1229
We have found that zinc cyanocuprates RCu(CN)ZnCl·2LiCl (Knochel reagents),7 generated in THF
at −10°C from alkylzinc chlorides and the soluble copper salt CuCN.2LiCl, react with bromoallenes
1 more slowly than the corresponding magnesium bromocuprates but afford acetylenes 2 with higher
regioselectivity (Table 1). In this case, acetylenic products are obtained with a generally high yield
even starting from hindered 3,3-disubstituted allenic substrates and secondary or α-branched primary
copper compounds (entries 1–6); only when a tertiary group is bonded to the copper atom do the
steric requirements of the substrate determine the product distribution (entries 8, 9). Interestingly,
even with 3-phenyl-1-bromopropadiene, 1c, zinc alkylcyanocuprates selectively afford 1-alkynes, while
with bromocuprates substantial amounts of polymeric byproducts are obtained (entries 10, 11).3 As
an exception, it is noteworthy that the phenylbromocuprate (PhCuBr)MgBr.LiBr provides 3-phenyl-1-
alkynes with a higher regioselectivity than the corresponding zinc-based cuprate (entries 12, 13).3
The zinc–cuprate procedure can be greatly extended to the preparation of a large variety of func-
tionalized acetylenic systems. In fact, bromoallenes 1d and 1f, as hindered model substrates, have been
converted in a regiospecific way into pure 1-alkynes by treatment with copper derivatives characterized by
various functional groups (entries 14–21). In general, the necessary organozinc chlorides were prepared
from the corresponding Grignard reagents by transmetallation with ZnCl2 (entries 14–20). However,
functionalized zinc derivatives can be directly obtained from organic halides with several methods7
avoiding the use of protection–deprotection steps as well as functional group interconversions (entry
21).
Finally, the cross-coupling reaction can be done with zinc reagents using catalytic amounts of copper.
Bromoallenes 1 react with alkylzinc chlorides in the presence of 5–10 mol% (relative to RZnCl) of
CuCN·2LiCl, or some other cuprous salts, affording alkynes 2 with high chemo and regioselectivity
(Table 2). The reaction rate is generally slow, especially increasing the steric requirements of both
the reagent and the substrate, but increasing the reaction temperature can overcome this inconvenience
(entries 28, 29).8
In all cases, carrying out the coupling process either with stoichiometric or catalytic zinc cuprates, the
conversion of enantioenriched bromoallenes 1 into optically active acetylenic compounds 2 proceeds in a
highly anti stereoselective fashion. Eq. (1) presents the stereochemical data5 obtained in the preparation
of (S)-3-methyl-3-propyl-1-heptyne from (S)-1-bromo-3-methyl-1,2-hexadiene via the copper catalyzed
coupling.
(1)
In this context it is worthwhile noting that: (i) the reaction of bromoallenes with Grignard reagents in
the presence of cuprous salts gives quantitatively the allenic derivatives 3 with complete inversion of the
allenyl moiety;6,9 (ii) the coupling of the same chiral substrates with organozinc chlorides promoted by
nickel or palladium complexes also affords allenes but with almost complete loss of stereochemistry.10
Acknowledgements
We thank the Ministero dell’Università e della Ricerca Scientifica e Tecnologica-Progetto Naz, le
Stereoselezione in Sintesi Organica, Metodologie ed Applicazioni for financial support.