A new synthetic route to P-chiral phosphine-boranes of high enantiopurity via stereocontrolled Pd(0)-Cu(I) cocatalyzed aromatic phosphorylation

Full text of DOI:10.1021/jo0003605

4776
J . Org. Chem. 2000, 65, 4776-4778
examining the Pd(0) mediated cross-coupling of (Sp)-
A New Syn th etic Rou te to P -Ch ir a l
methylphenylphosphine-borane (1)8 with 2-iodotoluene.
Unfortunately, initial efforts to achieve this transforma-
tion under the various sets of reaction conditions de-
scribed previously6 gave unsatisfactory results in that
partial loss of stereochemical integrity or modest yields
of the desired product (3a ) were obtained. In all likeli-
hood, the propensity of secondary phosphine-borane
anions to undergo pyramidal inversion9,10 was responsible
for the erosion of stereocontrol in these instances. It was
our expectation that base-mediated racemization of the
putative anionic intermediate could be effectively sup-
pressed by rapid complexation with an appropriate cation
to generate a configurationally stable metallophosphide
(Scheme 1). In accord with this hypothesis, the addition
of sub-stoichiometric quantities (10-30 mol %) of CuI13
was found to increase the efficiency and stereocontrol
associated with Pd(0) catalyzed aromatic phosphoryla-
tion. It is of additional significance that representative
cross-couplings were found to proceed at temperatures
of -10 °C to 0 °C in the presence of CuI.14,15 After
considerable experimentation, the conversion of 1 to 3a
could optimally be achieved by treatment with 2-iodot-
oluene (1.5 equiv) in the presence of preformed “Pd-
[P(Me)Ph2]2”16 (7.5 mol %), CuI (20-30 mol %) and (i-
Pr)2NEt (1.2 equiv) in THF-Me2S (4:1) at 0 °C.
A variety of alternative supporting ligands [including
tris(2-furyl)phosphine and Ph3As]17 and solvent systems
were evaluated and found to be inferior in representative
cross-coupling reactions. Specifically, the use of less polar
solvents (e.g., PhCH3 and Et2O) led to suppression of
reaction rates whereas more polar media [DMF, N-
methylpyrrolidinone or THF-HMPA (9:1)] provided ex-
cellent rates of substrate conversion but with lower
overall efficiency and reduced stereoselectivity. In ac-
cordance with our initial expectations, reaction of (Sp) 1
with 2-iodotoluene resulted in retention of configuration
P h osp h in e-Bor a n es of High En a n tiop u r ity
via Ster eocon tr olled P d (0)-Cu (I)
Coca ta lyzed Ar om a tic P h osp h or yla tion
Mohammad Al-Masum, G. Kumaraswamy, and
Tom Livinghouse*
Department of Chemistry and Biochemistry, Montana State
University, Bozeman, Montana 59717
tlivinghouse@hotmail.com
Received March 13, 2000
Enantiopure phosphine-boranes have come to be rec-
ognized as the precursors of choice for the synthesis of a
wide variety of diphosphine ligands which are used for
asymmetric catalysis.1 The methods which have been
most frequently employed for the synthesis of enantioen-
riched phosphine-boranes involve the formation of phos-
phorus-carbon bonds via successive nucleophilic dis-
placements at phosphorus.2,3 Nucleophilic substitution at
tetracoordinate phosphorus typically proceeds via pen-
tacoordinate intermediates in which stereochemical leak-
age can occur via pseudorotation.4 Consequently, the
utilization of this type of approach for the synthesis of
an extensive series of structurally varied phosphine-
boranes in high optical purity has not been realized. In
principle, electrophilic arylation of enantiomerically pure
secondary phosphine-boranes would provide a means by
which degradation of phosphorus stereointegrity via
pseudorotation could be avoided. In this communication
we show that (Sp)-methylphenylphosphine-borane (1)
undergoes Pd(0)-Cu(I) cocatalyzed cross-coupling5 with
aryl iodides with excellent levels of absolute stereocontrol.
