Construction of quaternary stereogenic carbon centers through copper-catalyzed enantioselective allylic cross-coupling with alkylboranes

Article abstract of DOI:10.1002/anie.201402386

A combination of an in situ generated chiral Cu^I/DTBM-MeO-BIPHEP catalyst system and EtOK enabled the enantioselective S_N2'-type allylic cross-coupling between alkylborane reagents and γ,γ- disubstituted primary allyl chlorides with enantiocontrol at a useful level. The reaction generates a stereogenic quaternary carbon center having three sp ³-alkyl groups and a vinyl group. This protocol allowed the use of terminal alkenes as nucleophile precursors, thus representing a formal reductive allylic cross-coupling of terminal alkenes. A reaction pathway involving addition/elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.

Full text of DOI:10.1002/anie.201402386

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Angewandte
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DOI: 10.1002/anie.201402386
Asymmetric Catalysis
Construction of Quaternary Stereogenic Carbon Centers through
Copper-Catalyzed Enantioselective Allylic Cross-Coupling with
Alkylboranes**
Kentaro Hojoh, Yoshinori Shido, Hirohisa Ohmiya,* and Masaya Sawamura*
Abstract: A combination of an in situ generated chiral CuI/
DTBM-MeO-BIPHEP catalyst system and EtOK enabled the
enantioselective SN2’-type allylic cross-coupling between alkyl-
borane reagents and g,g-disubstituted primary allyl chlorides
with enantiocontrol at a useful level. The reaction generates
a stereogenic quaternary carbon center having three sp3-alkyl
groups and a vinyl group. This protocol allowed the use of
terminal alkenes as nucleophile precursors, thus representing
a formal reductive allylic cross-coupling of terminal alkenes. A
reaction pathway involving addition/elimination of a neutral
alkylcopper(I) species with the allyl chloride substrate is
proposed.
struction of tertiary carbon stereogenic centers using g-
monosubstituted primary allylic substrates. Herein we report
that a combination of an in situ generated CuI/DTBM-MeO-
BIPHEP chiral catalyst system and EtOK enabled the
enantioselective SN2’-type allylic cross-coupling between
alkylborane (alkyl-9-BBN) reagents and g,g-disubstituted
primary allyl chlorides with enantiocontrol at a useful
level.[6–8] The reaction generates a quaternary carbon stereo-
genic center bearing three sp3-alkyl groups and a vinyl group.
The overall protocol employs terminal alkenes as nucleophile
precursors, thus representing a formal reductive allylic cross-
coupling of terminal alkenes.
C
atalytic enantioselective construction of all-carbon quater-
nary stereogenic centers in acyclic systems is one of the
biggest challenges in organic synthesis.[1] One of the obstacles
is low reactivity because of the steric repulsion that occurs in
the carbon–carbon bond-formation step. It is also difficult to
discriminate the enantiotopic faces because of steric conges-
tion and the diminished steric difference between the non-
hydrogen substituents. To this end, transition metal catalyzed
enantioselective allylic substitutions with organometallic
nucleophiles such as organolithium, Grignard, diorganozinc,
or triorganoaluminum reagents have proven to be effective
strategies.[2] Organoboron compounds have also been used for
enantioselective construction of all-carbon quaternary ste-
reogenic centers through allylic substitution, thus making this
strategy more tolerant to various functional groups.[3] How-
ever, applied organoboron reagents are limited to aryl-,
alkenyl-, allenyl-, and allylboron compounds. The method-
ology has not yet been generalized to allow the reaction of
non-allylic alkylboron nucleophiles.[4]
Our earlier investigation on the copper-catalyzed enan-
tioselective reaction between alkylboranes and g-monosub-
stituted primary allyl chlorides indicated that introducing 3,5-
di-tert-butyl-4-methoxyphenyl (DTBM) substituents on the
phosphorus atoms of chiral bis(phosphine)s was important for
