Dehydrogenation of [{(silox)3Nb}2(η-1,2; η-5,6-C8H8)] (silox = tBu3SiO) to [{(silox)3Nb}2(η-1,2;η-5,6- C8H6)] and its subsequent alkene-to-alkylidene rearra

Article abstract of DOI:10.1002/1521-3773(20011001)40:19<3629::AID-ANIE3629>3.0.CO;2-2

The resonance energy of COT^2- in [{(silox)₃Nb}₂(η-1,2;η-5,6-C₈H ₈)] (1) is indirectly responsible for its dehydrogenation to 2, but this olefin complex is thermodynamically less stable than the alkyli

Full text of DOI:10.1002/1521-3773(20011001)40:19<3629::AID-ANIE3629>3.0.CO;2-2

COMMUNICATIONS
[
1] a) A. Koskinen, Asymmetric Synthesis of Natural Products, Wiley,
Chichester, 1993, pp. 168 ± 191; b) D. E. Cane in Comprehensive
Natural Products Chemistry, Vol. 2 (Eds.: D. Barton, K. Nakanishi),
Elsevier, Oxford, 1999, pp. 1 ± 13.
Dehydrogenation of [{(silox) Nb} (h-1,2;
3
2
h-5,6-C H )] (silox ˆ tBu SiO) to
8
8
3
[{(silox) Nb} (h-1,2;h-5,6-C H )] and
3
2
8
6
[
2] Reviews for carotenoid synthesis: a) H. Pommer, Angew. Chem. 1960,
Its Subsequent Alkene-to-Alkylidene
Rearrangement**
72, 911 ± 915; b) O. Isler, Pure Appl. Chem. 1979, 51, 447 ± 462; c) E.
Widmer, Pure Appl. Chem. 1985, 57, 741 ± 752; d) J. Paust, Pure Appl.
Chem. 1991, 63, 45 ± 58; e) K. Bernhard, H. Mayer, Pure Appl. Chem.
Adam S. Veige, Peter T. Wolczanski,* and
Emil B. Lobkovsky
1991, 63, 35 ± 44.
[
3] Lycopene synthesis: a) P. Karrer, C. H. Eugster, E. Tobler, Helv.
Chim. Acta 1950, 33, 1349 ± 1352; b) O. Isler, H. Gutmann, H. Lindlar,
M. Montavon, R. Rüegg, G. Ryser, P. Zeller, Helv. Chim. Acta 1956,
The observed pyridine ring-opening of [(silox) Nb(h-C,N-
3
39, 463 ± 473; c) U. Hengartner, K. Bernhard, K. Meyer, G. Englert, E.
C H N)] (silox ˆ tBu SiO) to [(silox) NbˆCHCHˆCHCHˆ
5
5
3
3
Glinz, Helv. Chim. Acta 1992, 75, 1848 ± 1865; d) G. Pattenden, D. C.
Robson, Tetrahedron Lett. 1987, 28, 5751 ± 5754.
[1, 2]
CHNˆNb(silox) ], and related picoline chemistry
suggest-
3
ed that carbon ± carbon bond scission might occur by similar
pathways. 1,3,5,7-Cyclooctatetraene (COT) was considered a
prime candidate for ring opening because of its lack of
resonance stabilization energy, but in binding to two [(silox)3-
Nb] units, COT functions as an aromatic dianion, which
directs the chemistry toward C�H bond activation, dehydro-
[
4] a) M. Julia, J.-M. Paris, Tetrahedron Lett. 1973, 4833 ± 4836; b) M.
Julia, D. Arnould, Bull. Soc. Chim. France 1973, 746 ± 750; c) B. M.
Trost, H. C. Arndt, P. E. Strege, T. R. Verhoeven, Tetrahedron Lett.
1976, 3477 ± 3478; d) M. Julia, M. Launay, J.-P. Stacino, J.-N. Verpeaux,
Tetrahedron Lett. 1982, 23, 2465 ± 2468; e) J. Bremner, M. Julia, M.
Launay, J.-P. Stacino, Tetrahedron Lett. 1982, 23, 3265 ± 3266.
5] H. Choi, M. Ji, M. Park, I.-K. Yun, S.-S. Oh, W. Baik, S. Koo, J. Org.
Chem. 1999, 64, 8051 ± 8053.
