t-BuOK-mediated hydrophosphination of functionalized alkenes: A novel synthesis of chiral P,N- and P,P-ligands

Article abstract of DOI:10.1021/jo030383u

A novel synthesis of effective chiral P,N- and P,P-ligands has been developed by using a t-BuOK-mediated hydrophosphination of chiral alkenylpyridines and alkenylphosphine oxides. Ir complexes of chiral P,N-ligands 1 and 3 gave high enantioselectivities for the hydrogenation of (Z)-α-(acetamido)cinnamate 25 and (E)-1,2-diphenylpropene leading to the hydrogenated products with up to 97% ee.

Full text of DOI:10.1021/jo030383u

t-Bu OK-Med ia ted Hyd r op h osp h in a tion of F u n ction a lized Alk en es:
A Novel Syn th esis of Ch ir a l P ,N- a n d P ,P -Liga n d s
Tanasri Bunlaksananusorn and Paul Knochel*
Department Chemie, Ludwig-Maximilians-Universita¨t Mu¨nchen, Butenandtstrasse 5-13, Haus F,
81377 Mu¨nchen, Germany
paul.knochel@cup.uni-muenchen.de
Received December 17, 2003
A novel synthesis of effective chiral P,N- and P,P-ligands has been developed by using a t-BuOK-
mediated hydrophosphination of chiral alkenylpyridines and alkenylphosphine oxides. Ir complexes
of chiral P,N-ligands 1 and 3 gave high enantioselectivities for the hydrogenation of (Z)-R-
(acetamido)cinnamate 25 and (E)-1,2-diphenylpropene leading to the hydrogenated products with
up to 97% ee.
SCHEME 1
In tr od u ction
Tertiary phosphines are an important class of com-
pounds. They are widely employed both as ligands for
transition metal complexes and in various catalytic
processes.1 Thus, there is a considerable interest in
developing new methodologies allowing the stereoselec-
tive formation of carbon-phosphorus bonds. Taking atom
economy principles into consideration,2 a route involving
the addition of phosphines (HPR2) to alkenes would be
desirable. This reaction has been reported in the litera-
ture and was carried out in the presence of a radical
initiators,3 strong basic conditions,4 or transition metal
catalysis.5 The use of phosphine-borane complexes is
also possible and enables selective hydrophosphinations.6
Recently, we reported that t-BuOK-mediated addition
reactions of nucleophiles (carbonyl derivatives and phos-
phanes) led to a variety of functionalized alkenes.7 We
have applied this method for the preparation of modular
pyridine-type P,N-ligands 1-5 (Scheme 1). These modu-
lar P,N-ligands were proved to be efficient ligands for Ir-
catalyzed enantioselective hydrogenation reactions8 and
Pd-catalyzed allylic substitution reactions.9
Herein, we wish to report the full details for the
synthesis of novel chiral P,N-ligands 1-5 and the exten-
sion to the synthesis of chiral P,P-ligands using t-BuOK-
mediated hydrophosphination of alkenylpyridine 7 and
alkenylphosphine oxide 8 (eq 1).
(1) Brandsma, L.; Vasilesky, S. F.; Verkruijsse, H. D. Application
of Transition Metal Catalysts in Organic Synthesis; Springer-Verlag:
Berlin, 1999.
(2) (a) Trost, B. M. Angew. Chem. 1995, 107, 285; Angew. Chem.,
Int. Ed. 1995, 34, 259. (b) Trost, B. M. Science 1991, 254, 1471. (c)
Trost, B. M. Acc. Chem. Res. 2002, 35, 695.
Resu lts a n d Discu ssion
(3) (a) Therrien, B.; Ko¨nig, A.; Ward, T. R. Organometallics 1999,
18, 1565. (b) Mitchell, T. N.; Heesche, K. J . Organomet. Chem. 1991,
409, 163. (c) Therrien, B.; Ward, T. R. Angew. Chem. 1999, 111, 418;
Angew. Chem. Int. Ed. 1999, 38, 405.
(4) (a) Khachatryan, R. A.; Sayadyan, S. V.; Grigoryan, N. Y.;
Indzhikyan, M. G. Zh. Obshch. Khim. 1988, 58, 2472. (b) Arbuzova,
S. N.; Gusarova, N. K.; Malysheva, S. F.; Brandsma, L.; Albanov, A.
I.; Trofimov, B. A. Zh. Obshch. Khim. 1996, 66, 56. (c) Casey, C. P.;
Paulsen, E. L.; Beuttenmueller, E. W.; Proft, B. R.; Matter, B. A.;
Powell, D. R. J . Am. Chem. Soc. 1999, 121, 63.
(5) (a) Shulyupin, M. O.; Kazankova, M. A.; Beletskaya, I. P. Org.
Lett. 2002, 4, 761. (b) Douglass, M. R.; Marks, T. J . J . Am. Chem. Soc.
2000, 122, 1824. (c) Takaki, K.; Takeda, M.; Koshoji, G.; Shishido, T.;
Takehira, K. Tetrahedron Lett. 2001, 42, 6357. (d) Han, L.-B.; Mirzaei,
F.; Zhao, C.-Q.; Tanaka, M. J . Am. Chem. Soc. 2000, 122, 5407.
(6) (a) Bourumeau, K.; Gaumont, A.-C.; Denis, J .-M. Tetrahedron
Lett. 1997, 38, 1923. (b) Bourumeau, K.; Gaumont, A.-C.; Denis, J .-M.
J . Organomet. Chem. 1997, 529, 205.
(7) (a) Rodriguez, A. L.; Bunlaksananusorn, T.; Knochel, P. Org. Lett.
2000, 2, 3285. (b) Bunlaksananusorn, T.; Rodriguez, A. L.; Knochel,
P. Chem. Commun. 2001, 745. (c) Bunlaksananusorn, T.; Knochel, P.
Tetrahedron Lett. 2002, 43, 5817.
On the basis of our preliminary preparation of rac-
trans-aminophosphine oxide 9 and rac-trans-aminophos-
phine 10 (Scheme 2),7c we turned our attention to the
preparation of novel chiral P,N-ligands of type 1-5,
starting from readily available chiral building blocks such
as (+)-camphor (10) and (+)-nopinone (13).
The preparation of the corresponding alkenyl triflates
has been performed according to the literature.10 Treat-
ment of the lithium enolate anions of commercially
available (+)-camphor (11) and (+)-nopinone (13) with
N-phenyltrifluoromethanesulfonamide (Tf2NPh) in THF
(8) Bunlaksanusorn, T.; Polborn, K.; Knochel, P. Angew. Chem.
2003, 115, 4071; Angew. Chem., Int. Ed. 2003, 42, 3941.
(9) Bunlaksananusorn, T.; Luna, A. P.; Bonin, M.; Micouin, L.;
Knochel, P. Synlett 2003, 2240.
(10) McMurry, J . E.; Scott, W. J . Tetrahedron Lett. 1983, 24, 979.
