Total synthesis of hamigerans: Part 2. Implementation of the intramolecular Diels - Alder trapping of photochemically generated hydroxy-o-quinodimethanes; strategy and completion of the synthesis

Article abstract of DOI:10.1002/1521-3773(20011001)40:19<3679::AID-ANIE3679>3.0.CO;2-T

The synthesis of libraries of natural products is important for chemical biology studies. With this in mind, the intramolecular Diels - Alder reaction of photo-chemically generated hydroxy-o-quinodimethanes was used to produce the naturally occurring hami

Full text of DOI:10.1002/1521-3773(20011001)40:19<3679::AID-ANIE3679>3.0.CO;2-T

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A thorny problem in reaching the hamigeran structure was
expected to be the establishment of the relative stereochem-
istry at the four contiguous stereocenters situated at C5, C6,
C9, and C10. At the outset, the most direct approach to solve
this problem appeared to be the one initiated from benzalde-
hyde 5 (Scheme 2). Pleasantly, and as predicted from molec-
ular models, when benzaldehyde 5 was irradiated in deoxy-
genated benzene solution (450-W Hanovia lamp, pyrex filter)
the tricyclic system 7 was obtained in 91% yield, presumably
via the transient species 6 (E ˆ COOMe). The relative
Total Synthesis of Hamigerans: Part 2.
Implementation of the Intramolecular Diels ±
Alder Trapping of Photochemically Generated
Hydroxy-o-quinodimethanes; Strategy and
Completion of the Synthesis**
K. C. Nicolaou,* David Gray, and Jinsung Tae
In the preceding communication,[1] we detailed the devel-
opment of a suitable methodology for the expedient con-
struction of the benzannulated carbocyclic frameworks of
[
2]
members of the hamigeran class of natural products (e.g. 1 ±
, Scheme 1) as immediate synthetic targets. Based on the
4
OH
O
OH O
O
OH
X
Br
O
1
0
9
OMe
Me
10
9
Me
5
5
Me
Me
H
6
H
6
X
1
: X = H: debromohamigeran A 3: X = H: hamigeran B
2
: X = Br: hamigeran A
4: X = Br: 4-bromohamigeran B
OMe OH
MeO
O
X
Y
MeO
O
Me
Me
Me
Me
R
R
I
II
Scheme 1. Molecular structures of the hamigerans 1 ± 4 and retrosynthetic
analysis through photo-enolization and intramolecular trapping of reactive
hydroxy-o-quinodimethane species I.
photo-induced generation and trapping of hydroxy-o-quino-
dimethanes I, this synthetic technology was the centerpiece of
our synthetic strategy towards these biologically active
compounds as shown retrosynthetically in Scheme 1. In the
[
1]
same article
we also reported the construction of
two appropriately functionalized benzaldehydes (e.g. II,
Scheme 1), which are needed as potential precursors for the
total synthesis of the hamigerans. Herein we describe the
implementation of this strategy and the completion of the
total synthesis of hamigerans A and B (1 ± 4) and several of
their epimers.
[
*] Prof. Dr. K. C. Nicolaou, D. Gray, Dr. J. Tae
Department of Chemistry and
The Skaggs Institute for Chemical Biology
The Scripps Research Institute
1
0550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Scheme 2. Synthesis of the 5-epi-hamigeran series (11, 12, and 15).
Reagents and conditions: a) benzene, hn (450-W Hanovia lamp, pyrex
filter), 258C, 20 min, 91%; b) 1% HCl in MeOH, 608C, 30 min, 90%;
Fax : (‡ 1)858-784-2469
E-mail: kcn@scripps.edu
and
c) OsO
4
(0.08 equiv), NMO (2.0 equiv), py (2.0 equiv), THF/tBuOH/H
10:10:1), 258C, 12 h, 93% (ca. 12:1 mixture of two isomers); d) SO ´ py
3.0 equiv), Et N (6.0 equiv), DMSO/CH Cl (1:1), 08C, 2 h, 88%; e) BBr
10.0 equiv), CH
, � 788C, 3 h, 95%; f) NBS (1.05 equiv), iPr
2
O
Department of Chemistry and Biochemistry
University of California, San Diego
9
(
(
(
3
3
2
2
3
500 Gilman Drive, La Jolla, CA 92093 (USA)
2
Cl
2
2
NH
[
**] This work was financially supported by the National Institutes of
Health (USA) and The Skaggs Institute for Chemical Biology, and
grants from Abbott, Amgen, ArrayBiopharma, Boehringer-Ingel-
heim, Glaxo, Hoffmann-La Roche, DuPont, Merck, Pfizer, and
Schering Plough.
