Palladium-catalyzed enantioselective diboration of prochiral allenes

Article abstract of DOI:10.1021/ja044167u

Pd-catalyzed diboration of prochiral allenes occurs exclusively at the internal position and is remarkably accelerated in the presence of Lewis basic ligand structures. On the basis of preliminary observations, a chiral ligand was employed, and the enantiomeric excess of a variety of diboration products was found to be in the range of 86-92% ee. The chiral diboron reaction products should be useful in organic synthesis, and preliminary experiments suggest that they may participate in allylation reactions with a high level of chirality transfer. Copyright

Full text of DOI:10.1021/ja044167u

Published on Web 11/24/2004
Palladium-Catalyzed Enantioselective Diboration of Prochiral Allenes
Nicholas F. Pelz, Angela R. Woodward, Heather E. Burks, Joshua D. Sieber, and James P. Morken*
Department of Chemistry, Venable and Kenan Laboratories, The UniVersity of North Carolina,
Chapel Hill, North Carolina 27599-3290
Received September 25, 2004; E-mail: morken@unc.edu
Enantioselective metalation of prochiral organic substrates is an
active area of research in chemical synthesis. In particular, this area
of catalysis is attractive because it provides a starting point for the
development of cascade reaction sequences which may be useful
for the rapid construction of complex chiral structures. Because of
the remarkable breadth of stereospecific transformations available
to stereogenic carbon-boron bonds,1 recent research in our
laboratory has focused on development of new enantioselective
processes that allow for the construction of these chiral organo-
metallics. One method for constructing such chiral reactive reagents
is the asymmetric diboration of simple alkenes.2,3 To expand the
scope of this reaction, we have begun to examine the diboration of
related prochiral allenes.4 The product of this process contains both
allylboronate and vinylboronate functionality and should prove to
be a versatile intermediate in asymmetric synthesis. An analogous
asymmetric silylboration has been reported which employs a chiral
silylboron reagent in conjunction with a chiral catalyst;5 however,
an asymmetric diboration of allenes has not been described. We
envision that introduction of the process and development of ensuing
tandem reaction sequences will enable the rapid construction of
complex structures.
complexes with diboron reagents have not been detected, whereas
the corresponding platinum complexes have.7 Likely for these
reasons, Pd(0) complexes are heretofore unknown in classical
diboration reactions.8 We reasoned that, similar to the racemic
platinum-catalyzed allene diboration described by Miyaura,4a ad-
dition of external Lewis basic ligands may facilitate the Pd(0)-
catalyzed reaction and provide a direction for development of an
appropriate chiral catalyst. Initial experiments were conducted with
Pd2(dba)3, bis(pinacolato)diboron,9 and the simple allene (1)
depicted in Table 1. Reactions were conducted in toluene-d8 and
followed by NMR analysis. As can be seen in Table 1, addition of
Lewis basic ligand structures does indeed provide enhanced
reactivity. In contrast to the reported platinum-catalyzed allene
diboration reaction which requires 18 h at 50 °C for substituted
allenes, with an appropriate ligand, the palladium-catalyzed reaction
can proceed to completion in minutes at room temperature. While
alkyl phosphines provided the highest levels of reactivity enhance-
ment, phosphites and phosphorus triamides were also effective. As
might be expected based on the proposed mechanism for diboration
with group 10 complexes (active catalyst ) L-Pd),10 dppe was
completely ineffective in the reaction.
Initial attempts to execute a catalytic asymmetric diboration of
prochiral allenes using previously described chiral rhodium-based
diboration catalysts2a suffered from a lack of regioselectivity,
reactivity, and enantioselectivity. To develop a catalyst with
improved performance, we decided to examine new transition metal
complexes. Computational studies by Musaev, Morokuma, and
Sakaki suggest that for oxidative addition to diboron reagents,
palladium complexes face an activation barrier that is smaller than
that of their platinum analogues; however, this elementary step with
palladium is more endothermic than with platinum.6 Accordingly,
oxidative addition adducts arising from the reaction of Pd(0)
Motivated by the data in Table 1, we began to explore the utility
of chiral phosphoramidites in the allene diboration reaction. These
ligand structures are modular, highly tunable, and have proven
useful in a variety of catalytic asymmetric transformations.11 Initial
experiments surveyed binaphthol-derived phosphoramidites (2,
Scheme 1), and while these ligands gave good conversion, enantio-
selectivity was poor. In contrast, TADDOL-derived phosphora-
midite 312 afforded high levels of asymmetric induction and good
yields for a number of prochiral monosubstituted allene substrates
(Table 2).13 This reaction appears to be remarkably general and
provides similar levels of enantioselectivity whether aromatic,
aliphatic, large, or small substituents are appended to the allene.
