Table 3 Scope of the intermolecular linear-selective hydroacylation
employing alkyne 2a with various b-S-aldehydesa
an a-substituent (entry 10) enables the possibility for the
development of an asymmetric process.12
In conclusion, we have demonstrated a highly linear-selective
alkyne hydroacylation process. Using a dcpe-derived catalyst it is
possible to obtain excellent yields and regioselectivities for a range
of electron-rich and electron-poor aromatic aldehydes, in addition
to alkyl aldehydes and synthetically interesting enal substrates.
Excellent reactivity and selectivity is also observed for a range
of electron-deficient aromatic alkynes, as well as more electron-
rich examples. This methodology, in combination with our
previously reported branch-selective chemistry, allows ligand-
controlled regioselectivity switching across a broad range of
substrate combinations.
Entry
1
Aldehyde
Product
Regioselectivityb
>20 : 1
Yieldc
82%
3k
Notes and references
1 (a) M. C. Willis, Chem. Rev., 2010, 110, 725; (b) C. Jun, E. Jo, C.-H.
Jun, E.-A. Jo and J.-W. Park, Eur. J. Org. Chem., 2007, 1869.
2 Recent examples: (a) A. H. Roy, C. P. Lenges and M. Brookhart, J. Am.
Chem. Soc., 2007, 129, 2082; (b) S. Omura, T. Fukuyama, J. Horiguchi,
Y. Murakami and I. Ryu, J. Am. Chem. Soc., 2008, 130, 14094;
(c) F. Shibahara, J. F. Bower and M. J. Krische, J. Am. Chem. Soc.,
2008, 130, 14120; (d) V. M. Williams, J. C. Leung, R. L. Patman and
M. J. Krische, Tetrahedron, 2009, 65, 5024; (e) A. B. Chaplin, J. F.
Hooper, A. S. Weller, M. C. Willis and M. C. , J. Am. Chem. Soc., 2012,
134, 4885.
3 Recent examples: (a) M. Imai, M. Tanaka, K. Tanaka,
Y. Yamamoto, N. Imai-Ogata, M. Shimowatari, S. Nagumo,
N. Kawahara and H. Suemune, J. Org. Chem., 2004, 69, 1144;
(b) T. Tanaka, M. Tanaka and H. Suemune, Tetrahedron Lett.,
2005, 46, 6053; (c) K. Tanaka, Y. Shibata, T. Suda, Y. Hagiwara
and M. Hirano, Org. Lett., 2007, 9, 1215.
4 Y. Inui, M. Tanaka, M. Imai, K. Tanaka and H. Suemune, Chem.
Pharm. Bull., 2009, 57, 1158.
5 M. C. Coulter, K. G. M. Kou, B. Galligan and V. M. Dong, J. Am.
Chem. Soc., 2010, 132, 16330.
6 H.-J. Zhang and C. Bolm, Org. Lett., 2011, 13, 3900.
7 C.-H. Jun, H. Lee, J.-B. Hong and B.-I. Kwon, Angew. Chem., Int. Ed.,
2002, 41, 2146.
8 Dong has described a ligand-controlled branched to linear switch
for a single substrate employed in an intramolecular Rh-catalysed
alkene hydroacylation: M. M. Coulter, P. K. Dornan and
V. M. Dong, J. Am. Chem. Soc., 2009, 131, 6932.
2
3l
>20 : 1
73%
3
3m
3n
3o
3p
3q
>20 : 1
>20 : 1
>20 : 1
>20 : 1
>20 : 1
70%
94%
78%
85%
63%
4
5d
6
7
9 (a) M. C. Willis, S. J. McNally and P. J. Beswick, Angew. Chem., Int.
Ed., 2004, 43, 340; (b) M. C. Willis, H. E. Randell-Sly, R. L. Woodward
and G. S. Currie, Org. Lett., 2005, 7, 2249; (c) M. C. Willis,
H. E. Randell-Sly, R. L. Woodward, S. J. McNally and G. S. Currie,
J. Org. Chem., 2006, 71, 5291; (d) G. L. Moxham, H. E. Randell-Sly,
S. K. Brayshaw, R. L. Woodward, A. S. Weller and M. C. Willis,
Angew. Chem., Int. Ed., 2006, 45, 7618; (e) G. L. Moxham,
H. E. Randell-Sly, S. K. Brayshaw, A. S. Weller and M. C. Willis,
Chem.–Eur. J., 2008, 14, 8383; (f) J. D. Osborne and M. C. Willis, Chem.
Commun., 2008, 5025; (g) H. E. Randell-Sly, J. D. Osborne,
R. L. Woodward, G. S. Currie and M. C. Willis, Tetrahedron, 2009,
65, 5110; (h) R. J. Pawley, G. L. Moxham, R. Dallanegra,
A. B. Chaplin, S. K. Brayshaw, A. S. Weller and M. C. Willis,
Organometallics, 2010, 29, 1717; (i) P. Lenden, D. A. Entwistle and
M. C. Willis, Angew. Chem., Int. Ed., 2011, 50, 10657; (j) S. R. Parsons,
J. F. Hooper and M. C. Willis, Org. Lett., 2011, 13, 998; (k) P. Lenden,
8
3r
3s
>20 : 1
>20 : 1
84%
9e
80%f
10
3t
>20 : 1
>20 : 1
54%
74%
11
3u
P. M. Ylioja, C. Gonzalez-Rodrıguez, D. A. Entwistle and M. C. Willis,
´ ´
Green Chem., 2011, 13, 1980.
10 Specific substrate combinations lead to branched products: vinyl-
sulfone,9a diene,9a nitrile-substituted alkyne9c.
11 C. Gonzalez-Rodriguez, R. J. Pawley, A. B. Chaplin, A. L. Thompson,
A. S. Weller and M. C. Willis, Angew. Chem., Int. Ed., 2011, 50, 5134.
a
Conditions: aldehyde 1a (0.30 mmol), alkyne (0.45 mmol),
[Rh(nbd)2]BF4 (5 mol%), dcpe (5 mol%), acetone, (2 mL, 0.15 M),
RT, 1–2.5 h. Determined by 1H NMR analysis of crude reaction
b
c
d
mixtures. Yields of isolated products. Reaction carried out at 50 1C
for 18 h. Aldehyde used as a 9 : 1 mixture of anti:syn diastereomers.
e
12 (a) C. Gonza
M. C. Willis, Chem.–Eur. J., 2010, 16, 10950; (b) C. Gonza
Rodrıguez and M. C. Willis, Pure Appl. Chem., 2011, 83, 577.
´
lez-Rodrı
´
guez, S. R. Parsons, A. L. Thompson and
f
´
lez-
Obtained as a 9 : 1 mixture of anti:syn diastereomers.
´
c
This journal is The Royal Society of Chemistry 2012
6356 Chem. Commun., 2012, 48, 6354–6356