Total synthesis of (+)-pamamycin-607

Article abstract of DOI:10.1002/1521-3773(20020415)41:8<1392::AID-ANIE1392>3.0.CO;2-G

Complete stereoselectivity was observed in the total synthesis of pamamycin-607 (1), which proceeded by iodoetherification of γ-triethylsilyloxyalkenes in the presence of an essential additive, silver carbonate, to provide the requisite three cis-2,5-disu

Full text of DOI:10.1002/1521-3773(20020415)41:8<1392::AID-ANIE1392>3.0.CO;2-G

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Soc. 1994, 116, 6130 6141; c) B. H. Lipshutz, E. L. Ellsworth, S. H.
Dimock, R. A. J. Smith, J. Am. Chem. Soc. 1990, 112, 4404 4410;
B. H. Lipshutz, C. Hackmann, J. Org. Chem. 1994, 59, 7437 7444;
D. E. Stack, W. R. Klein, R. D. Rieke, Tetrahedron Lett. 1993, 34,
3063 3066.
3
6
1
O
O
O
10
O
11'
O
O
O
[8] TaCl5 has scarcely been used in organic synthesis. a) J. Howarth, K.
Gillespie, Tetrahedron Lett. 1996, 37, 6011 6012; b) H. Maeta, T.
Nagasawa, Y. Handa, T. Takei, Y. Osamura, K. Suzuki, Tetrahedron
Lett. 1995, 36, 899 902; c) K. Suzuki, T. Hashimoto, H. Maeta, T.
Matsumoto, Synlett 1992, 125 128; d) T. Hashimoto, H. Maeta, T.
Matsumoto, M. Morooka, S. Ohba, K. Suzuki, Synlett 1992, 340 342.
[9] There is a possibility that low-valent tantalum species are involved in
the reaction; however, the reaction mixture did not display significant
color.
1'
6'
3'
Me2N
18
1 : pamamycin-607
OH
O
[10] There are few examples of the conjugate prenylsilylation of enones
with TiCl4: ref. [2a] and R. L. Danheiser, D. M. Fink, Tetrahedron Lett.
1985, 26, 2509 2512.
HO2C
OTBS
O
HO
+
O
[11] Although we have no further information as yet, this order of
reactivity strongly indicates an electron transfer mechanism. J. Otera,
Y. Fujita, N. Sakuta, M. Fujita, S. Fukuzumi, J. Org. Chem. 1996, 61,
2951 2962.
3
2
N3
Scheme 1.
proposed as the intermediates. Construction of the double
bonds in 9 and 21 was planned by means of a sulfone
olefination[14] and the Horner Emmons reaction. The C2
methyl group could be installed by the cuprate epoxide
opening of 23 (see Scheme 4), in which the regioselectivity
was assumed to be dictated by the bulky substituent. In
addition, while the adjacent hydroxyl and methyl functional
groups of 9 were expected to be delivered from the known
alcohol 4 (Scheme 2),[15] those of 21 would be transformed by
a Paterson[16] aldol reaction and Evans anti reduction.[17]
To prepare the bottom subunit 2, alcohol 4 (78% de) was
consecutively subjected to silylation, hydroboration, Mitsu-
nobu reaction, and mCPBA oxidation to afford sulfone 5
(Scheme 2). The requisite aldehyde 8 (the coupling partner of
5) was obtained from the known diol 6[18] by a sequence of
benzylidene formation, DIBAH reduction,[19] and Swern
Total Synthesis of (‡)-Pamamycin-607**
Sung Ho Kang,* Joon Won Jeong, Yu Sang Hwang, and
Sung Bae Lee
The pamamycins are a novel family of naturally occurring
homologous macrodiolides, which are found in Streptomy-
9]
ces sp.[1 They induce the aerial mycelium formation in
S. alboniger to display autoregulatory activity.[1 3]. They also
exhibit antibiotic activity against Gram-positive bacteria and
pathogenic fungi,[1,2] inhibit myosin light chain kinase,[5] and
mediate hydrophilic ion transport through lipophilic phases.[6]
In addition, they show vasodilating,[7] anionophoric,[2 pro-
7]
tonophoric,[8] and autolytic properties.[9] A major component
of the family is pamamycin-607( 1), which has a molecular
weight of 607. While the structure and relative stereochem-
istry of pamamycin-607were elucidated by NMR spectro-
scopy, its absolute stereochemistry was later determined by a
correlation study.[10] The remarkable biological activity of
pamamycin-607and its unique structural features led us to
choose 1 as a synthetic target.[11] Herein we report an
asymmetric total synthesis of 1.