6] a) G. I. Zaitseva, V. M. Alꢁbitskaya, Zh. Org. Khim. 1969, 5, 612 ± 617;
b) A. Yasuda, M. Takahashi, H. Takaya, Tetrahedron Lett. 1981, 22,
[
[
genation, and a subsequent alkene-to-alkylidene rearange-
ment.
[3]
Reduction of [(silox) NbCl ] (1) with Na/Hg in THF with
3
2
2413 ± 2416; c) G. Martin, J. Sauleau, M. David, A. Sauleau, Can. J.
three equivalents of COT present resulted in the isolation of
Chem. 1992, 70, 2190 ± 2196.
[
[
7] a) T. Kar, R. N. P. Choudhary, Mater. Lett. 1997, 32, 109 ± 113; b) H.-J.
Nam, H. Kim, S. H. Chang, S.-G. Kang, S.-H. Byeon, Solid State Ionics
brown [(silox) Nb(h-C H )] (2-COT, 40%) [Eq. (1)].
3
8
8
1999, 120, 189 ± 195.
THF; 24 h
[
(silox)
3
NbCl
2
] ‡ L (excess)
�ꢀ [(silox)
3
NbL]
(1)
8] a) C. Y. Meyers, A. M. Malte, W. S. Matthews, J. Am. Chem. Soc. 1969,
Na=Hg; � 2 NaCl
9
9
1, 7510 ± 7512; b) G. Büchi, R. M. Freidinger, J. Am. Chem. Soc. 1974,
6, 3332 ± 3333; c) J. S. Grossert, J. Buter, E. W. H. Asveld, R. M.
2
6 10
-L (L ˆ COT, cC H )
Kellogg, Tetrahedron Lett. 1974, 2805 ± 2808; d) F. Näf, R. Decorzant,
S. D. Escher, Tetrahedron Lett. 1982, 23, 5043 ± 5046; e) M. Julia, D.
Lave, M. Mulhauser, M. Ramirez-Munoz, D. Uguen, Tetrahedron
Lett. 1983, 24, 1783 ± 1786; f) T.-L. Chan, S. Fong, Y. Li, T.-O. Man, C.-
D. Poon, J. Chem. Soc. Chem. Commun. 1994, 1771 ± 1772.
Abstraction of 4-picoline from [(silox) Nb(h-C,N-4-
3
[2]
MeC H N)] (2-4-pic) by [(silox) Ta] in the presence of 2-
5
4
3
COT afforded [(silox) Ta(h-4-pic)] and burgundy, crystalline
3
[
9] a) P. S. Manchand, M. Rosenberger, G. Saucy, P. A. Wehrli, H. Wong,
L. Chambers, M. P. Ferro, W. Jackson, Helv. Chim. Acta 1976, 59, 387 ±
[{(silox) Nb} (h-1,2;h-5,6-C H )] (2 -COT, 33%, Scheme 1).
3
2
8
8
2
The synthesis of 2 -COT must occur under mild conditions to
2
396; b) P. Chabardes, J. P. Decor, J. Varagnat, Tetrahedron 1977, 33,
avoid further reaction (vide infra). An X-ray crystal structure
2799 ± 2805; c) G. L. Olson, H.-C. Cheung, K. D. Morgan, C. Neukom,
[
4, 5]
determination of 2 -COT
revealed the [(silox) Nb] moi-
G. Saucy, J. Org. Chem. 1976, 41, 3287 ± 3293; d) J. Otera, H. Misawa,
T. Mandai, T. Onishi, S. Suzuki, Y. Fujita, Chem. Lett. 1985, 1883 ±
2
3
[6, 7]
2
2
eties (d(Nb�C) ˆ 2.20(5) Š (av))
in an anti-h ,h -config-
1886.
uration about a planar COT ligand, although disorder
problems hampered further analysis. The insolubility of 22-
COT in unreactive hydrocarbon solvents prevented spectral
characterization.
[
10] Trans-lycopene was obtained as a major product (80% or more) with
a small amount (20% or less) of cis-lycopene. This latter product was
believed to be the 9-cis isomer on the basis of characteristic peaks at
1
[3c]
d ˆ 6.06 and 6.79 in the H NMR spectrum.
Base-promoted
elimination of the sulfonyl groups produced mostly trans double
Upon thermolysis of two equivalents of [(silox) Nb(h-C,N-
3
bonds.
