Catalytic asymmetric hydroboration-amination

Article abstract of DOI:10.1039/a606918e

A one-pot asymmetric synthesis of primary amines from vinylarenes via catalytic hydroboration is described.

Full text of DOI:10.1039/a606918e

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Catalytic asymmetric hydroboration–amination
Elena Fernandez, Mark W. Hooper, Frances I. Knight and John M. Brown*
Dyson Perrins Laboratory, South Parks Road, Oxford, UK OX1 3QY
A one-pot asymmetric synthesis of primary amines from
vinylarenes via catalytic hydroboration is described.
under standard conditions (H2O2, NaOH) demonstrated that the
configurational integrity of the stereogenic centre had been
maintained. At this point we became aware of an early report
that primary alkylcatecholboronates react with 2 equiv. of
RMgBr by complete displacement of the catechol residue
giving the mixed trialkylborane.9 In accord with this, complete
displacement of catecholate without precipitation was observed
when the reaction between MeMgCl and borane 1 was carried
Despite considerable efforts to find alternatives, catecholborane
is the most useful borane and rhodium complexes are the most
useful catalysts in catalytic hydroboration.1 Synthetic applica-
tion of the resulting catecholborane adducts is however limited
to oxidation with basic H2O2, and hence the asymmetric
version2 is in turn limited to the synthesis of secondary alcohols,
for which many excellent alternative routes are already
available.3 Given the wealth of functional group transforma-
tions that can be performed with alkylboranes,4 there is an
incentive for developing further synthetic outlets for the
catalysed case. Our initial efforts were directed to the reaction of
isolated 1-phenylethylcatecholboronates† with electrophilic
aminating agents such as ClMgN(Me)OSiMe3, and although
some success was achieved in controlling enantioselectivity, the
chemoselectivity for secondary amine formation over alcohol
was moderate.5
In considering a direct route from alkylcatecholboronates to
amines, we were guided by prior results from Brown’s research
in which alkylboronates, which do not react directly with the
standard aminating agent H2NOSO3H,6 were converted by a
practical, albeit multistep, route into amines via the more
reactive dialkylborinate esters. In contrast, excess R2Zn is
reported to effect clean transmetallation of a range of dialkylvi-
nylboranes,7a trialkylboranes,7b alkylboronates and alkyldithio-
boronates,7c thus providing a route to less accessible alkenyl
and alkylzinc compounds. Reaction intermediates have not been
reported, although it is likely that the trialkylborane is an
intermediate in boronate ester transmetallations (vide infra).
Our own initial experiments were conducted in toluene
solution by reacting an isolated sample of catecholboronate
ester 1 with 1 equiv. of Et2Zn; we were delighted to observe that
a clean and quantitative displacement took place, resulting in
the transfer of two ethyl groups to boron to form 2 and removal
of the Zn from the reaction medium as an insoluble catecholate.8
The resulting borane was characterized by 1H NMR [dH(C7D8)
1.20 (q), 0.95(t)] and MS (m/z 205). Oxidation of the borane 2
Table 1 Hydroboration–amination of vinylarenesa
Regio-
select-
ivity
(%)b
Iso-
lated
yield
(%)
Ee
(%)c
Reactant
Product
NH2
Me
> 98
> 98
> 98
56
54
50
98
87
90
MeO
MeO
6
7
5
8
NH2
Me
NH2
Me
Et
9
10
12
NH2
> 98d
61
51
64
62
77
97
89
90
11
NH2
96
13
15
17
14
16
18
NH2
O
98e
92f
O
O
R
R
B
B
NH2
Me
O
NH2
Me
Me
Me
MeO
MeO
MeO
1
5
2 R = Et
3 R = Me
a
Hydroboration–amination experiments as per typical protocol (see
b
c
footnote ‡). Minor component is regioisomeric primary amine. Ees of
amines or their acetamides were analysed by GC using a 25 m CHIRAL-
DEX bonded silica column at 140–150 °C, achieving baseline separation in
all cases. From isolated organoborane. Not previously obtained in
enantiomerically enriched form, [a]D 255.21 (c 0.36, CHCl3) for
acetylamino derivative; configuration assigned by comparison with
–
CF3SO3
d
e
+
Rh
N
23
P
Ph2
f
(S)-chroman-4-ol (ref. 16) formed by hydroboration–oxidation. Analysis
by 1H NMR using Eu(tfc)3.
4
Chem. Commun., 1997
173

