Rhodium-catalyzed addition of organoboronic acids to aldehydes

Article abstract of DOI:10.1002/(SICI)1521-3773(19981217)37:23<3279::AID-ANIE3279>3.0.CO;2-M

Highly inert to ionic additions to aldehydes, aryl- and 1- alkenylboronic acids succumb to a catalytic variant mediated by a [Rh(acac)(CO)₂]-diphosphane complex in aqueous phase at 80-95°C to yield secondary alcohols [Eq. (a)]. A key step in the catalytic cycle is the transmetalation between the boron reagent and the rhodium complex. L(n) = diphosphane (e.g. 1,1'-bis(diphenylphosphanyl)ferrocene); R = aryl, 1- alkenyl; R'= alkyl, aryl; acac = acetylacetonate.

Full text of DOI:10.1002/(SICI)1521-3773(19981217)37:23<3279::AID-ANIE3279>3.0.CO;2-M

COMMUNICATIONS
addition reaction of organotin compounds to enones[ and to
3]
Glink, S. Menzer, C. Schiavo, N. Spencer, J. F. Stoddart, P. A. Tasker,
A. J. P. White, D. J. Williams, Chem. Eur. J. 1996, 2, 709 ± 728.
11] a) O. Mitsunobu, Synthesis 1981, 1, 1 ± 28; b) D. L. Hughes, Org. Prep.
Proced. Int. 1996, 28, 127 ± 164.
[4]
aldehydes has recently appeared. Here we report our first
[
[
attempts to extend the protocol to the addition of aryl- and
1-alkenylboronic acids to aldehydes in an aqueous solution
(Scheme 1). The insertion of carbonyl groups into transition
metal ± carbon bonds has not received much attention, but the
use of transition metals as catalysts may allow addition of
organometallics that are otherwise inert, asymmetric addi-
tion using a chiral phosphane complex,[ or reaction in an
aqueous phase.
1
12] The H NMR spectra showed the existence of the 1:1 pseudorotaxane
complex 4(5) and uncomplexed 4 under conditions of slow exchange
on the 1H NMR time scale. The association constant for the 1:1
3
� 1
complex in chloroform was determined to be 7.9 Â 10 m (21.88C)
from integration of the signals for the protons from complexed and
[5]
uncomplexed 4 using the expression K
for the 1:1 complex between the monotopic salt 5 and DB24C8 in
a
ˆ [4(5)]/[4][5]. The K
a
value
6]
4
� 1
[10]
[
D]chloroform was estimated to be 2.7 Â 10 m (258C). The lower
association constant for 1:1 complex 4(5) may be attributed to the
reduced accessibility and flexibility of the macrocyclic moiety of 4 due
to the bulky dendritic substituent.
[
Rh(acac)Ln]
R'
[
[
[
13] L. J. Twyman, A. E. Beezer, J. C. Mitchell, J. Chem. Soc. Perkin Trans.
RB(OH)2 + R'CHO
R
DME/H2O or dioxane/H2O
1
994, 4, 407 ± 422.
14] J. C. Hummelen, J. L. J. van Dongen, E. W. Meijer, Chem. Eur. J. 1997,
, 1489 ± 1493.
OH
Scheme 1. Rhodium-catalyzed addition of organoboronic acids to alde-
3
hydes. R ˆ aryl, 1-alkenyl; R' ˆ alkyl, aryl.
15] a) Z. Xu, M. Kahr, K. L. Walker, C. L. Wilkins, J. S. Moore, J. Am.
Chem. Soc. 1994, 116, 4537 ± 4550; b) J. W. Leon, J. M. J. Fr e chet,
Polym. Bull. Berlin 1995, 35, 449 ± 455.
A combination of [Rh(acac)(CO) ] (acac ˆ acetylaceto-
2
�
2
[
16] A solution of 4 (3.0 Â 10 m) was mixed with 1/3 molequiv of solid 1
for 3 d. The mixture was then filtered and the filtrate was concentrated
to afford a white solid, which was submitted for MALDI-MS analysis.
