Iridium/chiral diene-catalyzed asymmetric 1,6-addition of arylboroxines to α,β,γ,δ-unsaturated carbonyl compounds

Article abstract of DOI:10.1021/ja1034842

Iridium-catalyzed asymmetric 1,6-addition of arylboroxines to α,β,γ,δ-unsaturated carbonyl compounds to give δ-arylated carbonyl compounds in high yields with 90-99% enantioselectivity was realized by use of an iridium/chiral diene complex.

Full text of DOI:10.1021/ja1034842

Published on Web 05/19/2010
Iridium/Chiral Diene-Catalyzed Asymmetric 1,6-Addition of Arylboroxines to
r,ꢀ,γ,δ-Unsaturated Carbonyl Compounds
Takahiro Nishimura,* Yuichi Yasuhara, Takahiro Sawano, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Kyoto 606-8502, Japan
Received April 24, 2010; E-mail: tnishi@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp
Scheme 1
Transition-metal-catalyzed asymmetric 1,4-addition of organo-
metallic reagents to R,ꢀ-unsaturated carbonyl compounds has been
rapidly developed over the past decade.1 On the contrary, progress
in asymmetric addition to extended conjugated systems (e.g., 1,6-
addition to R,ꢀ,γ,δ-unsaturated carbonyl compounds) has been
modest to date because of the difficulty of controlling the regiose-
lectivity as well as the enantioselectivity. Copper reagents and
catalysts are often used for selective 1,6-addition reactions,1-3 and
reports of asymmetric 1,6-addition reactions catalyzed by rhodium4
and copper have recently appeared.5-7 Successful examples of
asymmetric 1,6-addition to dienones and dienoates having ꢀ-sub-
stituents to suppress the competing 1,4-addition have been reported
by us (Rh),4 Fillion (Cu),5 and Alexakis (Cu).6 In 2008, Feringa
succeeded in the highly enantioselective 1,6-addition of alkyl
Table 1. Ligand Screeninga
Grignard reagents to simple acyclic dienoates by use of a Cu/
bisphosphine catalyst.7 Here we report the enantioselective conju-
gate addition of arylboroxines to linear R,ꢀ,γ,δ-unsaturated carbonyl
compounds with perfect 1,6-selectivity, which is realized by the
use of a chiral iridium complex as a catalyst.8-10
We recently reported that perfect 1,6-selectivity is achieved in
the addition of arylboroxines to R,ꢀ,γ,δ-unsaturated carbonyl
compounds catalyzed by a hydroxoiridium complex coordinated
with 1,5-cyclooctadiene (cod).11 The findings prompted us to use
chiral diene ligands12 for the asymmetric variants of the iridium-
catalyzed 1,6-addition. Of chiral diene ligands in our hands, C2-
symmetric tetrafluorobenzobarrelenes (tfb’s)13 were found to display
high catalytic activity and enantioselectivity (Scheme 1 and entry
1 in Table 1). Thus, treatment of (3E,5E)-3,5-heptadien-2-one (1a)
with phenylboroxine (2m) (3 equiv of B) in the presence of
[IrCl((S,S)-Me-tfb*)]213b,14 (5 mol % Ir) and K2CO3 (5 mol %) in
MeOH at 30 °C for 20 h gave a 90% yield of a mixture of 1,6-
adducts consisting of (Z)-6-phenyl-4-hepten-2-one (3am) as the
major isomer, its E isomer 4am, and the conjugate enone 5am
(3am/4am/5am ) 86/10/4).15 The mixture was subjected to
isomerization mediated by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)
to give conjugate enone 5am as the major isomer (5am/4am )
94/6). Silica gel chromatography gave pure 5am in 85% yield
(based on 1a), whose ee was 99% (S).16 The use of phenyl- and
benzyl-substituted tfb ligands (Ph-tfb* and Bn-tfb*)13c gave, after
isomerization, 5am with 97 and 99% ee, respectively (Table 1,
entries2and3).Achiraldieneligandhavingabicyclo[2.2.2]octadiene
framework (Bn-bod*)17 displayed high enantioselectivity (99% ee),
although the yield of 5am was moderate (56%) because of
incomplete conversion of starting enone 1a (entry 4). The ligand
(R)-L1,18 which is readily derived from a natural product, gave
5am in 97% ee (entry 5). The 1,6-addition was not observed at all
in the presence of iridium catalysts with bisphosphine ligands
(binap, segphos) or a phosphoramidite.19
entry
ligand (L*)
isolated yield of 5am (%)
ee (%)
1
2
3
4
5
(S,S)-Me-tfb*
(S,S)-Ph-tfb*
(S,S)-Bn-tfb*
(S,S)-Bn-bod*
(R)-L1
85
72
73
56
67
99 (S)
97 (S)
99 (S)
99 (S)
97 (R)
a Reaction conditions: dienone 1a (0.30 mmol), phenylboroxine (2m)
(0.30 mmol, 3 equiv of B), [IrCl(L*)]2 (5 mol % Ir), K2CO3 (5 mol %),
MeOH (0.90 mL). See the Supporting Information for details.