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stirring, then left for 1 h. MeMgCl (3 m in thf, 333 ml, 1.0 mmol) was added
and the solution stirred for 30 min. The reactant solution was added to pre-
dried H2NOSO3H (169 mg, 1.5 mmol), with 0.7 ml of thf or diglyme, and
stirred under argon for ca. 15 h. HCl (1 m, 2 ml) was added, and the mixture
poured into H2O (4 ml). The aqueous layer was extracted with Et2O (3 3 20
ml) and then was made strongly alkaline with NaOH (1 m, 3 ml). The
mixture was then extracted with Et2O (3 3 20 ml). The Et2O extracts were
combined and dried with magnesium sulfate, and the solvent removed in
vacuo.
out in thf solution, the only product being 3 [dC 13.0 (JBC 82
Hz)].10 These displacement reactions were also shown to be
occur with other arylalkylboronates prepared by catalytic
hydroboration of vinylarenes with catecholborane.
With a clean route to enantiomerically enriched trialkyl-
boranes in hand, attention was then turned to developing a
synthetically useful amination procedure. It is known that in
aminations with H2NOSO3H, methyl is a poor migrating
group,11 and a protocol was developed accordingly. It was
established in an initial experiment that successive addition of 2
equiv. of MeMgCl and 3 equiv. of H2NOSO3H to an isolated
sample of borane 1 (86% ee) in thf gave amine 5 in 83% ee and
65% yield. Catalytic hydroboration was then carried out for
several vinylarenes in thf solution at ambient temperature,
employing the rhodium complex of (S)-quinap (4) in the manner
previously described.12 On completion of the hydroboration
reaction, 2 equiv. of MeMgCl (3 m solution in thf) were added
followed after 30 min by 3 equiv. of H2NOSO3H. After stirring
for 12 h the amine was isolated either directly, or as its
acetamide (MeCOCl) and the ee analysed as described in
Table 1. As far as can be determined, the ee values reflect the
enantioselectivity of the catalytic hydroboration step, since
H2O2–OH2 oxidation at the trialkylborane stage provides a
secondary alcohol whose enantiomeric purity is the same or
slightly lower than that of the primary amine (within experi-
mental error). For the acyclic side-chain amines derived from
alkenes 6, 7, 9 and 17, the results follow quite closely those
observed previously in hydroboration–oxidation, but superior
results have been obtained for the slower-reacting dihydro-
naphthalene 13 and 4-chromene 15 by very careful attention to
catalyst purity and freshness, although indene 11 was somewhat
inferior. A one-stage asymmetric synthesis of 1-aminotetralin
14 in 97% ee is of potential practical significance.
In summary, we have developed a method for the catalytic
asymmetric synthesis of primary amines from alkenes that
complements existing methods, which are most commonly
based on imine13 or enamide reduction,14 or allylic alkylation
procedures.15 The activation of catecholborane adducts offers
the possibility of further extending the range of catalytic
hydroboration (e.g. to Suzuki couplings and other C–C bond
forming reactions) and provides an incentive for us to improve
the scope and selectivity of the catalytic reaction itself.
