Desymmetrization of meso-dienyne by asymmetric Pauson-Khand type reaction catalysts

Article abstract of DOI:10.1039/b401288g

Desymmetrization of the meso dienynes, such as propargyl 1-vinylallyl N-tosylamides (1a-c) and propargyl 1-vinylallyl ethers (1d-e), by asymmetric Pauson-Khand type reaction catalysts was studied. The corresponding vinyl substituted bicyclic pentenones (2 and 3) were obtained with high diastereoselectivity and enantioselectivity.

Full text of DOI:10.1039/b401288g

Desymmetrization of meso-dienyne by asymmetric Pauson–Khand type
reaction catalysts†
Nakcheol Jeong,* Dong Hoon Kim and Jun Hun Choi
Department of Chemistry, Division of Molecular Engineering and Chemistry, Korea University, Seoul,
136-701, Korea
Received (in Cambridge, UK) 27th January 2004, Accepted 11th March 2004
First published as an Advance Article on the web 8th April 2004
Desymmetrization of the meso dienynes, such as propargyl
1-vinylallyl N-tosylamides (1a–c) and propargyl 1-vinylallyl
ethers (1d–e), by asymmetric Pauson–Khand type reaction
catalysts was studied. The corresponding vinyl substituted
bicyclic pentenones (2 and 3) were obtained with high diaster-
eoselectivity and enantioselectivity.
the cost of enantioselectivity. Enantioselectivity diminished from
77% to 71% for 3a. However, the general trend of the reaction
remained unchanged.
On the other hand, when 1a was subjected to neutral Ir( )-(R)-
I
BINAP catalyst, which was prepared by mixing 15 mol% of
[IrCl(COD)]2 and 30 mol% of (R)-BINAP in toluene, a couple of
interesting things were observed. The reaction became much
slower. A mixture of 1a and iridium catalyst in toluene was
refluxed under 1 atm of CO, and the reaction required 36 h for
completion. But, the overall chemical yield of this reaction was still
as high as those of rhodium catalyzed reactions.
More significant differences of this iridium catalyzed reaction
from the previous reactions were the reversal of diastereoselectivity
and much better enantioselectivity. 2a was obtained as a major
product in this case. It was obtained in 60% yield with satisfactory
Desymmetrization of meso compounds by chiral catalysts leading
to optically enriched or pure products is among the most efficient
strategies to generate new stereogenic centers from prochiral
substrates.1 Interesting recent reports in this line2 include de-
symmetrization by asymmetric ring-closing metathesis (ARMC)
catalysts.3 We have recently developed the asymmetric Pauson–
Khand reaction (APKR hereafter) employing a cationic chiral Rh(
catalyst.4 A neutral (tol)BINAP-Ir(
) catalyst, and a neutral BINAP-
Rh( ) catalyst coupled with aldehydes as the CO source were also
I)
I
I
reported to effect APKR afterwards.5 Meantime, we envisioned
that it would be attractive to employ these catalysts for the
preparation of optically pure bicyclic compounds from prochiral
meso-dienyne substrates by desymmetrization.
Table 1 Desymmetrization of meso-dienynes by asymmetric PKR catalysts
This desymmetrization of dienynes (1) by chiral PKR catalysts
would generate two stereogenic centers at the same time. Thus it
would lead to a mixture of diastereomers as well as enantiomers
(Scheme 1).
