Copper-catalyzed enantioselective substitution of allylic carbonates with diboron: An efficient route to optically active α-chiral allylboronates

Article abstract of DOI:10.1021/ja076634o

A method for the synthesis of α-chiral allylboronates featuring the Cu(I)-catalyzed enantioselective substitution of readily available allylic carbonates with a diboron is described. Using this method, various α-chiral allylboronates, including functionalized allylboronates, were successfully synthesized, with high enantiomeric purity. Copyright

Full text of DOI:10.1021/ja076634o

Published on Web 11/08/2007
Copper-Catalyzed Enantioselective Substitution of Allylic Carbonates with
Diboron: An Efficient Route to Optically Active r-Chiral Allylboronates
Hajime Ito,* Shinichiro Ito, Yusuke Sasaki, Kou Matsuura, and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido UniVersity, Sapporo 060-0810, Japan
Received September 3, 2007; E-mail: sawamura@sci.hokudai.ac.jp; hajito@sci.hokudai.ac.jp
Table 1. Asymmetric Reaction of Allylic Carbonates (Z)-1a or
(E)-1a with Diboron 2 in the Presence of Cu(I) Complex with
Various Chiral Ligandsa
Among the highly stereoselective addition reactions of allylbo-
ronates to carbonyl compounds, those that involve optically active
allylboronates that have a stereogenic carbon at the R-position of
the boryl group are able to offer a nearly perfect chirality transfer
to afford chiral building blocks.1 Typically, the synthesis of such
R-chiral allylboronates have focused on stoichiometric reactions
that utilize a chiral auxiliary on the boron atom.2 Recently reported
syntheses include more attractive catalytic enantioselective reactions
that involve an asymmetric hetero[4+2] reaction, 1,4-silaboration
of 1,3-diene, diboration of allenes, and alkylation of 3-halo- or
3-acetoxy-2-propenylboronates.3
Alternatively, nucleophilic boryl reagents have recently emerged
as a novel synthetic tool to afford boryl compounds.4-7 We have
previously reported a versatile Cu(I)-catalyzed synthesis of allyl-
boronates, which involves the reaction of an achiral nucleophilic
boryl-copper intermediate.5a Herein, we describe a novel method
for the synthesis of R-chiral allylboronates featuring the Cu(I)-
catalyzed enantioselective substitution of readily available allylic
carbonates with a diboron. Using this method, various R-chiral
allylboronates, including functionalized allylboronates, were suc-
cessfully synthesized, with high enantiomeric purity. Although the
asymmetric allylic alkylation using Cu(I) catalysts is an active area
in organic synthesis,8 our synthetic scheme, to the best of our
knowledge, represents the first example of a Cu(I)-catalyzed
asymmetric allylic substitution with a non-carbon nucleophile.
A series of Cu(I)-phosphine catalysts were prepared in situ by
mixing Cu(O-t-Bu) with chiral ligands. Catalytic activity and
enantioselectivity of the resulting Cu(I) complexes were determined
using the yields and ee values of allylboronate 3a (Table 1), which
was obtained via reaction between allylic carbonate 1a and bis-
(pinacolato)diboron (2) in the presence of 5 mol % catalyst. Good
yields of 3a with high enantiomeric excesses (94-96% ees) were
obtained for the reactions of (Z)-1a with the (R,R)-QuinoxP* chiral
ligand,9 in various solvents such as THP, THF, toluene, and DMI
(entries 1-4). In comparison, the reaction employing (R,R)-Me-
DuPhos showed good activity, but lower ee (80% ee, entry 5). The
use of (R,R)-i-Pr-DuPhos, which should have stronger steric effects
than that of Me-DuPhos, did not improve the enantioselectivity
(entry 6).
For these reactions that resulted in high selectivities (entries 1-6),
bis(dialkylphosphino)arene exists as a common structure among
the ligands. Moderate yield with a low ee value was obtained for
the reaction with (R)-DIOP (entry 7), whereas poor yields and low
selectivities were obtained for axially chiral ligands such as (R)-
SEGPHOS (entry 8) and (R)-BINAP (entry 9).