(0.1 equiv), CH
nBu NIO
CH Cl
2
Cl
2
, 08C, 3 h, 95%; g) KOH, MeOH, 708C, 2 h; then
(10.0 equiv),
4
4
(2.0 equiv), dioxane, 1008C, 1 h, 65%; h) BBr
3
2
2
, � 788C, 3 h, 95%; i) NBS (2.5 equiv), DMF, 08C, 3 h, 95%.
NMO ˆ 4-methylmorpholine N-oxide, py ˆ pyridine, NBS ˆ N-bromosuc-
cinimide.
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configuration of the substituents on the periphery of the
newly formed framework is apparently fully controlled by the
single C6 stereocenter of the starting substrate 5. All the
stereocenters in 7 were formed with single stereochemistries,
except for the one at C10, which was generated as a mixture of
isomers (ca. 3:1 ratio), a consequence of the E:Z mixture (ca.
logues, albeit epimeric at C5. Thus, selective monobromina-
tion[ ortho to the phenolic group of 11 (Scheme 2) was
smoothly effected by the action of NBS and catalytic amounts
of iPr NH in CH Cl at 08C, to furnish 5-epi-hamigeran A (12)
5]
2
2
2
in 95% yield. It was also found that basic hydrolysis of ester
10 (KOH/MeOH), followed by oxidative 1,2-cleavage pro-
[6]
3
:1) in the starting material 5. The trans relationship between
moted by nBu NIO in dioxane offers a practical entry into
4 4
the C6 isopropyl group and the C9 methyl moiety in 7 was
particularly crucial for the eventual success, as these were the
two permanently set centers. In contrast, the wrongly formed
stereochemistry at C5 could, in principle, be corrected by
epimerization. As seen from the next step (7 !8, HCl/MeOH,
the hamigeran B series. Thus, diketone 13 was obtained from
10 in 65% overall yield and was subsequently demethylated
(BBr , � 788C, 95% yield) to afford phenolic diketone 14.
3
Aromatic bromination of 14 (NBS, DMF) provided 5-epi-4-
bromohamigeran B (15) in 95% yield (for selected data, see
Table 1).
9
0% yield) the stereochemistry at C10 and C11 was at this
stage inconsequential, since it is removed at least temporarily.
This elimination step also converged the two C10 epimers
obtained in the cyclization reaction. Dihydroxylation of
Table 1. Selected data for compounds 15 and 34.
