Letter
Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydrocyanation
of Silyl-Substituted 1,3-Diynes
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ABSTRACT: A regiodivergent nickel-catalyzed hydrocyanation of
1-aryl-4-silyl-1,3-diynes is reported. When appropriate bisphos-
phine and phosphine−phosphite ligands are applied, the same
starting materials can be converted into two different enynyl
nitriles with good yields and high regioselectivities. The DFT
calculations unveiled that the structural features of different ligands
bring divergent alkyne insertion modes, which in turn lead to
different regioselectivities. Moreover, the synthetic value of the
cyano-containing 1,3-enynes has been demonstrated with several downstream transformations.
1,3-Enynes are prominent structural motifs that are often
found in many bioactive molecules and organic materials.1 The
1,3-enyne scaffold is also a versatile building block in synthetic
organic chemistry.2 Of note, 1,3-enynes with electron-with-
drawing groups (i.e., esters, ketones) are particularly attractive
as they bear the potential to be employed in the construction
of thiophenes,3 isoxazoles,4 furans,5 pyrrolines,6 allenes,7 1,3-
dienes,8 and many others. Among these active 1,3-enynes, the
use of cyano-substituted ones was rarely reported, although
particularly useful in annulation reactions. Indeed, cyano-
substituted 1,3-enynes enable the preparation of pharmaceuti-
cally interesting cyano-containing heterocycles.9 Obviously, the
lack of efficient synthetic methods for cyano-containing 1,3-
enynes restricts their potential applications.10 It is therefore of
high interest to develop efficient, highly regio- and stereo-
selective synthesis of cyano-containing 1,3-enynes.
Recently, the transition-metal-catalyzed functionalization of
1,3-diynes has attracted increasing attention.11 In the view of
atom-efficient organic synthesis, the hydrofunctionalization of
1,3-diynes paved a new avenue for accessing functionalized 1,3-
enynes. Based on our continuous interest in catalytic
hydrocyanation of unsymmetrical internal alkynes,12 we
envisioned that the hydrocyanation of 1-aryl-4-silyl-1,3-diynes
(silyl activated 1,3-diynes) might be an efficient approach for
the synthesis of cyano-substituted conjugated enynes because
1-aryl-4-silyl-1,3-diynes were readily available via Glaser
coupling. The corresponding products could be easily derived
through desilylation. In sharp contrast to the hydrocyanation
of alkynes,13 the hydrocyanation of 1,3-diynes still remains
elusive in the literature due to the intractable challenges in
regio- and stereoselectivity control for unsymmetrical internal
alkynes. Until now, only a limited number of special
unsymmetrical internal alkynes have been hydrocyanated
with high regio- and stereoselectivity.14 Obviously, the
hydrofunctionalization of unsymmetrical 1-aryl-4-silyl-1,3-
diynes would pose extra difficulties in regard to monoalkynes:
(a) Regioselectivity between two alkyne motifs (Scheme 1a,
A);11a,b,e (b) regioselectivity in each migratory insertion
(Scheme 1a, B),11d (c) selectivity between mono- and
dihydrofunctionalization (Scheme 1a, C),11c and (d) stereo-
selectivity in each migratory insertion (Scheme 1a, D).
Despite the lack of examples involving the hydrocyanation of
1-aryl-4-silyl-1,3-diynes, significant advancements in the hydro-
functionalization of 1-aryl-4-silyl-1,3-diynes have been made
over the past few decades. These hydrofunctionalizations
usually occurred at one alkyne of the unsymmetrical 1,3-diynes
with high regioselectivity (Scheme 1b). For example, hydro-
amidation,11a hydroesterification,11b hydroboration,11f and
hydrosilylation,11e of 1-aryl-4-silyl-1,3-diynes preferentially
took place at the 1,2-CC (Scheme 1b, left). Furthermore,
the Ge group reported a regiodivergent hydroboration of 1-
aryl-4-silyl-1,3-diynes in which the 1,2-CC bond inserted
into either a cobalt−hydride or cobalt−boryl intermediate
(Scheme 1b, left).11d To the best of our knowledge, the only
example concerning the selective hydrofunctionalization of the
3,4-CC bond of 1-aryl-4-silyl-1,3-diynes was reported by
Krische and co-workers wherein α-hydroxy esters were
constructed, and the reaction occurred exclusively at the
silyl-substituted CC bond (Scheme 1b, right).11g However,
the regiodivergent hydrofunctionalization of aryl-/silyl-sub-
stituted 1,3-diynes is an alluring but rather demanding task,
which may offer new tools for the construction of more
Received: April 14, 2021
Published: May 12, 2021
© 2021 American Chemical Society
Org. Lett. 2021, 23, 4045−4050
4045