Imamoto and Oshiki reported that both diastereomers
of menthyl phenylphosphinite-borane are capable of
taking part in palladium-catalyzed cross-coupling with
2-iodoanisole with essentially complete retention or
inversion of configuration at phosphorus as a function
of solvent polarity.6,7 We began our investigation by
(8) (a) The synthesis of 1 (optical purity >99%)8b was achieved by
the method of Imamoto involving the reduction of (menthyloxy)-
methylphenylphosphine-borane with lithium naphthalenide.9 b) The
optical purity of 1 was established by conversion to the P-benzyl
derivative [(a) n-BuLi, -78 °C; (b) BnBr] followed by HPLC analysis.18
(9) Oshiki, T.; Hikosaka, T.; Imamoto, T. Tetrahedron Lett. 1991,
32, 3371.
(10) Base-mediated P-benzylation of 1 under conditions which led
to the stereospecific alkylation (retention) of (Sp)-menthyl phenylphos-
phinite-borane11 results in complete racemization: Kumaraswamy,
G.; Livinghouse, T., unpublished observations.
(1) Pietrusiewicz, K. M.; Zablocka, M. Chem. Rev. 1994, 94, 1375
and references therein.
(2) (a) Corey, E. J .; Chen, Z.; Tanoury, G. J . J . Am. Chem. Soc. 1993,
115, 11000. (b) J uge, S.; Stephan, M.; Laffitte, J . A.; Genet, J . P.
Tetrahedron Lett. 1990, 31, 6357. (c) Brown, J . M.; Carey, J . V.; Russell,
M. J . H. Tetrahedron 1990, 46, 4877.
(3) (a) For a publication concerning the use of asymmetric depro-
tonation for the synthesis of P-chiral diphosphines, see: Muci, A. R.;
Campos, K. R.; Evans, D. A. J . Am. Chem. Soc. 1995, 117, 9075. (b)
For the synthesis of P-chiral phosphine-boranes via dynamic resolution,
see: Wolfe, B.; Livinghouse, T. J . Am. Chem. Soc. 1998, 120, 5116. (c)
For the use of crystallization-induced asymmetric transformation in
this context, see: Vedejs, E.; Donde, Y. J . Am. Chem. Soc. 1997, 119,
9293.
(11) Imamoto, T.; Oshiki, T.; Onozawa, T.; Kusumoto, T.; Sato, K.
J . Am. Chem. Soc. 1990, 112, 5244.
(12) Oshiki, T.; Imamoto, T. Bull. Chem. Soc. J pn. 1990, 63, 3719.
(13) The presence of sub-stoichiometric quantities of CuI has been
shown to increase the efficiency of certain Stille-type cross coupling
reactions as well as Castro-Stevens alkynylations: (a) Liebeskind, L.
S.; Riesinger, S. W. J . Org. Chem. 1993, 58, 408. (b) Myers, A. G.;
Alauddin, M. M.; Fuhry, M. A. M.; Dragovich, P. S.; Finney, N. S.;
Harrington, P. M. Tetrahedron Lett. 1989, 30, 6997. (c) Han, X.; Stoltz,
B. M.; Corey, E. J . J . Am. Chem. Soc. 1999, 121, 7600. (d) Additional
related work has been reported by Piers: Piers, E.; Romaro, M. A. J .
Am. Chem. Soc. 1996, 118, 1215.
(4) (a) DeBruin, K. E.; Naumann, K.; Zon, G.; Mislow, K. J . Am.
Chem. Soc. 1969, 91, 7031. (b) Lewis, R. A.; Mislow, K. J . Am. Chem.
Soc. 1969, 91, 7009.
(5) For an initial report concerning the use of the Cu(I)-Pd(0)
cocatalyst system for the arylation of racemic methylphenylphosphine-
borane, see: Al-Masum, M.; Livinghouse, T. Tetrahedron Lett. 1999,
40, 7731.