17] The apparent distribution of the complexes indicate partial dissoci-
nate) and a phosphane ligand in an aqueous solvent,
conditions that gave good results for the 1,4-addition of
organoboronic acids to enones,[ was also effective for the
addition to aldehydes (Table 1). The reaction was induced by
2]
[
3 2
ation of 1(4) into subunits 1(4) and 1(4) during ionization. It is also
noteworthy that MALDI-MS detectors are nonlinear with respect to
molecular mass and thus do not give molar response. For a review on
principles, instrumentation, and application of MALDI MS, see: F.
Hillenkamp, M. Karas, R. C. Beavis, B. T. Chait, Anal. Chem. 1991, 63,
[7a]
phosphane complexes having a large P-Rh-P angle, which
Table 1. Effect of ligand and solvent on the addition of phenylboronic acid
[a]
1193A ± 1203A. ESI-MS has to date given similar results; we are
2
to 4-methoxybenzaldehyde in the presence of [Rh(acac)(CO) ].
currently investigating the use of low sample cone voltage (V ) to
e
Entry
Ligand
Solvent
Yield [%][b]
minimize fragmentation. For reviews on characterization of hydrogen-
bonded assemblies by ESI-MS, see: a) K. C. Russell, E. Leize, A.
Van Dorsselaer, J.-M. Lehn, Angew. Chem. 1995, 107, 244 ± 248;
Angew. Chem. Int. Ed. Engl. 1995, 34, 209 ± 213; b) X. Cheng, Q. Gao,
R. D. Smith, E. E. Simanek, M. Mammen, G. M. Whitesides, J. Org.
Chem. 1996, 61, 2204 ± 2206.
1
2
3
4
5
6
7
8
9
3Ph P
3
3
3
DME/H O
DME/H O
DME/H O
DME/H O
2
2
2
2
2
0
< 1
5
3Ph As
3Cy P
[
c]
dppe
0
[
d]
e]
dppp
dppb
DME/H O
82 (79)
17
66
99 (83)
72
84
[
DME/H
DME/H
DME/H
dioxane/H
nPrOH/H
2
2
2
O
O
O
[
f]
diop
dppf
dppf
dppf
[
[
[
g]
g]
g]
2
O
1
0
2
O
[
[
a] A mixture of 4-MeOC
Rh(acac)(CO)
6
H
4
CHO (1 mmol), PhB(OH)
2
(2 mmol) and
Rhodium-Catalyzed Addition of
Organoboronic Acids to Aldehydes
2
]/ligand (3 mol%) was stirred at 808C for 16 h in solvent/
H O (1/1) (6 mL). [b] GC yields based on the aldehyde and yields of the
isolated product are given in the parentheses. [c] 1,2-Bis(diphenylphos-
phanyl)ethane. [d] 1,3-Bis(diphenylphosphanyl)propane. [e] 1,4-Bis(diphe-
nylphosphanyl)butane. [f] 2,3-O-Isopropylidene-2,3-dihydroxy-1,4-bis(di-
phenylphosphanyl)butane. [g] 1,1'-Bis(diphenylphosphanyl)ferrocene.
2
Masaaki Sakai, Masato Ueda, and Norio Miyaura*
The transmetalation between organo/main group metal
reagents and transition metal compounds is of great impor-
tance for application in organic synthesis, since it allows the
formation of new carbon ± carbon bonds between various
organometallic units and electrophiles. We previously dem-
onstrated the efficiency of transmetalation between boron
and palladium in the cross-coupling reaction of organoboron
may affect the rate of carbonyl insertion into the Rh�C
bond.[
7b±d]
Thus, monodentate phosphanes and dppe were
totally ineffective ligands (entries 1 ± 4), but the complexes
derived from dppp, diop, and dppf exhibited high catalytic
activity (entries 5, 7, and 8). However, the ligand dppb
unexpectedly resulted in a low yield although it has a similar
bite angle (entry 6). The reaction smoothly proceeded in
aqueous 1,2-dimethoxyethane (DME), dioxane, and propanol
at temperatures above 808C (entries 9 and 10), but it was very
slow in the absence of water or at temperatures below 808C.
