Highly regio- and stereoselective thermal migration of organoboranes in acyclic molecules [7]

Full text of DOI:10.1021/ja001283y

10218
J. Am. Chem. Soc. 2000, 122, 10218-10219
Scheme 1
Highly Regio- and Stereoselective Thermal Migration
of Organoboranes in Acyclic Molecules
Lars O. Bromm, Hamid Laaziri, Fre´de´ric Lhermitte,
Klaus Harms, and Paul Knochel*
Department of Chemistry, Ludwig-Maximilians-UniVersita¨t
Butenandtstrasse 5-13, D-81377 Mu¨nchen, Germany
ReceiVed April 13, 2000
The stereoselective setup of adjacent chiral centers in acyclic
molecules is a challenging problem.1 Herein, we wish to report a
new approach allowing the regio and stereoselective control of
up to three chiral centers using a new stereoselective migration
of organoboranes. In the case of organoboranes derived from
disubstituted olefins by hydroboration, the thermal isomerization
is known to proceed at elevated temperature (100-160 °C).2,3
However, in the case of cyclic4,5 and acyclic6 tetrasubstituted
olefins the resulting organoboranes undergo a thermal migration
under far milder conditions (50 °C). For acyclic tetrasubstituted
olefins with methyl groups, stereoselective migrations were
observed.6 Remote C-H activation leading to boracycles (five-
and six-membered rings) has also been shown to occur with high
stereoselectivity.6
Scheme 2
We have now found that this rearrangement allows a new
preparation of more elaborated acyclic molecules with control
of the relative stereochemistry of up to three adjacent centers as
well as an excellent regioselectivity of the rearrangement. The
migration toward higher alkyl substituents is much faster than
that toward methyl groups. If the alkyl substituent is bearing
diastereotopic hydrogen atoms, the migration will show high
diastereoselectivity. Thus, the hydroboration of tetrasubstituted
olefins of type 1 affords first the hydroboration product 2 which
undergoes a highly stereoselective thermal rearrangement at 50
°C to 60 °C leading to diastereomer 3a and not 3b (Scheme 1).
The hydroboration of 1,3-diphenyl-2-ethyl-1-butene (4)7 with
BH3 ‚ THF furnishes after heating at 50 °C for 4 h and subse-
quent oxidation with H2O2/NaOH the alcohol 5a as only one
diastereoisomer in 87% isolated yield.8 The allylation of the
intermediate organoborane 6 [(i) i-Pr2Zn, THF, room temperature;
(ii) CuCN ‚ 2 LiCl (20 mol %), -78 °C, allyl bromide] gives the
diastereomerically pure product 5b (Scheme 2).9 This stereo-
selectivity can be best explained by assuming that the primary
hydroboration product 7 undergoes a preferential dehydroboration
with the adjacent Ha (and not Hb) resulting in the formation of
the most stable olefin-borane complex 8 having the methyl group
trans to the most bulky substituent of the double bond.10 Although
the dissociation of 8 has no stereochemical consequences, this
type of borane-olefin complexes is a key intermediate to explain
the stereoselectivity observed for 14 and 19 (Schemes 4 and 5).