Me or Pr at the δ-position gave, after isomerization, the corre-
sponding conjugate enones 5bm-dm in good yields with g90%
ee (entries 2-4). Aryl groups having several substituents were
successfully introduced in the reactions of 1a or 1b with 2n-r,
giving the corresponding 1,6-addition products (5an, 5bn-br) in
good yields with very high enantioselectivity (98-99% ee; entries
5-10).
This iridium-catalyzed reaction can also be applied to conjugate
dienamides (1e and 1f) and a dienoate 1g to give, after hydrogena-
tion of the initially formed 1,6-adducts, the corresponding δ-arylated
amides and ester in high yields with high enantioselectivity (Table
3).
The results obtained for the iridium-catalyzed 1,6-addition of
arylboroxines to dienones are summarized in Table 2. Phenylation
of dienones substituted with Et or Bu at the carbonyl carbon and
The present asymmetric 1,6-addition enables a short synthesis
of a natural product, curcumene20 (Scheme 2). Thus, rhodium-
catalyzed 1,4-hydrosilylation21 of conjugate enone 5an obtained
t
9
7872 J. AM. CHEM. SOC. 2010, 132, 7872–7873
10.1021/ja1034842  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. 1,6-Addition to Dienonesa
while the use of (R,R)-Me-tfb* gave syn-adduct 10 with high
stereoselectivity.
In summary, we have developed an iridium-catalyzed asymmetric
1,6-addition of arylboroxines to R,ꢀ,γ,δ-unsaturated carbonyl
compounds that is realized by the use of an iridium/chiral diene
complex and gives δ-arylated carbonyl compounds in high yields
with high enantioselectivity.
entry
R1
R2
Ar
yield (%)b
ee (%)
1
2
3
4
5
6
Me
Et
Me (1a)
Me (1b)
Me (1c)
Pr (1d)
Me (1a)
Me (1b)
Me (1b)
Me (1b)
Me (1b)
Me (1b)
Ph (2m)
Ph (2m)
Ph (2m)
Ph (2m)
4-MeC6H4 (2n)
4-MeC6H4 (2n)
3-MeC6H4 (2o)
4-ClC6H4 (2p)
4-FC6H4 (2q)
2-naphthyl (2r)
85 (5am)
84 (5bm)
81 (5cm)
57 (5dm)
76 (5an)
81 (5bn)
85 (5bo)
83 (5bp)
82 (5bq)
76 (5br)
99
98
90
97
99
99
99
99
99
98
Acknowledgment. This work was supported by a Grant-in-Aid
for Scientific Research (S) (19105002) from the MEXT, Japan. Y.Y.
thanks the JSPS for a Research Fellowship for Young Scientists.
tBu
Et
Me
Et
Et
Et
Et
Supporting Information Available: Experimental procedures,
spectroscopic and analytical data for products, and crystallographic data
(CIF). This material is available free of charge via the Internet at http://
pubs.acs.org.
7
8c
9c
10
Et
a See the Supporting Information for details. b Isolated yield.
c Reaction for 48 h.
References
Table 3. 1,6-Addition to Dienamides and a Dienoatea
(1) For reviews, see: (a) Sibi, M. P.; Manyem, S. Tetrahedron 2000, 56, 8033.
(b) Krause, N.; Hoffmann-Ro¨der, A. Synthesis 2001, 171. (c) Hayashi, T.;
Yamasaki, K. Chem. ReV. 2003, 103, 2829. (d) Christoffers, J.; Koripelly,
G.; Rosiak, A.; Ro¨ssle, M. Synthesis 2007, 1279. (e) Harutyunyan, S. R.;
den Hartog, T.; Geurts, K.; Minnaard, A. J.; Feringa, B. L. Chem. ReV.
2008, 108, 2824.
(2) For reviews, see: (a) Yamamoto, Y. Angew. Chem., Int. Ed. Engl. 1986,
25, 947. (b) Krause, N.; Gerold, A. Angew. Chem., Int. Ed. Engl. 1997,
36, 186. (c) Krause, N.; Thorand, S. Inorg. Chim. Acta 1999, 296, 1.
(3) For recent examples of nonasymmetric 1,6-selective conjugate addition,
see: (a) Fukuhara, K.; Urabe, H. Tetrahedron Lett. 2005, 46, 603. (b) de la
Herra´n, G.; Murcia, C.; Csa´ky¨, A. G. Org. Lett. 2005, 7, 5629. (c) de la
Herra´n, G.; Csa´ky¨, A. G. Synlett 2009, 585.
entry
X
Ar
yield (%)b
ee (%)
1
2
3
NPh2 (1e)
NPh2 (1e)
NPh2 (1e)
Ph (2m)
99 (6em)
95 (6en)
96 (6es)
95 (6fm)
93 (6gm)
93
96
93
96
93
4-MeC6H4 (2n)
4-MeOC6H4 (2s)
Ph (2m)
(4) Hayashi, T.; Yamamoto, S.; Tokunaga, N. Angew. Chem., Int. Ed. 2005,
44, 4224.