unsaturated ester 8 with NMO/OsO (for abbreviations of
4
15: colorless syrup; R ˆ 0.5 (silica gel, hexane/EtOAc 4:1); IR (film):
f
�
1
1
reagents and protecting groups, see legends in schemes) in the
presence of pyridine resulted in the formation of the a-
dihydroxy compound 9 contaminated with small amounts of
its isomer in which dihydroxylation occurred from the b-face
nÄ max ˆ 2959, 1734, 1633, 1455, 1376, 1194 cm
;
3
H NMR (CDCl ,
5
00 MHz): d ˆ 13.1 (s, 1H), 3.29 (d, J ˆ 10.8 Hz, 1H), 2.78 (s, 3H), 2.25
(
m, 1H), 1.99 (m, 1H), 1.95 ± 1.85 (m, 2H), 1.67 ± 1.60 (m, 2H), 1.13 (s, 3H),
13
1
1
.01 (d, J ˆ 6.8 Hz, 3H), 0.80 (d, J ˆ 6.8 Hz, 3H); C NMR (CDCl
3
,
25 MHz): d ˆ 196.9, 185.5, 160.8, 150.8, 141.2, 119.0, 114.3, 114.0, 57.9,
(ca. 12:1 ratio, 93% total yield). The benzylic alcohol in 9 was
52.6, 41.1, 31.7, 29.8, 27.2, 22.1, 21.1, 19.2, 14.5; HR-MS (MALDI): calcd for
C
‡
then oxidized with SO ´ py/DMSO to give hydroxy ketoester
18
H
20Br
2
O
3
[M‡Na ]: 464.9671; found: 464.9659
3
2
2
1
0 in 88% yield. Demethylation of 10 proceeded smoothly
34: colorless solid; R
c ˆ 0.100, CHCl ); IR (film): nÄ max ˆ 3437, 2857, 1738, 1692, 1604, 1460,
222, 1083, 1026 cm ; H NMR (CDCl
f
ˆ 0.5 (silica gel, hexane/EtOAc 1:1); [a] ˆ ‡38.8
D
(
1
3
upon exposure to BBr at � 788C to afford 5-epi-debromo-
3
�
1
1
3
, 400 MHz): d ˆ 6.72 (s, 1H), 6.61
hamigeran A (11) in 95% yield. Attempts to epimerize 11 or
any of its precursors 7 ± 10 under a variety of conditions failed.
Of particular note was the effect of UV irradiation on a
benzene solution of hydroxy ketoester 10: upon irradiation
with a UV Hanovia lamp, 10 was converted into an
equilibrium mixture of C10 epimers (10/10' ꢀ 1:3; see
Scheme 3). A likely mechanism for this equilibration is a
(
(
s, 1H), 4.80 (s, 1H), 3.86 (s, 3H), 3.54 (d, J ˆ 5.9 Hz, 1H), 3.50 (s, 3H), 2.37
s, 3H), 1.95 (m, 1H), 1.70 (dd, J ˆ 14.8, 8.9 Hz, 1H), 1.58 ± 1.41 (m, 2H),
1.39 (s, 3H), 1.37 ± 1.22 (m, 2H), 1.16 (d, J ˆ 6.2 Hz, 3H), 0.72 (d, J ˆ
6
1
2
3
.4 Hz, 3H); 13C NMR (CDCl
3
, 100 MHz): d ˆ 192.1, 169.9, 158.6, 146.1,
45.7, 122.4, 117.3, 109.7, 84.1, 55.9, 53.1, 52.4, 51.3, 46.7, 34.3, 26.9, 26.8,
‡
4.6, 23.5, 22.6, 21.7; HR-MS (MALDI): calcd for C21
83.1829; found: 383.1817.
H
28
O
5
[M‡Na ]:
Our next attempt at the total synthesis of the hamigerans
involved the use of a second benzaldehyde (16, Scheme 4),
which incorporated an oxygen functionality at C6 in the hope
that this additional handle might provide the necessary
activation for the obligatory epimerization at C5. Further-
more, since this aldehyde was obtained by asymmetric
synthesis, as described in the preceding paper,[ this new
strategy was expected to provide an enantioselective route to
the targeted compounds. Thus, photo-irradiation of 16
1]
(
E/Z ꢀ 3:1, inconsequential) under the standard conditions
already described for 5 led to the tricyclic hydroxy ester 17 in
2% yield and as a mixture of C10 epimers (ca. 3:1, major
9
product shown, inconsequential). The heating of 17 in
methanolic HCl at 608C affected both the dehydration and
MOM cleavage, leading to hydroxy unsaturated ester 18 in
Scheme 3. Photo-induced epimerization of hydroxy ketoester 10 at C10 by
means of Norrish Type-I fragmentation ± recombination. a) 450-W Hano-
via lamp, pyrex filter, benzene, ambient temperature, 20 min, 93%,
equilibrium mixture of C10 epimers (10/10' ꢀ 1:3).