OH
TESO
N
S
OTBS
a-d
h
SO2
OTBS
5
4
OBn
OH
TESO
OTBS
OTBS
O
i-k
H
The two ester linkages of 1 were disconnected by retro-
synthetic analysis to provide alcohol 2 and carboxylic acid 3 as
the precursors of the C1' C11' and C1 C18 subunits,
respectively (Scheme 1). As we envisaged that the three cis-
2,5-disubstituted tetrahydrofurans comprising 2 and 3 could
be formed[12] by iodoetherification of g-triethylsilyloxyal-
kenes,[13] 9 (see Scheme 2) and 21 (see Scheme 3) were
2
9
OR
OBn
g
O
OH
8
6 : R=H
7 : R=Bn
e,f
Scheme 2. a) TESCl, imidazole, DMF, RT, 83% of desired diastereomer;
b) H3B ¥ SMe2, THF, RT, then aqueous NaOH, H2O2, RT, 85% ; c) Ph3P,
2-mercaptobenzothiazole, DEAD, THF, 08C !RT, 87%; d) mCPBA,
CH2Cl2, RT, 90%; e) TsOH, PhCHO, PhMe, reflux (ÀH2O), 94%;
f) DIBAH, PhMe, 08C, 88% for 7; g) Swern oxidation; h) LiHMDS,
THF, À788C, then 8, RT, 80%; i) I2, Ag2CO3, Et2O, RT, 92 %; j) Ph3SnH,
Et3B, THF, 08C, 90%; k) H2, 10% Pd/C, MeOH, RT, 99%. TES ˆ tri-
ethylsilyl, DMF ˆ N,N-dimethylformamide, DEAD ˆ diethyl azodicarbox-
ylate, mCPBA ˆ 3-chloroperoxybenzoic acid, Ts ˆ toluenesulfonyl,
DIBAH ˆ diisobutylaluminum hydride, LiHMDS ˆ lithium bis(trimethyl-
silyl)amide.
[*] Prof. Dr. S. H. Kang, J. W. Jeong, Yu. S. Hwang, S. B. Lee
Center for Molecular Design and Synthesis
Department of Chemistry, School of Molecular Science
Korea Advanced Institute of Science and Technology, Taejon 305-701
(Korea)
Fax : (‡82)42-869-2810
E-mail: shkang@kaist.ac.kr
[**] This work was supported by C.M.D.S. and the Brain Korea 21 Project.
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oxidation.[20] Addition of 8 to the lithium anion obtained from
5 provided a 1.2:1 mixture of trans- and cis-alkenes 9. After
several strategic model studies we chose the iodoetherifica-
tion of g-triethylsilyloxyalkenes, because our total synthesis
required the development of reliable methodology to form
cis-2,5-disubstituted tetrahydrofurans. Experimental optimi-
zation revealed that the most efficient outcome could be
attained by exposing 9 to iodine in the presence of silver
carbonate in diethyl ether. The iodocyclization of both the cis
and trans isomers proceeded with similar efficiency (since the
isomers were inseparable, the 1.2:1 mixture of trans- and cis-
alkenes 9 was subjected to iodoetherification to provide a
1.2:1 mixture of iodides in 92% yield). It is of note that the
addition of silver carbonate was unprecedented, to our
knowledge, and indispensable for the consistency, stereo-
selectivity, and completion of the iodocyclization. Remark-
ably, reductive deiodination[21] and debenzylation of the
cyclized products gave rise to 2 as the only stereoisomer.
Once the assembly of the C1' C11' subunit was complete,
the synthesis of the upper subunit 3 began with the formation
of sulfone 11, derived from alcohol 10[22] by Mitsunobu
reaction and mCPBA oxidation (Scheme 3). The coupling of
11 with 8 using KHMDS, and the ensuing desilylation,
produced a 7:1 separable mixture of trans- and cis-alkenes.