10.1021/jo030383u CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/04/2004
J . Org. Chem. 2004, 69, 4595-4601
4595

Bunlaksananusorn and Knochel
SCHEME 2
mixture by recrystallization or column chromatography
either using silica gel or alumina oxide were unsuccessful.
We considered the performance of the hydrophosphina-
tion with Ph2P(O)H (6), followed by reduction of 17a to
aminophosphine 1. Thus, the addition of phosphine oxide
6 to alkenylpyridine 7a in the presence of substoichio-
metric amounts of t-BuOK (20 mol %) in DMSO furnished
aminophosphine oxide 17a in 87% yield as a single
diastereomer (Scheme 5). Under these standard condi-
tions, a new class of modular chiral aminophosphine
oxides 17a -e was prepared in good yields (72-87%
yield). The products were characterized by NOESY NMR
experiments and by X-ray crystal structure analysis.8
Having the novel aminophosphine oxides 17a -e in hand,
the reduction of 17a -e was achieved with HSiCl3 and
Et3N in toluene upon heating to 120 °C, yielding chiral
aminophosphines 1-5 in 61-92% yield (Scheme 5).14
After these successful results for the synthesis of chiral
P,N-ligands, we extended our methodology for the syn-
thesis of chiral 1,2-diphosphines. Helmchen et al. previ-
ously reported the addition of diphenylphosphine to
Michael acceptors.15 Thus, we applied our methodology
for the synthesis of chiral 1,2-diphosphines by the addi-
tion of phosphine oxide 6 to the alkenylphosphine oxide
8a in the presence of t-BuOK (20 mol %) in DMSO.
Unfortunately, we observed solely starting material 8a
even after heating to 90 °C for 16 h (Scheme 6).
SCHEME 3a
Assuming that the steric hindrance of the substituents
on the phosphine oxide was accountable for this failure,
we changed the substituents on the phosphine oxide from
phenyl to 2-furyl group. First, Pd-catalyzed cross-
coupling16 of di-2-furylphosphine oxide 18 with alkenyl
triflate 12 led to alkenylphosphine oxide 8b in 58% yield.
Treatment of alkenylphosphine oxide 8b with phosphine
oxide 6 in the presence of t-BuOK (20 mol %) provided
chiral diphosphine oxide 20 in 70% yield. The reduction
of phosphine oxides 19 was performed under the same
conditions (HSiCl3/Et3N in toluene) furnishing the chiral
diphosphine ligand 20 in 68% yield (Scheme 7).
We have tested the novel chiral P,N-ligands 1-5 and
chiral P,P-ligand 20 in asymmetric catalysis. Pfaltz et
al. have reported that iridium phosphinooxazoline com-
plexes are highly effective catalysts for enantioselective
hydrogenation reactions of olefins including unfunction-
alized alkenes.17 Following Pfaltz’s procedure,18 Ir com-
plexes 1-4 were readily prepared by heating a solution
of [Ir(cod)Cl]2 and the respective P,N-ligands 1-4 in CH2-
Cl2 (1 h). After treatment with sodium tetrakis[3,5-bis-
a
Reagent and conditions: (a) LDA, THF, Tf2NPh, -78 to 0 °C,
16 h; (b) Pd(dba)2 (2 mol %), dppf (2 mol %), THF, LiCl, 70 °C,
16 h.
at 0 °C led to the desired alkenyl triflates in 90-92%
yield (Scheme 3). The chiral alkenyl triflates 12-14
smoothly underwent Negishi cross-coupling reactions11
with 2-pyridylzinc bromide 15a prepared from com-
mercially available 2-bromopyridine by direct Br-Li
exchange, affording the desired 2-alkenylpyridines 7a
and 7c in 78-85% yield (Scheme 3). 2-Alkenylquinoline
7b was obtained in satisfactory yield (60%) through a Pd-
catalyzed cross-coupling of 2-quinolylzinc bromide 15b
with alkenyl triflate 12 in the presence of LiCl as shown
in Scheme 3.
We have then examined the preparation of substituted
bromopyridines 7d ,e. A method developed by Cai12 allows
the formation of monometalated species. Subsequent
transmetalation with anhydrous zinc bromide, followed
by Negishi cross-coupling reactions, led to the expected
coupling products 16a ,b in 34-70% yield. Afterward, the
bromopyridines 16a ,b underwent a Suzuki cross-coupling
reactions with phenylboronic acid in the presence of a
catalytic amount of Pd(PPh3)4 giving 2-alkenyl-6-phen-
ylpyridines 7d ,e, respectively, in high yields (Scheme 4).13
Initially, treatment of alkenylpyridine 7a with Ph2PH
using t-BuOK in DMSO led to a mixture of P,N-ligand 1
and aminophosphine oxide 17a . Attempts to purify the
(14) Yasuhiro, U.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J . Org.
Chem. 1993, 58, 1945.
(15) Knu¨hl, G.; Sennhenn, P.; Helmchen, G. Chem. Commun. 1995,
1845. See also: Krotz, A. Dissertation, Universita¨t Heidelberg, Heidel-
berg, Germany, 1999.
(16) Gilbertson, S. R.; Fu, Z.; Starkey, G. W. Tetrahedron Lett. 1999,
40, 8509.
(17) (a) Schnider, P.; Koch, G.; Pre´toˆt, R.; Wang, G.; Bohnen, F. M.;
Kru¨ger, C.; Pfaltz, A. Chem. Eur. J . 1997, 3, 887. (b) Blackmond, D.
G.; Lightfoot, A.; Pfaltz, A.; Rosner, T.; Schnider, P.; Zimmermann, N.
Chirality 2000, 12, 442. (c) Pfaltz, A.; Blankenstein, J .; Hilgraf, R.;
Ho¨rmann, E.; McIntyre, S.; Menges, F.; Scho¨nleber, M.; Smidt, S. P.;
Wu¨stenberg, B.; Zimmermann, N. Adv. Synth. Catal. 2003, 345, 33.
(d) Powell, M. T.; Hou, D.-R.; Perry, M. C.; Cui, X.; Burgess, K. J . Am.
Chem. Soc. 2001, 123, 8878. (e) Hou, D.-R.; Reibenspies, J .; Colacot,
T. J .; Burgess, K. Chem. Eur. J . 2001, 7, 5391. (f) Drury, W. J ., III;
Zimmermann, N.; Keenan, M.; Hayashi, M.; Kaiser, S.; Goddard, R.;
Pfaltz, A. Angew. Chem., Int. Ed. 2004, 43, 70.
(11) (a) Negishi, E.-I. Acc. Chem. Res. 1982, 15, 340. (b) Negishi,
E.-I. In Metal-Catalyzed Cross Coupling Reactions; Diederich, F.,
Stang, P. J , Eds.; Wiley-VCH: Weinheim, 1998; Chapter 1. (c) Erdik,
E. Tetrahedron 1992, 48, 9577.
(12) (a) Cai, D.; Hughes, D. L.; Verhoeven, T. R. Tetrahedron Lett.
1996, 37, 2537. (b) Peterson, M. A.; Mitchell, J . R. J . Org. Chem. 1997,
62, 8237.