91% yield. This sequence allowed the multigram synthesis of
intermediate 18 with >99% enantiomeric purity as deter-
mined by chiral HPLC. The olefin 18 was then stereo-
selectively dihydroxylated by following the already estab-
lished protocol (see above) to yield triol 19 as the major
product in 91% yield (ca. 12:1 ratio of two separable isomers).
Selective protection of the vicinal hydroxy groups in 19 with
2-methoxypropene and catalytic amounts of PPTS followed
by Dess ± Martin oxidation of the remaining hydroxy group
gave the corresponding ketone acetonide 21. With the
Norrish Type-I homolysis[3, 4] of the C10�C11 bond to form
the diradical species 10'', which then closes with retention of
stereochemistry to form 10 again, or with inversion of
stereochemistry to form its epimer 10' (Scheme 3).
With enough quantities of precursor 10 in hand and with
future chemical biology studies in mind, we decided to
establish procedures for reaching further hamigeran ana-
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neighboring carbonyl group in place, base-induced isomer-
ization at C5 proved extremely facile, requiring only a ten-
minute exposure to DBU at 08C to afford the desired product
21 with the cis 5,6 junction (86% yield over three steps). The
carbonyl group also served its second purpose as an electro-
phile well, allowing the cerium-mediated introduction of the
required isopropyl group (21 !22), and thus marking our
arrival at intermediate 22 (exclusive attack from the exo face,
95% yield). An attempt to reductively remove the tertiary
alcohol group from 22 by treatment with TFA/Et SiH led,
3
remarkably, to the polycyclic ether 23 (65% yield), presum-
ably formed by trapping the incipient tertiary carbonium ion
with the proximal C10 oxygen atom, and reductive cleavage of
the benzylic C�O bond.
Having experienced similar side reactions under various
other conditions, we opted to proceed through olefin 24,
which was readily obtained from alcohol 22 by the action of
SOCl /py (� 608C, 94% yield) as an inseparable mixture with
2
its conjugated (24') and exocyclic (24'') double bond isomers
(
not shown, ꢀ10:2:1 ratio). However, the intended reduction
of this olefin to furnish the correct stereochemistry of the
hamigerans at C6 as expected from an exo face attack
(
compare addition of isopropyl group to the carbonyl
function, step 21 !22) proved elusive. In various reduction
experiments, the suspected incorrect C6 stereoisomer 25 was
contaminated by unreactive tetrasubstituted olefinic isomers
24' and 24'', thus plaguing this approach with further
complications. Therefore, it was decided to change course.
But before that, and as in the previous case (C5-epi
compounds), we moved to complete the synthesis of the
new series of hamigeran analogues attainable from 24. Thus,
acid-induced hydrolysis of the acetonide group from the
reduction product 25 with HCl (3n)/THF (1:1) at 808C led to
diol 26 (mixture of C11 epimers, ca. 1.3:1 ratio), whose
chromatographic purification and spectroscopic characteriza-
tion now became possible. The mixture of benzylic alcohols 26
was then oxidized with SO ´ py/DMSO to afford hydroxy
3
ketoester 27 in 82% yield and as a single stereoisomer.
Demethylation of 27 (BBr , � 788C, 95% yield) led to phenol
3
28, whose proton NMR spectroscopic analysis (NOE) con-
firmed that, indeed, the isopropyl group had the incorrect
stereochemistry (C6) and that compound 28 was 6-epi-
debromohamigeran A. This compound was smoothly con-
verted into 6-epi-hamigeran A (29) by exposure to stoichio-
metric amounts of NBS in the presence of iPr NH (95%
yield).
2
Scheme 4. Synthesis of the 6-epi-hamigeran series (28 and 29). Reagents
and conditions: a) benzene, hn (450-W Hanovia lamp, pyrex filter), 258C,
In the face of this new failure to establish the correct C6
stereochemistry, we began to search for a new branching
sequence from one of our readily available intermediates.