Although the mixture could be employed for the next
synthetic sequence, the trans and cis isomers were separated
for the purposes of spectroscopic interpretation in the
following steps, and then the trans-olefinic alcohol was
oxidized to aldehyde 12.
With access to the right part of 21 secure, it was necessary to
prepare its left part as alkyl iodide. Accordingly, the known
phosphonate 17[26] was olefinated with aldehyde 18 to furnish
exclusively the trans-alkene. The conjugated ketone was
reduced,[27] desilylated, protected as the acetonide, and
iodinated to give the racemic iodide 19. Transmetallation of
19 followed by the addition of amide 16 yielded the b-
hydroxyketone. Diastereoselective anti reduction of the
ketone gave a 20:1 mixture of the desired stereoisomeric
alcohols 20 and their corresponding diastereomers. After
disilylation of 20, double iodoetherification of the generated
silyl ethers 21 was performed under the aforementioned
cyclization conditions to supply tetrahydrofurans 22 with
complete cis stereoselectivity. Derivatization of 22 to form
epoxide 23 was achieved by successive acidic deprotection,
cyclization, reductive deiodination, and silylation (Scheme 4).
Methylation of 23 with lithium dimethylcuprate yielded only
the desired regioisomeric alcohols, with partially desilylated
secondary silyloxy groups. Hydrogenation of the mixture
removed the benzyl and triethylsilyl groups concurrently. The
produced tetraols 24 were subjected to Mitsunobu condi-
tions,[28] to convert the least hindered hydroxyl group into an
azido group chemoselectively. The resulting vicinal diols were
oxidized to give carboxylic acid 3.
With the synthesis of the two key subunits 2 and 3
completed, these units were coupled under Yamaguchi×s
conditions,[29] and the coupled ester 25 was desilylated, and
subsequently oxidized chemoselectively to carboxylic
acid 26.[30] Lactonization of 26 via the thiopyridyl ester, in
the presence of cupric bromide,[31] gave macrodiolide 27. The
azido group of 27 was reduced and the in situ addition of
formaldehyde to the generated amine under the hydrogena-
tion conditions produced pamamycin-607( 1). The synthetic 1
and its CF3COOD salt were identical to the natural pama-
Aldol condensation of the known ethylketone 13[23] with 12
occurred via an E-boron enolate to provide a 31:1 mixture of
the desired anti-aldol product 14 and the corresponding
diastereomers. Stereoselective anti reduction of the keto
group of 14 and the subsequent deprotection gave predom-
inantly the desired a-alcohol 15, along with a small amount of
the isomeric b-alcohol (>60:1). Alcohol 15 was chemoselec-
tively oxidized[24] to a six-membered lactone, which was
subjected to Weinreb-amide formation[25] and regioselective
monosilylation to yield the Weinreb amide 16.
mycin-607and its CF COOD salt in all aspects.[10a, 32]
3
A highly enantioselective total synthesis of pamamycin-607
has been attained from the readily available alcohol 10
through 27steps (5.4% overall yield). The synthetic sequence
culminated in a stereoselective double cyclization in the
OTBDPS
OTBDPS
O
Ph
N
c-e
f
a,b
+
OH
N
N
PMBO
O
BnO
BMPO
O
BnO
SO2
OH
N
12
13
14
11
10
i-k
g,h
MeO
Me
OTES
OH BnO
OH
N
HO
OH
BnO
RO
O
15
16
RO
O
O
q,r
TESO
20: R = H
I
l-p
O
OTBDPS
+
TESO
PO(OEt)2
O
s
BnO
O
O
21: R = TES
18
17
19
Scheme 3. a) 1-Phenyl-1H-tetrazole-5-thiol, Ph3P, DEAD, THF, RT, 86%; b) mCPBA, NaHCO3, CH2Cl2, RT, 93%; c) KHMDS, 8, DME, À788C !RT;
d) nBu4NF, THF, RT, 72% for trans isomer and 2 steps; e) Swern oxidation; f) 13, cHx2BCl, Et3N, Et2O, 0 8C, then 12, À78 ! À 208C, 85%;
g) Me4NBH(OAc)3, AcOH, MeCN, À30 ! À 208C, 88%; h) (NH4)2Ce(NO3)6, H2O, MeCN, 08C, 88%; i) TEMPO, NCS, nBu4NCl, aq. NaHCO3, K2CO3
(pH 8.6), CH2Cl2, RT, 97%; j) MeONHMe ¥ HCl, Me3Al, CH2Cl2, À788C, 92%; k) TESCl, imidazole, CH2Cl2, À408C, 99%; l) iPr2NEt, LiCl, MeCN, RT,
88%; m) NaBH4, CeCl3 ¥ 7 HO, MeOH, 08C, 96%; n) nBu4NF, THF, RT, 99%; o) p-TsOH, acetone, RT, 92%; p) I2, Ph3P, imidazole, THF, 08C !RT, 96 %;
2
q) tBuLi, Et2O, À78 ! À 200C, then 16, À50 ! À 208C, 82%; r) Me4NBH(OAc)3, AcOH, MeCN, À208C, 92%; s) TESOTf, Et3N, CH2Cl2, 08C, 98%.
