was 0.25%.4b,12 Our 0.01% catalyst loading thus represents
an unprecedentedly low amount.
Table 4. Tandem Reactions of Arylboronic Acids with Enals
Catalyzed by Orthoplatinated Triarylphosphite 4a
We have also employed 4 as the catalyst for the competi-
tive addition reaction of phenylboronic acid with chalcone
and 3-methylbutanal.13,14 We found that with 4 as the
catalyst, the reaction exclusively occurred at the chalcone
while with palladacycle 3 as the catalyst an almost 1:1 ratio
of 1,4-addition and 1,2-addition products were observed
(Scheme 2). Such a chemoselectivity difference could be
Scheme 2
.
Cross-Couplings vs. Addition Reactions for Type I
Palladacycles
a Reaction conditions: aldehyde (1.0 equiv), aryylboronic acid (3.0
equiv), toluene (2 mL), K3PO4 (2.0-6.0 equiv), 80 °C. b Isolated yields.
air/moisture-stable orthoplatinated triarylphosphite 4 was a
highly efficient catalyst for the addition reactions of aryl-
boronic acids with aldehydes, with unprecedentedly low
catalyst loading. The soft nature of Pt also allowed us to
develop a new tandem reaction sequence of arylboronic acids
with R,ꢀ-unsaturated aldehydes. The study described here
provided a new paradigm for the application of orthoplati-
nated triarylphosphites,18,19 and may pave the road for the
development of other platinum complexes as unique catalysts
for such addition reactions. In addition, our work may also
lead to the development of other tandem reactions involving
the addition reaction of arylboronic acids with aldehydes as
part of the reaction sequence.
explained by the fact that platinum is softer than palladium,
and the latter can activate the aldehyde carbonyl group better.
These results, combined with the results in Table 2 (entries
16 and 17), suggested that 4 could be an excellent catalyst
for a new addition reaction sequence of arylboronic acids
with R,ꢀ-unsaturated aldehydes: 1,4-addition followed by
1,2-addition. We thus also explored such a tandem reaction
sequence and our results are listed in Table 4. Our study
showed that the tandem reaction occurred smoothly, and
double addition products were obtained in good yields. To
our knowledge, previously reported addition reactions of
arylboronic acids with enals either afforded 1,2-addition
product, allylic alcohols, or 1,4-addition product, ꢀ-arylated
aldehydes;15,16 our results represent the first examples that
arylboronic acids add to R,ꢀ-unsaturated aldehydes succes-
sively to form 1,3-diaryl-1-propanols.17
Acknowledgment.WegratefullythanktheNSF(CHE0719311)
and NIH (GM69704) for funding. Partial support from the
PSC-CUNY Research Award Program is also gratefully
acknowledged. We also thank Frontier Scientific, Inc. for
its generous gifts of arylboronic acids.
In summary, we have demonstrated that readily available,
(14) For Rh(I)-catalyzed 1,4-addition of organoboronic acid with R,ꢀ-
unsturated ketones, see reviews: (a) Hayashi, T.; Yamasaki, K. Chem. ReV.
2003, 103, 2829–2844. (b) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103,
169–196. Selected recent examples: (c) Trenkle, W. C.; Barkin, J. L.; Son,
S. U.; Sweigart, D. A. Organometallics 2006, 25, 3548–3551. (d) Chen,
F.-X.; Kina, A.; Hayashi, T. Org. Lett. 2006, 8, 341–344. (e) Shintani, R.;
Supporting Information Available: General procedures
and characterizations of 4-catalyzed addition reactions. This
material is available free of charge via the Internet at
Duan, W.-L.; Hayashi, T. J. Am. Chem. Soc. 2006, 128, 5628–5629
.
OL800774C
(15) For Rh(I)-catalyzed 1,4-addition reactions of arylboronic acids with
enals, see: (a) Douglas, T. M.; Le Notre, J.; Brayshaw, S. K.; Frost, C. G.;
Weller, A. S. Chem. Commun. 2006, 3408–3410. (b) Fujita, N.; Motokura,
K.; Mori, K.; Mizugaki, T.; Ebitani, K.; Jitsukawa, K.; Kaneda, K.
Tetrahedron Lett. 2006, 47, 5083–5087. (c) Trenkle, W. C.; Barkin, J. L.;
Son, S. U.; Sweigart, D. A. Organometallics 2006, 25, 3548–3551. (d)
Paquin, J.-F.; Defieber, C.; Stephenson, C. R. J.; Carreira, E. M. J. Am.
Chem. Soc. 2005, 127, 10850–10851. (e) Hayashi, T.; Tokunaga, N.;
Okamoto, K.; Shintani, R. Chem. Lett. 2005, 34, 1480–1481. (f) Itooka,
R.; Iguchi, Y.; Miyaura, N. J. Org. Chem. 2003, 68, 6000–6004. (g) Paquin,
F.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M. Org. Lett. 2005, 7,
(17) 1,3-Diaryl-1-propanols are a common structural unit for a number
of biologically active compounds or intermediates for the preparation of
biologically active compounds. For examples see: (a) Gunn, D.; Akuche,
C.; Baryza, J.; Blue, M.-L.; Brennan, C.; Campbell, A.-M.; Choi, S.; Cook,
J.; Conrad, P.; Dixon, B.; Dumas, J.; Ehrlich, P.; Gane, T.; Joe, T.; Johnson,
J.; Jordan, J.; Kramss, R.; Liu, P.; Levy, J.; Lowe, D.; McAlexander, I.;
Natero, R.; Redman, A. M.; Scott, W.; Seng, T.; Sibley, R.; Wang, M.;
Wang, Y.; Wood, J.; Zhang, Z. Bioorg. Med. Chem. Lett. 2005, 15, 3053–
3057. (b) Boschetti, E.; Molho, D.; Chabert, J.; Grand, M.; Fontaine, L.
Chim. Ther. 1972, 7, 20–23. (c) Skytte, D.; Nielsen, S. F.; Chen, M.; Zhai,
L.; Olsen, C. E.; Brogger Christensen, S. J. Med. Chem. 2006, 49, 436–
3821–3824. For 1,2-additions, see refs 2i and 2x
.
(16) For Pd-catalyzed 1,4-additions of arylboronic acids with enals, see:
(a) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Tetrahedron Lett. 2007, 48,
4007–4010. (b) Lin, S.; Lu, X. Tetrahedron Lett. 2006, 47, 7167–7170. (c)
Lu, X.; Lin, S. J. Org. Chem. 2005, 70, 9651–9653. (d) Gini, F.; Hessen,
B.; Minnaard, A. J. Org. Lett. 2005, 7, 5309–5312. (e) Nishikata, T.;
Yamamoto, Y.; Miyaura, N. Organometallics 2004, 23, 4317–4324. (f)
Nishikata, T.; Yamamoto, Y.; Miyaura, N. Angew. Chem., Int. Ed. 2003,
440
.
(18) We found 4 was an excellent catalyst for the 1,4-addition of
arylboronic acid with R,ꢀ-unsaturated ketones; see the Supporting Informa-
tion
(19) The addition of phenylboronic acid with chalcone catalyzed by 4
(5% 4, room temperature, 1 h, 71% conversion) was recently reported; see
ref 9.
.
42, 2768–2770
.
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Org. Lett., Vol. 10, No. 12, 2008