(6) Oshiki, T.; Imamoto, T. J . Am. Chem. Soc. 1992, 114, 3975.
(7) For examples involving the Pd(0) catalyzed cross-coupling of
enantioenriched isopropyl arylmethyl phosphinates see: (a) Zhang, J .;
Xu, Y. J . Chem. Soc. Chem. Commun. 1986, 1606. (b) Zhang, J .; Xu,
Y.; Huang, G.; Guo, H. Tetrahedron Lett. 1988, 29, 1955. (c) Xu, Y.;
Wei, H.; Zhang, J .; Huang, G. Tetrahedron Lett. 1989, 30, 949.
(14) Representative cross-couplings that were conducted at higher
temperatures (e.g., 25 °C) resulted in lower product ee’s.
(15) Phosphine-borane 1 was found to undergo relatively rapid
racemization in the presence of Et3N in THF solution at 25 °C.
Significantly, Et3N-mediated racemization of 1 was shown to be a
comparatively slow process at 0 °C.
(16) Prepared in-situ by treating Pd(OAc)2 with Me(Ph)2P (3 equiv)
in THF: Kulasegaram, S.; Kulawiec, R. J . J . Org. Chem. 1994, 59,
7195.
(17) Farina, V.; Krishnan, B. J . Am. Chem. Soc. 1991, 113, 9585.
10.1021/jo0003605 CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/24/2000

Notes
J . Org. Chem., Vol. 65, No. 15, 2000 4777
Sch em e 1
Ta ble 1
at phosphorus to provide (Rp) 3a with excellent stereo-
selectivity.19 It is also of interest that the polarity of the
reaction medium had very little influence on the absolute
stereochemical outcome of substitution when CuI was
present. The latter result contrasts with the findings of
Imamoto involving menthyl phenylphosphinite-borane
in the absence of CuI.6 Although (Ph3P)4Pd was found
an effective catalyst, superior results and enhanced
reproducibility were obtained with catalysts generated
in-situ from Pd(OAc)2 + 3 R3P.16 In this connection it is
noteworthy that highly electron-rich phosphines [e.g.,
n-Bu3P, (n-Bu)2PhP, (i-Pr)2PhP and (Cy)3P] gave rela-
tively ineffective Pd(0) catalyst systems when compared
to the catalyst generated from Me(Ph)2P. A series of
representative cross-coupling reactions was subsequently
conducted employing 18 and various aryl iodides. The
results of this study are shown in Table 1.
Several features of the above results are worthy of
comment. Excellent levels of stereocontrol are maintained
over a rather wide range of sterically differentiated
reaction components.18 In this regard it is preparatively
significant that the overall yields and ee’s obtained via
Pd(0)-Cu(I) cross-coupling exceed those achievable by
direct nucleophilic alkoxide displacement.2b,12,19 In addi-
tion, representative arene phosphorylations can readily
be carried out on a preparative scale.
In summary, we have shown that Pd(0)-Cu(I) cocata-
lyzed aromatic phosphorylation is an excellent method
for the synthesis of phosphine-boranes in a very high
state of optical purity. The scope of this reaction is
currently being extended to the synthesis of new biden-
tate ligand domains for asymmetric catalysis.
a
b
Isolated yield. All ee’s were determined by HPLC chroma-
tography using a chiralpak AD HPLC column. c After recrystal-
lization from hexane/2-propanol.
Gen er a l P r oced u r e for Ster eocon tr olled Ar en e P h os-
ph or ylation . (R)-(2-Meth ylph en yl)ph en ylm eth ylph osph in e-
bor a n e (3a ). To a solution of Pd(OAc)2 (7.5 mol %, 8.5 mg) in
dry THF (0.5 mL) under an argon atmosphere was added
diphenylmethylphosphine (22 mol %, 0.022 mL) and the result-
ing mixture was allowed to stir for 10 min at room temperature.
