Zinc alkynylide

In 1999, Carreira identified Zn(II) as a metal that, like Ag(I) and Cu(I), is capable of effecting the metalation of terminal acetylenes under mild conditions. Thus, treatment of terminal alkynes with Zn(OTf)2 and NEt3 at room temperature led to the formation of zinc alkynylides (Eq. 4). The zinc salt and the amine base work in synergy to weaken the acetylenic proton, with the acetylene undergoing complexation to the Zn(II) center and the base effecting subsequent deprotonation (Fig. 1) [11]. 

A one-pot tandem process for the synthesis of (E j-enediynes that allows incorporation of ethynyl groups is via Pd-catalyzed coupling of ( j-bromoiodoethylene with zinc alkynylides. " " ... 

The best e.e. values reported to date were achieved by Carreira et al. by direct addition of terminal alkynes to aldehydes in the presence of (+)-A(-methylephedrine as chiral ligand. In several cases the e.e. has been 98%. This method was very general for both aU-phatic and aromatic aldehydes, the alkyne component was flexible, and the reaction conditions were very short. This method involves in situ generation of zinc alkynylide by mixing alkyne, Iriethyl amine, and Zn(OTf)2. Another very intriguing feature is that the method is very general and not substrate dependent (Table 21.4). 

The catalytic enantio-selective addition of zinc alkynylides to various trifluo-romethyl ketones with selectivities that surpass 94% ee has been reported. By using 0 pseudoenantiomeric cinchona alkaloids as chiral ligands (e.g. 22), both enantiomers of the trifluoromethylated products were synthesized. The first experimental and computational evidence has been provided in support of alkynyl group transfer from an intermediate complex formed by transmetallation reaction between the alkynylide and the titanium catalyst. 

In further developments of these C-H amination reactions, Du Bois has examined insertion reactions of ethers and dioxolanes as a strategy to provide access to iminium ions masked as intermediate oxathiazinane N,0-acetals. As an example, sulfamate 203 is transformed into 204 in 92% yield under mild conditions in the presence of 2-4 mol% Rh(I) catalyst. The intermediate acetals are susceptible to nucleophilic opening, as was showcased with the additions of zinc alkynylides in the presence of BF3 to give 205 as a single diastereomer [104], The synthetic versatility of this reaction sequence was ingeniously highlighted in Du Bois synthesis of saxi-toxin 206, a poison associated with oceanic red tides (Scheme 15.26) [106]. 

The new reactivity mode for the in-situ generation of metal alkynylides was exploited in addition reactions to aldehydes. Stoichiometric quantities of Zn(OTf)2 and NEt3 or Hiinig s base effected deprotonation of a number of alkynes which underwent smooth addition to various aldehydes to furnish the corresponding propargylic alcohols (Eq. 5) [13]. Subsequent studies revealed that apart from Zn(OTf)2 other zinc sources such as ZnCl2 and ZnC03 could be used in this reaction (Eq. 6) [14]. 

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