(13) Chelucci, G.; Culeddu, N.; Saba, A.; Valenti, R. Tetrahedron:
Asymmetry 1999, 10, 3537.
(18) Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem. 1998, 110,
3047; Angew. Chem., Int. Ed. 1998, 37, 2897.
4596 J . Org. Chem., Vol. 69, No. 14, 2004

Hydrophosphination of Functionalized Alkenes
SCHEME 4
SCHEME 5
tivity as shown by Hayashi.20 We have used the chiral
ligand 20 in the Rh-catalyzed asymmetric hydroboration
of styrene and have found a complete regioselectivity of
hydroboration leading to the branched alcohol 28 after
oxidation (30% H2O2, 2 M NaOH) in 72% yield and
moderate enantioselectivity (61% ee, Scheme 11).
SCHEME 6
(trifluoromethyl)phenyl]borate (NaBARF) in a biphasic
CH2Cl2-H2O system, the resulting orange BARF salts
(Ir-1-4) were purified by column chromatography on
silica gel (50% CH2Cl2 in pentane). These complexes were
stable toward oxygen and moisture (Scheme 8).
Con clu sion
In summary, novel chiral P,N-ligands 1-5 have been
prepared in high yield through t-BuOK-mediated addi-
tion of phosphine oxides 6 to alkenylpyridines 7a -e.
They are effective ligands in Ir-catalyzed asymmetric
hydrogenation reactions of (E)-1,2-diphenylpropene lead-
ing to the hydrogenated product in 95% ee. Remarkably,
we also reported for the first time that novel chiral P,N-
ligands could be used for asymmetric Ir-catalyzed hy-
drogenation reactions of dehydroamino acid derivatives
such as (Z)-R-(acetamido)cinnamate 26 leading to phen-
ylalanine derivative 27 in high enantioselectivity (97%
ee). We have described the preparation of chiral diphos-
phine ligand 20 through addition of Ph2P(O)H (6) to
alkenylphosphine oxide 8b in the presence of substoi-
chiometric amounts of t-BuOK (20 mol %) in DMSO.
Application in asymmetric catalysis such as Rh-catalyzed
hydroboration of styrene using chiral ligand 20 gave only
moderate enantioselectivity of 28 (61% ee). Further
applications in new asymmetric catalysis as well as the
synthesis of chiral modular chiral P,P-ligands are cur-
rently underway in our laboratories.
Among the Ir complexes of 1-4, Ir-3 exhibited high
enantioselectivities in hydrogenation reactions of (E)-1,2-
diphenylpropene and 2-(4-methoxyphenyl)-1-phenyl-1-
propene leading to the hydrogenated products 21 and 22
in 95% ee (Scheme 9). Additionally, trisubstituted func-
tionalized alkenes such as ethyl 3-phenylbutenoate (23),
2-methyl-3-phenylallyl alcohol (24), and 2-methyl-3-phen-
ylallyl acetate (25) were also hydrogenated in the pres-
ence of Ir-3 (1 mol %; 50 bar of H2, rt, 12 h). The
hydrogenated products were obtained with moderate to
good enantioselectivities (58-80% ee; see Scheme 9).
The hydrogenation of unsaturated enamides such as
26 to amino acid derivatives such as 27 is of special
interest. This enantioselective hydrogenation was exten-
sively studied using Rh catalysts.19 To the best of our
knowledge, no enantioselective Ir-catalyzed hydrogena-
tion reactions of these substrates were reported. We
describe for the first time that the hydrogenation of 26
in the presence of Ir-1 provided phenylalanine derivative
27 in high enantioselectivity (97% ee) with full conver-
sion. Remarkably, this reaction was carried out under 1
bar of H2 at 50 °C, 16 h (Scheme 10).
Exp er im en ta l Section
Gen er a l P r oced u r e for Negish i Cr oss-Cou p lin g Rea c-
tion s. A solution of n-BuLi (13.4 mL, 1.5 M in hexane, 20
mmol) was added dropwise at -78 °C to a solution of
The asymmetric hydroboration of styrene with cat-
echolborane using chiral BINAP gave high enantioselec-
(19) (a) Ojima, I. Catalytic Asymmetric Synthesis, 2nd ed.; VCH:
Weinheim, 2000. (b) Noyori, R. Asymmetric Catalysis in Organic
Synthesis; Wiley: New York, 1994. (c) Tang, W.; Zhang, X. Chem. Rev.
2003, 103, 3029.
(20) (a) Hayashi, T.; Matsumoto, Y.; Ito, Y. J . Am. Chem. Soc. 1989,
111, 3426. (b) Hayashi, T.; Matsumoto, Y. Tetrahedron: Asymmetry
1991, 2, 601.
J . Org. Chem, Vol. 69, No. 14, 2004 4597

Bunlaksananusorn and Knochel
SCHEME 7
MS (EI, 70 eV) 263 (M+, 70), 248 (100), 220 (62); HRMS calcd
for C19H21N (M+) 263.1674, found 263.1658.
SCHEME 8
2-[(1R,5S)-6,6-Dim et h ylb icyclo[3.1.1]h ep t -2-en -2-yl]-
p yr id in e (7c): 89% yield as a pale yellow liquid. Purification
by flash chromatography using 5% Et2O in pentane: [R]23
D
-27.0 (c 0.725, CHCl3); 1H NMR (300 MHz, CDCl3) δ 8.46 (ddd,
J ) 4.8, 1.8, 0.9 Hz, 1H), 7.48 (dt, J ) 7.5, 1.8 Hz, 1H), 7.32-
7.25 (m, 1H), 6.97 (ddd, J ) 7.5, 4.8, 0.9 Hz, 1H), 6.30-6.26
(m, 1H), 3.03-2.97 (m, 1H), 2.48-2.32 (m, 4H), 1.30 (s, 3H),
1.21 (d, J ) 8.7 Hz, 1H), 0.79 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 158.2, 149.4, 147.8, 136.4, 124.5, 121.6, 119.3, 43.2,
41.1, 38.2, 32.4, 31.9, 26.6, 21.3; IR (KBr, cm-1) 1624, 1585,
1562, 1432, 1465, 1365, 770; MS (EI, 70 eV) 198 (M+, 47), 184
(100), 156 (14); HRMS calcd for C14H17N (M+) 199.1361, found
199.1388.
2-Br om o-6-[(1R,5S)-6,6-d im et h ylb icyclo[3.1.1]h ep t -2-
en -2-yl]p yr id in e (16b): 70% yield as a pale yellow liquid.
Purification by flash chromatography using 2% Et2O in pen-
tane: 1H NMR (300 MHz, CDCl3) δ 7.35 (t, J ) 7.8 Hz, 1H),
7.24-7.14 (m, 2H), 6.48-6.42 (m, 1H), 2.93 (dd, J ) 5.7, 1.5
Hz, 1H), 2.48-2.36 (m, 3H), 2.14-2.08 (m, 1H), 1.31 (s, 3H),
1.18 (d, J ) 9.0 Hz, 1H), 0.77 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 159.2, 146.3, 142.1, 138.8, 126.5, 125.7, 117.6, 42.9,
40.9, 38.3, 32.5, 31.9, 26.6, 21.4; IR (KBr, cm-1) 1621, 1574,
1545, 1434, 1160, 1122, 782; MS (EI, 70 eV) 278 ([M + H]+,
70), 236 (100), 154 (46); HRMS calcd for C14H16BrN (M+)
277.0466, found 277.0476.