The enantioselectivity and absolute configuration of the product
are greatly influenced by the E/Z configuration of the substrate-
in contrast to that of (Z)-1a, the reaction of (E)-1a in the presence
of Cu(I)-QuinoxP* afforded (R)-3a with only 44% ee (entry 10).
As shown in Table 2, various (Z)-allylic carbonates (1b-h) were
subjected to the reaction with diboron using the Cu(I)-QuinoxP*
catalyst. Optically active allylboronates that possess alkyl substit-
uents (R ) CH3 (3b), CH3(CH2)4 (3c)) were obtained in good yields
time
(h)
yieldb
(%)
eec
(%)
entry
carbonate
ligand
solvent
1
2
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(Z)-1a
(E)-1a
(R,R)-QuinoxP*
(R,R)-QuinoxP*
(R,R)-QuinoxP*
(R,R)-QuinoxP*
(R,R)-Me-DuPhos
(R,R)-i-Pr-DuPhos toluene
(R,R)-DIOP
(R)-SEGPHOS
(R)-BINAP
(R,R)-QuinoxP*
THP
THF
toluene
DMI
THP
20
20
20
20
3
20
20
21
20
20
77d
85
78
65
97
72
59
19
16
94
94
95
96
94
80
79 (R)
37
20
31
3
4e
5
6
7
8
9
THP
THP
THP
THP
10
44 (R)
a Conditions: Cu(O-t-Bu) (0.025 mmol), ligand (0.025 mmol), 1a (0.5
mmol), 2 (1.0 mmol) at 0 °C in solvent (0.5 mL). b NMR yield. c The ee
value of 3a was determined by chiral GC analysis of the trifluoroacetate of
the allylic alcohol derived from H2O2/NaOH oxidation of 3a. d Isolated yield.
e The reaction was carried out at room temperature.
Table 2. Asymmetric Reaction of Allylic Carbonates (Z)-1 with
Diboron 2 in the Presence of Cu(O-t-Bu)/(R,R)-QuinoxP* Catalysta
catalyst
product (mol %)
yieldb
(%)
ee
(%)
entry
R
1c CH3 (1b)
3b
3c
3d
3e
3f
5
5
10
10
10
5
68 (75) 95 (S)
2
3
4
5
6
7
CH3CH2CH2CH2CH2 (1c)
(CH3)2CHCH2 (1d)
(CH3)2CH (1e)
(t-Bu)Me2SiOCH2CH2CH2 (1f)
PhCO2CH2CH2CH2 (1g)
(CH3)2CdCHCH2O(CH2)3 (1h)
67
62
0
94 (S)
91 (S)
70 (80) 94 (S)
67 (81) 94 (S)
64 (75) 90 (S)
3g
3h
10
a Conditions: Cu(O-t-Bu) (0.025 or 0.05 mmol), (R,R)-QuinoxP* (0.025
or 0.05 mmol), 1 (0.5 mmol), 2 (1.0 mmol) at 0 °C in THF (0.5 mL) unless
otherwise noted. b Isolated yield. H NMR yield is shown in parentheses.
1
c Based on a 4.0 mmol scale (1b).
with high enantioselectivities in the presence of 5 mol % of the
catalyst (entries 1 and 2). The reaction of an allylic carbonate with
a â-branched alkyl substituent (i-Bu, 1d) required a higher catalyst
loading (10 mol %) for a reasonable conversion (entry 3). No
reaction proceeded with the allylic carbonate (1e) substituted with
9
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J. AM. CHEM. SOC. 2007, 129, 14856-14857
10.1021/ja076634o CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Proposed Mechanism
On the other hand, in the case of (E)-1, both the lower-energy
TS3 and the higher-energy TS4 suffer from the steric repulsion
between the ligand t-Bu group and one of the substituents of the
substrate (Figure 1b). Accordingly, the energy difference between
TS3 and TS4 is smaller than that between TS1 and TS2.