Representative results are summarized in Table 2. The
reaction is rather sensitive to electronic effects both in
aldehydes and arylboronic acids, suggesting that the mecha-
nism proceeds through the nucleophilic attack of the aryl
group to the carbonyl. Thus, the reaction was facilitated in the
[
1]
compounds with organic electrophiles and the transmetala-
tion between boron and rhodium in the catalytic 1,4-addition
[
2]
of aryl- or 1-alkenylboronic acids to enones. An analogous
[
*] Prof. Dr. N. Miyaura, M. Sakai, M. Ueda
Division of Molecular Chemistry
Graduate School of Engineering
Hokkaido University
Sapporo 060-8628 (Japan)
Fax: (‡81)11-706-6561 or 11-706-7882
E-mail: miyaura@org-mc.eng.hokudai.ac.jp
Angew. Chem. Int. Ed. 1998, 37, No. 23
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1433-7851/98/3723-3279 $ 17.50+.50/0
3279

COMMUNICATIONS
Table 2. Addition of arylboronic acids to aldehydes.[a]
bidentate ligands such as diop and binap unfortunately
resulted in the formation of racemic alcohols.
Entry ArB(OH)
2
Aldehyde
Yield [%][b]
The reaction may involve the transmetalation between
arylboronic acid and the RO�Rh species (RO ˆ acac or OH)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
2
2
2
2
2
2
2
PhCHO
92
97
97
93
< 1
88
48 (76)
84
99
52
< 1
80 (86)
31 (43)
78
91
69
4-CF
4-NCC
4-MeCOC
4-NO
4-BrC
4-MeC
3
C
6
H
4
CHO
CHO
CHO
CHO
CHO
CHO
I
6
H
4
to give an Ar�Rh complex and the insertion of an aldehyde
6
H
4
into the Ar�Rh bond (Scheme 3). The arylrhodium(i)
[4]
[
c]
2
C
6
H
4
complexes are unstable such as to preclude isolation in pure
6
H
4
[
d]
6
H
4
4-MeOC
4-MeC
4-FC
4-MeCOC
2-MeC B(OH)
2,4,6-Me B(OH)
2
6
H
4
B(OH)
B(OH)
B(OH)
B(OH)
2
4-NCC
4-NCC
4-NCC
4-NCC
6
H
6
H
6
H
6
H
4
CHO
CHO
CHO
CHO
RB(OH)2
6
H
4
2
4
4
4
0
1
2
3
4
5
6
7
8
6
H
4
2
I
I
HORh •Ln
R-Rh •Ln
[
c]
6
H
4
2
[
[
d]
d]
6
H
4
2
4-MeOC
4-MeOC
2-furaldehyde
6
H
H
4
CHO
CHO
R'CHO
3
C
6
H
2
6
4
R'
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
2
2
2
2
R
1-naphthaldehyde
OH
C
C
5
H
H
11CHO
11CHO
[
d]
6
45 (95)
76
R'
(E)-C
4
H
9
CHˆCHB(OH)
2
6 4
4-NCC H CHO
R
I
ORh •Ln
[
a] A mixture of ArB(OH)
2
(2 mmol), aldehyde (1 mmol), [Rh(acac)-
O (1/1, 6 mL) was stirred
H2O
Scheme 3. Proposed catalytic cycle.
(
CO) ] (3 mol%), and dppf (3 mol%) in DME/H
2
2
at 808C for 16 h, unless otherwise noted. [b] Yields of products isolated by
chromatography over silica gel. [c] The aldehyde were recovered un-
changed. [d] The reactions were carried out at 958C for 16 h in dioxane/
form, but they have been reasonably speculated to be the key
intermediates in various coupling reactions with organic
2
H O (1/1, 6 mL).
halides[ and the addition to alkenes and alkynes. However,
9]
[10]
presence of an electron-withdrawing group in aromatic
aldehydes (entries 1 ± 7) and a donating group in arylboronic
acids (entries 8 ± 11). On the other hand, the addition to
electron-rich aldehydes (entry 7) and the arylation with
electron-deficient arylboronic acids (entries 10 and 11) were
slow at 808C. In the one exceptional case 4-nitrobenzaldehyde
remained intact during the reaction (entry 5).