4
-MeC H N)] (2-4-pic) and COT, 2-COT and presumably 2 -
5
4
2
COT were generated in situ, and dehydrogenation led to the
gold-brown cyclooctatrieneyne[ complex, [{(silox) Nb} (h-
8]
3
2
1
5
,2;h-5,6-C H )] (4; Scheme 1). Although 4 was isolated in
0% yield, H NMR spectroscopy revealed the conversion to
8 6
1
be >95% when the reaction was monitored in a sealed tube
C D ). Olefin substitution reactions of 2-4-pic, such as the
(
6
6
2
synthesis of the 1-butene complex, [(silox) Nb(h -C H )] (2-
3
4
8
[
*] Prof. P. T. Wolczanski, A. S. Veige, E. B. Lobkovsky
Department of Chemistry & Chemical Biology
Baker Laboratory, Cornell University
Ithaca, New York 14853 (USA)
Fax : (‡1)607-255-4137
E-mail: ptw2@cornell.edu
[**] We thank the US National Science Foundation for support of this
research.
Angew. Chem. Int. Ed. 2001, 40, No. 19
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4019-3629 $ 17.50+.50/0
3629

COMMUNICATIONS
5
2
,6-alkene binding (d(Nb�C) ˆ 2.153(10),
.177(9) Š; d(C�C) ˆ 1.335(12) Š) as the
near planarity of the C8-C1-Nb-C2-C3 atoms
attests.
The reversibility of the 2 -COTꢀ4 conver-
2
sion was probed by thermolysis of 4 under H .
2
Instead, dihydrogen catalyzed the rearrange-
ment of 4 to the orange alkylidene ± yne
1
2
complex, [{(silox) Nb} (h ;h -4,5-C H )] (6,
3
2
8
6
Scheme 1). Although 6 was isolated in about
0% yield, the reaction was observed to be
4
virtually quantitative when monitored in a
1
sealed tube by H NMR spectroscopy; with-
out dihydrogen, the conversion took three
days at 1558C. The single-crystal X-ray struc-
ture determination of 6 is shown in Fig-
ure 2.[
5, 10]
The alkyne is slightly skewed
(
d(Nb�C) ˆ 2.056(10), 2.145(11) Š), the
niobium ± alkylidene bond length of
.971(10) Š is normal,[
and the methylene
is a substituent on the alkylidene moiety.
1, 11]
1
1
2
When [{(silox) Nb} (h ;h -4,5-C H D)] (6-
3
2
8
5
D) was synthesized from 4 and D in a sealed
2
1
tube, its H NMR spectrum revealed that the
intensity of the methylene resonance at d ˆ
4.70 was halved, consistent with the incorpo-
2
Scheme 1. Synthesis of 2 -COT and its subsequent reactions to give 6.
ration of one deuterium atom. The overlap-
ping doublet of triplets at d ˆ 6.31 assigned to a proton
adjacent to the methylene group became a doublet of
doublets, and HD (solution) was observed as a 1:1:1 triplet
[
2]
C H ) [Eq. (2)], had been previously established, and
provided a practical synthesis of 4.
4
8
8
5 o C; 13 h
1
[
(silox)
3
Nb(4-pic)] ‡ 1-butene
�ꢀ
at d ˆ 4.42 (C D ). Variable-temperature H NMR resonance
6
6
C6 H6
2
-4-pic
(2)
experiments provided evidence in solution for the ring pucker
observed in the solid-state structure of 6. Decoalescence of
the CHH' group into two broad resonances was attributed to a
2
[
(silox)
3
Nb(h -C
-C
4
H
8
)] ‡ 4-picoline
2
4 8
H
Direct thermolysis of 2 -COT also afforded 4, but in lesser
purity. The single-crystal X-ray structure determination of 4 is
shown in Figure 1.
