Asymmetric construction of a ferrocenyl phosphapalladacycle from achiral enones and a demonstration of its catalytic potential

Article abstract of DOI:10.1021/om5007215

A new approach toward ferrocenyl phosphapalladacycle construction from achiral enones via asymmetric hydrophosphination and subsequent diastereoselective C-H activation is described. Its catalytic efficacy toward C-C bond formation is subsequently illustr

Full text of DOI:10.1021/om5007215

Communication
pubs.acs.org/Organometallics
Asymmetric Construction of a Ferrocenyl Phosphapalladacycle from
Achiral Enones and a Demonstration of Its Catalytic Potential
Kennard Gan, Abdul Sadeer, Chang Xu, Yongxin Li, and Sumod A. Pullarkat*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
21 Nanyang Link, Singapore 637371
*
S Supporting Information
ABSTRACT: A new approach toward ferrocenyl phosphapalladacycle construction from achiral enones via asymmetric
hydrophosphination and subsequent diastereoselective C−H activation is described. Its catalytic efficacy toward C−C bond
formation is subsequently illustrated.
errocenyl phosphines incorporating central and planar
We began our investigation by screening an array of
conditions for the asymmetric addition of diphenylphosphine
to 1a catalyzed by (S)-3 (Table 1).
F
chirality elements have a proven track record as powerful
1
auxiliaries in asymmetric synthesis. As a result, extensive efforts
2
have been invested in their challenging synthesis. These
a
pursuits focused on the development of ferrocenyl diphosphine
and phosphapalladacyclic systems, which contain both the
aforementioned stereogenic components on the same molecule.
The synthesis of ferrocenyl phosphapalladacycles generally
comprises two steps, i.e, (i) the formation of a C-chiral
monophosphine and (ii) subsequent palladation via C−H/C−
Br activation. There are a couple of traditional approaches by
which the former may be achieved, either through enantiose-
Table 1. Palladacycle-Catalyzed AHP of 1a
b
c
entry
solvent
t (h)
yield (%)
ee (%)
3
4
lective /diastereoselective lithiation controlled by pre-existing
chiral element(s) or secondary phosphine substitution of an
1
2
DCM
12
2
>99
>99
>99
49
60
60
Me0OH
MeOH
MeOH
5
enantiopure Ugi amine derivative. Both these methods
d
3
e
2
>99
n.d
although highly selective and synthetically relevant are,
however, limited by the necessity of employing an enantiopure
substrate. The desired ferrocenyl phosphapalladacycle may then
4
168
a
All reactions were performed in the presence of 0.27 mmol of HPPh2,
0
.27 mmol of 1a, 10 mol % (S)-3, and 0.27 mmol of NEt in 5 mL of
3
6
b
c
31
1
be secured by either diastereotopic C−H activation or
solvent at RT. Isolated yield. ee determined from P{ H} NMR
integration via use of chiral derivatizing agent. Absolute stereo-
chemistry determined via single-crystal X-ray crystallography. Dry
7
oxidative addition of palladium(0).
d
A hitherto unexplored route for the enantioselective
formation of monoferrocenyl phosphines is the palladium-
catalyzed asymmetric hydrophosphination (AHP) reaction.
The emergence of AHP of activated alkenes affording high
yields, short reaction times, and excellent selectivities offers an8
atom-economical yet efficient approach to achieve this goal.
However, ferrocenyl-appended substrates have been conspicu-
ously absent from this library. Furthermore, the use of these
chiral monophosphine adducts toward the preparation of viable
catalysts has rarely been explored. Herein, we report the AHP-
based enantioselective construction of a series of C-chiral
tertiary ferrocenyl phosphines and the subsequent diastereose-
lective cyclopalladation of one of the congeners.
e
MeOH. Dry MeOH, cat. (S)-4.
During the optimization process, it was evident that while the
AHP proceeded smoothly in DCM and MeOH, poor
conversions were obtained with THF, acetone, and acetonitrile.
Results show a pronounced difference between the perform-
ances of the two catalysts (entry 3 vs 4). While the N−C
palladacycle (S)-3 catalyzed the reaction within 2 h at RT, its
P−C analogue (S)-4 failed to deliver full conversion even after
Received: July 15, 2014
©
XXXX American Chemical Society
A
dx.doi.org/10.1021/om5007215 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
week. It was also noted that MeOH was a superior solvent as
Communication
1
cleavage of the N−C chelate with HCl under reflux. The crude
P{ H} NMR spectra of 8 displayed four sets of singlets at δ
70−72, indicating complete conversion to the P−C chelate
with an overall yield of 98%. Subsequent resolution with
sodium prolinate (Scheme 1) gave two singlets at δ 68.1 and
3
1
1
compared to DCM, yielding the product within 2 h while
offering the same selectivity (entry 1 vs 2). Further examination
with dry MeOH revealed a significant increase in selectivity of
up to >99% (entry 2 vs 3). Interestingly, when the AHP was
conducted in MeOH, the tertiary phosphine adduct precipi-
tated upon formation, thus enabling a facile procedure in which
the enantio-enriched tertiary phosphine product can be isolated
by mere filtration. Encouraged by these results, we proceeded
to substrate screening (Table 2).
