Stereoselective allylic C - H activation with tertiary alkylboranes: A new method for preparing cycloalkyl derivatives with three adjacent stereocenters

Article abstract of DOI:10.1002/(sici)1521-3773(19981002)37:18<2459::aid-anie2459>3.0.co;2-o

A regio- and stereoselective migration takes place under mild conditions for tertiary organoboranes obtained by hydroboration of tetrasubstituted cyclic alkenes. A subsequent amination proceeds with perfect control of the stereo-chemistry. The scheme shows an example of this for the reaction of bicyclo[4.3.0]-non-1(6)-ene (1) to 2 via intermediates 3 and 4. Compound 2 is formed as the single diastereomer in 69% yield.

Full text of DOI:10.1002/(sici)1521-3773(19981002)37:18<2459::aid-anie2459>3.0.co;2-o

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The hydroboration of tetrasubstituted cyclic alkenes produces tertiary
organoboranes, which undergo a stereoselective rearrangement to furnish
organoboranes bearing three adjacent stereocenters. These species can be
converted into a variety of products.
Further details
are given on the
following pages.
With bicyclic systems, a preferential migration in the direction of
the five-membered ring is observed.
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Stereoselective Allylic C ± H Activation with
Tertiary Alkylboranes: A New Method for
Preparing Cycloalkyl Derivatives with Three
Adjacent Stereocenters**
 Â
Scheme 2. Synthesis of 4a.
Frederic Lhermitte and Paul Knochel*
Dedicated to Professor Gernot Boche
on the occasion of his 60th birthday
The functionalization of unreactive carbon ± hydrogen
bonds is an active field of investigation.[1] Transition metal
complexes have been used with great success for selectively
activating C ± H bonds,[1, 2] and a few examples involving main
group organometallic compounds have been described.[3]
Herein, we report a highly stereoselective C ± H activation
of an allylic position that allows the construction of three
adjacent stereocarbon centers by making use of a rearrange-
ment of a tertiary alkylborane. Whereas most organoboranes
undergo rearrangements at elevated temperature,[4] it was
noticed by Rickborn and Wood[5] and Field and Galagher[6]
that cyclic tetrasubstituted alkenes undergo such a dyotropic
rearrangement[7] under much milder conditions. We found
that this approach allows a highly stereoselective conversion
of various cyclic or acyclic tetrasubstituted alkenes of type 1
into polyfunctional products of type 2 in a one-pot reaction
via the intermediate organoboranes 3 and 4 (Scheme 1).
Scheme 3. Synthesis of 6 ± 11.
of 4a with 30% H2O2 affords the cyclopentanol 6 in 92%
overall yield as a single stereoisomer. Treatment of 4a with
boron trichloride followed by benzyl azide[8] (258C, 1 h)
provides the amine 7 as one stereoisomer in 81% overall
yield. Transmetalation of 4a to the corresponding organozinc
compound[9] by treatment with iPr2Zn (2 equiv) and subse-
quent transformation to the zinc ± copper reagent[10] by
addition of CuCN ´ 2LiCl furnishesÐafter reaction with
electrophiles such as allyl bromide, benzoyl chloride, 2-
phenylethynyl bromide, or 1-bromo-2-trimethylsilylacetyl-
eneÐthe expected products 8 ± 11 with diastereomeric ex-
cesses of greater than 97% and in 40 ± 61% overall yield.
Extention of this rearrangement to other tetrasubstituted
alkenes has been examined (Scheme 4). Both 1,2-dimethylcy-
clopentene (1b) and the bicyclic alkene 1c undergo the
Scheme 1. Synthesis of 2 from 1 by hydroboration ( !3) and migration
( !4). n ˆ 1, 2.
Thus, 1,2-diphenylcyclopentene (1a) was smoothly hydro-
borated with BH3 ´ THF (THF, 508C, 3 h) to provide the
tertiary alkylborane 3a, which undergoes a stereoselective syn
migration leading to the less sterically hindered secondary
organoborane 4a (Scheme 2). The high stereochemical con-
trol is explained by assuming a dehydroboration of 3a to form
the alkene ± borane complex 5, which undergoes a second
hydroboration. Here, there can be no dissociation from the
alkene, as this would result in a decrease in stereoselectivity.[5, 6]
The alkylborane 4a was trapped with several electrophiles
with retention of stereochemistry (Scheme 3). Thus, oxidation
Scheme 4. Synthesis of 12 and 13.