1,2-Alkyne ligation (d(Nb�C) ˆ
.091(8), 2.092(9) Š; d(C�C) ˆ 1.364(14) Š) is distinct from
=
� 1
2
ring inversion barrier of DG ˆ 10.7(3) kcalmol . The label-
ing experiment is consistent with hydrogenation of the alkene
of 4 to form transient alkyl-hydride 5, followed by an a-H-
[
5, 9]
2
[12]
abstraction by the hydride to give the alkylidene 6 (see
Scheme 1, ). The hydrogenation of 4 may occur through a
Figure 1. Molecular structure of 4. Selected distances [Š] and angles [8]:
Nb1-O 1.903(31) av, Nb2-O 1.912(47) av; Nb1-C1-C8 150.9(7), Nb1-C2-C3
Figure 2. Molecular structure of 6; C8 is the the methylene group. Selected
distances [Š] and angles [8]: Nb1-O 1.897(23) av, Nb2-O 1.900(30) av; Nb1-
C1-C2 107.0(8), Nb1-C1-C8 129.2(8), C1-C8-C7 108.5(9), Nb2-C4-C3
149.4(8), Nb2-C5-C6 156.8(8), Nb2-C4-C5 77.5(7), Nb2-C5-C4 69.3(7),
C3-C4-C5 129.0(10), C4-C5-C6 132.2(11).
1
52.3(8), Nb1-C1-C2 71.4(5), Nb1-C2-C1 71.4(5), C2-C1-C8 136.7(9), C1-
C2-C3 135.7(9), Nb2-C5-C4 111.2(6), Nb2-C6-C7 124.3, Nb2-C5-C6
2.6(6), Nb2-C6-C5 70.7(6), C4-C5-C6 131.3(9), C5-C6-C7 135.8(9).
7
3630
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4019-3630 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 19

COMMUNICATIONS
III
1
standard H (D ) oxidative addition to the putative Nb
±
from hexanes. H NMR (400 MHz, C
6
D
6
, 238C, TMS): d ˆ 1.25 (s, 81H;
), 2.38 ± 2.66 (m, 4H; C ), 2.78 (m, 2H;
, 238C): d ˆ 23.90 (C(CH ), 25.07 (C ), 28.46
), 70.76 (C ); elemental analysis calcd (%) for
Nb: C 61.4, H 11.2; found: C 61.2, H 11.0.
-COT: A 25 mL vial was charged with a mixture of [(silox)
4-pic) (209 mg, 0.252 mmol) and [(silox) Ta] (208 mg, 0.252 mmol). The
2
2
tBu), 1.50 ± 1.86 (m, 4H; C
g
H
2
b 2
H
alkene center of 4 followed by insertion to give 5, or by a
mechanistically indistiguishable s-bond metathesis path.
The COT dehydrogenation and rearrangement reactions
prompted an investigation of simple olefin complexes. Ex-
1
C
a
H); 13C{ H} NMR (C
6
D
6
3
)
3
g
(
C
b
), 31.21 (C(CH
3
)
3
a
42 3 3
C H91Si O
2
2
3
Nb(4-pic)] (2-
2
tended thermolysis of [(silox) Nb(h -cC H )] (2-cC H ,
3
6
10
6
10
3
[
Eq. (1)], 40%) induced the rearrangement to the cyclo-
6
mixture was dissolved in C H12 (5 mL), shaken vigorously for 2 min, and
left undisturbed for 45 min; a solution of 2-COT (230 mg, 0.252 mmol) in
cyclohexane (3 mL) was added. The solution turned dark burgundy after it
hexylidene complex, [(silox) NbˆC(CH ) CH ] (7-cC H ,
3
2
4
2
6
10
6
9% yield) [Eq. (3)]. Likewise, rearrangement of 1-butene
had been shaken vigorously for 30 s. Burgundy 2
260 mg, 33%) from this solution after it had been left to stand undisturbed
for 24 h.
: A 25 mL flask charged with 2-4-pic (500 mg, 0.600 mmol), 1,3,5,7-
2
-COT precipitated
(
4
cyclooctatetraene (0.5 equiv, 31 mg, 0.30 mmol), and benzene (20 mL) was
refluxed at 858C for four days. Golden brown 4 was isolated from pentane
1
(
232 mg, 50%). H NMR (C
6
D
6
, 238C, TMS): d ˆ 1.25 (s, 81H; tBu), 1.33 (s,
2
�
CHˆ), 6.98 (m, 2H;
2
81H; tBu), 3.19 (s, 2H, Nb(h -CHCH)), 6.81 (m, 2H;
complex [(silox) Nb(h -C H )] (2-C H ) to the butylidene
3
4
8
4
8
13
1
�
CHˆ); C{ H} NMR: d ˆ 23.94 (C(CH ) ), 24.18 (C(CH ) ), 31.39
3
3
3 3
complex [(silox) NbˆCH(CH ) CH ] (7-C H ) was evidenced
3
2
2
3
4
8
3 3 3 3
(C(CH ) ) 31.43 (C(CH ) ), 80.16 (Nb(h -CHCH)), 125.42, 129.07
2
[
Eq. (4)]. Thermolyses under H led to olefin hydrogenation.