Gen er a l P r oced u r e for Su zu k i Cr oss-Cou p lin g Rea c-
tion s. A solution of bromopyridine (0.50 mmol) and Pd(PPh3)4
(23 mg, 0.02 mmol, 4 mol %) in toluene (2 mL) was treated
with a solution of Na2CO3 (106 mg, 1 mmol) in H2O (1 mL),
followed by a solution of PhB(OH)2 (64 mg, 0.53 mmol) in
MeOH (1 mL). The mixture was stirred at 85 °C for 16 h. After
the mixture cooled to 25 °C, a solution of concentrated aqueous
NH3 (0.25 mL) in saturated Na2CO3 (2.5 mL) was added and
the mixture was extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were washed with brine and dried
(MgSO4). Removal of the solvent in vacuo gave a residue that
was purified by flash column chromatography, yielding the
desired product.
2-bromopyridine (20 mmol) in THF (20 mL). The reaction
mixture was stirred at -78 °C for 30 min, and then a solution
of ZnBr2 (12.4 mL, 1.7 M in THF, 21 mmol) was added
dropwise. After 15 min at -78 °C, the reaction mixture was
allowed to warm to room temperature for 30 min, and then a
solution of the alkenyl triflate (10 mmol), Pd(dba)2 (115 mg,
0.2 mmol, 2 mol %), and dppf (111 mg, 0.2 mmol, 2 mol %) in
THF (15 mL) was added dropwise. The reaction mixture was
heated to reflux (70 °C) for 15 h. The reaction mixture was
quenched with saturated aqueous NH4Cl (40 mL), and the
aqueous phase was extracted with Et2O (3 × 60 mL). The
organic phase was washed with brine and dried (MgSO4) and
concentrated in vacuo. Purification by flash chromatography
yielded the desired product.
2-[(1R,4R)-1,7,7-Tr im eth ylbicyclo[2.2.1]h ep t-2-en -2-yl]-
p yr id in e (7a ): 78% yield as a pale yellow liquid. Purification
by flash chromatography using 20% Et2O in pentane: [R]27
D
-176.4 (c 1.825, CHCl3); 1H NMR (300 MHz, CDCl3) δ 8.47
(ddd, J ) 4.8, 1.8, 0.9 Hz, 1H), 7.48 (dt, J ) 7.5, 1.8 Hz, 1H),
7.20 (m, 1H), 6.97 (ddd, J ) 7.5, 4.8, 1.2 Hz, 1H), 6.26 (d, J )
3.3 Hz, 1H), 2.35 (t, J ) 3.6 Hz, 1H), 1.92-1.82 (m, 1H), 1.68-
1.56 (m, 1H), 1.40-1.28 (m, 1H), 1.17 (s, 3H), 1.08-0.96 (m,
1H), 0.81 (s, 3H), 0.75 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
157.8, 149.8, 149.4, 136.1, 135.9, 121.5, 121.3, 57.3, 55.3, 52.2,
32.1, 26.0, 20.1, 14.5, 12.8; IR (KBr, cm-1) 2953, 2872, 1583,
1560, 1464, 1430, 1385, 775.
2-Br om o-6-[(1R,5S)-6,6-d im et h ylb icyclo[3.1.1]h ep t -2-
en -2-yl]p yr id in e (16a ): 34% yield as a pale yellow liquid.
Purification by flash chromatography using 2% Et2O in pen-
tane: 1H NMR (300 MHz, CDCl3) δ 7.32 (t, J ) 7.7 Hz, 1H),
7.20-7.12 (m, 2H), 6.37 (d, J ) 3.3 Hz, 1H), 2.34 (t, J ) 3.6
Hz, 1H), 1.94-1.82 (m, 1H), 1.64-1.55 (m, 1H), 1.36-1.28 (m,
1H), 1.20 (s, 3H), 1.08-0.98 (m, 1H), 0.78 (s, 3H), 0.75 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 158.6, 148.3, 141.6, 138.3, 137.7,
125.2, 119.7, 57.3, 55.2, 52.2, 31.9, 26.0, 20.0, 19.9, 12.7; IR
(KBr, cm-1) 1575, 1543, 1432, 1387, 1158, 1117, 985, 787.
2-P h en yl-6-[(1R,4R)-1,7,7-tr im eth ylbicyclo[2.2.1]h ep t-
2-en -2-yl]p yr id in e (7d ): 99% yield as a pale yellow liquid.
Purification by flash chromatography using 2% Et2O in pen-
tane; [R]21 -166.5 (c 0.585, CHCl3); 1H NMR (300 MHz,
D
CDCl3) δ 8.10-7.96 (m, 2H), 7.54 (t, J ) 7.7 Hz, 1H), 7.48-
7.28 (m, 4H), 7.20 (dd, J ) 7.5, 1.2 Hz, 1H), 6.31 (d, J ) 3.3
Hz, 1H), 2.37 (t, J ) 3.6 Hz, 1H), 1.94-1.82 (m, 1H), 1.68-
1.60 (m, 1H), 1.48-1.42 (m, 1H), 1.31 (s, 3H), 1.08-0.98 (m,
1H), 0.83 (s, 3H), 0.78 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
156.3, 154.7, 148.6, 138.8, 135.5, 127.6, 127.5, 125.8, 118.3,
116.1, 55.7, 54.1, 50.9, 30.7, 24.8, 18.7, 18.5, 11.7.
2-[(1R,4R)-1,7,7-Tr im eth ylbicyclo[2.2.1]h ep t-2-en -2-yl]-
qu in olin e (7b): 60% yield as a white solid. Purification by
flash chromatography using 5% Et2O in pentane: mp 96-98
1
°C; [R]23 -181.3 (c 0.45, CHCl3); H NMR (300 MHz, CDCl3)
D
δ 7.98-7.86 (m, 2H), 7.62-7.50 (m, 2H), 7.40-7.28 (m, 2H),
6.44 (d, J ) 3.6 Hz, 1H), 2.39 (t, J ) 3.6 Hz, 1H), 1.95-1.84
(m, 1H), 1.70-1.61 (m, 1H), 1.48-1.37 (m, 1H), 1.35 (s, 3H),
1.07-0.98 (m, 1H), 0.83 (s, 3H), 0.77 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 157.5, 150.1, 148.3, 137.8, 135.6, 130.0, 129.4,
127.6, 127.0, 125.9, 120.2, 57.1, 55.7, 52.5, 32.1, 26.2, 20.2, 19.9,
13.1; IR (KBr, cm-1) 1600, 1500, 1424, 1232, 1107, 820, 765;
2-[(1R,5S)-6,6-Dim eth ylbicyclo[3.1.1]h ep t-2-en -2-yl]-6-
p h en ylp yr id in e (7e): 91% yield as a pale yellow liquid.
