Pt-catalyzed enantioselective diboration of terminal alkenes with B 2(pin)2

Article abstract of DOI:10.1021/ja9047762

(Chemical Equation Presented) The Pt-catalyzed enantioselective addition of bis(pinacolato)diboron to simple monosubstituted alkenes is described. This reaction occurs in the presence of a readily available chiral phosphonite ligand and is effective with a variety of terminal alkene substrates. Importantly, the reaction can operate with catalyst loadings of only 1 mol % Pt. While oxidation of the intermediate 1,2-bis(boronate) ester provides the chiral 1,2-diol as the reaction product, the intermediate may also be subjected to homologation/oxidation to furnish a chiral 1,4-diol as the reaction product.

Full text of DOI:10.1021/ja9047762

Published on Web 08/25/2009
Pt-Catalyzed Enantioselective Diboration of Terminal Alkenes with B2(pin)2
Laura T. Kliman, Scott N. Mlynarski, and James P. Morken*
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467
Received June 11, 2009; E-mail: morken@bc.edu
Table 1. Effect of Chiral Ligand on the Catalytic Enantioselective
The transition-metal-catalyzed diboration is an enabling method
for the conversion of simple olefins to functionally and stereo-
chemically enriched products.1,2 Of the substrate classes that might
be considered for this reaction, terminal alkenes are among the most
attractive. 1,2-Diboration of a terminal olefin provides a reactive
intermediate with both primary and secondary boronate groups, and
the different environments of these elements cause them to exhibit
differential reactivity in subsequent transformations.3 To employ
these strategies in asymmetric synthesis, the issue of enantioselec-
tivity in alkene diborations is critical. This has been addressed in
our laboratory4 where it was determined that enantioselective
diboration could be accomplished with bis(catecholato)diboron in
the presence of Rh(I) and the chiral ligand Quinap.5 Unfortunately,
this process is not only impractical with respect to reaction cost
(both B2(cat)2 and the catalyst are expensive) but also suffers from
the fact that low enantioselectivity is observed for most 1-alkene
substrates. In this report we describe a practical and economical
enantioselective alkene diboration reaction that is highly effective
with terminal olefins, occurring with good yield and excellent
enantioselectivity.
Diboration of 1-Octenea
ligand
R
X
yield (%)b
ee (%)c
L1
L2
L3
L4
L5
L6
L7
H
Ph
Ph
Ph
NMe2
NMe2
NMe2
NMe2
24
81
74
35
77
40
35
60
83
80
40
80
57
40
Me
t-Bu
H
Me
t-Bu
Me
a Reaction carried out at 60 °C for 12 h, followed by oxidation with
30% H2O2 and 3 M NaOH for 3 h. b Percent yield of purified material.
c Enantiopurity of the derived acetonide determined by GC analysis
employing a chiral stationary phase.
Recently, we described the Pt-catalyzed enantioselective 1,4-
diboration of 1,3-dienes in the presence of taddol-derived
phosphonite ligands; after oxidation, the net 1,4-dihydroxylation
product is obtained.6 Of interest was the observation that
enantioselective 1,2-diboration occurs as a side reaction with
some 1,3-diene substrates. This feature prompted us to examine
the asymmetric diboration of 1-alkene substrates under the
influence of platinum complexes. Initial experiments with
1-octene showed that this process can be enantioselective and
that taddol-derived phosphonite and phosphoramidite ligands7
can provide elevated levels of enantioselection (Table 1). Ligand
L2 appeared optimal and was selected for further fine-tuning.
Subsequent experiments suggested that several parameters are
important for obtaining the highest enantioselectivity. First, 31P
NMR analysis revealed that preheating Pt2(dba)3 and the
phosphonite ligand at 80 °C for 30 min is required to achieve
complete complexation of the metal and ligand and that the
presence of B2(pin)2 aids in this complexation step; without this
pretreatment, diminished enantioselectivity is observed in the
diboration. Second, a ligand loading of 1.2 equiv, relative to
platinum, results in optimal selectivity and yield; with 2 equiv
of ligand precomplexed to Pt, only 9% yield of product is
obtained.8 Lastly, fine-tuning of the R substituent on L2 revealed
that the ethyl derivative (L8, Table 2) is more selective than
the methyl derivative and leads to the derived 1,2-diol in 92%
enantiomeric excess when combined with the above-described
modifications.
