Platinum-catalyzed enantioselective tandem alkylation/arylation of primary phosphines. Asymmetric synthesis of p-stereogenic 1-phosphaacenaphthenes

Article abstract of DOI:10.1021/ol801616s

(Chemical Equation Presented) Enantioselective tandem alkylation/arylation of primary phosphines with 1-bromo-8-chloromethylnaphthalene catalyzed by Pt(DuPhos) complexes gave P-stereogenic 1-phosphaacenaphthenes (AcePhos) in up to 74% ee. Diastereoselective formation of four P-C bonds in one pot with bis(primary) phosphines gave C₂-symmetric diphosphines, including the ophenylene derivative DuAcePhos, for which the rac isomer was formed with high enantioselectivity. These reactions, which appear to proceed via an unusual metal-mediated nucleophilic aromatic substitution pathway, yield a new class of heterocycles with potential applications in asymmetric catalysis.

Full text of DOI:10.1021/ol801616s

ORGANIC
LETTERS
2008
Vol. 10, No. 20
4425-4428
Platinum-Catalyzed Enantioselective
Tandem Alkylation/Arylation of Primary
Phosphines. Asymmetric Synthesis of
P-Stereogenic 1-Phosphaacenaphthenes
Brian J. Anderson,† Marites A. Guino-o,† David S. Glueck,*,† James A. Golen,‡
Antonio G. DiPasquale,‡ Louise M. Liable-Sands,‡,§ and Arnold L. Rheingold‡
6128 Burke Laboratory, Department of Chemistry, Dartmouth College,
HanoVer, New Hampshire 03755, Department of Chemistry, UniVersity of California,
San Diego, La Jolla, California 92093, and Department of Chemistry, Widener
UniVersity, Chester, PennsylVania 19013
glueck@dartmouth.edu
Received July 15, 2008
ABSTRACT
Enantioselective tandem alkylation/arylation of primary phosphines with 1-bromo-8-chloromethylnaphthalene catalyzed by Pt(DuPhos) complexes
gave P-stereogenic 1-phosphaacenaphthenes (AcePhos) in up to 74% ee. Diastereoselective formation of four P-C bonds in one pot with
bis(primary) phosphines gave C2-symmetric diphosphines, including the o-phenylene derivative DuAcePhos, for which the rac isomer was
formed with high enantioselectivity. These reactions, which appear to proceed via an unusual metal-mediated nucleophilic aromatic substitution
pathway, yield a new class of heterocycles with potential applications in asymmetric catalysis.
Several heteroatom-substituted acenaphthene derivatives 1 are
known (Figure 1; E ) O, S, NR, SiR2).1 Conspicuous by its
absence is the analogous phosphine (3, E ) PR), although this
heterocycle is presumably present in the phosphafullerene C59P
(2), which has been observed by mass spectrometry2 and
analyzed computationally.3,4 DuPhos and BPE, privileged
ligands in asymmetric catalysis, include phospholane rings,5
while P-stereogenic analogues like TangPhos6 and BeePhos7
are also valuable. The 1-phosphaacenaphthene 3 (AcePhos),
with reduced conformational flexibility due to the fused
naphthalene, might also be a useful ligand.8
We recently described a Pd-catalyzed asymmetric synthesis
of benzophospholanes via enantioselective cyclization of
† Dartmouth College.
‡ University of California.
§ Widener University.
(3) (a) Lu, J.; Zhou, Y.; Luo, Y.; Huang, Y.; Zhang, X.; Zhao, X. Mol.
Phys. 2001, 99, 1203–1207. (b) Simeon, T. M.; Yanov, I.; Leszczynski, J.
Int. J. Quantum Chem. 2005, 105, 429–436.
(1) (a) For a review, see: Mezheritskii, V. V.; Tkachenko, V. V. AdV.
Heterocycl. Chem. 1990, 51, 1–103. For examples, see: (b) Berry, D.; Smith,
D. C. C. J. Chem. Soc., Perkin Trans. 1 1972, 699–704 (O and NR). (c)
Folli, U.; Iarossi, D.; Taddei, F. J. Chem. Soc., Perkin Trans. 2 1974, 933–
937 (S). (d) Kiely, J. S.; Boudjouk, P. J. Organomet. Chem. 1979, 182,
173–183 (SiR2)
(4) For diphosphaacenaphthenes, see: (a) Mizuta, T.; Nakazono, T.;
Miyoshi, K. Angew. Chem., Int. Ed. 2002, 41, 3897–3898. (b) Mizuta, T.;
Satoru, K.; Katsuhiko, M. J. Organomet. Chem. 2004, 689, 2624–2632.
(c) Reiter, S. A.; Nogai, S. D.; Karaghiosoff, K.; Schmidbaur, H. J. Am.
Chem. Soc. 2004, 126, 15833–15843.
(2) Moschel, C.; Jansen, M. Z. Anorg. Allg. Chem. 1999, 625, 175–
177.
(5) Burk, M. J. Acc. Chem. Res. 2000, 33, 363–372.
10.1021/ol801616s CCC: $40.75
Published on Web 09/23/2008
2008 American Chemical Society

