Modular asymmetric synthesis of 1,2-diols by single-pot allene diboration/hydroboration/cross-coupling

Article abstract of DOI:10.1021/ol0616891

Chiral allyl vinyl boronates are generated by catalytic enantioselective diboration of prochiral allenes. They may then be reacted, in situ, with a hydroborating reagent to form a novel triboron intermediate. The least hindered and most reactive C-B bond

Full text of DOI:10.1021/ol0616891

ORGANIC
LETTERS
2006
Vol. 8, No. 20
4557-4559
Modular Asymmetric Synthesis of
1,2-Diols by Single-Pot Allene
Diboration/Hydroboration/Cross-Coupling
Nicholas F. Pelz and James P. Morken*
Department of Chemistry, The UniVersity of North Carolina at Chapel Hill,
Chapel Hill, North Carolina 27599-3290
morken@unc.edu
Received July 9, 2006
ABSTRACT
Chiral allyl vinyl boronates are generated by catalytic enantioselective diboration of prochiral allenes. They may then be reacted, in situ, with
a hydroborating reagent to form a novel triboron intermediate. The least hindered and most reactive C B bond then participates in cross-
coupling wherein the coupling is brought about by the same catalyst as that which catalyzed the diboration reaction. The remaining C
bonds are then oxidized in the reaction workup, thereby allowing for the modular synthesis of chiral diols in a concise single-pot fashion.
−
−B
Single-pot reaction sequences that accomplish fragment
couplings are important tools for the assembly of organic
molecules. Those that give rise to new chirality centers, in
a stereoselective fashion, offer an added advantage. As part
of a program to engineer new reaction sequences with the
abovementioned characteristics, we have developed the
enantioselective diboration of simple allene substrates (1f2,
Scheme 1) with the notion that the C-B linkages might be
employed in an array of useful bond constructions.1 For
instance, after the diboration reaction, the intermediate
organodiboron 2 may directly engage in stereoselective
carbonyl or imine allylation reactions.2 In this report, we
describe an alternate single-pot C-C bond-forming sequence
that arises from sequential allene diboration, hydroboration,
and Suzuki-Miyaura cross-coupling reactions.3,4 This se-
quence proceeds through an unusual organotriboron inter-
mediate (4) and, upon oxidative workup, provides optically
enriched 1,2-diols. Of note, many of the products of this
Scheme 1
(1) (a) Pelz, N. F.; Woodward, A. R.; Burks, H. E.; Sieber, J. D.; Morken,
J. P. J. Am. Chem. Soc. 2004, 126, 16328. For nonenantioselective processes,
see: (b) Ishiyama, T.; Kitano, T.; Miyaura, N. Tetrahedron Lett. 1998, 39,
2357. (c) Fang, F.-Y.; Cheng, C.-H. J. Am. Chem. Soc. 2001, 123, 761.
For borylsilation and borylstannation, see: (d) Suginome, M.; Ohmori, Y.;
Ito, Y. J. Organomet. Chem. 2000, 611, 403. (e) Onozawa, S.; Hatanaka,
Y.; Tanaka, M. Chem. Commun. 1999, 1863. For an asymmetric silaboration
with a chiral silylboron, see: (f) Suginome, M.; Ohmura, T.; Miyake, Y.;
Mitani, S.; Ito, Y.; Murakami, M. J. Am. Chem. Soc. 2003, 125, 11174.
10.1021/ol0616891 CCC: $33.50
© 2006 American Chemical Society
Published on Web 09/06/2006