Purification by flash chromatography using 2% Et2O in pen-
tane; [R]25 -13.2 (c 0.56, CHCl3); 1H NMR (300 MHz, CDCl3)
D
δ 8.02-7.96 (m, 2H), 7.58 (t, J ) 7.8 Hz, 1H), 7.48-7.24 (m,
5H), 6.50-6.46 (m, 1H), 3.17 (dd, J ) 5.7, 1.5 Hz, 1H), 2.40
(m, 3H), 2.52-2.49 (m, 1H), 1.34 (s, 3H), 1.24 (d, J ) 8.7 Hz,
4598 J . Org. Chem., Vol. 69, No. 14, 2004

Hydrophosphination of Functionalized Alkenes
SCHEME 9
SCHEME 10
1147, 740; MS (EI, 70 eV) 415 (M+, 6), 332 (30), 214 (100);
HRMS calcd for C27H30NOP (M+) 415.2065, found 415.2061.
Anal. Calcd for C27H30NOP: C, 78.05; H, 7.28; N, 3.37.
Found: C, 77.82; H, 7.17; N, 3.27.
SCHEME 11
2-[(1S,2R,3S,4S)-3-(Dip h en ylp h osp h or yl)-1,7,7-tr im eth -
ylb icyclo[2.2.1]h ep t -2-yl]-6-p h en ylp yr id in e (17d ): 72%
yield as a white solid. Purification by flash chromatography
using 10% Et2O in CH2Cl2: mp 69-72 °C; [R]22D -68.9 (c 0.505,
CHCl3); 1H NMR (300 MHz, CDCl3) δ 8.09-7.96 (m, 2H), 7.84-
7.74 (m, 2H), 7.48-7.24 (m, 10H), 6.96-6.88 (m, 1H), 6.80-
6.72 (m, 2H), 6.61 (m, 1H), 3.95 (m, 1H), 3.53 (ddd, J ) 10.5,
4.2, 0.9 Hz, 1H), 2.22 (dd, J ) 4.8, 2.1 Hz, 1H), 2.00-1.88 (m,
2H), 1.74-1.70 (m, 1H), 1.40 (s, 3H), 1.22-1-13 (m, 1H), 0.93
(s, 3H), 0.79 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 159.2, 155.2,
140.0, 136.4, 135.5, 134.8, (d, J ) 96.0 Hz), 133.2 (d, J ) 96.0
Hz), 131.6-131.4 (m), 130.7 (d, J ) 2.3 Hz), 129.1, 128.8 (d,
J ) 11.0 Hz), 127.6 (d, J ) 11.0 Hz), 126.9, 124.0, 117.8, 53.6
(d, J ) 2.9 Hz), 52.1 (d, J ) 5.2 Hz), 51.1, 48.1, 45.4 (d, J ) 70
Hz), 32.6 (d, J ) 13.7 Hz), 28.4, 21.1, 20.2, 14.6; 31P NMR (81
MHz, CDCl3) δ 32.6; IR (KBr, cm-1) 1570, 1438, 1195, 1115;
1H), 0.82 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 157.5, 156.4,
147.9, 140.2, 137.1, 129.0, 128.9, 127.3, 124.4, 118.1, 117.3,
43.0, 41.1, 38.3, 32.5, 31.9, 26.8, 21.4; IR (KBr, cm-1) 1587,
1565, 1456, 1365, 760; MS (EI, 70 eV) 275 (M+, 100), 260 (78),
232 (85); HRMS calcd for C20H21N (M+) 275.1674, found
275.1679.
Gen er a l P r oced u r e for th e P r ep a r a tion of Ch ir a l 1,2-
Am in op h osp h in e Oxid es 17a -e a n d Ch ir a l 1,2-Dip h os-
p h in e Oxid e 19. To a stirred solution of t-BuOK (22 mg, 0.2
mmol, 20 mol %) in DMSO (1 mL) were successively added
Ph2P(O)H (6) (202 mg, 1 mmol) and 2-alkenylpyridine (1 mmol)
in DMSO (2 mL) under argon. The reaction mixture was
stirred at 70 °C for 15 h. After the mixture cooled to room
temperature, water (5 mL) and CH2Cl2 were added (20 mL).
The organic phase was washed with brine, dried (MgSO4), and
concentrated in vacuo. Purification by flash chromatography
yielded the desired product.
MS (EI, 70 eV) 477 (M+, 7), 276 (100); HRMS calcd for C33H34
NOP (M+) 491.2378, found 491.2380.
-
(1S,2R,3R,5R)-6,6-Dim eth yl-2-(2-n aph th yl)bicyclo[3.1.1]-
h ep t-3-yl(d ip h en yl)p h osp h in e Oxid e (17c): 93% yield as
a white solid. Purification by flash chromatography using 5%
Et2O in CH2Cl2: mp 70-78 °C; [R]28 +83.4 (c 0.525, CHCl3);
2-[(1S,2R,3S,5R)-3-(Dip h en ylp h osp h or yl)-6,6-d im et h -
ylbicyclo[3.1.1]h ep t-2-yl]p yr id in e (17a ): 87% yield as a
white solid. Purification by flash chromatography using 10%
Et2O in CH2Cl2: mp 132-139 °C; [R]23D +78.9 (c 0.56, CHCl3);
1H NMR (300 MHz, CDCl3) δ 8.40-8.30 (m, 1H), 7.96-7.86
(m, 2H), 7.52-7.36 (m, 5H), 7.32-7.24 (m, 1H), 7.10-6.88 (m,
4H), 6.67-6.60 (m, 1H), 3.71 (dd, J ) 8.4, 6.3 Hz, 1H), 3.50
(ddd, J ) 20.7, 8.7, 2.1 Hz, 1H), 2.20 (d, J ) 9.2, 3.8 Hz, 1H),
1.96-1.80 (m, 2H), 1.72-1.60 (m, 1H), 1.41 (s, 3H), 1.20-1.08
(m, 1H), 0.92 (s, 3H), 0.75 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 159.7, 148.5, 135.4, 134.6 (d, J ) 94.0 Hz), 133.4 (d, J )
94.0 Hz), 131.6-131.3 (m), 130.7 (d, J ) 2.7 Hz), 128.9 (d, J )
11 Hz), 127.7 (d, J ) 11 Hz), 125.6, 121.4, 53.3 (d, J ) 2.9
Hz), 52.2 (d, J ) 5.1 Hz), 51.0, 48.1, 45.2 (d, J ) 70.4 Hz),
32.3 (d, J ) 13.7 Hz), 28.2, 21.2, 20.2, 14.5; 31P NMR (81 MHz,
CDCl3) δ 32.8; IR (KBr, cm-1) 1589, 1478, 1433, 1390, 1206,
D
1H NMR (300 MHz, CDCl3) δ 8.00-7.80 (m, 3H), 7.70-7.55
(m, 3H), 7.44-6.55 (m, 6H), 6.78-6.58 (m, 4H), 4.01 (t, J )
7.5 Hz, 1H), 3.58 (dd, J ) 20, 2.1 Hz, 1H), 2.17 (dd, J ) 9.3,
3.8 Hz, 1H), 1.93-1.60 (m, 3H), 1.35 (s, 3H), 1.18-0.95 (m,
1H), 0.85 (s, 3H), 0.75 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
160.1, 147.5, 135.1, 134.9 (d, J ) 96.0 Hz), 133.1 (d, J ) 96.0
Hz), 131.6-131.4 (m), 130.4 (d, J ) 2.7 Hz), 129.6-128.8 (m),
127.6-127.4 (m), 127.2, 125.9, 123.9, 54.2 (d, J ) 2.4 Hz), 52.7
(d, J ) 4.6 Hz), 51.3, 48.0, 45.0 (d, J ) 70.0 Hz), 32.4 (d, J )
14.0 Hz), 28.3, 21.2, 20.2, 14.9; 31P NMR (81 MHz, CDCl3) δ
32.9; IR (KBr, cm-1) 1600, 1503, 1437, 1194, 1114, 837; MS
(EI, 70 eV) 465 (M+, 3), 382 (7), 264 (100); HRMS calcd for
C
C
31H32NOP (M+) 465.2222, found 465.2245. Anal. Calcd for
31H32NOP: C, 79.97; H, 6.93; N, 3.01. Found: C, 79.64; H,
6.94; N, 3.05.