Scheme 1. Cyclopalladation
Table 2. Asymmetric Hydrophosphination of Ferrocenyl
a
Enones
b
c
entry
1
R (product)
2-furyl (2a)
t (h)
yield (%)
ee (%)
2
72
>99
>99
>99
>99
>99
>99
66
d
2
3-thienyl (2b)
Ph (2c)
6
8.8 with a ratio of 1:5.3, indicating an efficient cyclopalladation
d
3
d
96
84
de of ca. 66%. The diastereoselectivity achieved is controlled
solely by the pre-existing C-chirality introduced during the
AHP. Subsequent crystallization afforded enantiopure (R S
4
(p-OMe)C H (2d)
168
216
>99
42
6
4
5
Me (2e)
c
pl
a
11
All reactions were performed in the presence of 0.27 mmol of HPPh2,
S )-7. Treatment of (R S S )-7 with LiCl and AcOH in
pro
c
pl pro
0
.27 mmol of 1a−e, 10 mol % (S)-3, and 0.27 mmol of NEt in 5 mL
3
MeOH regenerated (R S )-8 in quantitative yield with full
b
c
31
1
c
p
of dry MeOH at RT. Isolated yield. ee determined from P { H}
integrated via use of chiral derivatizing agent. Absolute stereochemistry
determined via X-ray crystallography. AHP conducted at −80 °C.
chirality transfer. This protocol thus provides an efficient
alternative for accessing ferrocenyl palladacycles from achiral
activated alkenes via an efficient enantioselective hydro-
phosphination of achiral substrates followed by a diastereose-
lective orthopalladation.
With the newly synthesized ferrocenyl phosphapalladacycle
in hand, we proceeded to conduct a prelimary illustration of its
catalytic potential toward aryl boronic acid addition to 2-
cyclohexenone.
d
Although good conversions were attained with most
substrates, both the 2-pyrrole and (p-NO )C H conjoined
2
6
4
enones failed to reach full conversion even after 1 week. This
can be attributed to the ability of these substrates to form
chelates on Pd, thus disrupting the catalyst regeneration
8
c
process. The results attained with ferrocenyl enone 1a
showed unparalled selectivity in comparison with other
substrates (1b−e) when the AHP was conducted at RT. In
an effort to achieve improved selectivities, we conducted a
series of low-temperature experiments (Table 2, entries 2−5).
Furthermore, it is observed that the AHP with aromatic
substituents generally resulted in higher selectivities as
compared to their aliphatic counterpart (Table 2, entries 1−4
vs 5).
Scheme 2. p-Tolylphenylboronic Acid Addition to 2-
Cyclohexenone
We proceeded to integrate planar chirality into the ferrocenyl
skeleton via cyclopalladation. The fixing of planar chirality onto
the ferrocene framework demands appropriate chiral control,
through either an existing internal stereogenic center or an
external chiral auxiliary. Previous reports by Dunina adopted
Pd(OAc)2 and cyclopalladated ligand exchange (CLE) as
primary means to consummate a ferrocenyl P−C-ligated
palladium(II) complex. Although palladation attempts via
This result compares favorably with those previously
reported from Pd(II)-catalyzed protocols and is evidence of
the potential for this phosphapalladacycle.
9
10
7
In conclusion, we have developed a highly enantioselective
AHP-based protocol for accessing ferrocenyl phosphine motifs
from achiral substrates as well as a viable alternate protocol for
achieving the subsequent diastereospecific orthopalladation of
the ferrocenyl enone in order to generate cyclopalladated
systems of interest incorporating both central and planar chiral
elements. The catalytic demonstration indicated that such
complexes are of relevance in asymmetric synthesis, and this set
of protocols can yield a tool set to generate more analogues of
interest. Our current efforts are focused on the application of
the catalyst to other organic transformations.
Pd(OAc) and CLE generated the targeted palladated product
2
within 3 h, poor yields of 20% and 10% were obtained,
respectively. Ensuing studies with PdCl , Na PdCl , and
2
2
4
PdCl (NCMe) all failed to stimulate effective C−H activation.
2
2
These disappointing results could be attributed to insufficient
steric promotion of the Cp−H bond by the −PPh moiety,
2
9
resulting in the formation of only coordination compounds.