Notably, the reaction is insensitive to the nature of the alkyl
substituent with large groups (entries 5 and 6) and small groups
(entry 1) equally tolerated. Also of note, substrates bearing
protected oxygen functionality undergo clean diboration with
excellent levels of enantioselection. Surprisingly, substrates with
allylic oxygenation do not suffer from competing π-allyl
chemistry as has been documented in related catalyzed reactions
between diboron reagents and allylic ethers.4b,10 Remarkably,
the catalytic diboration of allylic ethers (i.e., entry 9) only occurs
in the presence of ligand (R,R)-L8; in the absence of (R,R)-L8
or with PCy3 as the ligand, the diboration/oxidation product
cannot be detected. Also of note is that styrene reacts with useful
levels of enantioselectivity; in Rh-Quinap catalyzed diboration,
this substrate reacts with anomalously low selectivity (33% ee).4a
Operation of the Pt-catalyzed asymmetric diboration on a large
scale would be most practical with reaction conditions that employ
diminished catalyst loading and benign reaction solvent.11 As
depicted in Scheme 1, ethyl acetate can also be employed as the
reaction solvent, although in this solvent the product is furnished
with slightly diminished enantiomeric purity relative to THF.
Scheme 1
As depicted in Table 2, Pt-catalyzed diboration of many
1-alkene substrates occurs in a highly enantioselective fashion.
Generally, only 1.05 equiv of the diboron reagent are required
and the products can be isolated in good yield. In addition to
1-octene, other aliphatic R-olefins undergo selective diboration.9
9
13210 J. AM. CHEM. SOC. 2009, 131, 13210–13211
10.1021/ja9047762 CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Catalytic Enantioselective Diboration of 1-Alkenesa
oxidative workup provides the derived 1,4-diol in good yield and
excellent enantiomeric purity.
In conclusion, we have described the first highly enantioselective
asymmetric diboration of simple terminal alkenes. In addition to
the oxidation and homologation reactions described here, many
other transformations should be available to the diboron intermedi-
ate. Additional studies in this regard, and on further development
of the catalytic reaction, are underway.
Acknowledgment. Support by the NIGMS (GM-59417) is
gratefully acknowledged, as is the NSF (DBI-0619576) for support
of the BC Mass Spectrometry Center. We also thank AllyChem,
Co., Ltd. for a generous donation of B2(pin)2.
Supporting Information Available: Characterization and proce-
dures. This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(1) Recent reviews: (a) Burks, H. E.; Morken, J. P. Chem. Commun. 2007,
4717. (b) Ramirez, J.; Lillo, V.; Segarra, A. M.; Fernandez, E. Comp. Rend.
Chim. 2007, 10, 138. (c) Beletskaya, I.; Moberg, C. Chem. ReV. 2006, 106,
2320. (d) Ishiyama, T.; Miyaura, N. Chem. Record 2004, 3, 271. (e) Marder,
T. B.; Norman, N. C. Top. Catal. 1998, 5, 63.
(2) Pt-catalyzed alkene diboration, see: (a) Ishiyama, T.; Yamamoto, M.;
Miyaura, N. Chem. Commun. 1997, 689. (b) Iverson, C. N.; Smith, M. R.,
III. Organometallics 1997, 16, 2757. (c) Marder, T. B.; Norman, N. C;
Rice, C. R. Tetrahedron Lett. 1998, 39, 155. (d) Mann, G.; John, K. D.;
Baker, R. T. Org. Lett. 2000, 2, 2105. (e) Lillo, V.; Mata, J.; Ramirez, J.;
Peris, E.; Fernandez, E. Organometallics 2006, 25, 5829. For catalytic
alkene diboration with other metals, see: (f) Baker, R. T.; Nguyen, P.;
Marder, T. B.; Westcott, S. A. Angew. Chem., Int. Ed. Engl. 1995, 34,
1336. (g) Dai, C.; Robins, E. G.; Scott, A. J.; Clegg, W.; Yufit, D. S.;
Howard, J. A. K.; Marder, T. B. Chem. Commun. 1998, 1983. (h) 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. (i) Ram´ırez,
J.; Corbera´n, R.; Sanau´, M.; Peris, E.; Ferna´ndez, E. Chem. Commun. 2005,
3056. (j) Lillo, V.; Mas-Marza´, E.; Segarra, A. M.; Carbo´, J. J.; Bo, C.;
Peris, E.; Ferna´ndez, E. Chem. Commun. 2007, 3380. (k) Ramirez, J.;
Mercedes, S.; Ferna´ndez, E. Angew. Chem., Int. Ed. 2008, 47, 5194.
(3) For differential transformation of 1,2-bis(boronate) esters, see: (a) Miller,
S. P.; Morgan, J. B.; Nepveux V, F. J.; Morken, J. P. Org. Lett. 2004, 6,
131. (b) Kalendra, D. M.; Duen˜es, R. A.; Morken, J. P. Synlett 2005, 1749.
