Mononuclear η2(4e)-bonded phosphaalkyne complexes; selective formation of a 1,2-diphosphacyclobutadiene tantalum complex

Article abstract of DOI:10.1002/1521-3773(20010903)40:17<3221::AID-ANIE3221>3.0.CO;2-V

Only the 1,2-diphosphacyclobutadiene and none of its 1,3 isomer was obtained in the reaction of 1 with tBuC≡P to give 2. In complex 1, which was prepared from [TaCl₂(η⁵-C₅Me₅)(CO) ₂(thf)] and tBuC≡P, the phosphaalkyne adopts an η²(4e) bonding mode according to NMR data, crystal structure analysis, and theoretical calculations.

Full text of DOI:10.1002/1521-3773(20010903)40:17<3221::AID-ANIE3221>3.0.CO;2-V

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Mononuclear h2(4e)-Bonded Phosphaalkyne
Complexes; Selective Formation of a
1,2-Diphosphacyclobutadiene Tantalum
Complex**
and the reaction mixture changed color from yellow to deep
purple. Removal of the solvent in vacuo and extraction of the
residue with hexane afforded the air-sensitive complex 1
(Scheme 1) in 85% yield as a deep purple powder, which
Andrew D. Burrows, Alk Dransfeld, Michael Green,*
John C. Jeffery, Cameron Jones, Jason M. Lynam, and
Minh T. Nguyen*
Dedicated to Professor Paul Binger
An interest in h2(4e)-bonded alkyne complexes[1] together
with the recognition that the chemistry of coordinated
tBuC P frequently mirrors that of alkynes[2] led us to explore
ꢀ
the possibility that phosphaalkynes might also adopt a h2(4e)
bonding mode in mononuclear complexes. Here we describe
the synthesis and structural characterization of the d2
5
2
ꢀ
tantalum complex [TaCl2(h -C5Me5){h (4e)-tBuC P}] and its
ꢀ
reaction with an excess of tBuC P to selectively form the 1,2-
diphosphacyclobutadiene complex [TaCl2(h5-C5Me5){s,s,p-
1,2-P2C2tBu2}].
ꢀ
In seeking to establish whether phosphaalkynes (RC P)
can adopt a h2(4e) bonding mode involving p !M(s),
Scheme 1. Synthesis of h2(4e)-bonded phosphaalkyne complexes.
k
*
*
M(dp) !p , p !M(dp), and possibly M(dd) !p orbital
k
?
?
interactions, we sought to prepare analogues of h2(4e)-bonded
could be recrystallized from hexane or pentane at 308C.
Complex 1 was characterized by elemental analysis, NMR
spectroscopy, and single-crystal X-ray crystallography as the
phosphaalkyne-substituted d2 complex [TaCl2(h5-C5Me5)-
mononuclear alkyne complexes in which the alkyne is
2
ꢀ
replaced by a h -bonded tBuC P ligand. We reasoned that a
comparison of the structural data for the two complexes
would provide an insight into the nature of the bond between
the metal center and the phosphaalkyne. In this study we
focused on the report that the well-characterized (NMR, X-
ray) d2 complex [TaCl2(h5-C5Me5){h2(4e)-PhC2Ph}][3] can be
2
ꢀ
{h (4e)-tBuC P}]. The cor-
responding reaction with
the adamantyl-substituted
phosphaalkyne afforded in
a similar fashion 2 in high
yield (Scheme 1), and it was
also found that KOtBu read-
ily (RT, 12 h) reacted in
toluene with 1 to form in
good yield the bis-alkoxy
complex 3 (Scheme 1).
ꢀ
synthesized by reaction of PhC CPh with the labile complex
[TaCl2(h5-C5Me5)(CO)2(thf)].[4] This suggested that the tanta-
ꢀ
lum dicarbonyl complex might also react with tBuC P to form
a novel h2(4e)-bonded phosphaalkyne complex.