Such a path was finally found starting with olefin 24 as shown
in Scheme 5. The crucial observation for this sequence was
2
(
(
0 min, 92%; b) 1% HCl in MeOH, 608C, 30 min, 91%; c) OsO
0.08 equiv), NMO (2.0 equiv), py (2.0 equiv), THF/tBuOH/H
10:10:1), 258C, 12 h, 91% (ca. 12:1 mixture of isomers); d) 2-methox-
Cl 08C, 30 min, 93%; e) DMP
, 08C, 1 h; then DBU (0.3 equiv), CH Cl , 08C,
0 min, 92%; f) iPrMgCl (2.0 equiv), CeCl
(2.0 equiv), � 78 !08C, 1 h,
5%; g) TFA (20 equiv), Et SiH (50 equiv), CH Cl , 258C, 1 h, 65%;
(8.0 equiv), py, CH Cl
, � 608C, 15 min, 94% (10:2:1 mixture of
three isomers); i) PtO (0.2 equiv), H (3 atm), EtOH, 258C, 2 h, 94% (ca.
:1 mixture of C6 epimers); j) HCl (3n)/THF (1:1), 808C, 4 h, 70% (ca.
.3:1 mixture of C11 epimers); k) SO ´ py (3.0 equiv), Et N (6.0 equiv),
DMSO/CH Cl (1:1), 08C, 2 h, 82%; l) BBr (10.0 equiv), CH Cl
, � 788C,
h, 95%; m) NBS (1.05 equiv), iPr NH (0.1 equiv), CH Cl , 08C, 3 h, 95%.
4
2
O
ypropene, PPTS (0.5 equiv), CH
2.0 equiv), CH Cl
2
2
,
(
1
9
2
2
2
2
3
made when olefin 24 was hydroborated with BH ´ Me S under
3
2
3
2
2
h) SOCl
2
2
2
sonication conditions to give, upon oxidative workup, the
desired 6R,7R alcohol isomer 30 as the major product (exo
addition, 44% yield) together with its a-stereoisomer (endo
addition, 24% yield). The chromatographically separated
isomer 30 was then sequentially converted (PhOC(S)Cl/py)
into the phenylthionocarbonate (31, 85% yield) and then into
2
2
3
1
3
3
2
2
3
2
2
3
2
2
2
PPTS ˆ pyridinium p-toluenesulfonate, DMP ˆ Dess ± Martin periodinane,
DBU ˆ 1,8-diazabicyclo[5.4.0]undec-7-ene, TFA ˆ trifluoroacetic acid.
the deoxygenated product 32 by heating with nBu SnH/AIBN
3
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debromohamigeran A (1). An expedient conversion of hami-
geran A (2) into hamigeran B (3) was devised based on a
cascade reaction initiated by Ba(OH) in MeOH/H O (2:1)
2
2
under aerobic conditions involving: a) saponification; b) de-
carboxylation; and c) auto-oxidation (82% overall yield).
Finally, 4-bromohamigeran B (4) was generated from hami-
geran B (3) by NBS-facilitated introduction of the second
bromine atom (95% yield). 4-Bromohamigeran B (4) could
also be obtained from 1 by dibromination (NBS, DMF) fol-
lowed by treatment with Ba(OH) (65% overall yield). The spec-
2
troscopic data for all four synthetic hamigerans 1 ± 4 matched
those reported for the naturally derived compounds.[
2]
An interesting observation made during this study is worth
mentioning, particularly since it considerably expands the
scope of the developed hydroxy-o-quinodimethane based
technology. Thus, in our attempts to convert compound 34
(
Scheme 5) into the C10,C11-diketone system 35 (Scheme 6)
by the two-step protocol used in the conversion of 10 !13
Scheme 2; a) KOH; b) nBu NIO ), we observed considerable
(
4
4
amounts of a by-product whose structure was determined to
be 38 (Scheme 6). It was subsequently confirmed that this ring
contraction process could be accelerated by UV irradiation,
thus becoming a synthetically useful reaction under these
conditions (35 !38, 90% yield, Scheme 6). Presumably the
Scheme 5. Total synthesis of hamigerans A (1,2) and B (3,4). Reagents and
conditions: a) BH
.8:1 mixture of two isomers); b) PhOC(S)Cl (2.0 equiv), py, 258C, 2 h,
5%; c) nBu SnH (8.0 equiv), AIBN (0.2 equiv), benzene, reflux, 1.5 h,
5%; d) HCl (1n), THF/H O (1:1), 808C, 1 h, 88%; e) PDC (2.5 equiv),
Š molecular sieves, CH Cl 258C, 3 h, 83%; f) BBr (10.0 equiv),
, � 788C, 3 h, 95%; g) NBS (1.05 equiv), iPr NH (0.1 equiv),
, 08C, 3 h, 95%; h) Ba(OH) (15 equiv), MeOH/H O (2:1), air,
3 2
´ Me S (40 equiv), THF, sonication, 408C, 8 h, 68% (ca.