J . Org. Chem, Vol. 69, No. 14, 2004 4599

Bunlaksananusorn and Knochel
2-[(1S,2R,3S,5R)-3-(Dip h en ylp h osp h or yl)-6,6-d im et h -
ylbicyclo[3.1.1]h ep t-2-yl]p yr id in e (17b): 85% yield as a
white solid. Purification by flash chromatography using 5%
2-[(1S,2S,3R,4S)-3-(Dip h en ylp h osp h in o)-1,7,7-tr im eth -
ylbicyclo[2.2.1]h ep t -2-yl]p yr id in e (1): 87% yield as
a
viscous liquid; 1H NMR (300 MHz, CDCl3) δ 8.38-8.34 (m, 1H),
7.48-7.40 (m, 2H), 7.27-6.97 (m, 7H), 6.80-6.64 (m, 3H),
6.46-6.40 (m, 1H), 3.33-3.24 (m, 1H), 3.06-2.95 (m, 1H),
1.95-1.60 (m, 4H), 1.44 (s, 3H), 1.20-1.12 (m, 1H), 0.94 (s,
3H), 0.72 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 159.6, 147.0,
139.0 (d, J ) 15.0 Hz), 136.3 (d, J ) 15.0 Hz), 133.6, 133.6-
133.1 (m), 131.4 (d, J ) 17.3 Hz), 127.3-126.7 (m), 126.1 (d,
J ) 7.6 Hz), 123.6, 119.3, 55.6 (d, J ) 9.9 Hz), 50.4 (d, J )
3.85 Hz), 50.0, 48.1 (d, J ) 12.5 Hz), 42.6 (d, J ) 13.7 Hz),
Et2O in CH2Cl2: mp 57-63 °C; [R]26 -24.0 (c 0.56, CHCl3);
D
1H NMR (300 MHz, CDCl3) δ 8.29-8.25 (m 1H), 8.00-7.90
(m, 2H), 7.60-7.52 (m, 2H), 7.44-7.40 (m, 3H), 7.22-7.16 (m,
1H), 7.02-6.88 (m, 3H), 6.84-6.76 (m, 1H), 6.70 (d, J ) 7.8
Hz, 1H), 4.80-4.67 (m, 1H), 3.72 (ddd, J ) 22.0, 6.6, 2.7 Hz,
1H), 2.40-2.12 (m, 4H), 1.93-1.85 (m, 1H), 1.72 (d, J ) 9.9
Hz, 1H), 1.01 (s, 3H), 0.72 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 162.6 (d, J ) 2.7 Hz), 147.2, 135.9, 133.8 (d, J ) 82.0 Hz),
132.5 (d, J ) 82.0 Hz), 131.8-131.6 (m), 131.0 (d, J ) 2.7 Hz),
128.9 (d, J ) 11.2 Hz), 127.6 (d, J ) 11.2 Hz), 123.9, 121.0,
48.3 (d, J ) 5.6 Hz), 46.6, 40.7 (d, J ) 3.8 Hz), 39.1, 30.9, 27.9,
26.5 (d, J ) 2.1 Hz), 25.2 (d, J ) 71.0 Hz), 22.7; 31P NMR (81
MHz, CDCl3) δ 38.4; IR (KBr, cm-1) 1589, 1473, 1437, 1191,
1117; MS (EI, 70 eV) 401 (M+, 13), 283 (18), 200 (100); HRMS
calcd for C26H28NOP (M+) 401.1906, found 401.1906.
29.9 (d, J ) 7.3 Hz), 27.3, 20.0, 19.8 (d, J ) 20.0 Hz), 13.4; 31
P
NMR (81 MHz, CDCl3) δ -2.1; IR (KBr, cm-1) 1589, 1478,
1433, 1112, 740; MS (EI, 70 eV) 399 (M+, 27), 316 (39), 214
(100), 183 (59); HRMS calcd for C27H30NP (M+) 399.2116, found
399.2116.
2-[(1S,2R,3S,4S)-3-(Dip h en ylp h osp h in o)-1,7,7-tr im eth -
ylbicyclo[2.2.1]h ep t-2-yl]-6-p h en ylp yr id in e (2): 82% yield
1
as a viscous liquid; H NMR (300 MHz, CDCl3) δ 8.00-7.92
2-[(1S,2R,3S,5R)-3-(Dip h en ylp h osp h or yl)-6,6-d im et h -
ylbicyclo[3.1.1]h ep t-2-yl]-6-p h en ylp yr id in e (17e): 78%
yield as a white solid. Purification by flash chromatography
(m, 2H), 7.48-6.96 (m, 12H), 6.80-6.60 (m, 3H), 6.32 (m, 1H),
3.62 (t, J ) 8.1 Hz, 1H), 3.02-2.92 (m, 1H), 1.96-1.68 (m, 4H),
1.38 (s, 3H), 1.12-1.00 (m, 1H), 0.88 (s, 3H), 0.68 (s, 3H); 13
C
using 5% Et2O in CH2Cl2: mp 67-73 °C; [R]29 +59.2 (c 0.76,
D
NMR (75 MHz, CDCl3) δ 159.1, 153.7, 139.2 (d, J ) 15.0 Hz),
138.9, 136.2 (d, J ) 15.0 Hz), 134.5, 133.3 (d, J ) 18.8 Hz),
131.4 (d, J ) 18.8 Hz), 127.6-127.2 (m), 126.8, 126.1 (d, J )
8.0 Hz) 125.6, 122.3, 115.7, 55.7 (d, J ) 10.0 Hz), 50.4 (d, J )
4.1 Hz), 50.3, 48.1 (d, J ) 12.8 Hz), 42.4 (d, J ) 13.4 Hz), 30.1
(d, J ) 7.0 Hz), 27.4, 19.9, 19.7, 13.5; 31P NMR (81 MHz,
CDCl3) δ -2.1; MS (EI, 70 eV) 475 (M+, 26), 392 (18), 290 (100),
182 (32); HRMS calcd for C33H34NP (M+) 475.2429, found
475.2447.
