Readily Available [2.2.2]-Bicyclooctadienes as New Chiral Ligands for Ir(I): Catalytic, Kinetic Resolution of Allyl Carbonates

Article abstract of DOI:10.1021/ja0390707

We report an Ir(I)-catalyzed kinetic resolution of secondary allylic carbonates allowing for their isolation in up to 98% ee. Importantly, the study documents the synthesis and use of a new class of chiral [2.2.2]-bicyclooctadiene ligands for iridium. Cop

Full text of DOI:10.1021/ja0390707

Published on Web 01/27/2004
Readily Available [2.2.2]-Bicyclooctadienes as New Chiral Ligands for Ir(I):
Catalytic, Kinetic Resolution of Allyl Carbonates
Christian Fischer, Christian Defieber, Takeyuki Suzuki, and Erick M. Carreira*
Laboratorium f u¨ r Organische Chemie, ETH H o¨ nggerberg, CH-8093 Z u¨ rich, Switzerland
Received October 15, 2003; E-mail: carreira@org.chem.ethz.ch
The design, synthesis, and study of novel chiral ligands for metals
offer new opportunities in the development of reaction processes
leading to useful building blocks for chemical synthesis.1 The
advances in the application of late transition metals for asymmetric
catalysis have primarily been fueled by phosphorus and nitrogen
ligands. We have become interested in addressing the question of
whether chiral dienes could be employed as ligands for enantiose-
lective reaction processes involving late transition metals. In a recent
report, Hayashi documented a chiral norbornadiene-Rh complex
in the conjugate addition reaction of phenyl boronic acids to
Scheme 1
Chart 1
2
enones. Independently and concurrently, we have been investigat-
ing chiral dienes as ligands for catalytic iridium-mediated processes.
Herein we report chiral [2.2.2]-bicyclooctadienes as a new family
of ligands. These are notable because of their convenient preparation
in optically active form from (R)- or (S)-carvone. We demonstrate
the potential utility of these ligands in Ir(I)-catalyzed kinetic
resolution of allylic carbonates 2 (Scheme 1).3
Scheme 2
,4
Catalytic, enantioselective allylation reactions using transition-
metal complexes have become one of the work-horses in asym-
metric synthesis.5 Such processes can be quite general; they have
been shown to be amenable to variation in ligand and metal as
well as the allyl donors and nucleophilic reactants.7 These have
been the subject of in-depth mechanistic studies that have them-
selves become classics.9 Although the allylation reaction of
malonate and related nucleophiles has been the subject of intense
investigations, the use of phenols in enantioselective allylation
chemistry has only recently been studied.1 The Pd-catalyzed
reaction of allylic carbonates and phenols has been examined by
,6
,8
Scheme 3
0a
Trost using C
2
-symmetric chiral bisphosphine ligands.10 In a similar
fashion the use of the same phosphine ligands has permitted the
resolution of Baylis-Hillman adducts with substituted phenols to
give optically active â-phenoxy-R-methylene nitriles and esters.10b
Most recently, Hartwig has documented the use of monophosphine
complexes in the reaction of allylic carbonates and lithium
phenoxides.11
Our recent interest in catalysis by late transition metals12 led to
a study of chiral dienes as ligands for Ir(I) in allylic displacement
reactions. However, given the lack of precedence using chiral
diene-Ir complexes as catalysts, we set out to examine the general
reactivity of diene-Ir complexes which could subsequently be made
chiral and nonracemic. In this respect, the reaction of 2 (R ) Ph)
equaled that of [IrCl(COD)] . Thus, we decided to focus on [2.2.2]-
2
bicyclooctadiene ligands.13
A key factor that determines the utility of any ligand for
asymmetric catalysis is the ease with which it can be accessed.
We recognized that the core scaffold for a chiral [2.2.2]-bicyclooc-
tadiene could be derived from (R)- or (S)-carvone. Because of their
use in cosmetics and flavorings (e.g., spearmint chewing gum), both
are available in bulk cheaply at <$100/kg.14 Significantly, in two
steps (NBS/MeOH then KOtBu/tBuOH) this terpene is converted
into alkenyl ketone 6 in 68% yield as a mixture of diastereomers,
easily separated by chromatography on silica gel.1 Ketone 6 can
then be converted into the corresponding triflate which is a substrate
for Pd-mediated coupling reactions (46% yield, two steps), permit-
ting access to dienes 1a-d (Scheme 2).17 Thus, this family of
[2.2.2]-diene ligands can be synthesized in large scale in four steps.
This contrasts with the enantioselective synthesis of the [2.2.1]-
norbornadiene ligand which prescribes nine steps, proceeds in 10%
overall yield from the achiral norbornadiene, and consequently
5,16
with phenol and catalytic [IrCl(COD)]
formation of the phenyl ether proceeds to completion at 23 °C in
4 h. Accompanying studies revealed that [IrCl(COE) (COE )
2
served as a benchmark: the
2
2 2
]
cyclooctene) was inactive as a catalyst. Subsequent prospecting
studies with two [2.2.1]-bicyclo-heptadienes 4 and 5 as ligands gave
unsatisfactory results (Chart 1). Norbornadiene (4) only furnished
adducts after 4 days, with concomitant byproduct formation. The
2
necessitates the use of an expensive chiral ligand (MOP) for Pd.
2,5-diphenyl-substituted counterpart 5 failed altogether to form a
At the outset (Scheme 3), we noted that treatment of allylic
complex with Ir(I). In stark contrast, the simple [2.2.2]-bicyclooc-
carbonate 7 with phenol and Ir(I) complexes prepared in situ from
tadiene ligand 1a, however, gave a complex whose reactivity
2 2
[IrCl(COE) ] with 1a-d leads to formation of the phenyl ether
1628
9
J. AM. CHEM. SOC. 2004, 126, 1628-1629
10.1021/ja0390707 CCC: $27.50 © 2004 American Chemical Society