The reaction is specific for aldehydes. Aromatic ketones,
esters, nitriles, halides (Cl, Br) were unreactive, as evidenced
by the recovery of these substrates. Steric hindrance around
the boron atom retarded the reaction (entry 13), but the
reactions of ortho-monosubstituted arylboronic acids pro-
ceeded smoothly at 808C (entry 12). The additions to aliphatic
aldehydes such as hexanal and cyclohexanecarbaldehyde
were very slow at 808C because their electrophilicity is lower
than that of aromatic aldehydes, but the reaction at 958C in
the insertion of aldehydes into the carbon ± metal bond is very
rare in transition metals except the allylic derivatives.
[5, 11]
Experimental Section
2
Procedure for the reactions presented in Tables 1 and 2: [Rh(acac)(CO) ]
(
8 mg, 0.03 mmol, 3 mol%) and dppf (17 mg, 0.03 mmol, 3 mol%),
2
PhB(OH) (0.244 g, 2 mmol), and naphthaldehyde (0.156 g, 1.0 mmol)
were dissolved in DME (3 mL) and water (3 mL) under nitrogen. After the
mixture was stirred at 808C for 16 h, the product was extracted with
benzene, dried over MgSO , and finally purified by chromatography on
4
silica gel with hexane/ethyl acetate (20/1) to give (1-naphthyl)(phenyl)-
methanol (0.213 g, 0.91 mmol, 91%).
Asymmetric arylation (Scheme 2): [Rh(acac)(CH
2
ˆCH
2
)
2
]
(8 mg,
0
.03 mmol, 3 mol%) and (S)-MeO-MOP (28 mg, 0.06 mmol, 6 mol%),
2
PhB(OH) (0.243 g, 2 mmol), and naphthaldehyde (0.156 g, 1.0 mmol) were
dissolved in DME (3 mL) and water (3 mL) under nitrogen. The mixture
was stirred at 608C for 36 h and worked up. Chromatography on silica gel
with hexane/ethyl acetate (10/1) gave the tertiary alcohol (0.181 g,
dioxane/H O gave the tertiary alcohols in high yields (en-
2
tries 16 and 17). (E)-1-Hexenylboronic acid also participated
in the catalytic reaction, and its stereochemistry was retained
in the product (entry 18).
0
.77 mmol, 77%). The enantiomeric purity (41% ee) and the absolute
configuration (R) were established by high-pressure liquid chromatography
(
Daicel Chiracel OD-H, hexane/2-propanol 4/1) and by comparison with
The facile addition of arylboronic acids to aldehydes
encouraged us to examine the asymmetric version of this
protocol (Scheme 2). The monodentate ligand 2-(diphenyl-
phosphanyl)-2'-methoxy-1,1'-binaphthyl ((S)-MeO-MOP)[
gave rise to a moderate asymmetric induction: (R)-(‡)-(1-
[12]
the reported optical rotation.
Received: June 22, 1998 [Z12024IE]
German version: Angew. Chem. 1998, 110, 3475 ± 3477
8]
Keywords: aldehydes ´ boron ´ homogeneous catalysis ´
nucleophilic additions ´ rhodium
naphthyl)(phenyl)methanol was formed preferentially
0
(
[a]2 ˆ ‡9.3 (c ˆ 0.01, EtOH), 41% ee), though the chiral
D
[
[
1] N. Miyaura, A. Suzuki, Chem. Rev, 1995, 95, 2457 ± 2483.
2] M. Sakai, H. Hayashi, N. Miyaura, Organometallics, 1997, 16, 4229 ±
4230; for an asymmetric 1,4-addition of aryl- or 1-alkenylboronic acids
to enones, see Y. Takaya, M. Ogasawara, T. Hayashi, M. Sakai, N.