CHCl3); 1H NMR (300 MHz, CDCl3) δ 8.04-7.86 (m, 4H), 7.52-
7.20 (m, 10 H), 6.94-6.56 (m, 4H), 5.00-4.88 (m, 1H), 3.78
(ddd, J ) 22.0, 6.6, 2.7 Hz, 1H), 2.44-2.12 (m, 4H), 1.94-1.88
(m, 1H), 1.68 (d, J ) 9.6 Hz, 1H), 1.03 (s, 3H), 0.84 (s, 3H); 13
C
NMR (75 MHz, CDCl3) δ 162.6 (d, J ) 2.3 Hz), 154.4, 140.2,
136.9, 133.8 (d, J ) 95.0 Hz), 132.5 (d, J ) 95.0 Hz), 131.8-
131.5 (m), 130.9 (d, J ) 2.7 Hz), 129.1 (d, J ) 3.2 Hz), 128.9,
127.5 (d, J ) 11.3 Hz), 126.9, 122.4, 117.4, 48.3 (d, J ) 5.8
Hz), 46.9, 40.9 (d, J ) 4.1 Hz), 39.3, 31.4, 28.0, 26.6 (d, J )
2.0 Hz), 25.4 (d, J ) 71.0 Hz), 24.9, 23.0; 31P NMR (81 MHz,
CDCl3) δ 37.9; IR (KBr, cm-1) 1590, 1571, 1445, 1191, 1117;
2-[(1S,2R,3S,4S)-3-(Dip h en ylp h osp h in o)-1,7,7-tr im eth -
ylbicyclo[2.2.1]h ep t-2-yl]qu in olin e (3): 61% yield as a
viscous liquid; 1H NMR (300 MHz, CDCl3) δ 7.91 (m, 1H),
7.60-7.20 (m, 9H), 7.06-6.98 (m, 2H), 6.60-6.40 (m, 4H), 3.65
(t, J ) 8.1 Hz, 1H), 3.16 (m, 1H), 1.92-1.72 (m, 4H), 1.40 (s,
3H), 1.08-1.00 (m, 1H), 0.88 (s, 3H), 0.72 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 160.1, 146.3, 139.2 (d, J ) 15.0 Hz), 136.1
(d, J ) 15.0 Hz), 133.5-133.1 (m), 131.4 (d, J ) 17.2 Hz), 128.3,
127.4-126.8 (m), 126.0-125.8 (m), 125.4, 124.2, 122.2, 56.4
(d, J ) 10.1 Hz), 50.9 (d, J ) 3.8 Hz), 50.5, 48.1 (d, J ) 12.8
Hz), 42.3 (d, J ) 13.7 Hz), 30.0 (d, J ) 7.4 Hz), 27.4, 20.0,
MS (EI, 70 eV) 477 (M+, 7), 276 (100); HRMS calcd for C32H32
NOP (M+) 477.2222, found 477.2213.
-
[(1R,2S,3R,4S)-3-(Dip h en ylp h osp h or yl)-1,7,7-tr im eth -
ylb icyclo[2.2.1]h ep t -2-yl][d i(2-fu r yl)]p h osp h in e Oxid e
(19): 70% yield as a white solid. Purification by flash chro-
1
matography using 50% Et2O in CH2Cl2: mp 271-273 °C; H
NMR (300 MHz, CDCl3) δ 7.66-7.52 (m, 5H), 7.38-7.20 (m,
7H), 6.89 (ddd, J ) 3.3, 1.8, 0.6 Hz, 1H), 6.45 (ddd, J ) 3.3,
1.8, 0.6 Hz, 1H), 6.37-6.34 (m, 1H), 5.92-5.89 (m, 1H), 3.50-
3.32 (m, 2H), 2.48-2.38 (m, 1H), 1.80-1.52 (m, 3H), 1.40-
1.14 (m, 1H), 1.04 (s, 3H), 0.60 (s, 3H), 0.38 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 147.7 (d, J ) 99.3 Hz), 148.0-147.9 (m),
145.9 (d, J ) 99.3 Hz), 135.3 (d, J ) 24.7 Hz), 134.0 (d, J )
24.7 Hz), 131.5-131.1 (m), 128.7-128.4 (m), 122.6-122.0 (m),
111.5 (d, J ) 8.5 Hz), 111.3 (d, J ) 8.5 Hz), 52.0, 51.2 (d, J )
12.0 Hz), 49.9 (d, J ) 5.0 Hz), 47.6 (d, J ) 44.0 Hz), 46.5 (d,
J ) 4.5 Hz), 41.5 (d, J ) 65.1 Hz), 31.4 (d, J ) 14.1 Hz), 31.2
(d, J ) 6.2 Hz), 19.8, 19.7; 31P NMR (81 MHz, CDCl3) δ 26.3
(d, J ) 7.7 Hz), 9.8 (d, J ) 7.7 Hz); IR (KBr, cm-1) 1460, 1438,
1200, 1133, 1012, 913, 771, 751, 714; EI (70 eV) 518 (M+, 15),
337 (61.2), 317 (100), 201 (29.9); HRMS calcd for C30H32O4P2
(M+) 518.1776, found 518.1760. Anal. Calcd for C30H32O4P2:
C, 69.49; H, 6.22. Found: C, 69.06; H, 6.45.
19.7, 13.7; 31P NMR (81 MHz, CDCl3) δ -1.5; IR (KBr, cm-1
)
1618, 1600, 1435, 834; MS (EI, 70 eV) 449 (M+, 28), 366 (17),
264 (100), 156 (33); HRMS calcd for C31H32NP (M+) 449.2272,
found 449.2301.
2-[(1S,2R,3S,5R)-3-(Dip h en ylp h osp h in o)-6,6-d im eth yl-
bicyclo[3.1.1]h ep t-2-yl]p yr id in e (4): 80% yield as a viscous
liquid; 1H NMR (300 MHz, CDCl3) δ 8.24-8.20 (m, 1H), 7.66-
7.58 (m, 2H), 7.32-7.12 (m, 6H), 6.88-6.68 (m, 5H), 4.34-
4.22 (m, 1H), 3.35 (ddd, J ) 18.3, 6.0, 2.4, 1H), 2.44-2.20 (m,
3H), 1.92-1.74 (m, 2H), 1.41 (d, J ) 8.7 Hz, 1H), 1.02 (s, 3H),
0.79 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 162.4 (d, J ) 2.6
Hz), 146.2, 136.8 (d, J ) 15.5 Hz), 136.2 (d, J ) 15.5 Hz),
134.1-132.6 (m), 132.7 (d, J ) 18.7 Hz), 127.6-127.1 (m),
126.2 (d, J ) 7.0 Hz), 122.0, 119.1, 50.7 (d, J ) 2.6 Hz), 47.8
(d, J ) 4.9 Hz), 40.6 (d, J ) 2.3 Hz), 38.1 (d, J ) 1.6 Hz), 30.4
(d, J ) 17.8 Hz), 30.0, 26.5, 21.7, 21.4 (d, J ) 8.1 Hz); 31P NMR
(81 MHz, CDCl3) δ 10.5; IR (KBr, cm-1) 1588, 1565, 1472, 1431,
1386; MS (EI, 70 eV) 385 (M+, 6), 308 (48), 200 (100); HRMS
calcd for C26H28NP (M+) 385.1959, found 385.1992.