Scheme 2.
Synthesis of Phosphines 4a,ba
Figure 1. Known 1-heteroatom-acenaphthenes 1, this ring system
in fullerene 2, target phosphine 3, and some related bis(phospholane)
ligands.
aBase ) NaH or KOH (phase-transfer conditions).12 For 4a, amine )
NHEt2, NEt3, DABCO, or piperazinomethyl polystyrene.13 For 4b, amine
) piperazinomethyl polystyrene.
bifunctional aryl iodide/secondary phosphine substrates,
shown in red in Scheme 1.9 These reactions could plausibly
Alkylation of PH2Ph(BH3) with bromide 5b under phase-
transfer conditions12 gave phosphine-borane 6b, which was
deprotected with piperazinomethyl polystyrene13 or HBF4
to yield phosphine substrate 4b.14
Scheme 1. Metal-Catalyzed Intramolecular Asymmetric
Arylation of Secondary Phosphines: Synthesis of
Benzophospholanes9 (in Red, X ) I) and Potential Extension to
1-Phosphaacenaphthenes 3a
In contrast, similar alkylations with iodide 5a were less
selective. Deprotonation of PH2Ph(BH3) with NaH,9 followed
by treatment with 5a, gave a mixture of 6a, the known
dehydrohalogenation product 7,15 and AcePhos-borane 8a
(see below). Instead, P-alkylation under phase-transfer condi-
tions suppressed ring formation, but dehydrohalogenation still
occurred. Phosphine-boranes 6a and 7 could be separated
with difficulty by recrystallization, but deprotection of 6a
gave AcePhos 3a (R ) Ph) in addition to the desired 4a.
This cyclization presumably occurred via deprotonation of
6a followed by intramolecular nucleophilic attack; no reac-
tion occurred on treatment of the less acidic phosphine 4a
with NEt3.
Pd(DuPhos)-catalyzed cyclization of 4 gave AcePhos 3a
quickly, but in racemic form (Scheme 1). However, the
observations of ring formation under basic conditions in the
synthesis of substrates 6a and 4a suggested that Pt-mediated
nucleophilic activation of 4 might enable enantioselective
cyclization.10 Indeed, this reaction occurred quickly with 4b
and Pt(DuPhos)(Ar)(Cl) catalyst precursors to afford 3a in
up to 6.2:1 er (72% ee, Table 1).
a[Pd*] ) Pd(diphos*)(trans-stilbene), [Pt*] ) Pt(DuPhos)(Ph)(Cl).
be extended to 1,8-naphthalene derivatives 4 to form 3 (Scheme
1). We report here that, although Pd-catalyzed synthesis of 3
was unselective, novel Pt-catalyzed cyclizations yielded Ace-
Phos ligands enantio- and diastereoselectively (Scheme 1).10
These reactions, which expand the scope of Pt-catalyzed P-C
bond-forming processes,11 appear to proceed via an unusual
metal-mediated nucleophilic aromatic substitution.
Precursors to secondary phosphine substrates 4a,b (R )
Ph) were prepared from benzyl chlorides 5 (Scheme 2).1d
(6) Tang, W.; Zhang, X. Angew. Chem., Int. Ed. 2002, 41, 1612–1614.
(7) Shimizu, H.; Saito, T.; Kumobayashi, H. AdV. Synth. Catal. 2003,
345, 185–189.
These platinum catalysts mediated alkylation of secondary
phosphines with benzyl halides,10 suggesting that a one-pot
AcePhos synthesis from primary phosphines and 5, via
intermediate 4, might be possible. Indeed, when PH2Ph and
5b were treated with 2 equiv of NaOSiMe3 in the presence
(8) Phosphorus Ligands in Asymmetric Catalysis. Synthesis and Ap-
plications; Bo¨rner, A., Ed.; Wiley-VCH: Weinheim, 2008.
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Organometallics 2007, 26, 1788–1800 (Addition/Correction: Organome-
tallics 2007, 26, 5124). (c) Chan, V. S.; Stewart, I. C.; Bergman, R. G.;
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9322.
(11) (a) Glueck, D. S. Synlett 2007, 2627–2634. (b) Glueck, D. S. Coord.
Chem. ReV. 2008, 252, 2171-2179. (c) Glueck, D. S. Chem.sEur. J. 2008,
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b806138f).
(15) Stankevic, M.; Pietrusiewicz, K. M. Synlett 2003, 1012–1016.
4426
Org. Lett., Vol. 10, No. 20, 2008