In summary, we have successfully carried out various copper-
catalyzed enantioselective allylic substitution reactions with a boryl
nucleophile. These examples, which, to the best of our knowledge,
are the first reported instances of such reactions, offer an efficient
route to R-chiral allylboronates.
a bulkier isopropyl group (entry 4).10 Importantly, our asymmetric
reaction was applicable over a wide range of functionalities:
allylboronates that have silyloxy, benzoate, or prenyloxy groups
were obtained with high enantioselectivities (entries 5-7).
To confirm the synthetic utility of the R-chiral allyboronates, a
Lewis acid-mediated stereoselective reaction between 3c and an
aldehyde was carried out under similar conditions as reported by
Hall.3d,11 In our case, optically active (R)-(E)-homoallylic alcohol
4 (93%, E/Z ) 35:1, 94% ee) was obtained from (S)-3c (94% ee)
(eq 1).
Acknowledgment. This work was supported by Grants-in-Aid
for Scientific Research on Priority Area “Advanced Molecular
Transformations of Carbon Resources” from the Ministry of
Education, Culture, Sports, Science and Technology. This paper is
dedicated to the memory of the late Professor Yoshihiko Ito.
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
via the Internet at http://pubs.acs.org.
References
(1) (a) Hoffmann, R. W. In Stereocontrolled Organic Synthesis; Trost, B.
M., Ed.; Blackwell Scientific Publications: Oxford, England, 1994; pp
259-274. (b) Matteson, D. S. Stereodirected Synthesis with Organobo-
ranes; Springer: Berlin, 1995. (c) Boronic Acids; Hall, D. G., Ed.; Wiley-
VCH Verlag: Weinheim, Germany, 2000.
(2) For the selected synthesis of R-chiral allylboronates with chiral auxiliary,
see: (a) Hoffmann, R. W. Pure Appl. Chem. 1988, 60, 123-130. (b)
Hoffmann, R. W.; Niel, G.; Schlapbach, A. Pure Appl. Chem. 1990, 62,
1993-1998. (c) Matteson, D. S. Tetrahedron 1998, 54, 10555-10606.
(d) Pietruszka, J.; Schone, N. Angew. Chem., Int. Ed. 2003, 42, 5638-
5641. (e) Fang, G.; Aggarwal, V. Angew. Chem., Int. Ed. 2007, 46, 359-
362.
(3) For the synthesis of R-chiral allylboronates through asymmetric catalysis,
see: (a) Gao, X.; Hall, D. G. J. Am. Chem. Soc. 2003, 125, 9308-9309.
(b) Pelz, N.; Woodward, A.; Burks, H.; Sieber, J.; Morken, J. J. Am. Chem.
Soc. 2004, 126, 16328-16329. (c) Gerdin, M.; Moberg, C. AdV. Synth.
Catal. 2005, 347, 749-753. (d) Carosi, L.; Hall, D. G. Angew. Chem.,
Int. Ed. 2007, 46, 5913-5915. (e) Peng, F.; Hall, D. G. Tetrahedron Lett.
2007, 48, 3305-3309.
(4) For studies on reactions of boryl nucleophiles, see: (a) Ito, H.; Yamanaka,
H.; Tateiwa, J.; Hosomi, A. Tetrahedron Lett. 2000, 41, 6821-6825. (b)
Takahashi, K.; Takagi, J.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2000,
126-127. (c) Ramachandran, P. V.; Pratihar, D.; Biswas, D.; Srivastava,
A.; Reddy, M. V. R. Org. Lett. 2004, 6, 481-484. (d) Laitar, D. S.; Tsui,
E. Y.; Sadighi, J. P. J. Am. Chem. Soc. 2006, 128, 11036-11037.
(5) For transition metal-catalyzed allylic substitution with diboron, see: (a)
Ito, H.; Kawakami, C.; Sawamura, M. J. Am. Chem. Soc. 2005, 127,
16034-16035. (b) Ishiyama, T.; Ahiko, T.; Miyaura, N. Tetrahedron Lett.