Here we report our preliminary study on diastereoselectivity and
enantioselectivity during the course of desymmetrization by APKR
catalysts.
yield (%)b (ee (%)c)
dre
We began our study with the substrate 1a.6 Three different
conditions reported to date were examined to figure out the
characteristics of the reaction and to find the optimum condi-
tions.
entry sub
cata
lig
t/h
0.5
0.5
0.5
0.5
3
2
3
3
36
2
3
(2 : 3)
1
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1c
1c
1c
1d
1d
1d
1e
1e
1e
A
A
A
A
B
B
B
B
C
C
C
C
A
B
C
A
B
C
A
B
C
A
B
C
4–1
4–2
4–3
4–4
4–1
4–2
4–3
4–4
4–1
4–2
4–3
4–4
4–3
4–2
4–3
4–2
4–2
4–3
4–1
4–3
4–2
4–2
4–2
4–3
9 (51)
11 (52)
8 (52)
14 (33)
9 (51)
10 (52)
7 (52)
16 (33)
60 (93)
61 (92)
75 (96)
64 (85)
22 (5)
12 (34)
60 (90)
24 (50)
14 (41)
30 (32)
51 (90)
65 (87)
62 (92)
60 (86)
84 (80)
80 (90)
57 (77)
61 (80)
57 (73)
54 (53)
73 (71)
74 (74)
74 (71)
70 (44)
5 (67)
8 (65)
1 (33)
5 (45)
64 (60)
81 (63)
11 (9)
35 (67)
46 (50)
1 : 6
1 : 6
1 : 7
1 : 4
1 : 8
1 : 7
1 : 11
1 : 4.
12 : 1
8 : 1
75 : 1
13 : 1
1 : 3
1 : 7
6 : 1
1 : 2
1 : 3
1 : 1
As illustrated by entry 1 of Table 1, methyl-substituted substrate
1a was first subjected to the cationic Rh( )-(R)-BINAP catalyst,
I
3
4
5
6
7
8
9
which was prepared in situ by mixing 3 mol% of [RhCl(CO)2]2, 9
mol% of (R)-BINAP and 12 mol% of AgOTf prior to the addition
of 1a in THF. The reaction mixture was refluxed under 1 atm of
CO. The reaction proceeded to completion in 0.5 h to give a mixture
of 2a and 3a in 9% and 57% yield,7 respectively. The diaster-
eoselectivity observed here is the opposite to the previously known
analogy.8 The enantiomeric excesses were determined to give 51%
for the minor 2a and 77% for the major 3a, respectively.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
36
24
36
Subsequently, 1a was allowed to react by neutral Rh( )-(R)-BINAP
I
1.5
4
36
1
2
18
0.1
2
12
2.5
in cinnamoylaldehyde under argon. Cinnamoylaldehyde served as
both solvent and CO source at the same time. It was observed that
there were substantial improvements in overall chemical yield as
well as diastereoselectivity (1 : 8 in entry 5 from 1 : 6 in entry 1) at
31 (30)
d
14 (84)
5 : 1
d
d
4
18
6 (72)
14 : 1
d
a A: [Rh(CO)2Cl]2 (3 mol%), ligand (9 mol%), AgOTf (12 mol%) in THF
at 90 °C under CO (1atm), B: [Rh(cod)Cl]2 (5 mol%), ligand (10 mol%),
cinnamaldehyde (20 eq) at 120 °C under Ar (1atm), C: [Ir(cod)Cl]2 (15
mol%), ligand (30 mol%) in toluene at 130 °C under CO (1atm). b Isolated
yields. c The ees were determined by chiral HPLC. d Only trace amounts of
this isomer were detected by tlc analysis. e Diastereomeric ratio.
Scheme 1 Desymmetrization of meso-dienynes by asymmetric PKR.
† Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b4/b401288g/
1134
C h e m . C o m m u n . , 2 0 0 4 , 1 1 3 4 – 1 1 3 5
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

enantiomeric excess (93%), while 3a was obtained in only 5% yield
with somewhat inferior enantioselectivity (67% ee).