Gen er a l P r oced u r e for th e Red u ction of P h osp h in e
Oxid es 17a -e a n d 19 to Am in op h osp h in es 1-5 a n d
Dip h osp h in e 20. A tube was charged with the phosphine
oxide (0.5 mmol), toluene (15 mL), trichlorosilane (0.5 mL, 10
equiv, 5 mmol), and triethylamine (1.4 mL, 20 equiv, 10 mmol)
under argon, sealed, and heated for 16 h at 120 °C. After
cooling to 25 °C, the reaction mixture was transferred to a 100
mL flask filled with argon. Toluene and excess trichlorosilane
were evaporated in vacuo. The residue was dissolved in toluene
(15 mL) and carefully quenched with degassed 10% aqueous
NaHCO3 (3 mL). The separated organic phase was filtered and
transferred by cannulation in a second flask flushed with
argon. Toluene was evaporated in vacuo, and the residue was
washed with Et2O (30 mL). After filtration, remaining solvents
were evaporated in vacuo, yielding the desired product.
2-[(1S,2R,3S,5R)-3-(Dip h en ylp h osp h in o)-6,6-d im eth yl-
bicyclo[3.1.1]h ep t-2-yl]-6-p h en ylp yr id in e (5): yield 92% as
1
a viscous liquid; H NMR (300 MHz, CDCl3) δ 8.00-7.94 (m,
2H), 7.68-7.60 (m, 2H), 7.42-7.20 (m, 10H), 6.82-6.66 (m,
3H), 6.61 (m, 1H), 4.64-4.54 (m, 1H), 3.44-3.32 (m, 1H), 2.44-
2.28 (m, 3H), 1.96-1.80 (m, 2H), 1.44-1.36 (m, 1H), 1.04 (s,
3H), 0.85 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 161.9 (d, J )
2.3 Hz), 153.0, 138.9, 136.9 (d, J ) 15.5 Hz), 136.1 (d, J )
15.5 Hz), 135.0, 133.2 (d, J ) 18.8 Hz), 132.7 (d, J ) 18.8 Hz),
127.6-127.2 (m), 126.1 (d, J ) 7.4 Hz), 125.6, 120.5, 115.5,
50.7 (d, J ) 19.0 Hz), 47.7 (d, J ) 5.2 Hz), 40.7 (d, J ) 2.5
4600 J . Org. Chem., Vol. 69, No. 14, 2004

Hydrophosphination of Functionalized Alkenes
Hz), 38.4, 30.6 (d, J ) 18.5 Hz), 30.3, 26.6, 21.9, 21.4 (d, J )
8.3 Hz); 31P NMR (81 MHz, CDCl3) 10.1; MS (EI, 70 eV) 461
(M+, 2), 384 (5), 276 (100); HRMS calcd for C32H32NP (M+)
461.2272, found 461.2241.
mixture was stirred at 50 °C for 2 h. CH2Cl2 and MeOH were
removed, and the crude product was passed through a short
silica gel column with Et2O as the eluent. After evaporation
of the solvent, (S)-27 was obtained in quantitative yield (97%
ee): GC (140 °C, column) tr/min ) 10.5 (R), 11.5 (S); 1H NMR
(300 MHz, CDCl3) δ 7.24-7.14 (m, 3H), 7.02-7.00 (m, 2H),
6.04 (d, J ) 7.2 Hz, 1H), 4.84-4.76 (m, 1H), 3.64 (s, 3H), 3.12-
2.96 (m, 2H), 1.89 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 171.5,
169.0, 135.3, 128.6, 127.9, 126.4, 52.5, 51.6, 37.1, 22.4.
[(1R,2S,3R,4S)-3-(Dip h en ylp h osp h in o)-1,7,7-tr im eth yl-
bicyclo[2.2.1]h ep t-2-yl][d i(2-fu r yl)]p h osp h in e (20): 68%
1
yield as a foam; H NMR (300 MHz, CDCl3) δ 7.60-7.48 (m,
1H), 7.32-7.04 (m, 11H), 6.60-6.54 (m, 1H), 6.28-6.20 (m,
2H), 5.80-5.72 (m, 1H), 3.40-3.28 (m, 1H), 2.48-2.36 (m, 1H),
2.24-2.12 (m, 1H), 1.84-1.70 (m, 1H), 1.40-1.20 (m, 2H), 0.89
(s, 3H), 0.84-0.72 (m, 1H), 0.58 (s, 3H), 0.31 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 150.8 (d, J ) 18.5 Hz), 148.2 (d, J ) 12.3
Hz), 145.3, 138.5-138.1 (m), 134.3 (d, J ) 21.0 Hz), 131.6 (d,
J ) 21.0 Hz), 127.5-126.6 (m), 120.8 (d, J ) 24.5 Hz), 119.6
(d, J ) 25.7 Hz), 109.7-109.5 (m), 50.2-50.0 (m), 49.3-48.1
(m), 43.9-43.3 (m), 30.6 (d, J ) 2.6 Hz), 29.3 (d, J ) 23.9 Hz),
18.7, 12.8; 31P NMR (81 MHz, CDCl3) δ 8.00 (d, J ) 2.3 Hz)
and -57.5; EI (70 eV) 486 (M+, 100), 350 (39), 252 (49), 165
(41); HRMS calcd for C30H32O2P2 (M+) 486.1878, found 486.1870.
Gen er a l P r oced u r e for Ir -Ca ta lyzed En a n tioselective
Hyd r ogen a tion Rea ction s of R-Aceta m id ocin n a m a te Es-
ter 27. Ir complex catalyst 1 (4.7 mg, 3 µmol, 1 mol %), methyl
(Z)-R-(acetamido)cinnamate 26 (66 mg, 0.3 mmol), CH2Cl2 (3
mL), and MeOH (0.3 mL) were placed in an autoclave. The
autoclave was sealed and pressurized to 1 bar of H2, and the
Ack n ow led gm en t. We thank Dr. Kurt Polborn for
the X-ray determination of compound 17a , 17e, and 19
and the Fonds der Chemischen Industrie for financial
support. We thank the BASF AG (Ludwigshafen), Bayer
Chemicals (Leverkusen), and Chemetall GmbH (Frank-
furt) for the generous gift of chemicals.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for all compounds not described in the text, 1H and
13C NMR spectra of compounds 1-5, 17a -e, 19, and 20, and
X-ray data for 17a , 17e, and 19. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O030383U
J . Org. Chem, Vol. 69, No. 14, 2004 4601