(CHˆCH).
2
2
-C
4
H
8
:
A
50 mL bomb flask was charged with 2-4-pic (500 mg,
(20 mL), and 1-butene (ca. 5 equiv) at 77 K and placed
0
.600 mmol), C H
6 6
in an 858C oil bath for 13 h. Green 2-C
upon removal of the volatiles. H NMR (C
4
H
8
(385 mg, 81%) was isolated
, 238C, TMS): d ˆ 1.24 (s,
ˆCH�), 1.95 (dd, 1H;
1
6
D
6
8
1H; tBu), 1.35 (t, 3H; CH
CH
ˆCH), 2.5 (m, 1H; CH ˆCH), 2.69 (m, 2H; CH
CH ), 23.85 (C(CH ), 31.11 (C(CH 33.82 (CH
CH
ˆCH); elemental analysis calcd (%) for C40
1.3; found: C 60.3, H 11.3.
3 2
), 1.73 (m, 1H; CH
13
1
2
2
2
); C{ H}: d ˆ 21.14
), 70.12, 84.02
3 3
H89Si O Nb: C 60.4, H
(
(
1
3
3
)
3
3
)
3
)
2
2
As Scheme 1 indicates, a logical dehydrogenation sequence
involves C�H bond activation of 2 -COT to give an inter-
2
6
: A 50 mL bomb charged with 4 (80 mg, 0.050 mmol), benzene (10 mL)
(500 Torr; 77 K) was placed in a 708C oil bath for about two days.
mediate alkenyl ± hydride (3), followed by a b-H abstraction
and H
2
[
13±15]
by the hydride
to afford 4 and dihydrogen. An alternative
Crystallization from pentane at � 788C afforded orange 6 (30 mg, 40%).
0
1
path requires b-H elimination to a d alkyne ± dihydride
H NMR (C
6
D
6
, 238C, TMS): d ˆ 1.27 (s, 81H; tBu), 1.32 (s, 81H; tBu), 4.70
3
3
(
br d, J ˆ 8 Hz, 2H; CH
2
), 6.31 (dt, J ˆ 10, 8 Hz, 1H; CH
2
CHˆ), 7.20 (d,
intermediate and subsequent elimination of H . Upon C�H
2
3
3
J ˆ 10 Hz, 1H; ˆCH�), 8.30 (d, J ˆ 11 Hz, 1H; NbˆCCHˆCH�), 5.70 (d,
bond activation, the COT likely remains a planar dianion in
3
13
1
J ˆ 11 Hz, 1H; ˆCH�); C{ H} NMR (C
D
6
, 238C): d ˆ 23.36 (C(CH
3 3
) ),
6
the alkenyl hydride (3) derived from 2 -COT. A b-abstraction
2
23.45 (C(CH ) ), 30.68 (C(CH ) ) 30.90 (C(CH ) ), 41.82 (CH ), 111.75,
3
3
3
3
3
3
2
by the niobium hydride of 3 is aided by the favorable
geometry of the planar COT, whose b-hydrogen atom is
jammed into the Nb center (aNb-C-C ꢁ a/C-C-H ꢁ 112.58);
b-abstractions are known to be exquisitely sensitive to
132.34, 134.73, 137.43 (�Cˆ), 206.63, 211.54 (NbCC).
-cC 10: A 50 mL glass bomb charged with 2-cC 10 (600 mg, 0.732 mmol)
7
6
H
6
H
and benzene (25 mL) was placed in an 858C bath for 13 days. Green 7-
1
cC
6
H
10 (415 mg, 69%) was obtained from pentane. H NMR (C
6
D
H
g 2
6
, 238C,
), 3.78
), 29.12 (C ),
not observed; elemental analysis calcd (%)
for C H Si O Nb: C 61.6, H 11.9; found: C 60.9, H 11.8.
TMS): d ˆ 1.16 (m, 2H; C
d
H
2
), 1.28 (s, 81H; tBu), 1.59 (m, 4H; C
); C{ H} NMR: d ˆ 23.67 (C(CH ), 26.96 (C
), 40.99 (C ), C
[
13]
[16±20]
geometry.