KHMDS ˆ potassium bis(trimethylsilyl)amide, DME ˆ 1,2-dimethoxyethane, cHx ˆ cyclohexyl, Ac ˆ acetyl, TEMPO ˆ 2,2,6,6,-tetramethyl-1-piperidinyl-
oxy, NCS ˆ N-chlorosuccinimide, OTf ˆ trifuloromethanesulfonate.
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I
O
O
O
O
a
b-d
e,f
g,h
21
TESO
O
O
TESO
TESO
HO
HO
OH
O
O
I
O
22
23
24
BnO
BnO
HO
O
O
O
O
O
O
O
i
j,k
l
3
O
O
HO
COOH
HO
O
O
O
O
O
OTBS
O
O
O
X
N3
N3
27: X = N3
1: X = NMe2
m
26
25
Scheme 4. a) I2, Ag2CO3, Et2O, RT, 81 %; b) 2 n HCl, MeOH, reflux, then K2CO3, RT, 86%, c) Ph3SnH, Et3B, THF, 08C, 96%; d) TESOTf, Et3N, CH2Cl2,
À208C, 89%; e) Me2CuLi, Et2O, 5 8C; f) H2, Pd(OH)2/C, EtOH, RT, 88% for 2 steps; g) HN3, Ph3P, DEAD, PhH, 08C, 97%; h) NaIO4, tBuOH, H2O, RT,
then 1.25m NaH2PO4, 1m KMnO4, RT, 87%; i) 2,4,6-trichlorobenzoyl chloride, Et3N, THF, RT, then 2, DMAP, PhH, RT, 90%; j) nBu4NF, THF, RT, 94%;
k) TEMPO, NaClO2, NaH2PO4 buffer (pH 6.7), NaOCl, MeCN, RT, 91%; l) (PyS)2, Ph3P, MeCN, then CuBr2, MeCN, RT, 62%; m) H2, 10% Pd/C, MeOH,
RT, then 37% aq. HCHO, AcOH, RT, 89%. DMAP ˆ 4-dimethylaminopyridine, (PyS)2 ˆ 2,2'-dipyridyl disulfide.
[1] a) P. A. McCann, B. M. Pogell, J. Antibiot. 1979, 32, 673 678; b) W.-G.
presence of the unprecedented additive silver carbonate, and
the sterically controlled, regioselective cuprate epoxide open-
ing.
Chou, B. M. Pogell, Biochem. Biophys. Res. Commun. 1981, 100, 344
350; c) W.-G. Chou, B. M. Pogell, Antimicrob. Agents Chemother.
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[2] S. Kondo, K. Yasui, M. Natsume, M. Katayama, S. Marumo, J.
Antibiot. 1988, 41, 1196 1204; b) M. Natsume, J. Tazawa, K. Yagi, H.
Abe, S. Kondo, S. Marumo, J. Antibiot. 1995, 48, 1159 1164.
Experimental Section
[3] M. Natsume, J. Antibiot. 1992, 45, 1026 1028.