promotion of the reaction.[5] We assumed that the introduc-
tion of the DTBM substituents would induce the deaggrega-
tion of the alkylcopper(I) species to form a catalytically active
monomeric copper complex.[9] On the basis of this consider-
ation, we examined copper complexes prepared from
[CuOTf·(toluene)0.5] (10 mol%) and various DTBM-substi-
tuted chiral bisphosphine ligands for catalytic activity, g-
regioselectivity, and enantioselectivity in the reaction of the
g,g-disubstituted allyl chloride (E)-3a with alkylborane 2a in
the presence of EtOK in 1,4-dioxane/CH2Cl2 (1:3) at 258C for
20 hours (3a/2a/EtOK 1:1.25:1.1) (Table 1, entries 1–4).[5,10,11]
As in the previous study with g-monosubstituted allyl
chlorides, 2a was prepared in advance through hydroboration
of 3,4-dimethoxy-1-allylbenzene (1a) with (9-BBN-H)2 (3a/
1a/B 1:1.3:1.25) at 608C for 1 hour and was used without
purification. The conversion of 1a into 2a with a full
consumption of 9-BBN-H was confirmed by 1H and
11B NMR spectroscopy. The amount of EtOK was adjusted
so that 2a was in a slight excess (2a/EtOK 1.1:1) to ensure full
consumption of EtOK for the formation of CuOEt and
a borate (2a’) species.[12] Accordingly, yields of the allylation
product 4aa were calculated based on 3a. Specifically, the
catalyst prepared from the DTBM-substituted TunePHOS-
type chiral bis(phosphine) L1 did not promote the reaction at
all (entry 1).[13] (R)-DTBM-BINAP (L2) induced only low
Earlier, we reported the enantioselective SN2’-type reac-
tion between alkylboron compounds (alkyl-9-BBN) and
substituted allyl chlorides under the catalysis of a CuI/
DTBM-SEGPHOS system [Eq. (1); Tf = trifluoromethane-
sulfonyl].[5] However, the protocol was limited to the con-
[*] K. Hojoh, Y. Shido, Prof. Dr. H. Ohmiya, Prof. Dr. M. Sawamura
Department of Chemistry, Faculty of Science
Hokkaido University, Sapporo 060-0810 (Japan)
E-mail: ohmiya@sci.hokudai.ac.jp
sawamura@sci.hokudai.ac.jp
Homepage: http://wwwchem.sci.hokudai.ac.jp/~orgmet/
index.php
[**] This work was supported by Grants-in-Aid for Young Scientists (A)
and Challenging Exploratory Research, JSPS, to H.O. and by CREST
and ACT-C, JST, to M.S.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402386.
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dihedral angle of the axially chiral biaryl scaffolds in the CuI/
bis(phosphine) complexes.
Table 1: Copper-catalyzed enantioselective cross-coupling between 2a
and (E)-3a under various reaction conditions.[a]
The product yield with the Cu/L4 system could be
increased to 56% by changing the solvent to THF/CH2Cl2
(1:3) with the enantioselectivity almost unchanged (81% ee;
Table 1, entry 5). The yield was further improved to 65% by
conducting the reaction at 158C with an increased amount of
the 2a/EtOK reagent (3a/2a/EtOK 1:1.7:1.5; entry 6).
The reaction of the Z-configured allyl chloride (Z)-3a
under the conditions optimal for the reaction of (E)-3a
(Table 1, entry 6) provided (R)-4aa, the antipode of the
product derived from (E)-3a, with 61% ee in 85% yield
[Eq. (2)].[10,11] This enantioselectivity is lower than that for the
reaction of (E)-3 (see below for discussion on enantioselec-
tion models).
Entry
L
Solvent
T
Yield g/a[c]
[8C] [%][b]
ee
[%][d]
1
2
3
4
L1 1,4-1,4-dioxane/CH2Cl2 25
0
–
–
L2 1,4-dioxane/CH2Cl2
L3 1,4-dioxane/CH2Cl2
L4 1,4-dioxane/CH2Cl2
L4 THF/CH2Cl2
25
25
25
25
15
38
15
26
56
65
3.5:1 21
6:1 47
>20:1 83
>20:1 81
>20:1 81
5
6[e]
L4 THF/CH2Cl2
[a] Reaction conditions for hydroboration: 1a (0.26 mmol), (9-BBN-H)2
(0.125 mmol; 1a/B 1.05:1); 608C, 1 h. 2a (0.25 mmol) was used without
purification. Reaction conditions for enantioselective coupling reaction:
(E)-3a (0.2 mmol), 2a (0.25 mmol), EtOK (0.22 mmol), [CuOTf·-
(toluene)0.5] (10 mol%), L (10 mol%), solvent (0.8 mL), 20 h. [b] Yield of
the isolated product. [c] Determined by 1H NMR analysis of the crude
reaction mixture. [d] The enantiomeric excess was determined by HPLC
analysis. [e] Reaction at 0.3 mmol scale. 2a (0.52 mmol) and EtOK
(0.45 mmol) were used. THF=tetrahydrofuran.