1996, 37, 6889-6892. (c) Olsson, V. J.; Sebelius, S.; Selander, N.; Szabo,
K. J. J. Am. Chem. Soc. 2006, 128, 4588-4589.
A possible reaction mechanism for the copper-catalyzed reaction
is illustrated in Scheme 1. First, boryl-copper intermediate B is
formed through the reaction between alkoxycopper A and a diboron.
After the formation of Cu-alkene π-complex C, addition of the
B-Cu bond across the C-C double bond would afford â-boryla-
lkylcopper intermediate D such that the Cu and B atoms are located
at the â- and γ-positions, respectively. Stereoelectronic effects that
stabilize the σ(Cu-Câ) bond through interactions with the σ*(CR-
O) bond would induce the regioselectivity. Finally, â-alkoxy
elimination from alkylcopper intermediate D would produce the
R-chiral allylboronate and a copper carbonate, which in turn, would
regenerate alkoxycopper A through decarboxylation. This addition-
elimination mechanism is supported by DFT calculations (see
Supporting Information).12,13
The stereochemical outcome of the Cu(I)-catalyzed reactions of
(Z)-1 can be explained by comparing the transition states that occur
during the addition of the Cu-B bond across the C-C double bond
(Figure 1a). A rigid four-centered diastereomeric transition state is
responsible for the high efficiency of the enantiofacial discrimina-
tion. The favored transition state TS1 is free from steric repulsion
between the substituents of (Z)-1 and the t-Bu groups of the
QunioxP* ligand, thus delivering (S)-3 as the major enantiomer.
In contrast, the less-favored TS2 is largely destabilized by steric
congestion between the substituents of (Z)-1 and one of the ligand
t-Bu groups.
(6) For studies on boryllithiums and borylmagnesiums, see: (a) Segawa, Y.;
Yamashita, M.; Nozaki, K. Science 2006, 314, 113-115. (b) Yamashita,
M.; Suzuki, Y.; Segawa, Y.; Nozaki, K. J. Am. Chem. Soc. 2007, 129,
9570-9571.
(7) For borylation of activated alkenes catalyzed by a chiral Cu(I) complex,
see: Mun, S.; Lee, J.; Yun, J. Org. Lett. 2006, 8, 4887-4889.
(8) For reviews of copper-catalyzed asymmetric allylic alkylation, see: (a)
Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2005, 44, 4435-4439.
(b) Alexakis, A.; Malan, C.; Lea, L.; Tissot-Croset, K.; Polet, D.; Falciola,
C. Chimia 2006, 60, 124-130.
(9) Imamoto, T.; Sugita, K.; Yoshida, K. J. Am. Chem. Soc. 2005, 127,
11934-11935.
(10) No reaction occurred when R is a cyclohexyl group.
(11) For Lewis acid-mediated reactions of allylboronates with aldehydes, see:
(a) Ishiyama, T.; Ahiko, T.; Miyaura, N. J. Am. Chem. Soc. 2002, 124,
12414-12415. (b) Kennedy, J. W. J.; Hall, D. G. J. Am. Chem. Soc. 2002,
124, 11586-11587.
(12) For experimental and theoretical studies on addition of neutral boryl-
copper(I) species across C-C double bonds, see: (a) Laitar, D. S.; Tsui,
E. Y.; Sadighi, J. P. Organometallics 2006, 25, 2405-2408. (b) Dang,
L.; Zhao, H.; Lin, Z.; Marder, T. B. Organometallics 2007, 26, 2824-
2832.
(13) The involvement of (π-allyl)copper(III) species, which are key intermedi-
ates in allylic substitution with diorganocuprates, is unlikely. The neutral
boryl-copper species (B) should be less reactive toward oxidative addition
than anionic diorganocuprates owing to lower nucleophilicity. See:
Yamanaka, M.; Kato, S.; Nakamura, E. J. Am. Chem. Soc. 2004, 126,
6287-6293.
Figure 1. Transition-state models for the addition of the borylcopper (B)
to (Z)- and (E)-1.
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