An alkene-to-alkylidene transformation
13
1
(
m, 4H; C
b
H
2
3
)
3
d
g
would incur a disruption in the resonance stabilization energy
3
1.07 (C(CH
3
)
3
b
a
2�
of the C H8 ligand of 2 -COT. As Figure 1 reveals, the
8
2
42 89
3
3
dehydro-COT ligand of 4 has lost its dianionic character,
hence its rearrangement to the alkylidene occurs rather than
another dehydrogenation. Investigations continue into the
mechanism of the olefin-to-alkylidene (e.g., 4 ꢀ6, 2-C H ꢀ
7
4 8 4 8
-C H : A 50 mL bomb charged with 2-C H (350 mg, 0.440 mmol) and
benzene (20 mL) was heated at 1558C for 8.5 h. Red 7-C
4
H
8
(90 mg, 26%)
, 238C, TMS): d ˆ
), 1.29 (s, 81H; tBu), 3.49 (m,
1
was obtained from cold (� 788C) Et
.86 (t, J ˆ 7.2 Hz, 3H; CH
J ˆ 7.2 Hz, 2H; CH
), 8.17 (bs, 1H; NbˆCH); C{ H} NMR: d ˆ 13.74
(CH ), 26.71 (CH ), 23.96 (C(CH ) ), 30.99 (C(CH ) ), 44.10 (CH ), 249.0
2
O. H NMR (C
6
D
6
0
3
), 1.12 (m, 2H; CH
2
4
8
13
1
2
6
-C H and 2-cC H ꢀ6-cC H ) rearrangements that provide
4
8
6
10
6
10
3
2
3
3
3
3
2
a rationale for the generation of olefin metathesis catalysts.
(NbˆC, HMQC).; elemental analysis calcd (%) for C H Si O Nb: C 60.4,
40
89
3
3
H 11.3; found: C 60.2, H 11.4.
Experimental Section
Received: May 11, 2001 [Z17089]
All manipulations were performed by using either glovebox (N
vacuum techniques (Ar), and dried, deoxygenated solvents.
2
) or high-
2
1
(
-COT: A 50 mL flask was charged with [(silox)
.23 mmol), 1,3,5,7-cyclooctatetraene (386 mg, 3.70 mmol), 0.9% Na/Hg
2.1 equiv, 70 mg Na in 7.75 g Hg) and THF (20 mL) at 77 K. Upon stirring
3 2
NbCl ] (1) (1.00 g,
[
[
[
1] T. S. Kleckley, J. L. Bennett, P. T. Wolczanski, E. B. Lobkovsky, J. Am.
Chem. Soc. 1997, 119, 247 ± 248; T. S. Kleckley, PhD thesis, Cornell
University, 1998.
2] A. S. Veige, T. S. Kleckley, R. L. M. Chamberlin, D. R. Neithamer,
C. E. Lee, P. T. Wolczanski, E. B. Lobkovsky, W. V. Glassey, J.
Organomet. Chem. 1999, 591, 194 ± 203.
at 238C for 28 h, dark brown 2-COT (410 mg, 40%) was obtained from cold
1
(
� 788C) diethyl ether. H NMR (C
6
D
6
, 238C, TMS): d ˆ 1.23 (s, 81H;
); C{ H} NMR: d ˆ 24.18 (C(CH ), 31.35
Nb:
1
3
1
tBu), 5.64 (s, 8H; C
8
H
8
3 3
)
89Si
(
C(CH
C 62.7, H 10.6; found: C 60.4, H 10.1.
-cC 10: A 100 mL flask charged with 1 (1.50 g, 1.85 mmol), 0.65% Na/Hg
2.1 equiv, 89 mg Na in 13.76 g Hg), C 10 (3 mL), and THF (30 mL, 77 K).
10 (600 mg, 40%) was obtained
3
)
3
), 112.17 (HC); elemental analysis calcd (%) for C44
H
3
O
3
3] R. E. LaPointe, P. T. Wolczanski, G. D. Van Duyne, Organometallics
1
985, 4, 1810 ± 1818.