C O MMU N I C A T I O N S
Table 1. Kinetic Resolution of Allylic Carbonates (Scheme 1)a
Acknowledgment. We acknowledge the help of Satoru Kaneko
in an early stage of the project. We are grateful for the support of
this research by Sumika Ltd., Japan.
yield/% (%)b
ee/% c
entry
R
1
2
3
4
5
6
7
8
9
C6H5
32 (72)
33 (81)
28 (78)
37 (87)
38 (88)
39 (87)
34 (82)
40 (90)
37 (83)
45 (94)
46 (91)
39 (89)
28 (78)
30 (68)
32 (77)
93
94
90
97
97
91
85
88
96
95
80
80
87
>98
84
2-naphthyl
1-naphthyl
(3-MeO)C6H4
(4-Br)C6H4
(4-Cl)C6H4
(4-F)C6H4
(3-Br)C6H4
(4-CF3)C6H4
(4-NO2)C6H4
(4-CO2Me)C6H4
(3-Me)C6H4
(4-Me)C6H4
cC6H11
Supporting Information Available: Experimental procedures and
spectral data for all products (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(
1) (a) Noyori, R., Ed. Asymmetric Catalysis in Organic Synthesis; Wiley:
New York, 1994. (b) Ojima, I., Ed. Catalytic Asymmetric Synthesis;
Wiley: New York, 2000.
10
11
12
13
14
15
(2) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc.
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(
3) For a recent review on kinetic resolution, see: Robinson, D. E. J. E.;
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(
4) For examples of kinetic resolution see: (a) Martin, V. S.; Woodard, S.
S.; Katsuki, T.; Yamada, Y.; Ikeda, M.; Sharpless, K. B. J. Am. Chem.
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A.; Sigman, M. S. J. Am. Chem. Soc. 2003, 125, 7005.
BnOCH2
a
Reactions conducted with 1.5 mol % [IrCl(COE)2]2, 3.6 mol % 1d and
b
0
.5 mmol 2 in 3 mL of CH2Cl2. The combined yield of recovered optically
c
active carbonate and optically active phenyl ether in parentheses. ee was
determined by chiral HPLC; the absolute configuration has been established
as (R) for entries 1, 3, and 6. For details see Supporting Information.
(
5) Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395.
(6) Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. ComprehensiVe Asym-
metric Catalysis; Springer: Berlin, 1999; Vols. 1-3, Chapter 24.
(
7) For recent studies on catalytic asymmetric substitution with malonates:
Ir: (a) Bartels, B.; Helmchen, G. Chem. Commun. 1999, 741. (b) Fuji,
K.; Kinoshita, N.; Tanaka, K.; Kawabata, T. Chem. Commun. 1999, 2289.
Pd: (c) Burckhardt, U.; Baumann, M.; Togni, A. Tetrahedron: Asymmetry
with enantiomeric excesses ranging from 51 to 71%. The recovered
starting carbonate was isolated in good yield and 80-93% ee. While
both are isolated in optically active form, the enantioselectivity of
the recovered starting material is particularly noteworthy as a lead
1
997, 8, 155. (d) Kawatsura, N.; Uozumi, Y.; Hayashi, T. Chem. Commun.
1998, 217. (e) Glorius, F.; Neuburger, M.; Pfaltz, A. HelV. Chim. Acta
001, 84, 3178.
2
(
8) For recent studies on kinetic resolution on metal-catalyzed allylation:
Pd: (a) Reetz, M. T.; Sostmann, S. J. Organomet. Chem. 2000, 603, 105.
(b) L u¨ ssem, B. J.; Gais, H.-J. J. Am. Chem. Soc. 2003, 125, 6066. Mo:
result, given that the optically active allyl carbonates reisolated are
preparatively useful as chiral building blocks.1
8,19
Because diene
(
c) Hughes, D. J.; Palucki, M.; Yasuda, N.; Reamer, R. A.; Reider, P. J.
1d proved optimal (with respect to scope along with selectivity)
J. Org. Chem. 2002, 67, 2762.
(
9) W: (a) Lehmann, J.; Lloyd-Jones, G. C. Tetrahedron 1995, 51, 8863.
Rh: (b) Evans, P. A.; Nelson, J. D. J. Am. Chem. Soc. 1998, 120, 5581.
Ir: (c) Takeuchi, R.; Kashio, M. J. Am. Chem. Soc. 1998, 120, 8647. (d)
Bartels, B.; Garcia-Yerba, C.; Rominger, F.; Helmchen, G. Eur. J. Inorg.
Chem. 2002, 2569. Pd: (e) Hayashi, T.; Kawatsura, M.; Uozumi, Y. J.
Am. Chem. Soc. 1998, 120, 1681. (f) Lloyd-Jones, G. C.; Stephen, S. C.
Chem. Eur. J. 1998, 4, 2539.
and was crystalline, it was chosen for subsequent study.
As shown in Table 1,20 the reaction is conveniently carried out
at room temperature with 1.5 mol % [IrCl(COE)
2
]
2
and 3.6 mol %
21