[4] M. Natsume, K. Yasui, S. Kondo, S. Marumo, Tetrahedron Lett. 1991,
22: Silver carbonate (970 mg, 3.50 mmol) was stirred with iodine (1.23 g,
8.76 mmol) in Et2O (15 mL) at room temperature for 5 min. The hetero-
geneous solution was cooled to 08C and then 21 (390 mg, 0.438 mmol)
dissolved in Et2O (4 mL) was added. The resulting solution was warmed to
room temperature immediately and stirred for 15 h. After quenching with
aqueous Na2S2O3 (10%, 30 mL), the mixture was extracted with Et2O (3 Â
32, 3087 3090.
[5] S. Nakanishi, K. Kita, Y. Uosaki, M. Yoshida, Y. Saitoh, A. Mikara, J.
Kawamoto, Y. Matsuda, J. Antibiot. 1994, 47, 855 861.
[6] a) C. Stengel, G. Reinhardt, U. Gr‰fe, J. Basic Microbiol. 1992, 32,
339 345; b) U. Gr‰fe, R. Schlegel, K. Dornberger, W. Ihn, M. Ritzau,
5 mL). The combined organic layers were dried over Na2SO4, filtered, and
C. Stengel, M. Beran, W. G¸nther, Nat. Prod. Lett. 1993, 265 271;
the solvent evaporated in vacuo. The residue was purified by flash
chromatography (SiO2, EtOAc:hexane 1:30) to give 22 (323 mg, 81%).
c) U. Gr‰fe, C. Schlegel, U. Mˆllmann, L. Heinisch, Pharmazie 1994,
49, 343 346.
1: 1H NMR (400 MHz, CDCl3): d ˆ 4.88 (1H, dd, J ˆ 10.8, 0.6 Hz), 4.82
[7] K. Fujii, O. Hara, S. Marumo, Y. Sakagami, Bioorg. Med. Chem. Lett.
(1H, dddd, J ˆ 11.4, 6.6, 4.8, 4.0 Hz), 4.15 (1H, ddd, J ˆ 8.6, 5.5, 2.2 Hz),
1995, 5, 843 846.
4.01 (1H, td, J ˆ 9.5, 5.0 Hz), 3.95 (1H, ddd, J ˆ 9.0, 6.9, 2.2 Hz), 3.86 (1H,
[8] P. A. Grigoriev, A. Berg, R. Schlegel, U. Gr‰fe, Bioelectrochem.
br t, J ˆ 8.5 Hz), 3.77 3.71 (1H, m), 3.60 (1H, td, J ˆ 10.2, 3.9 Hz), 3.34
Bioenerg. 1996, 39, 295 298.
(1H, dt, J ˆ 10.0, 6.7Hz), 3.12 (3H, d, J ˆ 5.2 Hz), 2.82 (3H, d, J ˆ 5.0 Hz),
[9] A. Hartl, A. Stelzner, R. Schlegel, S. Heinze, H. H¸lsmann, W. Fleck,
2.58 (1H, qd, J ˆ 6.9, 2.2 Hz), 2.24 1.12 (27H, m), 1.05 (3H, d, J ˆ 7.0 Hz),
U. Gr‰fe, J. Antibiot. 1998, 51, 1040 1046.
1.04 (3H, d, J ˆ 6.8 Hz), 0.97(3H, t, J ˆ 7.1 Hz), 0.86 (3H, t, J ˆ 7.3 Hz),
[10] a) S. Kondo, K. Yasui, M. Katayama, S. Marumo, T. Kondo, H.
0.77 (3H, d, J ˆ 6.6 Hz), 0.77 (3H, d, J ˆ 6.9 Hz); the protons adjacent to
Hattori, Tetrahedron Lett. 1987, 28, 5861 5864; b) M. Natsume, S.
that at 4.82 ppm appear at 2.24 1.12 ppm (27H, m), the other J ˆ 11.4 Hz
Kondo, S. Marumo, J. Chem. Soc. Chem. Commun. 1989, 1911 1913.
coupling is buried in this region. 13C NMR (100 MHz, CDCl3) d ˆ 173.7,
[11] For a total synthesis of 1 see : a) O. Germany, N. Kumar, E. J. Thomas,
173.2, 82.2, 80.2, 78.5, 78.3, 76.4, 74.5, 74.4, 71.1, 66.9, 47.2, 43.0, 41.4, 41.0,
Tetrahedron Lett. 2001, 42, 4969 4974; b) E. Lee, E. J. Jeong, E. J.