There was a hint that s-withdrawer ligands significantly slowed
down the reaction rate and gave poorer stereoselectivity. When
substrate 1a was reacted with a cationic rhodium( ) catalyst coupled
I
with 4–2 or 4–3, it did not provide much change in chemical yield
and stereoselectivity of 2 and 3 (entries 2 and 3). But, a catalyst
coupled with electron withdrawer 4–4 diminished the ster-
eoselectivity substantially (entry 4). Neutral rhodium catalyst did
not respond to the electronic character of the ligands as sensitively
as cationic rhodium. Instead, beneficial effects of better s-donors
Fig. 1 ORTEP drawing of 6a.
became more evident in case of the iridium( ) catalyst. Almost
I
exclusive formation of 2a was realized with highest enantiomeric
excess (96%) (entry 11). In spite of these facts, it is hard to
withdraw the generalized correlation at the moment between
stereoselectivities and electronic character of the ligands. Only the
best combinations in our hands are listed in Table 1 for the rest of
the examples.
Aryl substituted substrates 1b, which are known to give poorer
stereoselctivity than alkyl substituted substrates,4 were subjected to
the same conditions. Generally speaking, most outcomes including
the stereoselectivities still exhibited the same trend, but the
numbers obtained for 1b were uniformly lower than 1a. Treatment
shown to be dependent on the substrates and catalysts. The origin of
the diastereoselectivity will be clarified in due course. Further
application to natural products synthesis starting from desymme-
trization products is under investigation as well.
We thank KOSEF (grant No. R02-2002-000-00128-0 of the
Basic Research Program) and CMDS for financial support. DHK
and JHC are grateful to the BK21 fellowship. Efforts by Professor
Jaheon Kim to integrate crystallographic data are also greatly
appreciated.
Notes and references
of 1b with the cationic Rh(
major (64%, 60% ee) and 2b as a minor product (22%, 5% ee).
Neutral Rh( ) with 4–2 also provided 81% (63% ee) of 3b and 12%
(34% ee) of 2b. Again, neutral Ir( ) provided the opposite
I
) catalyst bearing 4–3 provided 3b as a
‡
Crystal data: 2a: C17H19NO3S, M = 317.39, orthorhombic, P212121
(no. 19), a = 5.794(8), b = 14.0776(12), c = 19.4686(13) Å, U = 1588(2)
Å3, Z = 4, Dc = 1.327 Mg m23, m(Mo-Ka) = 2.16 mm21, 1064 reflections
measured, 1064 unique (Rint = 0.000) which were used in all calculations.
The final R(F2) was 0.0490 using 1002 reflections with I > 2s(I) and
wR(F2) was 0.1298 (all data). 6a: C23H35N3O3S, M = 433.60, monoclinic,
P21 (no. 4), a = 11.130(2), b = 7.964(2), c = 13.859(2) Å, b = 106.16(2)°,
I
I
diastereoselectivity to give 2b in 60% yield with excellent
enantioselectivity (90% ee) together with 3b in 11% yield (9% ee).
Terminal alkyne substrate 1c was also tested, but the diaster-
eoselectivity and enantioselectivity became much poorer (entries
U = 1179.9(4) Å3, Z = 2, Dc = 1.220 Mg m23, m(Mo-Ka) = 1.65 mm21
,
1318 reflections measured, 1252 unique (Rint = 0.039) which were used in
all calculations. The final R(F2) was 0.0482 using 1172 reflections with I >
2s(I) and wR(F2) was 0.1024 (all data) with absolute structure parameter,
20.1(2). CCDC 230163 and 230164. See http://www.rsc.org/suppdata/cc/
b4/b401288g/
16–18 in Table 1). Interestingly, a cationic Rh( ) catalyst gave the
best results in this specific example.
I
Next, we turned our attention to the oxygen-tethered substrates.
Several things are worth mentioning. 1) Both neutral Rh( ) and Ir(
provided better chemical yield than cationic Rh( ) did. This might
I
I
)
I
be attributed to the sensitivity of the oxygen functionality to the
more acidic catalyst. The differences are more exaggerated in aryl
substituted 1–e (entries 22–24) than alkyl substituted 1–d. 2) In
contrast to substrate 1a–c, diastereomers 2 were obtained almost
exclusively in all cases regardless of the catalyst employed. 3)
Diastereoselectivities (exclusive formation of 2 in most cases) and
enantioselectivities ( > 90%) for the products from 1d–e are
uniformly higher than those of 1a–c.