2-Iodotoluene (2a ) (1.5 equiv, 0.09 mL) was then added and
stirring was continued at room temperature. In another flask,
CuI (30 mol %, 30 mg) was dissolved in a mixture of THF (0.25
mL) and Me2S (0.2 mL) under argon and then (i-Pr)2NEt (1.2
equiv, 0.1 mL) and (Sp)-Methylphenylphosphine-borane 1 (0.5
mmol, 0.078 mL) were sequentially added at 0 °C. The solution
of the palladium complex was then added to the phosphine-
borane solution by cannula and the resulting mixture was stirred
for 3 days at 0 °C. The reaction mixture was quenched by the
addition of water, extracted with CH2Cl2 and the organic layer
was dried over anhydrous Na2SO4. After removal of the solvent
in vacuo, the crude product was subjected to silica gel chroma-
tography using hexane followed by hexane/CH2Cl2 (5/1). The
pure product 3a was isolated as a colorless liquid (85 mg, 75%)
(entry 1). 1H NMR (CDCl3, 300 MHz): δ 7.73-7.14 (m, 9H,
-C6H5, -C6H4-), 2.17 (s, 3H, CH3), 1.85 (d, J ) 9.9 Hz, 3H,
-CH3), 1.54-0.48 (br m, 3H, BH3). 13C NMR (CDCl3, 75.5
MHz): δ 142.8, 132.8, 131.9, 129.3, 126.5, 22.1, 13.6. 31P NMR
Exp er im en ta l Section
Gen er a l Meth od s. All experiments were carried out under
an argon atmosphere in oven-dried glassware. Tetrahydrofuran
(THF) and diethyl ether (Et2O) were distilled from sodium-
benzophenone ketyl. Methyldiphenylphosphine and palla-
dium(II) acetate were purchased from Strem Chemicals, Inc.,
and copper(I) iodide was purified by precipitation from aqueous
KI. All other reagents were either prepared according to
published procedures or were available from commercial sources
and used without further purification. Column flash chroma-
tography was performed on Merck silica gel 60 (230-400 mesh)
and Aldrich neutral alumina (∼150 mesh). Chiral HPLC was
performed using a chiralpak AD [250 × 4.6 mm (L X I. D.)]
HPLC column (Daicel Chemical Industries).
(18) Enantiomeric purity was established by HPLC using a Chiral-
pak AD HPLC column.
(19) An authentic specimen of phosphine-borane 3a was prepared
by the procedure of J uge2b for comparative purposes and shown to
possess a configuration identical18 to that synthesized via Pd(0)-Cu-
(I) cocatalyzed cross-coupling. It is also of significance that the sample
of 3a prepared in this manner was obtained in lower enantiomeric
purity and yield when compared to the present cross-coupling proce-
dure.

4778 J . Org. Chem., Vol. 65, No. 15, 2000
Notes
(CDCl3, 121 MHz): δ 10.76. HRMS: calcd for C14H15P (M+
-
Ack n ow led gm en t. Generous support for this re-
search by a grant from the National Science Foundation
is gratefully acknowledged. The authors thank Mr.
Young Kwan Kim of these laboratories for performing
the 5.0 mmol scale cross-couplings.
BH3) 214.0913, found 214.0911. [R]25D ) -27° (c ) 1.0, CH3OH).
Separation of enantiomers by chiral HPLC (Daicel Chiral Pak
AD column, flow rate 1 mL/min, 99% hexane, 1% 2-propanol,
Tr 11.79, 12.66 min) determined the ee to be >99%.
In case of compound 3f and 3g the crude products were
subjected to purification by chromatography on neutral alumina.
Cross-coupling reactions performed using 5.0 mmol of starting
phosphine-borane provide arylation products in comparable
yields and enantiopurity.
Su p p or tin g In for m a tion Ava ila ble: Spectral data for
compounds 3b-g. This material is available free of charge via
the Internet at http://pubs.acs.org.
J O0003605