Thus, we resorted to a two-step process involving the
coordination of (R)-2a to dimer 6 followed by subsequent
B
dx.doi.org/10.1021/om5007215 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
(
c) Dunina, V. V.; Gorunova, O. N.; Livantsov, M. V.; Grishin, Y. K.;
ASSOCIATED CONTENT
Supporting Information
Details of experiments and characterization data of products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
■
Kuz’mina, L. G.; Kataeva, N. A.; Churakov, A. V. Inorg. Chem.
Commun. 2000, 3, 354−357. (d) Roca, F. X.; Motevalli, M.; Richards,
C. J. J. Am. Chem. Soc. 2005, 127, 2388−2389.
*
S
(7) (a) Suzuma, Y.; Yamamoto, T.; Ohta, T.; Ito, Y. Chem. Lett. 2007,
36, 470−471. (b) Suzuma, Y.; Yamamoto, T.; Ohta, T.; Ito, Y.
Tetrahedron: Asymmetry 2009, 20, 2751−2758. (c) He, P.; Lu, Y.;
Dong, C.-G.; Hu, Q.-S. Org. Lett. 2007, 9, 343−346.
AUTHOR INFORMATION
Corresponding Author
(S. A. Pullarkat) Fax: (+) 6316-8906. E-mail: sumod@ntu.
edu.sg. Homepage: http://www3.ntu.edu.sg/home/Sumod.
■
*
(8) (a) Huang, Y.; Pullarkat, S. A.; Li, Y.; Leung, P. H. Chem.
Commun. 2010, 46, 6950−6952. (b) Huang, Y.; Chew, R. T. J.;
Pullarkat, S. A.; Li, Y.; Leung, P. H. J. Org. Chem. 2012, 77, 6849−
6
854. (c) Chang, X.; Gan, J. H.; Hennersdorf, F.; Li, Y.; Pullarkat, S.
Notes
A.; Leung, P. H. Organometallics 2012, 31, 3022−3026. (d) Huang, Y.;
Chew, R. T. J.; Li, Y.; Pullarkat, S. A.; Leung, P. H. Org. Lett. 2011, 13,
The authors declare no competing financial interest.
5
862−5865. (e) Huang, Y.; Pullarkat, S. A.; Teong, S.; Chew, R. T. J.;
Li, Y.; Leung, P. H. Organometallics 2012, 31, 4871−4875. (f) Yang,
M. J.; Liu, Y. J.; Gong, J. F.; Song, M. P. Organometallics 2011, 30,
3793−3803. (g) Chen, Y. R.; Duan, W. L. Org. Lett. 2011, 13, 5824−
5826. (h) Feng, J. J.; Chen, X. F.; Shi, M.; Duan, W. L. J. Am. Chem.
Soc. 2010, 132, 5562−5563. (i) Du, D.; Duan, W. L. Chem. Commun.
ACKNOWLEDGMENTS
■
We gratefully thank the Ministry of Education, Singapore, for
financial support and Nanyang Technological University for a
research scholarship to K.G.
2
011, 47, 11101−11103. (j) Lu, J.; Ye, J.; Duan, W. L. Chem. Commun.
014, 50, 698−700. (k) Huang, M.; Li, C.; Huang, J.; Duan, W. L.; Xu,
2
REFERENCES
■
S. Chem. Commun. 2012, 48, 11148−11150.
(
1) (a) Arrayas
́
, R. G.; Adrio, J.; Carretero, J. C. Angew. Chem., Int. Ed.
(9) Gorunova, O. N.; Livantsov, M. V.; Grishin, Y. K.; Kataeva, Y. K.;
2
006, 45, 7674−7715. (b) Dai, L. X.; Hou, X. L. In Chiral Ferrocenes in
Asymmetric Catalysis; Wiley-VCH: Weinheim, 2010.
Kochetkov, K. A.; Churakov, A. V.; Kuz’mina, L. G.; Dunina, V. V.
Polyhedron 2012, 31, 37−43.
(
2) (a) Blaser, H. U.; Brieden, W.; Pugin, B.; Spindler, F.; Studer, M.;
(10) (a) Dunina, V. V.; Razmyslova, E. D.; Gorunova, O. N.;
Togni, A. Top. Catal. 2002, 19, 3−16. (b) Studer, M.; Blaser, H. U.