1 For related reviews, see: (a) R. S. Ward, Chem. Soc. Rev., 1990, 19, 1; (b)
C. S. Poss and S. L. Schreiber, Acc. Chem. Res., 1994, 27, 9–17; (c) M.
C. Willis, J. Chem. Soc., Perkin Trans. 1, 1999, 1765–1784.
2 For selected recent examples of metal catalyzed desymmetrization
reaction, see: (a) S. L. Schreiber, T. S. Schreiber and D. B. Smith, J. Am.
Chem. Soc., 1987, 109, 1525–1529; (b) K. Mikami, S. Narisawa, M.
Shimizu and M. Terada, J. Am. Chem. Soc., 1992, 114, 6566–6568; (c) K.
D. Shimizu, B. M. Cole, C. A. Krueger, K. W. Kuntz, M. L. Snapper and
A. H Hoveyda, Angew. Chem., Int. Ed. Engl., 1997, 36, 1704–1707; (d)
T. Iida, N. Yamamoto, H. Sasai and M. Shibasaki, J. Am. Chem. Soc.,
1997, 119, 4783–4784; (e) B. M. Trost and D. E. Patterson, J. Org.
Chem., 1998, 63, 1339–1341.
3 (a) D. S. La, J. B. Alexander, D. R. Cefalo, D. D. Graf, A. H. Hoveyda
and R. R. Schrock, J. Am. Chem. Soc., 1998, 120, 9720–9721; (b) D. S.
La, E. S. Sattely, J. G. Ford, R. R. Schrock and A. H. Hoveyda, J. Am.
Chem. Soc., 2001, 123, 7767–7778; (c) A. F. Kiely, J. A. Jernelius, R. R.
Schrock and A. H. Hoveyda, J. Am., Chem. Soc., 2002, 124,
2868–2869.
The absolute configuration of 2a obtained by using (R)-
(4-CH3OC6H4)-BINAP-Ir( ) catalyst (from entry 11 in Table 1)
I
was determined unambiguously by a single crystal structure
determination after chemical modifications. 2a was hydrogenated
doubly by Pd/C under hydrogen pressure to give 5a., which was
coupled with SAMP9 to yield a hydrazone 6a and its rotamer.
Single crystal structure determination of 6a by X-ray crystallog-
raphy‡ revealed the absolute stereochemistry as (C1: S, C2: R)
(Scheme 2 and Fig. 1).
In conclusion, we have demonstrated that the desymmetrization
of meso-dieneynes by APKR catalysts is a useful tool for the
preparation of optically active bicyclic[3,3,0]octanes. Diaster-
eoselectivities and enantioselectivities are good to excellent and
4 N. Jeong, B. K. Sung and Y. K. Choi, J. Am. Chem. Soc., 2000, 120,
6771–6772.
5 (a) T. Shibata and K. Tagaki, J. Am. Chem. Soc., 2000, 120, 9852–9853;
(b) T. Shibata, N. Toshida and K. Tagaki, J. Org. Chem., 2000, 67,
7446–7450.
6 Details for the preparation of substrates 1a-1e are described in ESI†.
7 Characterization and stereochemical assignment of products 2–3 were
carried out by spectroscopic methods including NOE experiments and
single crystal structure determination. Full details can be found in
ESI†.
8 P. Magnus, L. M. Principe and M. J. Slater, J. Org. Chem., 1987, 52,
1483–1486.
9 SAMP: (S)-(2)-1-amino-2-(methoxymethyl)pyrrolidine. D. Enders, L.
Wortmann, B. Ducker and G. Raabe, Helv. Chim. Acta, 1999, 82,
1195–1201.
Scheme 2 Derivatization of PKR products for the determination of absolute
configuration.
C h e m . C o m m u n . , 2 0 0 4 , 1 1 3 4 – 1 1 3 5
1135