Stereochemistry of palladium-mediated synthesis of PAMP-BH3: Retention of configuration at P in formation of Pd-P and P-C bonds

Article abstract of DOI:10.1021/ja029404c

Treatment of Pd((S,S)-Chiraphos)(o-An)(I) (3, o-An = o-MeOC₆H₄) with either enantiomer of highly enantioenriched PH(Me)(Ph)(BH₃) (1) gave the phosphido-borane complex Pd((S,S)-Chiraphos)(o-An)(P(Me)(Ph)(BH₃)) (4

Full text of DOI:10.1021/ja029404c

Published on Web 01/11/2003
Stereochemistry of Palladium-Mediated Synthesis of PAMP-BH3: Retention
of Configuration at P in Formation of Pd-P and P-C Bonds
Jillian R. Moncarz,† Tim J. Brunker,† David S. Glueck,*,† Roger D. Sommer,‡ and
Arnold L. Rheingold‡
6128 Burke Laboratory, Department of Chemistry, Dartmouth College, HanoVer, New Hampshire, 03755, and
Department of Chemistry, UniVersity of Delaware, Newark, Delaware 19716
Received November 19, 2002 ; E-mail: glueck@dartmouth.edu
Scheme 2
Palladium-catalyzed cross-coupling of organophosphorus com-
pounds containing a P-H bond with aryl or vinyl halides or triflates
is a useful method for P-C bond formation.1 P-chirogenic substrates
with a PdO group undergo coupling with retention of configuration
at phosphorus.2 With phosphine-boranes, however, Imamoto ob-
served that coupling of enantiopure PH(Me)(Ph)(BH3) (1) with
o-AnI (o-An ) o-MeOC6H4) to give P(o-An)(Me)(Ph)(BH3)
(PAMP-BH3, 2, a precursor to the historically and industrially
important DiPAMP ligand)3 led to retention or inversion of P
stereochemistry depending on base, solvent, and temperature.4 More
recently, Livinghouse showed that adding Cu(I) to similar reactions
gave tertiary phosphine-boranes in high enantiomeric excess (ee)
with retention of configuration at phosphorus.5 These stereochemical
results were ascribed to the Pd-P bond formation step (transmeta-
lation), assuming that P-C bond formation (reductive elimination)
proceeds with retention of configuration at phosphorus (Scheme
1).5,6 However, these steps could not be separated and observed
directly.
ratio depends on conditions, as described below).8,9 After separation
by recrystallization, X-ray crystallographic studies of both diaster-
eomers (Figure 1) established the absolute configuration of the
phosphido-borane P centers.10
Scheme 1
Figure 1. ORTEP diagrams of (RP)-Pd((S,S)-Chiraphos)(o-An)(P(Me)(Ph)-
(BH3)) (4b) and (SP)-Pd((S,S)-Chiraphos)(o-An)(P(Me)(Ph)(BH3)) (4a).
Treatment of 3 with highly enantioenriched (SP)- or (RP)-111 and
NaOSiMe3 in THF-d8 at -78 °C gave (RP)-4b or (SP)-4a, re-
spectively, in high de, with retention of configuration at phosphorus
(Table 1, entries 1-2).12
Table 1. Stereochemistry of Pd-P Bond Formation
(Transmetalation) in the Reaction of 3 with 1 and NaOSiMe3
in THF-d8
More generally, such fundamental information on the stereo-
chemistry of organometallic reactions, while important in asym-
metric catalysis, is incompletely documented.6 For example, a
standard textbook states that “A great deal of evidence suggests
that the formation of C-C, C-H, and C-X bonds by reductive
elimination always proceeds with retention of stereochemistry at
carbon, although no case has been reported in which an isolated
starting material of known stereochemistry has eliminated a product
of known stereochemistry.”7 Here we show by direct observation
that reductive elimination indeed proceeds with retention of
configuration at phosphorus in an analogous Pd-mediated synthesis
of PAMP-BH3. Transmetalation also occurred with retention at
low temperature, and the effect of reaction conditions on stereo-
control in this step was studied directly.
temperature
ee of 1a
de of 4b
entry
(°C)
(%)
(%)
1
2
3
4
5
-78
-78
21
21
21
95 (R)
99 (S)
95 (R)
97 (S)
0
94 (S, 4a)c
94 (R, 4b)
86 (S, 4a)d
63 (R, 4b)
23 (S, 4a)d
a From chiral HPLC (Chiralcel OJ-H). b From integration of the 1H NMR
spectrum; the ee and de values obtained at -78 °C (entries 1-2) are the
same, within experimental error. c Average of two runs. d Average of three
runs.