We thank the University of Tarragona for leave (to E. F.) and
Johnson-Matthey for the loan of rhodium salts. F. I. K. was
supported through a Studentship from LINK Asymmetric
Synthesis, and we warmly thank Dr A. J. Blacker (Zeneca) for
his help and interest. Dr H. Doucet made helpful contribu-
tions.
References
1 S. Pereira and M. Srebnik, Organometallics, 1995, 14, 3127; E. A.
Bijpost, R. Duchateau and J. H. Teuben, J. Mol. Catal., 1995, 95, 121;
X. M. He and J. F. Hartwig, J. Am. Chem. Soc., 1996, 118, 1696.
2 K. Burgess and M. J. Ohlmeyer, Chem. Rev., 1991, 91, 1089; J. M. Valk,
G. A. Whitlock, T. P. Layzell and J. M. Brown, Tetrahedron:
Asymmetry, 1995, 6, 2593.
3 E.g. B. Weber and D. Seebach, Tetrahedron, 1994, 50, 6117; A. Fujii,
S. Hashiguchi, N. Uematsu, T. Ikariya and R. Noyori, J. Am. Chem.
Soc., 1996, 118, 2521; A. W. Douglas, D. M. Tschaen, R. A. Reamer
and Y. J. Shi, Tetrahedron: Asymmetry, 1996, 7, 1303.
4 A. Pelter, K. Smith and H. C. Brown, Borane Reagents, Academic
Press, New York, 1988.
5 F. I. Knight, A. J. Blacker, J. M. Brown, D. Lazzari and A. Ricci,
unpublished results.
6 H. C. Brown, K. W. Kim, T. E. Cole and B. Singaram, J. Am. Chem.
Soc., 1986, 108, 6761; H. C. Brown, M. V. Rangaishenvi and
B. Singaram, J. Org. Chem., 1991, 56, 3286.
7 (a) W. Oppolzer and R. N. Radinov, Helv. Chim. Acta, 1992, 75, 170;
M. Srebnik, Tetrahedron Lett., 1991, 32, 2449; (b) F. Langer,
A. Devasagayaraj, P. Y. Chavant and P. Knochel, Synlett, 1994, 410;
H. Eick and P. Knochel, Angew. Chem., Int. Ed. Engl., 1996, 35, 218; (c)
F. Langer, J. Waas and P. Knochel, Tetrahedron Lett., 1993, 34,
5261.
8 For the X-ray structure of a Zn catecholate, see H. E. Mabrouk,
D. G. Tuck and M. A. Khan, Inorg. Chim. Acta, 1987, 129, 75.
9 S. Cabiddu, A. Maccioni and M. Secci, Gazz. Chim. Ital., 1972, 102,
555; this work has occasionally been cited, but never been extended
despite its obvious usefulness.
10 Dr K. K. Hii, personal communication.
11 B. Carboni and M. Vaultier, Bull. Soc. Chim. Fr., 1995, 132, 1003.
12 J. M. Brown, D. I. Hulmes and T. P. Layzell, J. Chem. Soc., Chem.
Commun., 1993, 1673.
13 N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya and R. Noyori, J. Am.
Chem. Soc., 1996, 118, 4916; C. A. Willoughby and S. L. Buchwald,
J. Am. Chem. Soc., 1994, 116, 8952.
14 M. J. Burk, Y. M. Wang and J. R. Lee, J. Am. Chem. Soc., 1996, 118,
5142.
15 P. Von Matt, O. Loiseleur, G. Koch, A. Pfaltz, C. Lefeber, T. Feucht and
G. Helmchen, Tetrahedron: Asymmetry, 1994, 5, 573; A. Togni,
U. Burckhardt, V. Gramlich, P. S. Pregosin and R. Salzmann, J. Am.
Chem. Soc., 1996, 118, 1031; H. Kubota and K. Koga, Heterocycles,
1996, 42, 543.
Footnote
16 H. L. Holland, T. S. Manoharan and F. Schweizer, Tetrahedron:
Asymmetry, 1991, 2, 335.
† IUPAC name: ortho-phenylene 1-phenylethylboronate.
‡ Freshly prepared complex 4 (4.0 mg, 0.005 mmol, 1.0 mol%) and thf (0.5
ml) were placed in a vial under argon with the alkene (0.5 mmol). Freshly
distilled catecholborane (53.3 ml, 59.5 mg, 0.5 mmol) was added with
Received, 9th October 1996; Com. 6/06918E
174
Chem. Commun., 1997