PharmaChem 2002, 33−34. (c) Dunina, V. V.; Gorunova, O. N.;
Livantsov, M. V.; Grishin, Y. K.; Kuz’mima, L. G.; Kataeva, N. A.;
Churakov, A. V. Tetrahedron: Asymmetry 2000, 3967−3984. (d) Roca,
F.; Motevalli, M.; Richards, C. J. J. Am. Chem. Soc. 2005, 127, 2388−
Livantsov, M. V.; Grishin, Y. K. Tetrahedron: Asymmetry 2003, 14,
2
331−2333. (b) Dunina, V. V.; Gorunova, O. N.; Kuznetsova, E. D.;
Turubanova, E. I.; Livantsov, M. V.; Grishin, Y. K.; Kuz’mina, L. G.;
Churakov, A. V. Russ. Chem. Bull., Int. Ed. 2006, 55, 2193−2211.
(
11) Supporting Information Section 2.2. CCDC 991269.
2
389.
(
3) (a) Laufer, R. S.; Veith, U.; Taylor, N. J.; Snieckus, V. Org. Lett.
2
000, 2, 629−631. (b) Metallinos, C.; Szillat, H.; Taylor, N. J.;
Snieckus, V. Adv. Synth. Catal. 2003, 345, 370−382. (c) Dixon, A. J.;
McGrath, M. J.; O’Brien, P. Org. Synth. 2006, 83, 141−154. (d) Price,
D.; Simpkins, N. S. Tetrahedron Lett. 1995, 36, 6135−6136.
(
2
e) Metallinos, C. U.S. Patent No. 61/117, 400 (submitted
4112008).
4) (a) Aratani, T.; Gonda, T.; Nozaki, H. Tetrahedron Lett. 1969, 10,
265−2268. (b) Marquarding, D.; Klusacek, H.; Gokel, G.; Hoffmann,
(
2
P.; Ugi, I. J. Am. Chem. Soc. 1970, 92, 5389−5393. (c) Ireland, T.;
Grossheimann, G.; Wieser-Jeunesse, C.; Knochel, P. Angew. Chem., Int.
Ed. 1999, 38, 3212−3215. (d) Ireland, T.; Tappe, K.; Grossheimann,
G.; Knochel, K. Chem.Eur. J. 2002, 8, 843−852. (e) Boaz, N. W.;
Ponasik, J. A., Jr.; Large, S. E. Tetrahedron Lett. 2006, 47, 4033−4035.
(
̀
f) Rebiere, F.; Riant, O.; Richard, L.; Kagan, H. B. Angew. Chem., Int.
Ed. Engl. 1993, 32, 568−570. (g) Riant, O.; Argouarch, G.; Guillaneux,
D.; Samuel, O.; Kagan, H. B. J. Org. Chem. 1998, 63, 3511−3514.
(
h) Lagneau, N. M.; Chen, Y.; Robben, P. M.; Sin, H. S.; Takasu, K.;
Chen, J. S.; Robinson, P. D.; Hua, D. H. Tetrahedron 1998, 54, 7301−
334. (i) Riant, O.; Samuel, O.; Flessner, T.; Taudien, S.; Kagan, H. B.
J. Org. Chem. 1997, 62, 6733−6745. (j) Wolfle, H.; Kopacka, H.;
Wurst, K.; Ongania, K. H.; Gortz, H. H.; Preishuber-Pflugl, P.;
7
̈
̈
̈
Bildstein, B. J. Organomet. Chem. 2006, 691, 1197−1215. (k) Balavoine,
G. G. A.; Daran, J. C.; Iftime, G.; Manoury, E.; Moreau-Bossuet, C. J.
Organomet. Chem. 1998, 567, 191−198. (l) Nishibayashi, Y.; Uemura,
S. Synlett 1995, 79−81. (m) Nishibayashi, Y.; Segawa, K.; Ohe, K.;
Uemura, S. Organometallics 1995, 14, 5486−5487. (n) McManus, H.
A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151−4202.
(
5) (a) Lotz, M.; Schuecker, R.; Mereiter, K.; Knochel, P.
Organometallics 2010, 29, 6503−6508. (b) Zirakzadeh, A.;
Schuecker, R.; Gorgas, N.; Mereiter, K.; Spindler, F.; Weissensteiner,
W. Organometallics 2012, 13, 4241−4250.
(
6) (a) Dunina, V. V.; Razmyslova, E. D.; Gorunova, O. N.;
Livantsov, M. V.; Grishin, Y. K. Tetrahedron: Asymmetry 2003, 14,
2
331−2333. (b) Dunina, V. V.; Gorunova, O. N.; Kuznetsova, E. D.;
Turubanova, E. I.; Livantsov, M. V.; Grishin, Y. K.; Kuz’mina, L. G.;
Churakov, A. V. Russ. Chem. Bull., Int. Ed. 2006, 55, 2193−2211.
C
dx.doi.org/10.1021/om5007215 | Organometallics XXXX, XXX, XXX−XXX