sequence are difficult to access from alternate catalytic
asymmetric reactions.
of the electron-rich allylic C-B bond with the reacting
π-system. Similar to the “H-inside” preference in the Still5a
and Houk9 models for hydroboration of chiral allylic alco-
hols, the syn diastereomer in Scheme 1 may arise from Model
A. Support for this hypothesis arises from the hydrobora-
tion with borane as the reductant, which proceeds with 2:1
syn/anti stereoselection (data not shown). Arguably, with the
smaller borane, the benzyl group may adopt the inside
position (i.e., Model B) thereby alleviating an A(1,2)
interaction between the Bn and B(pin) groups that is present
in Model A. Also consistent with this model is the observa-
tion that stereoselection is diminished as the size of the allene
substituent is enhanced (vide infra). This outcome likely
arises from an enhanced A(1,2) interaction in Model A that
can be alleviated by adopting Model C.
Effective deployment of the catalytic diboration/hydro-
boration/cross-coupling sequence for stereoselective organic
synthesis requires that hydroboration of the allene diboration
product (2, Scheme 1) proceeds in a stereoselective fashion
and provides a primary organoboron (4) that is able to
participate in cross-coupling reactions. Diastereoselective
hydroboration of R-chiral 1,1-disubstituted olefins5 is well
studied, as is the hydroboration of chiral allylsilanes.6
However, the hydroboration of unsaturated organoboron
compounds is less studied, with only a few investigations
on the reaction of vinylborons7 and allylborons.8 To assess
the stereoselection in hydroboration of allene diboration
products, experiments were conducted on purified racemic
5 (Scheme 2). As can be observed in Scheme 2, when
B-Alkyl Suzuki cross-coupling reactions often employ
9-BBN-derived organoboranes and are catalyzed by pal-
ladium complexes in conjunction with phosphorus-based
ligands.4,10 Accordingly, the sequential diboration/hydro-
boration/cross-coupling reaction was examined. Noting that
the characteristics of the catalyst for the diboration are similar
to those of common cross-coupling catalysts, the reaction
sequence was attempted without introduction of an additional
catalyst for the cross-coupling, beyond that which is present
from the diboration process. In the event, catalytic diboration
of 1,2-tridecadiene was accomplished with 2.5 mol % of
Pd2(dba)3 and 6 mol % of (R,R)-3 in toluene solvent. After
12 h of reaction, 9-BBN was added directly to the reaction
mixture which was stirred for 14 h. Then, simply adding
iodobenzene and 2 equiv of cesium carbonate, without an
additional palladium catalyst or ligand, was sufficient to
bring about cross-coupling in good yield and diastereose-
lection and with excellent control of the absolute configu-
ration. This “recycling” of the original palladium diboration
catalyst for the Suzuki cross-coupling thereby reduces both
reaction cost and generation of palladium waste. The de-
scribed reaction sequence was examined with the allenes
Scheme 2
compound 5 was subjected to hydroboration with 9-BBN,
followed by oxidation and acylation (to ease manipulation
and analysis), the resulting triacetate was obtained in good
yield and diastereoselection. Similar to the stereoelectronic
effect proposed by Fleming6 to explain the stereochemical
favoritism in the hydroboration of allylic silanes, the origin
of diastereoselectivity in Scheme 2 can be rationalized
beginning with a transition structure that involves alignment
Table 1. Single-Pot Diboration/Hydroboration/Suzuki
Coupling/Oxidationa
(2) (a) Woodward, A. R.; Burks, H. E.; Chan, L. M.; Morken, J. P. Org.
Lett. 2005, 7, 5505. (b) Sieber, J. D.; Morken, J. P. J. Am. Chem. Soc.
2006, 128, 74.
(3) For a related sequential asymmetric alkene diboration/cross-coupling,
see: Miller, S. P.; Morgan, J. B.; Nepveux, F. J.; Morken, J. P. Org. Lett.
2004, 6, 131.
(4) For many examples of fragment couplings based on B-alkyl Suzuki
reactions, see: Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew.
Chem., Int. Ed. 2001, 40, 4544.
(5) (a) Still, W. C.; Barrish, J. C. J. Am. Chem. Soc. 1983, 105, 2487.
(b) McGarvey, G. J.; Bajwa, J. S. Tetrahedron Lett. 1985, 26, 6297. (c)
Evans, D. A.; Bartroli, A.; Godel, T. Tetrahedron Lett. 1982, 23, 4577. (d)
Birtwistle, D. H.; Brown, J. M.; Foxton, M. W. Tetrahedron Lett. 1986,
27, 4367. (e) Midland, M. M.; Kwon, Y. C. J. Am. Chem. Soc. 1983, 105,
3725.
(6) (a) Fleming, I.; Lawrence, N. J. J. Chem. Soc., Perkin Trans. 1 1992,
3309. (b) Fleming, I.; Lawrence, N. J. Tetrahedron Lett. 1988, 29, 2077.
(c) Fleming, I.; Lawrence, N. J. Tetrahedron Lett. 1988, 29, 2073.
(7) (a) Pasto, D. J.; Chow, J.; Arora, S. K. Tetrahedron Lett. 1967, 723.
(b) Aronovich, P. M.; Bogdanov, V. S.; Mikhailov, B. M. IzV. Akad. Nauk.
SSSR, Ser. Khim. 1969, 362. (c) Matteson, D. S.; Bowie, R. A.; Srivasta, G
J. Organomet. Chem. 1969, 16, 33. (d) Pasto, D. J.; Chow, J.; Arora, S. K.
Tetrahedron 1969, 25, 1557. (e) Wiesauer, C.; Weissensteiner, W.
Tetrahedron: Asymmetry 1996, 7, 5.
a Conditions: 2.5 mol % of Pd2(dba)3, 6 mol % of ligand, 1.2 equiv of
B2(pin)2, PhMe, room temp, 14 h; then 1.2 equiv of 9-BBN, 9 h; then 2.25
equiv of Cs2CO3, 2.25 equiv of PhI, 80 °C, 12 h; then oxidative workup
with H2O2/NaOH, 8 h.
(8) Mikhailov, B. M.; Pozdnev, V. F.; Kiselev Dokl. Akad. Nauk SSR
1963, 151, 577.
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Org. Lett., Vol. 8, No. 20, 2006