1
8
7
4
3
2
2
2
,
3
CH
CH
2
2
Cl
Cl
2
2
2
2
2
258C, 2 h, 82%; i) NBS (1.5 equiv), DMF, 258C, 1 h, 95%; j) NBS
(
3.0 equiv), DMF, 258C, 1 h, 95%; k) same procedure as step h above,
Scheme 6. Proposed mechanism for the photo-induced decomposition of
65%. AIBN ˆ azobisisobutyronitrile, PDC ˆ pyridinium dichromate.
35 to form 38.
(
benzene, reflux, 75% yield). Formation of intermediate 32
Norrish Type-I mechanism shown in Scheme 6 operates in this
transformation. The potential of this ring contraction process
in organic synthesis is under further investigation.
paved the way for the completion of the synthesis of all four
targeted natural products. Thus, the acetonide protecting
group was removed from 32 by heating at 808C with HCl (1n)
in THF (1:1) to afford diol 33 in 88% yield. Although the
The chemistry described herein and in the preceding
[1]
communication demonstrates the power of the inter- and
standard SO ´ py/DMSO protocol for the oxidation of the
3
intramolecular trapping of photochemically generated hy-
droxy-o-quinodimethanes in complex molecule construction.
Furthermore, the reported expedient and efficient total
syntheses of the hamigerans and their analogues are expected
benzylic position gave low yields, PDC succeeded admirably
in converting 33 into 34 (83% yield; for selected data, see
Table 1). The first natural product in this series, debromoha-
migeran A (1), was generated from 34 (95% yield) by the
BBr -induced cleavage protocol employed above for the epi
series, whereas the second product, hamigeran A (2), was
[7]
to facilitate chemical biology investigations of these scarce,
3
and therefore, little-studied marine natural products.
obtained from the NBS-mediated bromination (95% yield) of
Received: June 7, 2001 [Z17244]
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[
[
[
[
1] K. C. Nicolaou, D. Gray, J. Tae, Angew. Chem. 2001, 113, 3787 ± 3790;
Angew. Chem. Int. Ed. 2001, 40, 3675 ± 3678, preceding communication.
2] K. D. Wellington, R. C. Cambie, P. S. Rutledge, P. R. Bergquist, J. Nat.
Prod. 2000, 63, 79 ± 85.
phous boron nitride by means of chemical vapor deposition
[2]
(
CVD).
To shine light on the processes during the CVD of BN,
Reinhardt et al. recently investigated the energetic course of
3] J. A. Barltrop, J. D. Coyle, J. Chem. Soc. Chem. Commun. 1969, 19,
[3]
1081 ± 1082.
the gas-phase reaction of BCl with NH . They were able to
3 3
4] For recent studies on the Norrish Type-I reaction and for further
references, see: E. W.-G. Diau, C. Kötting, A. H. Zewail, ChemPhys-
Chem 2001, 2, 273 ± 293; E. W.-G. Diau, C. Kötting, A. H. Zewail,
ChemPhysChem 2001, 2, 294 ± 309.
show that the substitution of the first chlorine atom of BCl in
3
the gas phase is a two-step reaction (Figure 1): the formation
of an NH ´ BCl adduct in the first step is followed by the
3
3
[
[
[
5] K. Krohn, S. Bernhard, U. Floerke, N. Hayat, J. Org. Chem. 2000, 65,
elimination of hydrogen chloride to yield aminodichlorobor-
ane. The elimination requires the surmounting of a barrier of
3
218 ± 3222.