no)benzene 10c, for which bis(secondary) phosphine 11 and
other intermediates were observed. While formation of 9a,b
occurred with low stereoselectivity, “DuAcePhos” 9c was
formed with good diastereoselection, and the rac isomer was
highly enantioenriched.18
Table 1. Pt-Catalyzed Cyclization of 4b To Yield 3aa
Scheme 3. Proposed Mechanism for Pt-Catalyzed Tandem
Alkylation/Arylation of Primary Phosphines with 5ba
entry
catalyst precursor
yield (%)
er (ee,%)
1
2
3
Pt((R,R)-Me-DuPhos)(Ph)(Cl)
Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl)
Pt((R,R)-Me-DuPhos)(Phen)(Br)d
ndb
86
50
2.0 (33)
-6.2 (-72)c
1.6 (23)
a Reactions were done in THF with 5 mol % catalyst loading. b nd )
not determined. c The i-Pr-Duphos and Me-DuPhos catalyst precursors
preferentially yielded opposite enantiomers of 3a. d Phen ) 9-phenanthryl.
of a Pt catalyst, secondary phosphine 4b formed and was
then converted to 3a. Similarly, the alkylphosphines PH2Cy
and PH2CH2Fc16 gave heterocycles 3b,c (Table 2).
Tandem alkylation/arylation was also successful with
bis(primary) phosphines, directly yielding C2-symmetric
diphosphines 9a-c (Table 2). This reaction occurred smoothly
for unhindered 1,2-bis(phosphino)ethane (10a), but was much
slower for 1,1′-ferrocene derivative17 10b and bis(phosphi-
aThe intermediates shown in black were observed in stoichiometric and/
or catalytic reactions, but 15 (in red) was not observed. [Pt] ) Pt(DuPhos),
R ) Ph or Cy, X ) Cl or Br, Ar ) 8-bromo-1-naphthyl.
Table 2. Pt-Catalyzed One-Pot Synthesis of Mono- and
Bis-1-phosphaacenaphthenes from Primary Phosphines and
Bis(primary) Phosphinesa
The mechanism proposed in Scheme 3 is consistent with
observations on catalytic and stoichiometric reactions with
PH2Ph and PH2Cy.10 Treatment of Pt catalyst precursors with
a primary phosphine and NaOSiMe3 gave the primary
phosphido complexes Pt(DuPhos)(Ph)(PHR) (12). Alkylation
with 5b gave a mixture of secondary phosphines 4b, their
cationic Pt complexes 13, and Pt halide 14. Deprotonation
of 13 with another equiv of base would give secondary
phosphido complex 15, which was not observed, presumably
because its subsequent reactions are fast. Intramolecular
nucleophilic aromatic substitution by the activated Pt-
phosphido group in 15 (path a) would give AcePhos complex
16,19 from which product displacement by a phosphine
substrate and base would complete the catalytic cycle.
Alternatively, proton transfer from a primary phosphine to
15 (path b) could regenerate 12 and yield a secondary
phosphine.20 Competition between paths a and b would
depend on steric effects and on the nucleophilicity of the
phosphido group in 15.
yield
(%)
er
(ee, %)
dr
entry
substrate (product)
(de, %)b
1
2
3
4
5
6
PH2Ph (3a)
PH2Cy (3b)
PH2CH2Fc (3c)
H2P(CH2)2PH2 (9a)
1,1′-Fc(PH2)2 (9b)
1,2-C6H4(PH2)2 (9c)
80
85
85
78
69
85
6.7 (74)
1.7c (26)
3.0d (50)
4e (60)
1.5 (20)f
1.9 (31)
4.5 (64)
2.3e (39)
>100g (>98)
a The catalyst precursor was Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl) (entries 1
and 2, 5 mol %), Pt((R,R)-Me-DuPhos)(Ph)(Cl) (entry 3, 5 mol %, and
entry 6, 10 mol %; for entries 4 and 5, the initial loading was 10 mol %,
and an additional 4 mol % and 10 mol %, respectively, was added during
the reaction). R ) Ph (3a), Cy (3b), FcCH2 (3c), Ar (in 11) ) 8-Br-1-
naphthyl. Solvent ) toluene (entries 1 and 4-6) or THF (entries 2 and 3).
b dr ) rac/meso ratio for the diphosphine. c The same er was observed for
the mesylate 1-Br-8-CH2OMs-C10H6. d With Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl)
(5 mol %), the er was 4.5 (64% ee); the opposite enantiomer was favored.
e for the rac diphosphine. f With Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl) (10 mol %),
dr ) 1.6 (23% de), er ) 4.5 (64% ee); the opposite enantiomer was favored.
g The minor enantiomer (which was prepared independently as the major
product using Pt((R,R)-i-Pr-DuPhos)(Ph)(Cl); dr ) 4.3 (62% ee)) was not
observed.
(16) Goodwin, N. J.; Henderson, W.; Nicholson, B. K. Chem. Commun.
1997, 31–32.
(17) Burk, M. J.; Gross, M. F. Tetrahedron Lett. 1994, 35, 9363–9366.
(18) For the conceptually related synthesis of i-Pr-BeePhos, see ref 7.
(19) Herbert, J. M.; Woodgate, P. D.; Denny, W. A. Heterocycles 1987,
26, 1037–1041.
(20) Wicht, D. K.; Paisner, S. N.; Lew, B. M.; Glueck, D. S.; Yap,
G. P. A.; Liable-Sands, L. M.; Rheingold, A. L.; Haar, C. M.; Nolan, S. P.
Organometallics 1998, 17, 652–660.
Org. Lett., Vol. 10, No. 20, 2008
4427