ꢀ
When tBuC P (1.1 molequiv) was added at room temper-
ature to a stirred solution of [TaCl2(h5-C5Me5)(CO)2(thf)] in
THF, both CO ligands were readily (5 min) displaced (IR),
An X-ray crystallographic
Figure 1. ORTEP represention of
1. Thermal ellipsoids shown at the
30% probability level. Selected
bond lengths [Š] and angles [8]:
P1-C1 1.694(10), P1-Ta1 2.438(3),
C1-Ta1 2.079(9), Ta1-Cl1 2.346(2),
study[5] on a suitable single
[*] Prof. Dr. M. Green, Dr. J. C. Jeffery, Dr. J. M. Lynam
School of Chemistry
crystal of 1 obtained from
pentane ( 308C) establish-
ed the three-legged piano-
stool structure illustrated in
Figure 1, which closely re-
sembles that reported for
University of Bristol
Bristol, BS81TS (UK)
Fax : (‡44)117-929-0509
E-mail: michael.green@bris.ac.uk
Ta1-Cl2
131.5(7).
2.378(2);
P1-C1-C2
Prof. Dr. M. T. Nguyen, Dr. A. Dransfeld
Department of Chemistry, University of Leuven
Celestijueleua 200F, 3001 Leuven (Belgium)
Fax : (‡32)16-32-79-92
5
2
2
ꢀ
[TaCl2(h -C5Me5){h (4e)-PhC2Ph}]. In 1 an h -bonded tBuC P
ꢀ
replaces the alkyne ligand: both PhC2Ph and tBuC P adopt
E-mail: minh.nguyen@chem.kuleuven.ac.be
the same orientation in these complexes. Since a characteristic
feature of h2(4e)-bonded alkyne complexes is a short metal ±
carbon bond[6] it is especially interesting that in complex 1 the
Ta C1 distance is also short (2.079(9) Š) and is of similar
length to the Ta C(alkyne) bond length of 2.067(6) Š in
[TaCl2(h5-C5Me5){h2(4e)-PhC2Ph}]. In contrast, a long Ti C-
(phosphaalkyne) distance (2.187(6) Š) is observed in the d2
Dr. A. D. Burrows
Department of Chemistry, University of Bath
Bath, BA27AY (UK)
Dr. C. Jones
Department of Chemistry, University of Wales at Cardiff
PO Box 912, Cardiff, CF13TB (UK)
[**] We thank the EPSRC and K.U. Leuven Research Council (GOA
program) for financial support. We also thank Dr. N. Carr for
preliminary experiments.
5
2
[7]
ꢀ
complex [Ti(h -C5H5)2{h (2e)-tBuC P}(PMe3)], in which
the metal center has 18 electrons and cannot accept more
than two electrons from the phosphaalkyne triple bond.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
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Similarly, there is a difference in the P C bond lengths and
P-C-R ªbend-backº angles, which are larger in the Ta complex
(1.694(10) Š, 131.5(7)8) than in the titanium complex
(1.636(2) Š, 133.4(7)8). All of these observations, but espe-
cially the short Ta C(phosphaalkyne) bond, are consistent
of isolobal analogies that such a shift is characteristic of a
h2(4e) bonding mode. In contrast, higher field 31P chemical
shifts were reported for the d2 titanium (d ˆ 122.7) and
zirconium (d ˆ 196.9) complexes [M(h5-C5H5)2{h2(2e)-
[7]
ꢀ
tBuC P}(PMe3)] (M ˆ Ti, Zr), in which the phosphaalkyne
with involvement of the phosphaalkyne p orbital in bonding
cannot donate more than two electrons to the metal center.
Similarly, the 31P chemical shift of the phosphaalkyne P atom
?
to the tantalum atom in 1.
2
[16, 17]
ꢀ
This conclusion is also supported by Extended Hückel MO
(EHMO) calculations[8] using the bond parameters found for
complex 1. The complex was divided into Ta(h5-C5Me5)Cl2
in [Pt{h (2e)-tBuC P}(PPh3)2]
is d ˆ 84.1, characteristic
of a 2e donor and to much higher field than the signals of the
tantalum complexes 1, 2, and 3. The 31P chemical shift (d ˆ
ꢀ
and tBuC P fragments, and the orbital interactions between
416.3) of complex 3 can be rationalized by a decrease in p
?