[*] Prof. Dr. P. Knochel, Dr. F. Lhermitte
Fachbereich Chemie der Universität
Hans-Meerwein-Strasse, D-35032 Marburg (Germany)
Fax: (‡49)6421-28-21-89
stereoselective rearrangement. Amination of 1b and 1c
(1. BH3 ´ THF, 508C, 3 h; 2. BCl3, 258C, 3 h; 3. PhCH2N3,
258C, 1 h)[8] led to the desired stereoisomers 12 and 13 in 60 ±
69% overall yield.[11]
Interestingly, in the case of 1c the migration takes place
almost exclusively in the direction of the five-membered ring.
E-mail: knochel@ps1515.chemie.uni-marburg.de
[**] We thank the DFG (SFB 260, Leibniz program) and the Fonds der
Chemischen Industrie for financial support. F. L. thanks the Alexan-
der Von Humboldt Foundation for a fellowship. We thank BASF AG,
Bayer AG, and WITCO for the generous gift of chemicals.
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solution was heated at 508C for 3 h. The solvent and excess borane were
removed under vacuum, and the residue was treated with a solution of
iPr2Zn (0.8 mL, 2 equiv, 4 mmol, 5.0m) in ether at 258C for 4 h. After
removal of the solvent and excess of iPr2Zn under vacuum, the residue was
diluted with THF (10 mL). The black precipitate of zinc was removed by
filtration, and the filtrate was slowly treated at 908C with a solution of
CuCN ´ 2LiCl in THF (0.4 mL, 0.2 equiv, 1.0m) and after 15 min with allyl
bromide (6 mL, 3 equiv, 6 mmol, 1.0m) in THF. The reaction was allowed to
warm up to 258C and was quenched after 1 h with aq HCl (10 mL, 3.0m)
and extracted with ether. The crude product obtained after evaporation of
the solvent was purified by chromatography (pentane) to provide analyti-
cally pure 8 (320 mg, 1.2 mmol, 61% yield).
This may be due to the proper alignment of the adjacent C ± H
bond with the C ± B bond in the five-membered ring
facilitating the dehydroboration. In a six-membered ring,
there would be an angle of about 608 between the C ± H and
C ± B bonds; this alignment would require a higher energy of
activation.
With bicyclo[4.4.0]dec-1(6)-ene (1d) the hydroboration
must be carried out, as expected, at 708C in refluxing THF
(Scheme 5). In this case also, a highly stereoselective migra-
tion takes place despite the elevated temperature. After
Received: April 16, 1998 [Z11741IE]
German version: Angew. Chem. 1998, 110, 2597 ± 2599
Keywords: asymmetric synthesis
rearrangements ´ zinc
´
hydroborations
´
Scheme 5. Synthesis of 14.
[1] J. C. W. Lohrenz, H. Jacobsen, Angew. Chem. 1996, 108, 1403; Angew.
Chem. Int. Ed. Engl. 1996, 35, 1305, and references therein.
[2] B. A. Arndtsen, R. G. Bergmann, Science 1995, 270, 1970; L. D. Field,
A. V. George, B. A. Messerle, J. Chem. Soc. Chem. Commun. 1991,
1339; N. A. Williams, Y. Uchimaru, M. Tanaka, J. Chem. Soc. Chem.
Commun. 1995, 1129; F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani,
M. Sonoda, N. Chatani, S. Murai, Bull. Chem. Soc. Jpn. 1995, 68, 62;
Y.-G. Lim, Y. H. Kim, J.-B. Kang, J. Chem. Soc. Chem. Commun. 1994,
2267; P. J. Alaimo, B. A. Arndtsen, R. G. Bergman, J. Am. Chem. Soc.
1997, 119, 5269.
amination (1. BH3 ´ THF, 708C, 7 h; 2. BCl3, 258C, 3 h;
3. PhCH2N3, 258C, 1 h)[8] the bicyclic amine 14 was obtained
in 62% yield as a single stereoisomer.