The erosion of stereochemistry in room-temperature transmeta-
lation (entries 3-4) is presumably due to inversion of the
phosphido-borane anion before reaction with the Pd complex
occurs.13 With racemic 1, dynamic kinetic resolution was observed
(entry 5); one enantiomer of the anion [P(Me)(Ph)(BH3)]- appears
to react more quickly with chiral 3 than the other (kR > kS), and
Treatment of Pd((S,S)-Chiraphos)(o-An)(I) (3) with racemic 1
and NaOSiMe3 gave a mixture of the diastereomers Pd((S,S)-
Chiraphos)(o-An)(P(Me)(Ph)(BH3)) (4a, 4b, Scheme 2; the product
† Dartmouth College.
‡ University of Delaware.
9
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J. AM. CHEM. SOC. 2003, 125, 1180-1181
10.1021/ja029404c CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
anion interconversion (kinv) can occur before transmetalation
(Scheme 3). This is consistent with the greater loss of stereochem-
Acknowledgment. We thank the National Science Foundation,
Union Carbide (Innovation Recognition Program), and DuPont for
support. We are grateful to Professors Tsuneo Imamoto (Chiba
University) and Tom Livinghouse (Montana State University) for
advice and sharing unpublished results on the preparation of
enantiopure 1.
Scheme 3
Supporting Information Available: Experimental procedures and
characterization data (PDF) and details of the X-ray crystallographic
studies (CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
ical information in entry 4 versus entry 3 and suggests that
transmetalation occurs somewhat more quickly than P inversion
under these conditions, but the rates of these processes are
competitive.14
Knowledge of the absolute configurations of 4a and 4b and of
the enantiomers of PAMP-BH3 (2) allowed for direct observation
of the stereochemistry of reductive elimination.3,5 Heating either
diastereomer of 4 to 50 °C in the presence of 4 equiv of
diphenylacetylene gave 2 and Pd((S,S)-Chiraphos)(PhCtCPh) (5)
as the major products, along with anisole and other unidentified
MeO-containing byproducts.15 The phosphine-borane, isolated by
preparative TLC, was formed in high ee, with retention of
configuration at phosphorus (Scheme 4, Table 2). Diastereomers
References
(1) For examples, see: (a) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D.
L.; Verhoeven, T. R.; Reider, P. J. Org. Synth. 1999, 76, 6-11. (b) Al-
Masum, M.; Livinghouse, T. Tetrahedron Lett. 1999, 40, 7731-7734.
(c) Lipshutz, B. H.; Buzard, D. J.; Yun, C. S. Tetrahedron Lett. 1999, 40,
201-204. (d) Montchamp, J.-L.; Dumond, Y. R. J. Am. Chem. Soc. 2001,
123, 510-511. (e) Kazankova, M. A.; Chirkov, E. A.; Kochetkov, A. N.;
Efimova, I. V.; Beletskaya, I. P. Tetrahedron Lett. 1998, 39, 573-576.
(2) (a) Xu, Y.; Zhang, J. J. Chem. Soc., Chem. Commun. 1986, 1606 and
references therein. (b) Johansson, T.; Stawinski, J. Chem. Commun. 2001,
2564-2565.
(3) Imamoto, T.; Oshiki, T.; Onozawa, T.; Kusumoto, T.; Sato, K. J. Am.
Chem. Soc. 1990, 112, 5244-5252.
(4) Imamoto, T.; Oshiki, T.; Onozawa, T.; Matsuo, M.; Hikosaka, T.;
Yanagawa, M. Heteroat. Chem. 1992, 3, 563-575. For analogous results
with another secondary phosphine-borane, see also: Oshiki, T.; Imamoto,
T. J. Am. Chem. Soc. 1992, 114, 3975-3977.
(5) Al-Masum, M.; Kumaraswamy, G.; Livinghouse, T. J. Org. Chem. 2000,
65, 4776-4778.
Scheme 4 a
(6) For a review, see: (a) Flood, T. C. In Topics in Stereochemistry; Geoffroy,
G. L., Ed.; Wiley: New York, 1981; Vol. 12, pp 37-117. For recent
studies of transmetalation to Pd, see: (b) Matos, K.; Soderquist, J. A. J.
Org. Chem. 1998, 63, 461-470. (c) Ridgway, B. H.; Woerpel, K. A. J.
Org. Chem. 1998, 63, 458-460. (d) Hatanaka, Y.; Hiyama, T. J. Am.
Chem. Soc. 1990, 112, 7793-7794. (e) Labadie, J. W.; Stille, J. K. J.
Am. Chem. Soc. 1983, 105, 669-670.