Miyaura, J. Am. Chem. Soc. 1998, 120, 5579 ± 5580.
PhB(OH)2 (2 equiv)
Rh(acac) (CH2 = CH2)] (3 mol %)
[
Ph
(
S)-MeO-MOP (6 mol%)
R
CHO
DME/H2O (1/1)
OH
6
0 °C, 36 h
Scheme 2. Asymmetric addition.
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
[
[
3] S. Oi, M. Moro, S. Ono, Y. Inoue, Chem. Lett. 1998, 83 ± 84.
4] S. Oi, M. Moro, Y. Inoue, J. Chem. Soc. Chem. Commun. 1997, 1621 ±
1622.
7
8%, 41% ee
3
280
1433-7851/98/3723-3280 $ 17.50+.50/0
Angew. Chem. Int. Ed. 1998, 37, No. 23

COMMUNICATIONS
acid side chains. Examples include salt bridges, lactams,[6]
[
5]
[
5] H. Nakamura, H. Iwama, Y. Yamamoto, J. Am. Chem. Soc. 1996, 118,
641 ± 6647.
6] H. Nakamura, K. Nakamura, Y. Yamamoto, J. Am. Chem. Soc. 1998,
6
[7]
[8]
disulfide bridges, hydrophobic interactions, and metal
ligation between natural[ and unnatural amino acids.[10] In
several of these cases, it was found that substantial helix
stabilization was achieved when the linkage was placed
between the i and i ‡ 4 residues in the peptide backbone.
Such a linkage encompasses approximately one turn of the
helical peptide backbone and places the tethered side chains
on the same side of the helix. Recently, the extraordinary
[
9]
120, 4242 ± 4243; J. M. Nuss, R. A. Rennels, Chem. Lett. 1993, 197 ±
200.
[
7] The P-Rh-P angles increase in the order of dppe < dppp < dppb <
dppf; see a) K. Angermund, W. Baumann, E. Dinjus, R. Fornika, H.
Görls, M. Kessler, K. Krüger, W. Leitner, F. Lutz, Chem. Eur. J. 1997, 3,
755 ± 764; for the effect on hydroformylation of alkenes, see b) C. P.
Casey, G. T. Whiteker, M. G. Melville, L. M. Petrovich, J. A. Gav-
ney Jr., D. R. Powell, J. Am. Chem. Soc. 1992, 114, 5535 ± 5543; c) M.
Kranenburg, Y. E. M. van der Burgt, P. C. J. Kamer, P. W. N. M.
van Leeuwen, K. Goubitz, J. Fraanje, Organometallics, 1995, 14,
functional group tolerance of olefin metathesis catalyst
has enabled the synthesis of
cyclic amino acids and peptides exhibiting b-turn and b-
[11]
[
(PCy ) Cl RuˆCHPh] (1)
3
2
2
3
081 ± 3089; for the effect on hydrogenation of CO
H. Görls, B. Seemann, W. Leitner, J. Chem. Soc. Chem. Commun.
995, 1479 ± 1481.
2
, see d) R. Fornika,
[12]
[13]
[14]
sheet secondary structure by ring-closing olefin metathesis
(RCM).[ This transformation effectively introduces non-
native carbon ± carbon bond constraints which may afford
enhanced biostability. Here we present a concise synthesis and
structural analysis of a series of cyclic helical peptides wherein
RCM is used to incorporate a carbon ± carbon tether between
amino acid side chains.
We chose to study hydrophobic peptide model systems
from the outset, because the use of apolar sequences permits
characterization of conformation in poorly solvating organic
solvents where folding is mainly controlled by intramolecular
hydrogen bonding, nonbonding interactions, and electrostatic
effects.[ We became interested in a hydrophobic peptide (2)
studied by Karle and Balaram et al., whose solubility in
organic solvents would be compatible with alkylidene 1.[
Heptapeptide 2 contains two repeat units of valine ± alanine ±
leucine (Val-Ala-Leu) separated by one a-aminoisobutyric
acid residue (Aib), as shown schematically in Figure 1. The
Aib residue is known to stabilize 3 - and/or a-helical
1
15]
[
[
8] Y. Uozumi, T. Hayashi, J. Am. Chem. Soc. 1991, 113, 9887 ± 9888.