ꢀ
the two were examined. The frontier orbitals on the tBuC P
donation from the phosphaalkyne ligand and implies that the
two tBuO ligands donate more p-electron density to the
tantalum atom than the chloro ligands in 1 and 2.
ligand[9] corresponding to p , p , and p all showed significant
interactions with the TaCl2(h5-C5Me5) fragment; the electron
*
k
k
?
populations of these orbitals were 1.81, 1.02, and 1.85
Whereas the 31P chemical shifts exhibit a diagnostically
useful wide range (d ˆ 84 ± 515) which spans the h2(2e) to
h2(4e) phosphaalkyne bonding modes, the corresponding 13C
chemical shifts, in contrast to those of h2(2e)- to h2(4e)-
alkynes,[6] show a much narrower and hence less useful range
(d ˆ 240 ± 337) for two- to four-electron donor phosphaal-
kynes. Thus, the 13C{1H} NMR spectra of 1, 2, and 3 recorded
in C6D6 at room temperature showed signals at d ˆ 337.2 (d,
*
respectively, and the population of the p orbital of 0.04
?
implies little or no interaction with the metal center. These
results compare well with those reported (EHMO calcula-
tion) by Curtis et al.[10] for [NbCl2(h5-C5H5){h2(4e)-HC2H}]
*
*
(p 1.74, p 0.81, p 1.68, and p 0.02) and indicate that, as in
k
k
?
?
the alkyne complex, the phosphaalkyne ligand in 1 is a four-
electron donor. A similar calculation on [Ti(h5-C5H5)2{h2(2e)-
1
1
ꢀ
ꢀ
ꢀ
tBuC P}(PMe3)] showed orbital populations consistent with
JP, C ˆ 113.3 Hz, P C), d ˆ 335.6 (d, JP, C ˆ 110.5 Hz, P C),
1
ꢀ
*
the proposed bonding mode of the phosphaalkyne (p 1.87, p
and d ˆ 326.5 (d, JP, C ˆ 108.5 Hz, P C), respectively, which
k
k
5
2
2
ꢀ
*
1.02, p 1.94, and p 0.04).
are similar to the signal of [Mo(h -C5H5){h (4e)-tBuC P}{h -
?
?
1
Further insight into the na-
ture of complex 1 was provided
by ab initio calculations on the
P(OMe)2OBF2OP(OMe)2}] (d ˆ 328.5, d, JP,C ˆ 114 Hz,
[16]
ꢀ
P C),
but only to slightly lower field than those of
5
2
ꢀ
[M(h -C5H5)2{h (2e)-tBuC P}(PMe3)] (M ˆ Ti: d ˆ 298.6,
model complexes [TaCl2(h5-
1JP, C ˆ 83.4 Hz; M ˆ Zr: d ˆ 310.6, JP, C ˆ 97.7 Hz)[7] and
1
2
2
[18]
ꢀ
ꢀ
[Pt{h (2e)-tBuC P}(PPh3)2] (d ˆ 240.8).
C5H5){h (4e)-RC P}] (R ˆ H
(A), Me (B)) with the Gaussi-
an 98 package of programs; the
structure depicted in Figure 2
was obtained.[11±13] The geomet-
rical parameters of A and B are
in reasonable agreement with
those of 1 in the crystal. Due
to a low barrier to rotation
of the phosphaalkyne ligand
(<20 kJmol 1; see Supporting
Information) various geome-
The lack of reactivity of the complexes [MCl2{h2(4e)-
alkyne}(h5-C5Me5)] (M ˆ Nb, Ta) towards alkynes has been
rationalized in terms of the large (2 eV) HOMO ± LUMO
gap.[10] A similar EHMO calculation on 1 also showed a
HOMO ± LUMO gap of 2 eV, which implies that this complex
would also be unreactive towards alkynes. Interestingly 1 is
Figure 2. Calculated
lowest
energy geometry for complex
A. Selected bond lengths [Š]
and angles [8]: P1-C1 1.672, P1-
Ta 2.486, C1-Ta 2.086, Ta-Cl1
2.339, Ta-Cl2 2.337, C1-H1
1.099; a ˆ 114.8, P1-C1-H1
135.73.
ꢀ
reactive towards an excess of tBuC P.
A solution of 1 in C6D6 was treated with tBuC P (ca.
