtained from alkynyl enones 22 always provide conjugated dienones 23 by protonation at G-4 (possibly... 

Similar to the addition reactions of acceptor-substituted dienes (Scheme 16), the outcome of the transformation depends on the regioselectivity of the nucleophilic attack of the organocopper reagent (1,4- vs. 1,6-addition) and of the electrophilic capture of the enolate formed. The allenyl enolate obtained by 1,6-addition can afford either a conjugated diene or an allene upon reaction with a soft electrophile, and thus opens up the possibility to create axial chirality. The first copper-mediated addition reactions to Michael acceptors of this type, for example, 3-alkynyl-2-cyclopentenone 75,... 

The last example is the acidity of the ethynyl-expanded cubane 3. Inspired by the synthesis of the methoxy-substituted buta-l,3-diynediyl expanded cubane 4, Bachrach examined some of the properties of its smaller homolog 3. Since the s-character of the C-H bonds of 3 should be large and its conjugate base 3cb can potentially delocalize the anion into three neighboring alkynyl units, 3 might be quite acidic. 

---