1d. A broad range of aryl- and alkyl (entries 14 and 15)-substituted
allylic carbonates can be successfully employed, with respect to
the former, both electron-rich and -deficient serve as substrates for
the reaction.22
The reactivity differences of the Ir(I) complexes as a function
of the structure of the bicyclic diene ([2.2.1] versus [2.2.2]) observed
in the prospecting studies were intriguing. We proceeded to examine
whether such differences would be manifest in other reactions, such
(
10) (a) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1998, 120, 815. (b)
Trost, B. M.; Tsui, H.-C.; Toste, F. D. J. Am. Chem. Soc. 2000, 122,
3534.
(
11) Lopez, F.; Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 3426.
12) Fischer, C.; Carreira, E. M. Org. Lett. 2001, 3, 4319.
(
(13) For the relevance of C
1
symmetry in catalysis see: Helmchen, G.; Pfaltz,
A. Acc. Chem. Res. 2000, 33, 336.
(
14) The Southern African Essential Oil Producers Association quotes a price
of $24/kg. Seema International sells (+)-carvone for about $100/kg.
15) A roughly 1:1 mixture of diastereomers is obtained: Ruggles, E. L.;
Maleczka, R. E., Jr. Org. Lett. 2002, 4, 3899.
(
2
as the conjugate addition reaction of PhB(OH) to cyclohexenone
2
reported by Hayashi. In this regard, although chiral 2,5-dibenzyl-
(16) In preliminary experiments it was shown that ligands derived from the
C(8)-epimer of 6 are equally effective.
NBD‚Rh(I) was reported to work well, the corresponding 1d‚Rh-
(
17) The versatility of the ligand synthesis can be exemplified by a route to
(I) complex furnished product in only 52% yield and 71% ee. Thus,
another [2.2.2]-bicyclooctadiene skeleton, under current investigation.
the [2.2.1] and [2.2.2] ligands complement each other, and display
different preferences as a function of metal and reaction processes.
These observations suggest that further investigations on the use
of both are warranted and potentially fruitful.
In conclusion, we report a novel chiral diene ligand. A salient
feature of the bicyclooctadiene ligand is its convenient synthesis
in four steps from readily available, inexpensive (R)- or (S)-carvone.
Another attractive aspect of the route to the ligand is the fact that
the modulating group is introduced in the last step of the synthetic
sequence and, more generally, that it provides access to a variety
of [2.2.2]-dienes which are of potential interest for other transition-
metal catalyzed processes. We have introduced their use in the
context of the Ir(I)-catalyzed kinetic resolution of chiral allylic
carbonates, which can be isolated in up to 98% ee and are useful
in numerous asymmetric processes for complex molecule synthe-
(
18) The fact that the phenyl ethers vary in enantioselectivity much more than
the isolated carbonates, for a given conversion, is an interesting mechanistic
aspect which is currently being investigated.
(
19) Evans, P. A.; Leahy, D. K. J. Am. Chem. Soc. 2000, 122, 5012.
(20) The yields (%) and ees (%) of the phenyl ethers are: entry 1: 40, 66 ee;
entry 2: 48, 80 ee; entry 3: 50, 73 ee; entry 4: 50, 77 ee; entry 5: 50,
8
7 ee; entry 6: 48, 87 ee; entry 7: 48, 53 ee; entry 8: 50, 80 ee; entry
9: 46, 82 ee; entry 10: 49, 86 ee; entry 11: 45, 92 ee; entry 12: 50, 45
ee; entry 13: 50, 75 ee, entry 14: 38, 72 ee; entry 15: 45, 61 ee; for
details, see Supporting Information.
(21) The selectivity factors were roughly calculated to be in general range
between 5 and 15 for most substrates (with single entries as high as 30).
(
22) For a stereochemical model see Supporting Information.
(23) (a) Evans, P. A.; Robinson, J. E. J. Am. Chem. Soc. 2001, 123, 4609. (b)
Evans, P. A.; Leahy, D. K. J. Am. Chem. Soc. 2003, 125, 8974.
23
sis. Further studies and applications are at present being conducted
and will be reported in due time.
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J. AM. CHEM. SOC.
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