was distorted.21 Details of similar observations on 6a
are given in the Supporting Information. In contrast, in
DuAcePhos 9c and phosphine-boranes 8a and 8c,22 the peri
substituents were bent toward each other, distorting the
naphthalene in the other direction.23 Structural constraints
of the ring resulted in a small intra-annular CPC bond angle
(about 91° for DuAcePhos, 93° in 8a and 8c), which may
result in unusual properties for these phosphines in coordina-
tion chemistry and catalysis.
In summary, we report an asymmetric synthesis of a new
class of structurally characterized phosphorus heterocycles
(AcePhos) via Pt-catalyzed alkylation of primary phosphines,
followed by intramolecular arylation. A convenient one-pot
procedure enables the synthesis of C2-symmetric P-stereo-
genic diphosphines; these ring-fused phospholanes may be
useful ligands in asymmetric catalysis.
Acknowledgment. We thank the National Science Foun-
dation for support, the Department of Education for a
GAANN fellowship to B.J.A., and Cytec Canada for gifts
of reagents.
Figure 2. ORTEP diagrams of phosphine-borane 6b, phosphine
4a, and AcePhos-borane derivatives 8a and 8c (see the abstract
for an ORTEP diagram of 9c, DuAcePhos).
Supporting Information Available: Experimental pro-
cedures and characterization data. This material is available
free of charge via the Internet at http://pubs.acs.org.
Several of the new phosphacycles and their precursors
have been structurally characterized by X-ray crystal-
lography. The structures of 6b and 4a (Figure 2) showed
features typical of peri-crowding; the 1- and 8-substituents
were bent away from each other, and the naphthalene ring
OL801616S
(21) Balasubramaniyan, V. Chem. ReV. 1966, 66, 567–641.
(22) Prepared from 3a and 3c by treatment with BH3(SMe2).
(23) Schweizer, W. B.; Procter, G.; Kaftory, M.; Dunitz, J. D. HelV.
Chim. Acta 1978, 61, 2783–2808.
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