The reaction also shows a very high regioselectivity. The
unsymmetrical olefin 1,1-diphenyl-2-methyl-1-butene7 (9) pro-
vides after hydroboration and thermal rearrangement (50 °C, 4 h)
only the rearrangement products 10a and 10b where the boron
migration has proceeded only in the direction of the ethyl group.11
This regioselectivity can again be explained by the higher stability
of the intermediate olefin-borane complex 11a compared to 11b
and 11c (Scheme 3). In this reaction also only one diastereoiso-
meric organoborane 12 is formed. Subsequently, after oxidation
with H2O2/NaOH the diastereomerically pure alcohol (10a; 87%)
is obtained. After amination [(i) BCl3; (ii) BnN3] the benzylamine
10b (>99.9% one diastereoisomer, 83%) is isolated.12
The thermal rearrangement of acyclic organoboranes allows
the preparation of diastereomerically defined molecules having
three adjacent stereocenters. Thus, the reaction of (Z)-3,4-
diphenyl-3-hexene7 (13a) with BH3 ‚ THF, thermal rearrange-
ment (65 °C, 12 h) and subsequent allylation furnishes, via the
intermediate secondary organoborane (14a),13 the allylated product
15a with an excellent diastereoselectivity (>97:3) in 53% yield,
showing that both the intermediate organozinc compound and
(9) Typical procedure for a transmetalation to the zinc organometallic
and allylation. To a solution of 2-ethyl-1,1-diphenyl-1-butene (4) (709 mg,
3.0 mmol) in THF (25 mL) at 25 °C was added BH3‚THF (9 mL, 9 mmol,
1 M in THF). The resulting solution was stirred for 10 min at 25 °C and for
4 h at 50 °C. After the solution was cooled to 0 °C, the solvent and an excess
of borane were removed under vacuum (0.1 mmHg, 60 min). i-Pr2Zn (2.4
mL, 6 mmol, 2 equiv, 2.5 M in THF) was added at 25 °C. After change of
color to dark gray (2 h), stirring was continued for 45 min. The excess of
i-Pr2Zn was removed under vacuum at 0 °C and the residue was diluted with
THF (25 mL). The resulting mixture was cooled to -78 °C and a solution of
CuCN‚2 LiCl (0.4 mL, 0.2 equiv, 1 M in THF) was slowly added. Stirring
at -78 °C was continued for 15 min. Then allyl bromide (0.8 mL, 9 mmol,
3 equiv) was added. The reaction mixture was warmed to 25 °C, stirred for
1 h, and quenched with 3 M aqueous HCl (25 mL). After typical workup, the
residue obtained after evaporation of the solvents was purified by flash
chromatography (pentane) affording (4R*,5S*)-5-benzhydryl-4-methyl-1-
heptene (5b) (516 mg, 62%) as a clear oil.
(10) The nature of the intermediates of type 8 is currently being studied
using theoretical calculations.
(11) The relative stereochemistry of the borane 12 has been determined
by forming the alcohol 10a and comparing its 1H NMR with published
data: (a) Zayas, J.; Platz, M. S. J. Am. Chem. Soc. 1985, 107, 7065. (b)
Dinnocenzo, J. P.; Zuilhof, H.; Lieberman, D. R.; Simpson, T. R.; McKechney,
M. W. J. Am. Chem. Soc. 1997, 119, 994.
(1) Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis; VCH:
Weinheim, 1996.
(2) (a) Brown, H. C.; Zweifel, G. J. Am. Chem. Soc. 1966, 88, 1433. (b)
Brown, H. C.; Bhatt, M. V. J. Am. Chem. Soc. 1966, 88, 1433.
(3) R. Ko¨ster, W. Siebert, Methoden der Organischen Chemie (Houben-
Weyl), 4th ed.; Thieme: Stuttgart, 1952; 1982; Vol. 13, part 3a, pp 1-908.
(4) (a) Wood, S. E.; Rickborn, B. J. Org. Chem. 1983, 48, 555. (b) Field,
L. D.; Galagher, S. P. Tetrahedron Lett. 1985, 26, 6125.
(5) Lhermitte, F.; Knochel, P. Angew. Chem. 1998, 110, 2597; Angew.
Chem., Int. Ed. 1998, 37, 2460.
(6) (a) Laaziri, H.; Bromm, L. O.; Lhermitte, F.; Gschwind, R. M.; Knochel,
P. J. Am. Chem. Soc. 1999, 121, 6940. (b) Unpublished results, Munich 2000.
(7) All alkenes were prepared using McMurry reactions: Leimner, J.;
Weyerstahl, P. Chem. Ber. 1982, 115, 3697
(8) The relative stereochemistry of the borane 6 has been established by
conversion of alcohol 5a to the 3,5-dinitrobenzoate and X-ray analysis of the
obtained crystals.
10.1021/ja001283y CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/03/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 41, 2000 10219
Scheme 3
Scheme 5
Scheme 4
Scheme 6
organocopper reagent have a high configurational stability.14 By
starting with the corresponding (E)-3,4-diphenyl-3-hexene (13b),
the intermediate organoborane 14b is formed and after the same
allylation procedure, the diastereomerically pure product 15b is
obtained (Scheme 4).
in 69% yield (d.r. ) 96:4). It should be noticed that the initial
hydroboration is not regioselective, but that a rapid isomerization
seems to occur between the two regioisomers under the reaction
conditions. Only the product derived from regioisomer 18 is
observed since migration to ethyl or higher alkyl groups has been
found to be substantially faster.