ꢀ
1.6 molequiv), and the subsequent reaction was monitored by
31P{1H} NMR spectroscopy. Over a period of three weeks the
signal at d ˆ 509.0 for 1 decreased in intensity and was
replaced by a new singlet at d ˆ 31.8, with no evidence for any
phosphorus-containing intermediates. The color of the sol-
ution changed from purple to red. Removal of the C6D6 in
vacuo and extraction of the residue with hexane gave a deep
red solution of complex 4 [Eq. (1)]. Concentration of the
solution and cooling to 208C afforded crystals of 4, but due
to the high solubility of 4 in hexane, the amount isolated was
tries were considered in the GIAO calculation of the NMR
parameters.[14, 15] Based on ECP/DFT calculations on B, 31P
NMR chemical shifts of d ˆ 492, when the phosphaalkyne lies
parallel to the Cl Cl vector, and of d ˆ 525, when it is
perpendicular to the Cl Cl axis with the methyl group away
from the h5-C5H5 ligand, are predicted. This is in agreement
with the experimental values for 1 and 2 (d ˆ 509.0 and 515.3
in C6D6, respectively). The 13C chemical shifts of the
phosphaalkyne C atom in B, calculated at the same level of
theory, were d ˆ 299 (P C parallel to Cl Cl) and d ˆ 327
(P C perpendicular to Cl Cl). The difference of Dd ꢁ 10 ± 37
between dcalcd(13C) and dexp(13C) of the corresponding carbon
atoms in 1 and 2 could be due to the different substituents.
The observed and calculated low-field 31P NMR chemical
shifts are consistent with our earlier finding that the complex
5
2
2
[16]
ꢀ
[Mo(h -C5H5){h (4e)-tBuC P}{h -P(OMe)2OBF2OP(OMe)2}]
shows a low-field (d ˆ 467.8) 31P chemical shift for the
coordinated phosphaalkyne, and it was argued on the basis
3222
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relatively low, even though the conversion of 1 to 4 was
essentially quantitative. Complex 4 was characterized by
elemental analysis, NMR spectroscopy, and single-crystal
X-ray crystallography as the 1,2-diphosphacyclobutadiene
complex [TaCl2(h5-C5Me5)(s,s,p-1,2-P2C2tBu2)].[19] This is es-
pecially interesting since there is only one previously reported
example of a 1,2-diphosphacyclobutadiene complex: [Ti(h8-
C8H8)(h4-1,2-P2C2tBu2)] was formed (30% yield) along with
[Ti(h8-C8H8)(h4-1,3-P2C2tBu2)] (30% yield) in an unselective
(1.827(6) Š) in the 1,2-dihydro-1,2-diiododiphosphete.[23] The
corresponding calculated bond lengths for the model complex
[TaCl2(h5-C5H5)(1,2-P2C2H2)] show the same trend with an
even longer P P bond and shorter C C bond. An obvious
interpretation of these findings is that the 1,2-P2C2tBu2 ligand
in complex 4 adopts a s,s,p bonding mode, as illustrated in
Equation (1).
As might be expected, the NMR parameters of the 1,2-
P2C2tBu2 ligand in 4 differ from those of the corresponding Ti
complex. The 31P{1H} NMR spectrum of 4 showed one singlet
at d ˆ 31.8 to high field of that of [Ti(h8-C8H8)(h4-1,2-
P2C2tBu2)] (d ˆ 133.6), and the 13C{1H} NMR spectrum of 4
reaction
(1/1)
between
tBuC P and [Ti(h8-C8H8)-
(h4-C8H8)].[20] In all other stud-
ies on the formation of diphos-
ꢀ
exhibited an apparent doublet of doublets at d ˆ 168.5 (1JP,C
ˆ
phacyclobutadiene
ligands,
23.9 Hz, 2JP, C ˆ 18.4 Hz) not dissimilar to that reported for the
Ti complex at d ˆ 153.9 (app t, JP, C ˆ 49.5 Hz) and in the
region typical for sp2 carbon atoms. Again the data are
consistent with a s,s,p bonding mode for complex 4.
only the 1,3-isomer has been
observed, even though calcu-
lations on the free ligand have
predicted that the 1,2-isomer
is thermodynamically more
stable.[21, 22]
Neither the selective or the stepwise [1 !4] formation of a
1,2-diphosphacyclobutadiene has been previously observed.