38.6, 37.4, 37.0, 36.9, 34.3, 31.5, 31.1, 30.5, 29.6, 29.5, 27.6, 27.3, 19.5, 18.0, 14.1
Kang, L. T. Sung, S. K. Hong, J. Am. Chem. Soc. 2001, 123, 10131
(2 peaks), 13.8, 10.3, 9.6, 8.7; IR (neat): nÄ2966, 2875, 1737, 1466, 1385, 1265,
10132; c) Y. Wang, H. Bernsmann, M. Gruner, P. Metz, Tetrahedron
À1
1189, 1127, 1112, 1071, 1054 cm ; HRMS (EI) calcd for C35H61NO7:
Lett. 2001, 42, 7801 7804. For synthetic approaches to 1 see : a) R. D.
607.4448, found: 607.4447; (a[ ]2D0> ˆ ‡10.9, c ˆ 0.30, MeOH), ([a]3D2>
ˆ
Walkup, S. W. Kim, S. D. Wagy, J. Org. Chem. 1993, 58, 6486 6490;
b) R. D. Walkup, S. W. Kim, J. Org. Chem. 1994, 59, 3433 3441;
c) R. D. Walkup, Y. S. Kim, Tetrahedron Lett. 1995, 36, 3091 3094;
d) I. Mavropoulos, P. Perlmutter, Tetrahedron Lett. 1996, 37, 3751
3754; e) G. Mandville, C. Girard, R. Bloch, Tetrahedron Asymmetry
1997, 8, 3665 3673; f) G. Mandville, R. Bloch, Eur. J. Org. Chem.
‡21.7, c ˆ 0.30, MeOH), ([a]3D2> ˆ ‡23.0, c ˆ 0.30, MeOH).
‡
1 ¥ D CF3COOÀ: The synthetic 1 (7mg, 0.0115 mmol) was dissolved in
[D6]acetone (0.5 mL) in the presence of CF3COOD (5 mL, 0.0649 mmol) in
a glove box. This solution was sampled for NMR spectral analysis. 1H NMR
(400 MHz, [D6]acetone): d ˆ 4.99 (1H, dd, J ˆ 11.0, 0.8 Hz), 4.92 (1H,
dddd, J ˆ 11.8, 6.7, 5.1, 3.8 Hz), 4.28 (1H, ddd,J ˆ 9.0, 5.6, 2.3 Hz), 4.09 (1H,
ddd, J ˆ 9.1, 6.9, 2.2 Hz), 3.92 3.81 (2H, m), 3.71 (1H, ddd, J ˆ 10.8, 9.9,
4.0 Hz), 3.66 3.59 (1H, m), 3.41 3.34 (1H, m), 3.23 (3H, s), 2.98 (3H, s),
2.74 (1H, dq, J ˆ 6.8, 2.2 Hz), 2.26 (1H, dq, J ˆ 10.2, 7.0 Hz), 2.31 2.26
(1H, m), 2.09 1.10 (25H, m), 1.09 (3H, d, J ˆ 7.0 Hz), 1.05 (3H, d, J ˆ
6.8 Hz), 1.00 (3H, t, J ˆ 7.2 Hz), 0.87 (3H, t,J ˆ 7.3 Hz), 0.85 (6H, d, J ˆ
6.7Hz); 13C NMR (100 MHz, [D6]acetone): d ˆ 175.0, 173.8, 83.2, 81.1, 80.0,
79.3, 77.3, 75.3, 75.2, 71.5, 68.7, 47.9, 43.8, 42.1, 41.6, 39.5, 37.9 (2 peaks), 36.6,
34.3, 32.1, 31.6, 31.2, 30.1, 29.0, 28.1, 28.0, 20.4, 18.8, 14.3, 14.1, 14.0, 10.4, 9.8,
8.7.