(7) (a) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles
and Applications of Organotransition Metal Chemistry; University Science
Books: Mill Valley, CA, 1987; p 333. (b) C-N bond formation at a Ni
center led to inversion at carbon, but in this oxidatively induced reductive
elimination, the nature of the Ni(III) intermediate could not be determined
(Lin, B. L.; Clough, C. R.; Hillhouse, G. L. J. Am. Chem. Soc. 2002,
124, 2890-2891).
(8) For related Pd phosphido-borane complexes, see: Gaumont, A.-C.;
Hursthouse, M. B.; Coles, S. J.; Brown, J. M. Chem. Commun. 1999,
63-64.
a [Pd] ) Pd((S,S)-Chiraphos). Results with diastereomer 4b were similar;
2 was formed with retention.
Table 2. Stereochemistry of P-C Bond Formation (Reductive
Elimination) in Reaction of 4 with 4 equiv of Diphenylacetylene in
THF-d8 at 50 °C
time
(h)
conversion
(%)a
yield
(%)a,b
isomer de
(%)a
ee (2)c
(%)
entry
1
2
3
4
72
96
37
48
84
87
96
91
51(21)
73(20)
54(20)
70(21)
4a (94, S)
4a (94, S)
4b (100, R)
4b (88, R)
91(93) (S)
87(93) (S)
98 (R)
(9) Complex 3 exists as a 6:1 mixture of atropisomers due to restricted rotation
about the Pd-C bond (Brown, J. M.; Perez-Torrente, J. J.; Alcock, N.
W. Organometallics 1995, 14, 1195-1203). Likewise, atropisomers of
both diastereomers 4a and 4b were observed.
93(92) (R)
1
(10) The H NMR spectrum of the single crystal of 4b used for the structure
determination matched that of bulk 4b, confirming the stereochemical
assignment.
a Conversions, NMR yields, and de values for 4 were determined by
1
integration of the H NMR spectrum versus a ferrocene internal standard.
(11) (a) Wolfe, B.; Livinghouse, T. J. Org. Chem. 2001, 66, 1514-1516. (b)
b Format: NMR yield (isolated yield of pure material after preparative TLC
on silica). Yields are not corrected for conversion. c Format: ee (theoretical
maximum ee corrected for conversion) (configuration); ee values from chiral
HPLC (Chiralpak AD). Because 4a and 4b undergo reductive elimination
at different rates, at incomplete conversion, unreacted 4 becomes enriched
in the “slow” diastereomer 4a, while 2 becomes enriched in the product
formed from the “fast” diastereomer 4b. Therefore, at incomplete conversion,
the maximum ee of 2 may be higher than the de of precursor 4.
References 3 and 4.
(12) The apparent inversion (for example, (SP)-1 yields (RP)-4b) is due to the
convention for assigning absolute configuration.
(13) (a) Oshiki, T.; Hikosaka, T.; Imamoto, T. Tetrahedron Lett. 1991, 32,
3371-3374. (b) Miura, T.; Yamada, H.; Kikuchi, S.; Imamoto, T. J. Org.
Chem. 2000, 65, 1877-1880.
(14) (a) Similar dynamic kinetic resolution (26% de) was observed in toluene
on a larger scale. Because of the limited solubility of 3 in toluene, NMR-
scale experiments such as those in Table 1 were not possible in this solvent.
(b) These observations suggest that, if reductive elimination from 4 were
faster, catalytic synthesis of enantioenriched PAMP-BH3 from racemic
1 would be possible. We are currently investigating this possibility with
related Pd catalysts.
(15) In analogous C-X (X ) N, S, O) reductive eliminations from Pd(II),
adding a trap for Pd(0) improved yield and/or selectivity of the reaction:
(a) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 8232-
8245. (b) Mann, G.; Baranano, D.; Hartwig, J. F.; Rheingold, A. L.; Guzei,
I. A. J. Am. Chem. Soc. 1998, 120, 9205-9219. (c) Widenhoefer, R. A.;
Zhong, H. A.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 6787-
6795. Similarly, after screening other trapping agents (none, o-AnI, (S,S)-
Chiraphos) and temperatures, these conditions were found to give the
cleanest reaction. The origin of anisole and the other unidentified
byproducts remains unclear; likewise, the mechanism of formation of the
arene byproduct in Pd-catalyzed aryl amination could not be elucidated
(Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 3694-3703).
4a and 4b undergo reductive elimination at different rates;
approximate half-lives under these conditions are 30 and 10 h,
respectively.
In summary, direct observation showed that both Pd-P bond
formation (transmetalation) and P-C bond formation (reductive
elimination) proceeded with retention of configuration at phosphorus
in this system. In addition to providing detailed mechanistic
information on this useful class of Pd-mediated reactions, this work
has more general significance in confirming long-held assumptions
about the stereochemistry of these fundamental processes and
suggests that the reactions of M-P and M-C bonds are similar in
stereochemistry.
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