Reaction with most substrates results in moderate yields after 14
h. However, with a large tert-butyl substituent (entry 7), the rate
diminishes and an extended reaction time (48 h) is required to
achieve a useful product yield. Whereas the Pt-catalyzed allene
diboration reaction often affords mixtures of regioisomeric addition
products, with the Pd-phosphoramidite catalyst, only the internal
Table 1. Effect of Additional Ligand on the Palladium-Catalyzed
Diboration of 1
1
position of the allene reacts, as determined by H NMR analysis
of crude reaction mixtures.
While the allene diboration products are bench-stable compounds
and may be isolated and purified by silica gel chromatography,
ligand
% conversiona
none
PPh3
dppe
PCy3
PPh2Cy
PPhMe2
P(OEt)3
P(OPh)3
P(NMe2)3
DMAP
<5
<5
<5
100
86
83
41
10
82
Scheme 1
<5
1
a Conversion determined by H NMR analysis at 20 min. All reactions
exhibit <10% side products, as determined by NMR analysis.
9
16328
J. AM. CHEM. SOC. 2004, 126, 16328-16329
10.1021/ja044167u CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Catalytic Enantioselective Diboration of Prochiral Allenes
with Pd2(dba)3-Phosphoramidite (3)
tures. Current efforts are focused on developing the scope of these
transformations.
Acknowledgment. We thank Andre de Vries and David Ager
of DSM for a generous donation of phosphoramidite ligands. This
work was supported by the NIH (GM 59417). J.P.M. is a fellow of
the Alfred P. Sloan foundation and thanks AstraZeneca, Bristol-
Myers Squibb, DuPont, GlaxoSmithKline, and the Packard Founda-
tion for support.
entry
R
% yielda
% eeb
1
2
3
4
5
6
7
8
decyl
61
62
73
65
68
75
91
89
90
90
92
87
cyclohexyl
PhCH2CH2
Bn
Supporting Information Available: Complete experimental pro-
cedures, characterization data (1H and 13C NMR, IR, and mass
spectrometry), enantiomeric purity data (chiral GC, SFC), and structure
proofs (authentic syntheses). This material is available free of charge
via the Internet at http://pubs.acs.org.
CH3
Ph
tert-Bu
BnOCH2CH2
42 (58)c
57
89 (88)c
91
a Isolated yield of diboron adduct after silica gel chromatography.
Average of two experiments with a difference in yield of <10% in each
case. b Enantiomeric excess determined by chiral GLC or SFC analysis of
diol obtained from hydrogenation (diimide) of the vinylboronate followed
by oxidation (NaOH, H2O2) of the resulting saturated 2,3-bis(pinacolbor-
onate) product. The absolute configuration of each product was determined
by comparing the derived 2,3-diol to authentic enantiomers. c Number in
parentheses is that obtained after 48 h of reaction.
References
(1) (a) Organoboranes for Synthesis; Ramachandran, P. V., Brown, H. C.,
Eds.; ACS Symposium Series 783; American Chemical Society: Wash-
ington, DC, 2001. (b) Brown, H. C.; Singaram, B. Acc. Chem. Res. 1988,
21, 287.
(2) (a) Morgan, J. B.; Miller, S. P.; Morken, J. P. J. Am. Chem. Soc. 2003,
125, 8702. (b) Miller, S. P.; Morgan, J. B.; Nepveux, F. J.; Morken, J. P.
Org. Lett. 2004, 6, 131.
(3) For nonasymmetric processes, see: (a) Baker, R. T.; Nguyen, P.; Marder,
T. B.; Westcott, S. A. Angew. Chem., Int. Ed. Engl. 1995, 34, 1336. (b)
Dai, C.; Robins, E. G.; Scott, A. J.; Clegg, W.; Yufit, D. S.; Howard, J.
A. K.; Marder, T. B. Chem. Commun. 1998, 1983. (c) Nguyen, P.; Coapes,
R. B.; Woodward, A. D.; Taylor, N. J.; Burke, J. M.; Howard, J. A. K.;
Marder, T. B. J. Organomet. Chem. 2002, 652, 77. (d) Iverson, C. N.;
Smith, M. R., III. Organometallics 1997, 16, 2757. (e) Ishiyama, T.;
Yamamoto, M.; Miyaura, N. Chem. Commun. 1997, 689. (f) Marder, T.
B.; Norman, N. C.; Rice, C. R. Tetrahedron Lett. 1998, 39, 155. (g)
Ishiyama, T.; Momota, S.; Miyaura, N. Synlett 1999, 1790.