Å
2
(
6
H
[4] 2
79.61(3), b ˆ 83.19(3), g ˆ 78.57(3)8; Vˆ 2621.5(9) Š ; Z ˆ 2,
Si
Nb; Tˆ 173(2) K; l ˆ 0.71073; 9126 reflections, 5396
2
-COT: triclinic; P1; a ˆ 12.297(3), b ˆ 12.424 3), c ˆ 17.864(4) Š, a ˆ
3
6
H
Upon stirring at 238C for 12 h, green 2-cC
6
H
H
97
C
46
O
3
3
Angew. Chem. Int. Ed. 2001, 40, No. 19
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
1433-7851/01/4019-3631 $ 17.50+.50/0
3631

COMMUNICATIONS
�
1
independent; R1 ˆ 0.0793 (I > 2s(I)), wR2 ˆ 0.1523; m ˆ 0.332 mm
Enantioselective Total Synthesis of the
Cyclophilin-Binding Immunosuppressive Agent
Sanglifehrin A**
2
(
SADABS); full-matrix, least-squares on F .
[
5] Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication nos.
Maosheng Duan and Leo A. Paquette*
2
CCDC-163099 (2 -COT), CCDC-163100 (4), and CCDC-163101 (6).
Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-
The sanglifehrins are structurally unusual Streptomyces
metabolites discovered in a soil sample from Malawi. The A
336-033; e-mail: deposit@ccdc.cam.ac.uk).
[1]
[
6] H. C. Strauch, K. Bergander, G. Kehr, R. Fröhlich, G. Erker, Eur. J.
Inorg. Chem. 1999, 1461 ± 1466; K. Mashima, Y. Nakayama, M.
Kaidzu, N. Ikushima, A. Nakamura, J. Organometal. Chem. 1998, 557,
factor 1 holds particular interest because of its strong cyclo-
philin-binding properties and remarkable capability to inhibit
the proliferation of B and T cells. Since neither FK binding
protein binding activity nor calcineurin-inhibiting capability is
displayed, 1 exerts its powerful immunosupressive action in a
manner quite different from that adopted by cyclosporin A,
FK506, and rapamycin.[ The complex structural and stereo-
chemical features associated with 1 and its congeners,
3
2
1
± 12; G. E. Herberich, U. Englert, P. Roos, Chem. Ber. 1991, 124,
663 ± 2666; R. R. Schrock, L. J. Guggenberger, J. Am. Chem. Soc.
976, 98, 903 ± 913; L. J. Guggenberger, R. R. Schrock, J. Am. Chem.
Soc. 1975, 97, 6693 ± 6700.
[
[
7] F. Vanbolhuis, A. H. Klazinga, J. H. Teuben, J. Organomet. Chem.
2, 3]
1981, 206, 185 ± 195.
8] For related C complexes that arise from double H abstractions by
8
H
6
alkyl groups, see: F. G. N. Cloke, P. B. Hitchcock, S. C. P. Joseph, J.
Chem. Soc. Chem. Commun. 1994, 1207 ± 1208; P.-J. Sinnema, A.
Meetsma, J. H. Teuben, Organometallics 1993, 12, 184 ± 189.
[4]
[5]
ultimately corroborated by partial and total synthesis,
have provided a bevy of challenging opportunities for de
novo molecular assembly.
Å
[
9] 4: triclinic; P1; a ˆ 13.0793(5), b ˆ 13.1076(4), c ˆ 31.0368(11) Š, a ˆ
3
8
H
6.89(1), b ˆ 89.21(1), g ˆ 60.82(1)8; Vˆ 4638.2 3) Š ; Z ˆ 2,
Recent synthetic efforts in this laboratory have resulted in
the successful acquisition of certain subunits central to the
construction of sanglifehrin A (1) in convergent and highly
enantiocontrolled fashion.[ Herein, we report useful refine-
ments in these protocols as well as the successful conjoining of
components 2 ± 4 to arrive at 1 having all of its seventeen
stereogenic centers properly installed.
165
C
80
O
6
Si
6
Nb
2
; Tˆ 173(2) K; l ˆ 0.71073; 20040 reflections, 12883
� 1
independent; R1 ˆ 0.0805 (I > 2s(I)), wR2 ˆ 0.1759; m ˆ 0.368 mm
2
[5]
(SADABS); full matrix, least squares on F .