9] L. S. Hegedus, P. M. Kendall, S. M. Lo, J. R. Sheats, J. Am. Chem. Soc.
1
1
975, 97, 5448 ± 5452; M. F. Semmelhack, L. Ryono. Tetrahedron Lett.
973, 2967 ± 2970.
[
[
10] M. Michman, M. Balog, J. Organomet. Chem. 1971, 31, 395.
11] T. Kondo, H. Ono, N. Satake, T. Mitsudo, Y. Watanabe, Organo-
metallics, 1995, 14, 1945.
[
12] O. Cervinka, V. Suchan, B. Masar, Collect. Czech. Chem. Commun.
1965, 30, 1693 ± 1699.
16]
[17]
18]
Highly Efficient Synthesis of Covalently
Cross-Linked Peptide Helices by
Ring-Closing Metathesis**
Helen E. Blackwell and Robert H. Grubbs*
10
Due to the frequency of helical secondary structures in
[
1]
peptides and proteins, considerable effort has been directed
toward the design of small-molecule helix mimetics and
stabilized helix structures. Designed organic template mole-
cules that initiate a-helix formation in peptide sequences have
2
= Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe
3,4 =
Boc-Val-X-Leu-Aib-Val-X-Leu-OMe
H
H
[
2]
been reported. Short a-helical peptides have also been
Boc
N
Boc N
stabilized by incorporation of naturally occurring capping
motifs and by stabilization of the intrinsic helix dipole.
Notably, significant progress has been made toward stabilizing
synthetic a-helical peptides through the incorporation of
covalent or noncovalent linkages between constituent amino
i
i
n
[
3]
[4]
O
O
i + 4
i + 4
n
MeO
MeO
C
C
O
O
[
*] Prof. R. H. Grubbs, H. E. Blackwell
Arnold and Mabel Beckman Laboratories of Chemical Synthesis
Division of Chemistry and Chemical Engineering
California Institute of Technology
2
3: X = Ser (n = 2)
: X = Hse (n = 1)
4
Figure 1. Karle and Balaramꢁs heptapeptide 2, and two dienic analogues 3
and 4. Boc ˆ tert-butoxycarbonyl.
Pasadena, CA 91125 (USA)
Fax: (‡1)626-564-9297
E-mail: rhg@its.caltech.edu
[
**] Financial support has been generously provided by the National
Institutes of Health and Zeneca Pharmaceuticals. H. E. B. is grateful
to the ACS Division of Organic Chemistry for a pre-doctoral
fellowship (supported by Pfizer, Inc.). We thank Dr. Keith Russell
conformations in apolar oligopeptides and is frequently found
in peptides produced by microbial sources.[ Examples of
such Aib-rich peptides include the antibiotics alamethicin,
zervamicin, and trichogin AIV, which are purported to adopt
helical conformations within lipid bilayer membranes and
aggregate therein to form ion channels. Heptapeptide 2 was
shown to adopt an a-helical conformation in the solid state by
X-ray crystallography and was found to adopt a similar helical
19]
(Zeneca) for instrumental discussions and Dr. Saeed Khan (UCLA)
for X-ray crystallographic analyses. Dr. Isabella L. Karle, Prof.
Barbara Imperiali, Prof. Scott J. Miller, and Prof. Daniel J. OꢁLeary
are acknowledged for helpful discussions.
Supporting information for this article is available on the WWW
under http://www.wiley-vch.de/home/angewandte/ or from the
author.
conformation in CDCl by solution-phase 2D NMR analyses.
3
Angew. Chem. Int. Ed. 1998, 37, No. 23
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1433-7851/98/3723-3281 $ 17.50+.50/0
3281