(4) (a) Ishiyama, T.; Kitano, T.; Miyaura, N. Tetrahedron Lett. 1998, 39,
2357. For borylsilation and borylstannation, see: (b) Suginome, M.;
Ohmori, Y.; Ito, Y. J. Organomet. Chem. 2000, 611, 403. (c) Onozawa,
S.; Hatanaka, Y.; Tanaka, M. Chem. Commun. 1999, 1863.
(5) Suginome, M.; Ohmura, T.; Miyake, Y.; Mitani, S.; Ito, Y.; Murakami,
M. J. Am. Chem. Soc. 2003, 125, 11174.
(6) (a) Cui, Q.; Musaev, D. G.; Morokuma, K. Organometallics 1998, 17,
742. (b) Sakaki, S.; Kikuno, T. Inorg. Chem. 1997, 36, 226.
(7) (a) Iverson, C. N.; Smith, M. R., III. J. Am. Chem. Soc. 1995, 117, 4403.
(b) Ishiyama, T.; Matsuda, N.; Murata, M.; Ozawa, F.; Suzuki, A.;
Miyaura, N. Organometallics 1996, 15, 713. (c) Lesley, G.; Nguyen, P.;
Taylor, N. J.; Marder, T. B.; Scott, A. J.; Clegg, W.; Norman, N. C.
Organometallics 1996, 15, 5137.
they also exhibit reactivity with appropriate electrophiles. As
depicted in Scheme 2, addition of benzaldehyde to the reaction
vessel at the end of a diboration reaction, followed by addition of
basic hydrogen peroxide, results in formation of the â-hydroxyke-
tone 4 in a 91:9 enantiomer ratio (e.r.). Comparison of the optical
purity of the diboron intermediate (94:6 e.r.; see Table 2) to that
of product 4 suggests that near-perfect levels of chirality transfer
may occur in allylboration reactions with allene diboration adducts.
Comparison of the â-hydroxyketone (4) configuration (R) with that
of the intermediate diboron adduct (S) suggests that the preferred
allylation pathway is through transition state A (Scheme 2). The
selectivity for this transformation is arguably a result of an A(1,2)
interaction in transition state B, rendering reaction through this
pathway energetically less favorable compared to reaction through
structure A.14
(8) For a Pd(0)-catalyzed diboration that appears not to proceed by oxidative
addition of Pd(0) to a B-B bond, see: Yang, F. Y.; Cheng, C. H. J. Am.
Chem. Soc. 2001, 123, 761.
Access to chiral allene diboration adducts in an enantioselective
fashion provides new opportunities for asymmetric synthesis
through tandem reaction sequences. While allylmetalation processes
appear promising and will be the subject of a detailed future report,
one can imagine a number of other allene diboration-based cascade
sequences that may be useful for assembling functional substruc-
(9) B2(pin)2 is commercially available from Aldrich Chemical Company and,
on scale, from BASF.
(10) (a) See ref 7. (b) Iverson, C. N.; Smith, M. R., III. Organometallics 1996,
15, 5155. (c) Thomas, R. L.; Souza, F. E. S.; Marder, T. B. J. Chem.
Soc., Dalton Trans. 2001, 1650.
(11) For a review, see: (a) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346. For
select examples of hydrogenation, see: (b) ven den Berg, M.; Minnard,
A. J.; Schudde, E. P.; van Esch, J.; de Vries, A. H. M.; de Vries, J. G.;
Feringa, B. L. J. Am. Chem. Soc. 2000, 122, 11539. (c) For examples of
hydrosilation, see: Jensen, J. F.; Svendsen, B. Y.; la Cour, T. V.; Pedersen,
H. L.; Johannsen, M. J. Am. Chem. Soc. 2002, 124, 4558. (d) For examples
of hydroboration, see: Ma, M. F. P.; Li, K.; Zhou, Z.; Tang, C.; Chan.
A. S. C. Tetrahedron: Asymmetry 1999, 10, 3259.
Scheme 2
(12) Keller, E.; Maurer, J.; Naasz, R.; Schader, T.; Meetsma, A.; Feringa, B.
L. Tetrahedron: Asymmetry 1998, 9, 2409.
(13) Allenes were either commercially available (entry 5, Table 2) or
conveniently prepared from terminal alkenes by cyclopropanation with
dibromocarbene (Makosza, M.; Fedorynski, M. Synth. Commun. 1973, 3,
305) followed by treatment with Mg° (Xu, L.; Tao, F.; Yu, T. Tetrahedron
Lett. 1985, 26, 4231).
(14) The high level of chirality transfer for this reaction stands in stark contrast
to that of reactions of analogous R-alkyl chiral allylboronates which lack
the vinylic boronate group: Hoffmann, R. W. Pure Appl. Chem. 1988,
60, 123.
JA044167U
9
J. AM. CHEM. SOC. VOL. 126, NO. 50, 2004 16329