A mechanistic alternative for the intramolecular hydroboration of homoallylic amine and phosphine borane complexes

Article abstract of DOI:10.1021/ja034655m

Intramolecular hydroboration is demonstrated starting from homoallylic amine boranes upon activation by iodine. The process involves a B-iodoborane complex as the intermediate and may occur via internal displacement of iodide by the alkene to generate a cationic borane-alkene π-complex on the way to hydroboration products. The reaction can be carried out using a catalytic amount of iodine. Copyright

Full text of DOI:10.1021/ja034655m

Published on Web 08/06/2003
A Mechanistic Alternative for the Intramolecular Hydroboration of Homoallylic
Amine and Phosphine Borane Complexes
Matthew Scheideman, Peter Shapland, and Edwin Vedejs*
Department of Chemistry, UniVersity of Michigan, Ann Arbor, Michigan 48109
Received February 13, 2003; E-mail: edved@umich.edu
Table 1. Iodine-Promoted Hydroboration of Acyclic Homoallylic
Amines
There have been many attempts to demonstrate intramolecular,
heteroatom-directed hydroboration, dating back more than 30
years.1-3 Although circumstantial evidence consistent with an
internal mechanism has been reported in some cases,1b there are
very few convincing examples. The most definitive examples
involve transition-metal-catalyzed internal hydroborations of allylic
and homoallylic substrates with potentially coordinating functional
groups.2 Panek et al. have reported another system where intramo-
lecular hydroboration is supported by substantial evidence,3 but
questions remain regarding the mechanistic details.
entrya
substrate
yield (%)
products
ratiob
1
2
3
1a
1b
1c
1d
1a
83
82
90
82
78
2a/3a
2b/3b
2c/3c
2d/3d
2a/3a
11:1
10:1
1:3
2:1
10:1
4
5c
Under metal-free conditions, intramolecular hydroboration might
occur upon heating a borane Lewis acid-Lewis base complex I
(Scheme 1, path a). For complex I to undergo internal hydrobo-
ration, the alkene must displace the heteroatom leaving group to
give an olefin complex III. With X ) oxygen, this mechanism
would involve the same bonding interactions that are proposed for
the intermolecular hydroboration using borane etherates, as indicated
by theoretical considerations.4 However, the process represented
by transition state II would amount to a nucleophilic substitution
reaction involving an endocyclic B-X bond as the formal leaving
group. There are no established precedents for such reactions
involving five- or six-center transition states, a consequence of
unfavorable geometry for the necessary orbital interactions.5
Therefore, reactions of isolable complexes I (X ) N, P) require
heating to dissociate the complex6 and take place by intermolecular
hydroboration via the free borane.6f
a Activation with 50 mol % iodine unless noted. b NMR assay. c Acti-
vation using 10 mol % iodine, 1 h at room temperature in CDCl3.
heterolysis of the B-I bond be necessary (path c), the resulting
trivalent borenium ion VI is expected to be a highly electrophlic
hydroborating reagent that operates in an SN1-like mode. The key
result of either mechanism is the formation of an olefin-borane π
complex VII that is configured for internal hydroboration via a
transition state having ion pair character.
To test the feasibility of this proposal, we opted to use readily
accessible homoallylic amine boranes. These complexes should be
easily activated by iodine according to literature precedents for
saturated analogues.7 Hydroboration would then occur by an
intramolecular pathway via a fused bicyclic or a bridged bicyclic
transition state, either of which is stereoelectronically feasible.8
Substrates 1a and 1b were complexed with 1.0 equiv of BH3‚
THF. Treatment of each complex with 50 mol % of iodine resulted
in rapid hydrogen evolution, presumably due to formation of an
iodoborane complex.7 After 30 min at room temperature, followed
by oxidation, major products 2a and 2b were obtained (Table 1,
entries 1 and 2, 10-11:1 ratio). A control experiment using 1a
and excess borane at room temperature gave a 2.4:1 ratio of 2a:
3a. Therefore, the regioselectivity of Table 1, entry 1, clearly
indicates an intramolecular pathway. A more demanding test for
internal direction utilized an amine containing a terminal double
bond (Table 1, entry 3). The results show that steric bias favoring
C-B bonding at the less hindered position is dominant in this case.
Amine 1d also displays lower regioselectivity (2:1), a finding that
is consistent with previous reports for the intermolecular hydrobo-
ration of styrenes as compared to simple alkenes.9,10
Scheme 1
The cyclic amine borane 4 undergoes facile iodine-promoted
hydroboration and was a useful substrate to verify that product
stereochemistry is consistent with a four-center hydroboration
pathway (Scheme 2). The amino alcohol 5, obtained after hydrobo-
ration and oxidation, is expected to display a trans relationship
between Ha and Hb, resulting from syn delivery of boron and
hydride to the olefin. NMR analysis was possible after benzoylation