In agreement with our previous DFT calculations, it is
noteworthy that the recent calculations also show that the
observed product has the lowest energy and is the most stable
isomer. Therefore, the reaction might be considered to be
thermodynamically controlled. However, so far only a tilted
1,3-diphosphabicyclo[1.1.0]butanediyl[22] has been identified
as a potential intermediate in the reaction. It is hoped that the
progressive replacement of the chloro ligands in 1 followed by
a study of the reaction of the resulting phosphaalkyne
The single-crystal X-ray
structure of 4 (from hexane,
208C) is shown in Figure 3,
and selected bond parameters,
along with those calculated
(ECP/DFT geometry optimi-
Figure 3. ORTEP represention
of complex 4. Thermal ellipsoids
shown at the 30% probability
level. For selected bond lengths
and angles, see Table 1.
zation) for the model complex [TaCl2(h5-C5H5)(h4-1,2-
P2C2H2)] and reported for the titanium complex [Ti(h8-
C8H8)(h4-1,2-P2C2tBu2)] are listed in Table 1. Examination of
these data shows that the bonding mode adopted by the 1,2-
P2C2tBu2 ligand in the tantalum complex 4 is different from
ꢀ
complexes with further tBuC P might enable us to tune the
system and thus allow a deeper understanding of this
interesting reaction.
In conclusion, single-crystal X-ray crystallography, NMR
spectroscopy, and theoretical (EHMO, DFT) studies show
that the phosphaalkyne ligand in [TaCl2(h5-C5Me5){h2-
Table 1. Observed and DFT-calculated (in square brackets) bond param-
eters (bond length [Š], angle [8]) for the 1,2-diphosphacyclobutadiene
ligand.
2
ꢀ
tBuC P}] (1) adopts a h (4e) bonding mode. Surprisingly, 1
ꢀ
reacts with an excess of tBuC P to form the complex
Bond or angle Complex 4
[TaCl2(h5-C5H5)- [Ti(h8-C8H8)-
[TaCl2(h5-C5Me5)(1,2-P2C2tBu2)]; the X-ray data indicate a
s,s,p bonding mode for the 1,2-diphosphacyclobutadiene
ligand. This is only the second time that the formation of a
1,2-diphosphacyclobutadiene has been observed, but in this
case there is no evidence for the formation of the 1,3-isomer.
(h4-1,2-P2C2H2)]
(h4-1,2-P2C2tBu2)][11]
P1 P2
2.204(2)
1.820(5)
1.840(5)
1.410(6)
2.4992(13)
2.5116(13)
2.684(5)
2.655(5)
[2.250]
[1.808]
[1.809]
[1.385]
[2.554]
[2.552]
[2.456]
[2.454]
[103.8]
[76.2]
2.175(1)
1.815(5)
1.806(2)
1.429(3)
2.487(1)
2.494(1)
2.392(2)
2.381(2)
P1 C11
P2 C21
C11 C21
M P1
M P2
M C11
Experimental Section
M C21
C21-C11-P1
C11-P1-P2
P2-C21-C11
P1-P2-C21
103.0(3)
102.0(1)
Full experimental details (both syntheses and calculations) are provided in
the Supporting Information.
77.7(2)
102.1(3)
77.3(2)
77.8(1)
101.8(1)
78.4(1)
[103.9]
[76.2]
Received: April 2, 2001 [Z16883]
that reported for [Ti(h8-C8H8)(h4-1,2-P2C2tBu2)], which was
described as a h4-bonded delocalized p system. Thus, the
P1 P2 distance of 2.204(2) Š in 4 is essentially the same as the
P P single-bond length in 3,4-di-tert-butyl-1,2-dihydro-1,2-
diiododiphosphete[23] (2.192(4) Š), and perceptibly longer
than that in the Ti complex (2.175(1) Š). Although the
C11 C21 bond length (1.410(6) Š) in 4 is apparently shorter
than that in the Ti complex (1.429(3) Š), the difference is not
statistically significant, and the P C bond lengths (1.820(5) Š,
1.840(5) Š) in 4 are close to the P C single-bond length
[1] a) C. J. Beddows, A. D. Burrows, N. G. Connelly, M. Green, J. M.