4
NMe(OMe) (1f)
5c
OtBu (1g)
Ph (2m)
(5) Fillion, E.; Wilsily, A.; Liao, E.-T. Tetrahedron: Asymmetry 2006, 17, 2957.
(6) He´non, H.; Mauduit, M.; Alexakis, A. Angew. Chem., Int. Ed. 2008, 47,
9122.
(7) den Hartog, T.; Harutyunyan, S. R.; Font, D.; Minnaard, A. J.; Feringa,
B. L. Angew. Chem., Int. Ed. 2008, 47, 398.
(8) For enantioselective silyl 1,6-addition to a ꢀ-substituted cyclic dienone,
see: Lee, K.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132, 2898.
(9) For an organocatalytic asymmetric 1,6-addition of ꢀ-ketoesters to δ-un-
substituted dienones, see: Bernardi, L.; Lo´pez-Cantarero, J.; Niess, B.;
Jørgensen, K. A. J. Am. Chem. Soc. 2007, 129, 5772.
(10) For iron-catalyzed diastereoselective 1,6-addition to dienamides, see: Okada,
S.; Arayama, K.; Murayama, R.; Ishizuka, T.; Hara, K.; Hirone, N.; Hata,
T.; Urabe, H. Angew. Chem., Int. Ed. 2008, 47, 6860.
(11) Nishimura, T.; Yasuhara, Y.; Hayashi, T. Angew. Chem., Int. Ed. 2006,
45, 5164.
a Hydrogenation was carried out with [Ir(cod)(PCy3)(py)]PF6 (4 mol %)
for entries 1-4 and Pd/C (4 mol %) for entry 5. See the Supporting
Information for details. b Isolated yield of 6. c Reaction at 50 °C for
12 h.
with 99% ee (Table 2, entry 5) followed by triflation via a lithium
enolate gave alkenyl triflate 7. Iron-catalyzed cross-coupling22 with
MeMgBr gave (S)-curcumene (8) {[R]2D0 ) +48 (c 1.19, CHCl3);
lit20b [R]D20 ) +43 (c 2, CHCl3) for (S)-curcumene}.
We also succeeded in the stereoselective synthesis of doubly
phenylated ketones by using rhodium-catalyzed asymmetric 1,4-
addition to conjugate enone 5am (Scheme 3). The use of a rhodium
complex coordinated with (S,S)-Me-tfb* in the asymmetric addition
of phenylboronic acid to 5am gave anti-diphenylated ketone 9,
(12) For reviews, see: (a) Defieber, C.; Gru¨tzmacher, H.; Carreira, E. M. Angew.
Chem., Int. Ed. 2008, 47, 4482. (b) Shintani, R.; Hayashi, T. Aldrichimica
Acta 2009, 42, 31.
(13) (a) Nishimura, T.; Yasuhara, Y.; Nagaosa, M.; Hayashi, T. Tetrahedron:
Asymmetry 2008, 19, 1778. (b) Nishimura, T.; Ichikawa, Y.; Hayashi, T.;
Onishi, N.; Shiotsuki, M.; Masuda, T. Organometallics 2009, 28, 4890.
(c) Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem.
Commun. 2009, 5713. (d) Nishimura, T.; Wang, J.; Nagaosa, M.; Okamoto,
K.; Shintani, R.; Kwong, F.; Yu, W.; Chan, A. S. C.; Hayashi, T. J. Am.
Chem. Soc. 2010, 132, 464.
Scheme 2
(14) Crystal data are reported in the Supporting Information.
(15) The reactions of 1a with PhBF3K, 5,5-dimethyl-2-phenyl-1,3,2-dioxabori-
nane, and PhSnBu4 also gave the 1,6-addition products in 62, 84, and 58%
yield, respectively.
(16) The absolute configuration of 5am was assigned by analogy with (S)-5an
(Scheme 2).
(17) Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005,
70, 2503.
(18) Okamoto, K.; Hayashi, T.; Rawal, V. H. Chem. Commun. 2009, 4815.
(19) The phosphoramidite derived from (S)-binol and bis((S)-1-phenylethyl)-
amine was used.
Scheme 3
(20) For selected examples, see: (a) Honwad, V. K.; Rao, A. S. Tetrahedron
1965, 21, 2593. (b) Fuganti, C.; Serra, S.; Dulio, A. J. Chem. Soc., Perkin
Trans. 1 1999, 279. (c) Ehara, T.; Tanikawa, S.; Ono, M.; Akita, H. Chem.
Pharm. Bull. 2007, 55, 1361.
(21) (a) Mori, A.; Kato, T. Synlett 2002, 1167. (b) Ojima, I.; Togure, T.
Organometallics 1982, 1, 1390.
(22) Scheiper, B.; Bonnekessel, M.; Krause, H.; Fu¨rstner, A. J. Org. Chem.
2004, 69, 3943.
JA1034842
9
J. AM. CHEM. SOC. VOL. 132, NO. 23, 2010 7873