6] E. Santaniello, F. Ponti, A. Manzocchi, Tetrahedron Lett. 1980, 21,
655 ± 2656.
� 1
� 1
25 kJmol with respect to the reactants, or 151 kJmol
2
relative to the adduct. The second and third substitutions
follow the same mechanism. The reaction barriers become
lower with decreasing chlorine content, and the heats of
reaction become smaller. As a result of its high-lying
transition state, the first chlorine substitution is the rate-
determining step, and the reaction that yields BN is expected
to proceed only at elevated temperatures. However, the
7] We thank Professor P. S. Rutledge and Professor R. C. Cambie for
informing us about the scarcity of these compounds. Apparently the
small amounts of the originally isolated compounds have now been
exhausted.
The Influence of Excess Ammonia
on the Mechanism of the Reaction
of Boron Trichloride with
AmmoniaÐAn Ab Initio
Molecular Dynamics Study**
Silke Reinhardt, Christel M. Marian,*
and Irmgard Frank
The reaction of boron trichloride with
ammonia is well known. Already in 1921, BN
was produced by ammonolysis of boron
trichloride in liquid ammonia and subse-
[
1]
quent heating of the primary products.
Today, the reaction of BCl with NH is used
Figure 1. Energy course of the gas-phase reaction of boron trichloride with one ammonia
molecule (top curve) and two ammonia molecules (bottom curve), determined at the BLYP level
3
3
for the preparation of hexagonal and amor- of theory (RI-MP2 values are given in parentheses). z ˆ Reaction coordinate.
[
*] Priv.-Doz. Dr. C. M. Marian
GMD Forschungszentrum Informationstechnik GmbH
Institut für Algorithmen und Wissenschaftliches Rechnen (SCAI)
Schloss Birlinghoven, 53754 St. Augustin (Germany)
Fax: (‡49)2241-14-2656
ammonolysis of BCl is known to occur spontaneously in the
3
condensed phase even at low temperatures and to be very
[1]
exothermic. It can therefore be concluded that additional
NH molecules strongly affect the energetic course and the
3
E-mail: christel.marian@gmd.de
mechanism of the reaction.
S. Reinhardt
The aim of the work herein is to study the influence of
additional ammonia molecules on the mechanism and on the
energy profile of the first chlorine substitution by an amino
group. According to the results of time-independent RI-MP2
calculations (see Calculation Methods), the barrier of the gas
phase reaction is lowered in the presence of another NH3
molecule owing to the formation of a six-centered transition
state (Figure 1). However, with respect to the H N ´ BCl
Institut für Physikalische und Theoretische Chemie
Universität Bonn
Wegelerstrasse 12, 53115 Bonn (Germany)
Dr. I. Frank
Institut für Physikalische Chemie
Ludwig-Maximilians-Universität
Butenandtstrasse 5 ± 13, 81377 München (Germany)
[
**] This work was supported by the Deutsche Forschungsgemeinschaft in
the framework of the Sonderforschungsbereich 408 ªAnorganische
Festkörper ohne Translationssymmetrieº. We thank Mauro Boero
from the Joint Research Center for Atom Technology, Tsukuba
3
3
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1
adduct the barrier is still rather high (125 kJmol ). Further-
more, the product side of the reaction is only slightly
(Japan) for the reoptimization of the Martins ± Troullier pseudopo-
stabilized by a single NH molecule. Because solvent mole-
3
tentials for boron and chlorine, as well as the John-von-Neumann-
Institut für Computing, Jülich, for making computer time available to
us.
cules participate actively in the reaction, the influence of
excess NH cannot be simulated by means of a continuum
3
Angew. Chem. Int. Ed. 2001, 40, No. 19
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