(4) (a) Morgan, J. B.; Miller, S. P.; Morken, J. P. J. Am. Chem. Soc. 2003,
125, 8702. (b) Trudeau, S.; Morgan, J. B.; Shrestha, M.; Morken, J. P. J.
Org. Chem. 2005, 70, 9538. See also: (c) Ram´ırez, J.; Segarra, A. M.;
Fera´ndez, E. Tetrahedron: Asymmetry 2005, 16, 1289.
a Unless otherwise indicated, (R,R)-L8 was employed with reaction at
60 °C for 12 h, followed by oxidation with 30% H2O2 and 3 M NaOH
for 3 h. b Percent yield of purified material. Value is an average of two
experiments. For entries 2, 5, and 10 product coelutes with pinacol.
c Determined by GC or SFC analysis employing a chiral stationary
phase. d Oxidation carried out with H2O2 in a buffer at pH ) 7.
Racemization by silyl transfer occurs under basic conditions.
(5) (a) Alcock, N. W.; Brown, J. M.; Hulmes, D. I. Tetrahedron: Asymmetry
1993, 4, 743. (b) Lim, C. W.; Tissot, O.; Mattison, A.; Hooper, M. W.;
Brown, J. M.; Cowley, A. R.; Hulmes, D. I.; Blacker, A. J. Org. Process
Res. DeV. 2003, 7, 379.
(6) Burks, H. E.; Kliman, L. T.; Morken, J. P. J. Am. Chem. Soc. 2009, 131,
9134.
(7) (a) Sakaki, J.; Schweizer, W. B.; Seebach, D. HelV. Chem. Acta. 1993, 76,
2654. (b) Seebach, D.; Hayakawa, M.; Sakaki, J.; Schweizer, W. B.
Tetrahedron 1993, 49, 1711. (c) Alexakis, A.; Burton, J.; Vastra, J.;
Benhaim, C.; Fournioux, X.; van den Heuvel, A.; Leveque, J.-M.; Maze,
F.; Rosset, S. Eur. J. Org. Chem. 2000, 4011. (d) Bee, C.; Han, S. B.;
Hassan, A.; Iida, H.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 2746.
(8) L1Pd complexes have been postulated in alkyne diboration reactions, see:
(a) Lesley, G.; Nguyen, P.; Taylor, N. J.; Marder, T. B.; Scott, A. J.; Clegg,
W.; Norman, N. C. Organometallics 1996, 15, 5137. (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.
(9) With these conditions, trans-2-octene and R-methyl styrene are unreactive.
Reaction of 1-octene with B2(cat)2 occurred in 17% yield and 62% ee.
Lower yields in Table 2 reflect a lack of conversion; hydroboration products
are not detected.
(10) (a) Ishiyama, T.; Ahiko, T.; Miyaura, N. Tetrahedron Lett. 1996, 37, 6889.
(b) Murata, M.; Watanabe, S.; Masuda, Y. Tetrahedron Lett. 2000, 41,
5877. (c) Ito, H.; Kawakami, C.; Sawamura, M. J. Am. Chem. Soc. 2005,
127, 16034. (d) Ito, H.; Ito, S.; Sasaki, Y.; Matsuura, K.; Sawamura, M.
J. Am. Chem. Soc. 2007, 129, 14856. (e) Olsson, V. J.; Sebelius, S.;
Selander, N.; Szabo´, K. J. J. Am. Chem. Soc. 2006, 128, 4588.
(11) B2(pin)2 is a readily available inexpensive reagent ($800/kg, AllyChem,
Co., Ltd. (www.allychem.com)).
Importantly, the catalyst loading can also be decreased to 0.5 mol
% of the Pt dimer and 1.2 mol % ligand. With these conditions the
reaction still occurs efficiently and in a reasonable time frame.
An attractive feature of the Pt-catalyzed asymmetric diboration
is that the reaction conditions are compatible with many subsequent
transformations of the chiral bis(boronate) ester and, thereby, enable
single-flask transformations without an intermediate reaction work-
up. An example of this strategy is depicted in Scheme 2 where
1-octene is subjected to catalytic asymmetric diboration. After 12 h
of reaction at 60 °C, the reaction mixture is cooled to -78 °C and
treated with 2 equiv of ClCH2Li. Under these conditions, clean
methylene insertion12 into each carbon-boron bond occurs and
Scheme 2
(12) (a) Sadhu, K. M.; Matteson, D. S. Organometallics 1985, 4, 1687. (b) Chen,
A. C.; Ren, Li.; Crudden, C. M. Chem. Commun. 1999, 611. (c) Chen,
A. C.; Ren, Li.; Crudden, C. M. J. Org. Chem. 1999, 64, 9704. (d) Ren,
L.; Crudden, C. M. Chem. Commun. 2000, 721.
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