Lynam, T. J. Paget, Organometallics 2001, 20, 231; b) S. J. Dosset, M.
Green, M. F. Mahon, J. M. McInnes, C. Vaughan, J. Chem. Soc. Dalton
Trans. 1997, 3671; c) C. Carfagna, N. Carr, R. J. Deeth, S. J. Dossett, M.
Green, M. F. Mahon, C. Vaughan, J. Chem. Soc. Dalton Trans. 1996,
415, and references therein.
[2] a) K. B. Dillon, F. Mathey, J. F. Nixon, Phosphorus: The Carbon Copy,
from Organophosphorus to Phosphaorganic Chemistry, Wiley, New
York, 1998; b) P. Binger in Multiple Bonds and Low Coordination in
Phosphorus Chemistry (Eds.: M. Regitz, O. J. Scherer), Thieme,
Stuttgart, 1990, pp. 90 ± 107.
Angew. Chem. Int. Ed. 2001, 40, No. 17
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[3] G. Smith, R. R. Schrock, M. R. Churchill, W. J. Youngs, Inorg. Chem.
1981, 20, 387.
Total Synthesis of Dermostatin A**
[4] D. Kwon, M. D. Curtis, Organometallics 1990, 9, 1.
[5] a) Crystal structure data of 1 (173 K) with MoKa radiation (l ˆ
0.71073 Š): Mr ˆ 487.16, crystal dimensions 0.40  0.35  0.35 mm,
Christopher J. Sinz and Scott D. Rychnovsky*
By virtue of their biological activity and structural com-
plexity, the polyene macrolides have attracted a great deal of
interest from the synthetic community.[1] We have been
engaged in the development of broadly applicable method-
ology for the stereochemical elucidation and the total syn-
thesis of highly oxygenated natural products. Pursuant to
these goals, a recent report from our group described a new
approach to the rapid stereochemical assignment of polyol-
containing natural products in which 2D-13C acetonide
analysis allowed for the stereochemical elucidation of der-
mostatin A (1) and B (2).[2] Herein, we disclose studies which
have culminated in the first total synthesis of dermostatin A
(1).
Å
triclinic, space group P1, a ˆ 7.555(2), b ˆ 9.712(2), c ˆ 13.263(4) Š,
3
a ˆ 68.626(4), b ˆ 80.968(5), g ˆ 77.277(4)8, Z ˆ 2, 1calcd ˆ 1.837 gcm
,
R1 ˆ 0.057 for 3340 data (I > 4sIo). b) Crystallographic data (exclud-
ing structure factors) for the structures reported in this paper have
been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC-160698 (1) and -160699 (4).
Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-
336-033; e-mail: deposit@ccdc.cam.ac.uk).
[6] J. L. Templeton, Adv. Organomet. Chem. 1989, 29, 1.
[7] P. Binger, B. Biedenbach, A. T. Herrmann, F. Langhauser, P. Betz, R.
Goddard, C. Krüger, Chem. Ber. 1990, 123, 1617.
[8] EHMO calculations were performed with the CACAO 98 program:
C. Mealli, D. M. Prosierpio, J. Chem. Educ. 1990, 67, 399.
*
[9] Note that the orbitals for 1 corresponding to the phosphaalkyne p , p
k
k
*
p , and p sets also showed some electron density on the tBu group,
?
?
but in each case the orbital comprised at least 70% carbon and
phosphorus p orbitals of suitable symmetry. Hence the populations of
the P C p bond contributions will be slightly lower than the figures
quoted above.
O
OH
OH
O
R
[10] M. D. Curtis, J. Real, D. Kwon, Organometallics 1989, 8, 1644.