A novel stereoselective borane rearrangement was found
upon use of 1,2-diphenylcyclobut-1-ene (1e; Scheme 6). After
initial hydroboration, cleavage of the cyclobutene ring
[3] L. Weber in Advances in Organometallic Chemistry, Vol. 41 (Eds.:
F. G. A. Stone, R. West), Academic Press, New York, 1997, pp. 1 ± 125.
[4] R. Köster, W. Siebert, Methoden Org. Chem. (Houben-Weyl), 4. ed.,
1952 ± , Vol. 13, part 3a, 1982, pp. 1 ± 908.
[5] S. E. Wood, B. Rickborn, J. Org. Chem. 1983, 48, 555.
[6] L. D. Field, S. P. Galagher, Tetrahedron Lett. 1985, 26, 6125.
[7] M. T. Reetz in Advances in Organometallic Chemistry, Vol. 16 (Eds.:
F. G. A. Stone, R. West), Academic Press, New York, 1977, pp. 1 ± 30.
[8] A. Suzuki, S. Ono, H. C. Brown, M. M. Midland, J. Am. Chem. Soc.
1971, 93, 4329; P.-Y. Chavant, F. Lhermitte, M. Vaultier, Synlett 1993,
519.
[9] L. Micouin, M. Oestreich, P. Knochel, Angew. Chem. 1997, 109, 274;
Angew. Chem. Int. Ed. Engl. 1997, 36, 245; C. Darcel. F. Flachsmann, P.
Knochel, Chem. Commun. 1998, 205.
Scheme 6. Synthesis of 16.
occured to provide the intermediate boracyclopentane 15.
After oxidation with H2O2 the meso-diol 16 was isolated in
90% yield as a pure diastereoisomer.
In summary, we have shown that the migration of tertiary
boranes constitutes a novel stereoselective method for
preparing cyclic and bicyclic rings. The rection corresponds
formally to an stereoselective activation of allylic C ± H bonds.
[10] P. Knochel, R. Singer, Chem. Rev. 1993, 93, 2117.
[11] The hydroboration of 1b provides, after oxidation with 30% H2O2,
the expected alcohol (80%) accompanied by the epimer at the
hydroxyl position (1 ± 2%) as well as tertiary alcohol (18%) that did
not undergo migration. However, by the amination procedure, only
the product resulting from the major isomer could be detected. The
boron ± zinc exchange of 4b obtained by the hydroboration of 1b
provides, after copper-catalyzed allylation, two epimeric allylated
products in the ratio 92:8 and in 51% yield upond isolation. This
shows that in this case the secondary cyclopentylzinc intermediate is
less configurationally stable.[9]
Experiment Section
Typical procedure for the amination: Preparation of (1R*,2R*,3R*)-N-
benzyl-2,3-dimethylcyclopentylamine (12): A BH3 ´ THF solution (3 mL,
1.5 equiv, 3 mmol, 1.0m) was slowly added to 1,2-dimethylcyclopentene
(1b; 192 mg, 2 mmol) in THF (10 mL) at 258C. After 10 min the resulting
solution was heated at 508C for 3 h. The solvent and excess of borane were
removed under vacuum, and the residue was diluted with CH2Cl2 (10 mL),
treated at 08C with a solution of BCl3 (8 mL, 4 equiv, 8 mmol, 1.0m) in
CH2Cl2, and stirred for 3 h at 258C. After removal of the solvent and excess
of BCl3 under vacuum, the residue was diluted with CH2Cl2 (10 mL) and
treated at 08C with a solution of benzyl azide (2.4 mL, 1.2 equiv, 1.0m) in
CH2Cl2. After 1 h at 258C the reaction was quenched with aq NaOH
(10 mL, 3.0m), extracted with ether, and dried (MgSO4). The crude residue
was purified as the hydrochloride by addition of a solution of dry HCl in
ether. Analytically pure 12 ´ HCl was obtained after filtration (287 mg,
1.2 mmol, 60% yield).
Typical procedure for the allylation: Preparation of (1S*,2S*,3S*)-1-allyl-
2,3-diphenylcyclopentane (8): A BH3 ´ THF solution (3 mL, 1.5 equiv,
3 mmol, 1.0m) was slowly added to 1,2-diphenylcyclopentene (1a;
440 mg, 2 mmol) in THF (10 mL) at 258C. After 10 min the resulting
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