A diastereoselective multiple migration has been observed in
the case of 1,1-diphenyl-2,3-dimethyl-1-butene (20).7 After oxida-
tive workup of the organoborane 21 (H2O2/NaOH) the diastereo-
merically pure alcohol 22 was isolated.16 However, for 1,1-
diphenyl-2,4-dimethyl-1-pentene7 (23) the migration led to the
intermediate organoborane 24 and after oxidative workup (H2O2/
NaOH) to the alcohols 25 as a 1:1 mixture of diastereoisomers
(Scheme 6).
By hydroboration of the unsymmetrical Z-olefin7 16 a prefer-
ential migration of the tertiary organoborane in compound 18
toward the ethyl group is observed. The resulting secondary
organoborane 1915 is converted to the diastereomerically pure
amine 17a after the usual amination procedure in 79% yield.
Similarly, the treatment of the organoborane 19 with i-Pr2Zn
followed by CuCN ‚ 2 LiCl and 1-bromohexyne provides the
alkyne 17b in 66% yield as one diastereoisomer (Scheme 5). By
the analogous reaction with PhCOCl, the ketone 17c is obtained
(12) Typical procedure for the amination. To a solution of 2-methyl-
1,1-diphenyl-1-butene (9) (667 mg, 3 mmol) in THF (25 mL) at 25 °C was
added BH3‚THF (9.0 mL, 9 mmol, 1 M in THF). The resulting solution was
stirred at 25 °C for 10 min and at 50 °C for 4 h. After the solution was cooled
to 0 °C, the solvent and the excess of borane were removed under vacuum
(0.1 mmHg, 60 min). The residue was dissolved in CH2Cl2 (25 mL) and BCl3
(12 mL, 4 mmol, 1 M in CH2Cl2) was added at 0 °C. The mixture was warmed
to 25 °C and was stirred for 3 h. The solvent and an excess of BCl3 were
removed under vacuum (0 °C, 0.1 mmHg, 60 min). The residue was dissolved
in CH2Cl2 (25 mL) and benzyl azide (479 mg, 3.6 mmol, 1.2 equiv) was
added at 0 °C. The solution was warmed to 25 °C and stirred for 1 h. The
reaction mixture was quenched with 3 M aqueous NaOH (25 mL) at 0 °C
and worked up as usual. Flash-chromatographic purification of the residue
(pentane:ether 2:1) afforded N-benzyl[(1R*,2S*)-1,2-dimethyl-3,3-diphenyl-
propyl]amine (10b) (821 mg, 83%) as a clear oil.
(13) The relative stereochemistry of 14a has been established by X-ray
analysis of the corresponding alcohol (oxidative workup: NaOH, H2O2).
(14) (a) Darcel, C.; Flachsmann, F.; Knochel, P. J. Chem. Soc., Chem.
Commun. 1998, 205. (b) Boudier, A.; Flachsmann, F.; Knochel, P. Synlett
1998, 1438. (c) Boudier, A.; Knochel, P. Tetrahedron Lett. 1999, 40, 687.
(15) The relative stereochemistry of 19 has been established by X-ray
analysis of the corresponding alcohol (oxidative workup: NaOH, H2O2).
In summary, we have described that organoboranes undergo
highly regio- and stereoselective thermal migrations affording
acyclic molecules with relative stereocontrol of three adjacents
carbon centers.
Acknowledgment. Dedicated to Henri B. Kagan on the occasion of
his 70th birthday. We thank the DFG (SFB 260, Leibniz-program) and
the Fonds der Chemischen Industrie for generous support. We thank the
BASF AG, BAYER AG, Chemetall GmbH and PPG-SIPSY SA (France)
for generous gift of chemicals.
Supporting Information Available: Spectral data for compounds
5, 10, 15, 17, 22, and 25 and X-ray data (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
JA001283Y
(16) The relative stereochemistry of 21 has been established by X-ray
analysis of the alcohol 22.