[11] The NMR data of A and B were calculated with a DFT/ECP geometry
optimization by using the Vosko ± Wilk ± Nusair[12] functional and the
6-31G(d,p) basis set for all atoms except Ta, which was described by
the Dolg ± Stoll ± Preuss ± Pitzer effective core potential.[13] Geometry
and magnetic shielding data have been deposited at the CCC
Erlangen at http://www.ccc.uni-erlangen.de/sharc with the registry
OH OH OH OH OH OH OH
1: R = H
2: R = Me
Dermostatin A (1) and B (2) are 36-membered macrolides
that were isolated from the mycelium of Streptomyces
viridogriseus Thirum.[3] Their flat structures were determined
by Rinehart and Pandey.[4] The dermostatins show potent
antifungal activity (comparable to amphotericin B) against a
large number of human pathogens,[5] and have been used
clinically as a treatment for deep vein mycoses.[6] Additionally,
in an evaluation of a variety of polyene macrolides as
potential HIV treatments, dermostatin A (1) and B (2)
showed the highest antiproliferative activity against HIV in
H9 cells.[7] Although the dermostatins have demonstrated a
broad range of biological activities, details of their mode of
action remain unknown.
We set out to develop a highly convergent synthetic
approach that would be sufficiently flexible to allow the
facile generation of analogues for studies of the mode of
action (Scheme 1). The central synthetic challenges posed by
dermostatin A (1) are the complex polyol region and the
conjugated hexaene. The acid- and light-sensitivity of the
polyene necessitates delaying its introduction until a late
stage. We intended to employ a palladium-mediated cross-
coupling with vinyl stannane 4 as the penultimate carbon
carbon bond construction. Previous studies from our group
have demonstrated the utility of cyanohydrin acetonide
numbers
alk,2000-05-27GMT081407
(A)
and
alk,1999-11-
28GMT133322 (B) and are also available as Supporting Information.
We are currently investigating the bonding in these phosphaalkyne
and alkyne complexes more thoroughly in a DFT study.
[12] S. H. Vosko, L. Wilk, M. Nusair, Can. J. Phys. 1980, 58, 1200.
[13] M. Dolg, H. Stoll, H. Preuss, R. M. Pitzer, J. Phys. Chem. 1993, 97,
5852.
[14] At the applied level of theory the isotropic magnetic shielding of
13C(TMS) is 191.8 and of 31P(PH3) is 606.3. The experimental values
d31P(PH3, liquid) ˆ 240 and d13C(TMS) ˆ 0 were used to convert
shieldings into chemical shifts.
[15] A similar approach to the calculation of 31P NMR chemical shifts in
transition metal complexes has been reported: M. Kaupp, Chem. Ber.
1996, 129, 535.
[16] G. Brauers, M. Green, C. Jones, J. F. Nixon, J. Chem. Soc. Chem.
Commun. 1995, 1125.
[17] J. C. T. R. Burckett-St. Laurent, P. B. Hitchcock, H. W. Kroto, J. F.
Nixon, J. Chem. Soc. Chem. Commun. 1981, 1141.
[18] G. Brauers, Ph.D. Thesis, University of Bath, 1995.
[19] Crystal structure data of
4
(173 K) with MoKa radiation (l ˆ
0.71073 Š): crystal dimensions 0.50  0.40  0.10 mm, monoclinic,
space group P21/n, a ˆ 9.085(2), b ˆ 15.400(4), c ˆ 16.560(2) Š, b ˆ
102.71(1)8, Z ˆ 4, 1calcd ˆ 1.726 gcm 3, R1 ˆ 0.030 for 5147 data (I >
2sIo).[5b]
[20] P. Binger, G. Glaser, S. Albus, C. Krüger, Chem. Ber. 1995, 128, 1261.
[21] M. T. Nguyen, M. T. Landuyt, L. G. Vanquickenborne, J. Org. Chem.
1993, 58, 2817.
[22] S. Creve, M. T. Nguyen, L. G. Vanquickenborne, Eur. J. Inorg. Chem.
1999, 1281.
[23] P. Binger, T. Wettling, R. Schneider, F. Zurmühlen, U. Bergsträsser, J.
Hoffmann, G. Maas, M. Regitz, Angew. Chem. 1991, 103, 208; Angew.
Chem. Int. Ed. Engl. 1991, 30, 207.
[*] Prof. S. D. Rychnovsky, C. J. Sinz
Department of Chemistry, University of California
Irvine, CA 92697-2025 (USA)
Fax : (‡1)949-824-6379
E-mail: srychnov@uci.edu
[**] This research was supported by a grant from the National Institutes of
Health (GM-43854). C.J.S. thanks Pharmacia for a graduate fellow-
ship.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
3224
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