¬
1999, 2303 2307; g) G. Solladie, X. J. Salom-Roig, G. Hanquet,
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¬
Lett. 2000, 2, 1529 1531; i) G. Solladie, X. J. Salom-Roig, G. Hanquet,
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Kocienski, A. Morley, Synlett. 1998, 26 28.
Received: December 19, 2001 [Z18413]
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COMMUNICATIONS
sulfilimido complexes,[5] multiple mechanistic pathways have
been uncovered based on multiple electron and atom/group
transfers. Examples include O atom,[6] NÀ ion,[7] HÀ ion,[8] and
[15] W. R. Roush, L. K. Hoong, M. A. J. Palmer, J. A. Staub, A. D.
Palkowitz, J. Org. Chem. 1990, 55, 4117 4126.
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7121 7124.
[17] D. A. Evans, K. T. Chapman, E. M. Carreira, J. Am. Chem. Soc. 1988,
110, 3560 3578.
[18] K. Kiegiel, P. Prokopowicz, J. Jurczak, Synth. Commun. 1999, 29,
3999 4005.
[19] S. Takano, M. Akiyama, S. Sato, K. Ogasawara, Chem. Lett. 1983,
1593 1596.
[20] A. J. Mancuso, D. Swern, Synthesis 1981, 165 185.
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61, 7452 7454.
NSC6H3Me2 transfer.[9] Kinetic studies have revealed the
2À
existence of proton-coupled electron-transfer pathways based
on bound oxo/hydroxo/aqua,[1, 10] dialkylhydrazido,[11] and
sulfilimido[12] ligands that occur with large H/D kinetic isotope
effects. Examples include kO-H/kO-D ˆ 30 Æ 1[10a] for the oxida-
tion of hydroquinone (H2Q) to benzoquinone (Q) by cis-
[RuIV(bpy)2(py)(O)]2‡ (bpy ˆ 2,2'-bipyridine and py ˆ pyri-
dine) [Eq. (1)].
cis-[RuIV(bpy)2(py)(O)]2‡ ‡ H2Q ! cis-[RuII(bpy)(py)(H2O)]2‡ ‡ Q (1)
Other examples are kN-H/kN-D ꢀ 41.4 Æ 1.3[11] for the reduc-
[25] a) J. L. Levin, E. Turos, S. M. Weinreb, Synth. Commun. 1982, 12,
989 993; b) D. A. Evans, S. L. Bender, J. Morris, J. Am. Chem. Soc.
1988, 110, 2506 2526.
[26] P. Sampson, V. Roussis, G. J. Drtina, F. L. Koerwitz, D. F. Wiemer, J.
Org. Chem. 1986, 51, 2525 2529.
[27] J.-L. Luche, J. Am. Chem. Soc. 1978, 100, 2226 2227.
[28] a) D. L. Hughes, Org. React. 1992, 42, 335 656; b) E. Fabiano, B. T.
Golding, M. M. Sadeghi, Synthesis 1987, 190 192.
[29] J. Inanagana, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull.
Chem. Soc. Jpn. 1979, 52, 1989 1993.
[30] M. Zhao, J. Li, E. Mano, Z. Song, D. M. Tschaen, E. J. J. Grabowski,
P. J. Reider, J. Org. Chem. 1999, 64, 2564 2566.
[31] S. Kim, J. I. Lee, J. Org. Chem. 1984, 49, 1712 1716.
[32] The physicochemical data of the natural pamamycin-607and its
CF3COOD salt were provided by Professor Masahiro Natsume at
Tokyo University of Agriculture and Technology.
‡
tion of Q to H2Q by trans-[OsIV(tpy)(Cl)2{N(H)N(CH2)4O}]
[Eq. (2); tpy ˆ 2,2':6',2''-terpyridine], and kS-H/kS-D ꢀ 31.1 Æ
0.2[12] for the oxidation of trans-[OsIV(tpy)(Cl)2{NS(H)-
‡
C6H3Me2}] by Q [Eq. (3)].
‡
2trans-[OsIV(tpy)(Cl)2{N(H)N(CH2)4O}] ‡ Q
!