to give 6, and J ) 9.5 Hz between Ha and Hb confirmed the
expected trans stereochemistry.
We have considered mechanistic alternatives for internal hy-
droboration that circumvent the problem of endocyclic leaving
group displacement (Scheme 1, paths b and c). Activating an amine
borane complex (X ) nitrogen) with iodine should generate an
intermediate IV that contains a reactive B-I bond.7 If the halogen
remains connected, a tethered olefin could undergo intramolecular
hydroboration by an SN2-like displacement of the exocyclic iodide
leaving group as shown by transition state V. Should initial
We considered the possibility that a catalytic amount of iodine
might be sufficient to promote hydroboration of homoallylic amine
9
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J. AM. CHEM. SOC. 2003, 125, 10502-10503
10.1021/ja034655m CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2
Table 2. TfOH-Promoted Internal Hydroboration of Homoallylic
Phosphines
entrya
substrate
yield (%)b
products
ratio
1
2
13a
13b
87
88
14a/15a
14b/15b
3:1
93:7
entries 3, 4). If one assumes that internal hydroboration occurs via
an alkene complex VII (X ) PPh2) and involves the usual four-
center transition state, then the phosphine boranes react with a
preference for fused, bicyclic transition states (five-center delivery
of boron to the nearest alkene carbon). In the nitrogen series,
bridged, bicyclic transition states (six-center delivery of boron to
the remote alkene carbon) are also significant, and this pathway
becomes dominant for the terminal alkene 1c (Table 1, entry 3).
Tentatively, the contrast with the phosphine boranes is attributed
to longer phosphorus versus nitrogen bonds, but leaving group
differences (triflate vs iodide) may also play a role.
In summary, the first examples of intramolecular hydroboration
starting from homoallylic amine or phosphine boranes are reported.
The process involves activation via incorporation of a leaving group
at boron, leading to a new mechanistic pathway for internal hydro-
boration. Pending further study, we suggest an ion pair π-complex
VII as the key species responsible for internal hydroboration.11
borane complexes (Scheme 2). This option was explored using
cyclic substrate 4. Treatment with 10 mol % of I2 at room
temperature resulted in complete consumption of olefin in less than
2 h, and the stable amine borane 9 (46%) was isolated after
chromatography. Alternatively, addition of 10% I2 followed by
oxidation provided the expected amino alcohol 5 in 87% yield.
While the details and efficiency of the catalytic cycle have yet to
be explored, the results show that iodoborane 7 (20 mol %, formed
in situ from 10 mol % I2) induces the conversion of at least 4
additional equiv of 4 to the cyclic isomer 9. Transfer of iodine
from the intermediate 8 to 4 is indicated by these observations. An
equally facile catalytic reaction occurred with 1a to give amino
alcohol products 2a and 3a (Table 1, entry 5). The intramolecular
process constitutes a new mechanism for catalytic hydroboration
from amine boranes.
Acknowledgment. This work was supported by the National
Science Foundation (phosphine boranes) and by the National
Institutes of Health (amine boranes).
Supporting Information Available: Experimental procedures and
characterization data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
Iodine-induced hydroboration starting from the cyclohexenyl
derivative 10 provides strong evidence for the intramolecular
pathway. Following oxidation, amino alcohols 11a, 12a, and
(tentatively) 12b were formed in a ratio of 10:3:1. The minor
component could not be purified, but the tentative assignment is
based on 1H NMR comparisons with the mixture of all four isomers
(1.2:1.2:1:1 11a:11b:12a:12b) obtained by reaction of 10 with
excess BH3‚THF. Clearly, 11a and 12a are formed by intramo-
lecular hydroboration. If the minor product is indeed 12b, then its
formation may be due to competing intermolecular hydroboration
by an unknown pathway.
The possibility of intramolecular hydroboration starting from
analogous phosphine boranes6e,f was also tested. Initial attempts to
activate 13a with iodine resulted in hydroboration as expected, but
the NMR spectrum revealed the formation of unknown byproducts.
An alternative method of activation proved more effective. Thus,
13a or 13b was treated with 1.1 equiv of triflic acid, resulting in
vigorous hydrogen evolution at ice bath temperatures. Warming to
room temperature and the usual oxidative workup resulted in the
oxidation of phosphorus as well as boron. This gave a mixture of
isomeric hydroxyalkylphosphine oxides 14 (major) and 15 (Table
2), while a control experiment from 13a (excess borane, room
temperature) afforded a typical 88:12 ratio in favor of 15a. The
triflic acid activation was also tested with the amine borane 1a and
was found to give results identical to those of Table 1, entry 1
(83% yield, 11:1 ratio of 2a:3a).
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