depicted in Table 1 and generally occurred in moderate yields
and with excellent enantioselection. The diastereoselection
was substrate dependent and varied in a manner that was
predictable based on the models in Scheme 2.
Other electrophiles were examined in the sequential
diboration/hydroboration/cross-coupling sequence, and these
are depicted in Table 2. In addition to iodobenzene which
the reaction product. These compounds might be difficult
to access in a regioselective fashion with dihydroxylation-
based approaches, and this highlights some attractive features
of this approach. As anticipated, vinyl triflates also par-
ticipate in the multistep sequence although, like the reac-
tion of vinyl halides, the yield appears diminished compared
to the reaction with aryl electrophiles. Surprisingly, even
the sterically encumbered (Z)-2-bromo-2-butene underwent
Suzuki cross-coupling and provided the chiral trisubstituted
alkene with good levels of diastereoselection. As expected,
the enantioselection was relatively constant and high, regard-
less of the nature of the electrophilic substrate employed in
the cross-coupling.
Table 2. Synthesis of Homoallylic/Bishomoallylic Diolsa
In summary, we have described an operationally simple,
single-pot diboration/hydroboration/Suzuki cross-coupling/
oxidation sequence that facilitates the synthesis of a variety
of chiral aromatic and alkenyl diols in an enantioselective
fashion. The protocol requires only purification of the final
product and uses the same palladium source to catalyze two
different steps in the sequence.
Acknowledgment. This work was supported by the NIH
(GM 59417). J.P.M. is a fellow of the Alfred P. Sloan
foundation.
Supporting Information Available: Complete experi-
mental procedures, characterization data (1H, 13C, IR, and
mass spectrometry), and enantiomeric purity data (chiral
1
SFC; H NMR). This material is available free of charge
via the Internet at http://pubs.acs.org.
OL0616891
a Conditions: 2.5 mol % of Pd2(dba)3, 6 mol % of ligand, 1.2 equiv of
B2(pin)2, PhMe, room temp, 14 h; then 1.2 equiv of 9-BBN, 9 h; then 2.25
of equiv Cs2CO3, 2.25 equiv of the coupling partner, 80 °C, 12 h; then
oxidative workup with H2O2/NaOH, 8 h.
(9) Wang, X. B.; Li, Y.; Wu, Y. D.; Paddonrow, M. N.; Rondan, N. G.;
Houk, K. N. J. Org. Chem. 1990, 55, 2601.
(10) Lead references: (a) Miyaura, N.; Ishiyama, T.; Ishikawa, M.;
Suzuki, A. Tetrahedron Lett. 1986, 27, 6369. (b) Ohe, T.; Miyaura, N.;
Suzuki, A. J. Org. Chem. 1993, 58, 2201. (c) Matos, K.; Soderquist, J. A.
J. Org. Chem. 1998, 63, 461. (d) Netherton, M. R.; Dai, C.; Neuschutz, K.;
Fu, G. C. J. Am. Chem. Soc. 2001, 123, 10099. Reviews: (e) Suzuki, A.
Pure Appl. Chem. 1991, 63, 419. (f) Suzuki, A. Pure Appl. Chem. 1994,
66, 213. (g) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
was employed in Table 1, it was found that phenyl triflate
was also effective as a cross-coupling partner. Notably, vinyl
halides are also reactive and provide homoallylic diols as
Org. Lett., Vol. 8, No. 20, 2006
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