6]
[
10] 6 ´ C
6
H
6
:
monoclinic, P2
1
/c; a ˆ 24.6813(4), b ˆ 17.6046(3), c ˆ
3
2
Si
5.4832(4) Š, b ˆ 116.96(1)8; Vˆ 9869.5(3) Š ; Z ˆ 4,
171 86 6
H C O -
6
Nb
2
; Tˆ 173(2) K; l ˆ 0.71073; 56059 reflections, 21816 independ-
ent; R1 ˆ 0.0864 (I > 2s(I), 14073 reflections), wR2 ˆ 0.2119; m ˆ
�
1
2 [5]
0
.368 mm (SADABS); full-matrix, least-squares on F .
11] A. Caselli, E. Solari, R. Scopelliti, C. Floriani C, J. Am. Chem. Soc.
999, 121, 8296 ± 8305.
[
[
1
Me
33
Me
Me
OH OH
O
26
12] a-H abstractions by hydride: R. R. Schrock, S. W. Seidel, N. C. Mösch-
Zanetti, K.-Y. Shih, M. B. OꢁDonohue, W. M. Davis, W. M. Reiff, J.
Am. Chem. Soc. 1997, 119, 11876 ± 11893; R. R. Schrock, S. W. Seidel,
N. C. Mösch-Zanetti, D. A. Dobbs, K.-Y. Shih, W. M. Davis, Organo-
metallics 1997, 16, 5195 ± 5208.
13] b-Abstractions typically occur by loss of RH: S. L. Buchwald, R. B.
Nielsen, Chem. Rev. 1988, 88, 1047 ± 1058; J. C a mpora, S. L. Buchwald,
Organometallics 1993, 12, 4182 ± 4187; S. L. Buchwald, S. M. King, J.
Am. Chem. Soc. 1991, 113, 258 ± 265; S. L. Buchwald, K. A. Kreutzer,
R. A. Fisher, J. Am. Chem. Soc. 1990, 112, 4600 ± 4601; S. L. Buchwald,
R. T. Lum, R. A. Fisher, W. M. Davis, J. Am. Chem. Soc. 1989, 111,
HO
17
Me
20
N
Me
Me
O
OH
Me
HN 13
H
O
O
O
H
N
NH
1
1
8
N
Me
4
O
O
[
O
Me
OH
Me
sanglifehrin A (1)
9
113 ± 9114.
Me
O
Me
33
Me
[
14] B. Hessen, J. K. F. Buijink, A. Meetsma, J. H. Teuben, G. Helgesson,
OH
O
26
HO
25
M. Hakansson, S. Jagner, A. L. Spek, Organometallics 1993, 12, 2268 ±
SnBu3
I
2276; G. A. Luinstra, J. H. Teuben, Organometallics 1992, 11, 1793 ±
Me
Me
O
OH
1
801.
Me
Me
HO
NH
1
O
13
[
15] K. M. Doxsee, J. J. J. Juliette, K. Zientara, G. Nieckarz, J. Am. Chem.
Soc. 1994, 116, 2147 ± 2148; K. M. Doxsee, J. J. J. Juliette, Polyhedron
4
2
3
O
2
000, 19, 879 ± 890.
16] J. S. Freundlich, R. R. Schrock, W. M. Davis, J. Am. Chem. Soc. 1996,
18, 3643 ± 3655.
Me
[
[
O
1
O
NH2
H
N
H
1
8 N
Me
CH3O
N
17] R. P. Hughes, S. M. Maddock, A. L. Rheingold, I. A. Guzei, Polyhe-
dron 1998, 17, 1037 ± 1043.
O
Me
[
[
18] G. A. Miller, N. J. Cooper, J. Am. Chem. Soc. 1985, 107, 709 ± 711.
19] L. Giannini, G. Guillemot, E. Solari, C. Floriani, N. Re, A. Chiesi-
Villa, C. Rizzoli, J. Am. Chem. Soc. 1999, 121, 2797 ± 2807.
20] G. J. Spivak, J. N. Coalter, M. Olivan, O. Eisenstein, K. G. Caulton,
Organometallics 1998, 17, 999 ± 1001.
OBoc
4
[
[
*] Prof. Dr. L. A. Paquette, M. Duan
Evans Chemical Laboratories
The Ohio State University
1
00 West 18th Avenue, Columbus, OH 43210 (USA)
Fax : (‡1)614-292-1685
E-mail: paquette.1@osu.edu
[
**] This work was financially supported by Eli Lilly and Company and a
Robert Mayer Graduate Fellowship (to M.D.). We thank Prof. K. C.
Nicolaou for providing authentic spectra of 1.
3632
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1433-7851/01/4019-3632 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 19