(2)
(3)
2trans-[OsV(tpy)(Cl)2{NN(CH2)4O}] ‡ H2Q
‡
‡
2trans-[OsIV(tpy)(Cl)2{NS(H)C6H3Me2}] ‡ Q
!
2trans-[OsV(tpy)(Cl)2(NSC6H3Me2)] ‡ H2Q
‡
We report here the first example of proton-coupled
electron transfer based on a phosphorus atom. Its existence
may have important implications for the redox reactivity of
organophosphorus compounds,[13] phosphoraniminato com-
plexes,[14] and biologically active substances containing P H
À
acids.[15]
A rapid reaction occurs between the osmium(vi) nitrido
complex, [OsVI(Tp)(Cl)2(N)] (TpÀ ˆ tris(pyrazolyl)borate),
and diethylphosphane (HPEt2) in CH2Cl2 under nitrogen at
room temperature to give the osmium(iv) phosphoranimi-
nato product, [OsIV(Tp)(Cl)2{NP(H)Et2}] (OsIVNP(H)Et2)
[Eq. (4)].
Proton-Coupled Electron Transfer from
Phosphorus: A P H/P D Kinetic Isotope
Effect of 178**
À
À
My Hang V. Huynh* and Thomas J. Meyer*
In the extensive redox chemistry of high oxidation state
ruthenium(iv) oxo,[1] osmium(vi) nitrido,[2] osmium(iv vi)
hydrazido,[3] osmium(iv) cyanoimido,[4] and osmium(iv)
[OsIV(Tp)(Cl)2(N)] ‡ HPEt2 ! [OsIV(Tp)(Cl)2{NP(H)Et2}]
(4)
The product was isolated (94% yield) and characterized by
elemental analysis,[16a] cyclic voltammetry,[16b] and UV/Vis,[16c]
and infrared[16d] spectroscopies. Similar to other d4 OsIV
phosphoraniminato complexes,[17] OsIV-NP(H)Et2 is paramag-
netic as shown by 1H NMR spectroscopy. Cyclic voltammetric
measurements in 1:1 (v/v) CH3CN:H2O (m ˆ 1.0 m in NH4PF6)
reveal that E1/2 for the osmium(v/iv) couple decreases by
57mV/pH unit from pH 0 ( E1/2 ˆ 0.560 V, versus sodium
saturated calomel electrode (SSCE)) to 3.5 (E1/2 ˆ 0.360 V,
versus SSCE) and is pH independent above pH 3.5.[18] From
these data, pKa ˆ 3.52 Æ 0.04 for the acid base equilibrium
shown in Equation (5), and Supporting Information Figure 1.
[*] Dr. T. J. Meyer
Associate Laboratory Director for Strategic Research
Los Alamos National Laboratory, MS A127
Los Alamos, NM 87545 (USA)
Fax : (‡1)505-667-5450
E-mail: tjmeyer@lanl.gov
Dr. M. H. V. Huynh
Director-Funded Postdoctoral Fellow
Los Alamos National Laboratory, Chemistry Division MS J514
Los Alamos, NM 87545 (USA)
Fax : (‡1)505-667-9905
E-mail: huynh@lanl.gov
[**] We are grateful to the Laboratory Directed Research and Develop-
ment Program for support of this research. M.H.V.H. gratefully
acknowledges postdoctoral fellowship support from the Director×s
Office of Los Alamos National Laboratory. Los Alamos National
Laboratory is operated by the University of California for the U.S.
Department of Energy under Contract W-7405-ENG-36.
Ka
‡
[OsIV(Tp)(Cl)2{NP(H)Et2}] „ [OsIV(Tp)(Cl)2(NPEt2)]À ‡ H
(5)
‡
Reminiscent of the [OsV(tpy)(Cl)2{NN(CH2)4O}] /
‡
[OsIV(tpy)(Cl)2{N(H)N(CH2)4O}]
and
[OsV(tpy)(Cl)2-
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
(NSC6H3Me2)] /[OsIV(tpy)(Cl)2{NS(H)C6H3Me2}]
couples,
‡
‡
Angew. Chem. Int. Ed. 2002, 41, No. 8
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4108-1395 $ 20.00+.50/0
1395