Various terminal alkenes were subjected to 9-BBN-
hydroboration and were used for coupling with (E)-3a using
[CuOTf·(toluene)0.5] (10 mol%), L4 (10 mol%), and EtOK in
THF/CH2Cl2 (1:3) at 158C for 20 hours (Table 2, entries 1–
7).[10,11] The copper-catalyzed coupling reactions proceeded
with excellent g-selectivity and good to high enantioselectiv-
ities. Various terminal alkenes having different functional
groups such as acetal, ester, chloro, silyl ether, and benzyl
ether moieties in the aliphatic chain were compatible with this
protocol (entries 1–6).
Ethylene also served as a suitable substrate (entry 7).[10,11]
This reaction delivered an ethyl group to the fully substituted
g-carbon atom of (E)-3a with enantioselectivity at a useful
level.
The scope with respect to the g,g-disubstituted allyl
chlorides (3) is also shown in Table 2 (entries 8–10).[10,11] An
additional trisubstituted alkene moiety in the allylic substrate
(E)-3b was tolerated for the formation of the diene 4ab
(entry 8). The copper catalyst system enabled the enantiose-
lective coupling of allyl chlorides having two alkyl substitu-
ents of almost equal steric demand at the g-position (entries 9
and 10). For example, the allyl chloride (E)-3c having ethyl
and phenylethyl groups at the g-position, reacted with a high
enantioselectivity (entry 9). Replacing the ethyl group at the
g-position of (E)-3c with a propyl group caused only a slight
reduction in the enantioselectivity (entry 10).
A possible catalytic cycle for the g-selective allylic
coupling is illustrated in Figure 1.[5,6a–c] As proposed for the
copper-catalyzed enantioselective reaction between alkylbor-
anes and g-monosubstituted primary allyl chlorides, the active
organocopper species is likely in the form of a neutral
organocopper(I) species (C) rather than a mono-organo-
heterocuprate, as EtOK is consumed for the formation of 2’
and the copper center bearing the alkyl ligand and L4 is
catalytic activity, g-selectivity, and enantioselectivity
(entry 2). (R)-DTBM-SEGPHOS (L3), which exhibited
high performance in the previously reported reaction with
g-monosubstituted primary allyl chlorides [Eq. (1)], imparted
moderate g-selectivity (g/a 6:1) and enantioselectivity (47%
ee), but the product yield was lower than that obtained with
L2 (entry 3). To our delight, the use of (R)-DTBM-MeO-
BIPHEP (L4) led to a significant improvement in the
regioselectivity and enantioselectivity (entry 4).[14] The alky-
lation occurred at the disubstituted g-carbon atom of 3a (g/
a > 20:1), thus constructing the all-carbon quaternary stereo-
genic center with 83% ee in favor of the formation of (S)-4aa
(Si face attack), albeit still with a low product yield. These
results suggest that the catalytic activity, g-selectivity, and
enantioselectivity of this reaction are very sensitive to the
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Table 2: Scope of enantioselective allylic cross-coupling with alkylboranes.[a]
ꢀ
allyl)copper(III) species with a C Cu s bond at either
the a- or g-carbon atom. Reductive elimination of
these allylcopper(III) intermediates may form a mix-
ture of the a- and g-coupling product as a minor
product.[15,16]
We propose the enantioselection models depicted
Entry Alkene
Chloride
Product
Yield ee
[%][b,c] [%][d] in Figure 2 based on the fact that the reactions of E
and Z isomers of 3a gave the each of the antipodes of
4, respectively, with the former showing higher
enantioselectivity [Table 1, entry 6 versus Eq. (2)].
In the p-complex C (see Figure 1), the allyl chloride
substrate (3) bound to the tetrahedral copper center is
in proximity to the two P substituents Ar1 and Ar3,
which are axial and equatorial substituents, respec-
tively, of the bis(phosphine)/Cu chelate ring. The axial
substituent Ar1 points toward the substrate more than
the equatorial Ar3. Rl and Rs indicate the larger and
smaller g-substituents, respectively, of 3. C1, which
leads to the major enantiomer of 4 in the reaction of
(E)-3, has steric repulsion only between Rs and Ar3,
while the corresponding p complex (C2), leading to
the minor enantiomer, has larger steric repulsions
between the ClCH2 group and Ar1 and between Ar3
and Rl. A similar discussion should be applicable for
the transition-state D-TS.
1
2
(E)-3a
(E)-3a
79
90
66
81
3[e]
4
(E)-3a
(E)-3a
(E)-3a
(E)-3a
(E)-3a
80
85
70
68
63
86
83
86
81
71
5[f]
6
7
In the case of the reaction of (Z)-3, the p-complex
C3 (Figure 2), which leads to the major enantiomer
and the antipode of the product from C1, has a steric
repulsion between Ar3 and Rl, and it should be larger
than the steric repulsion that occurs in C1 (Rl versus
Rs). In contrast, the steric repulsion between Ar3 and
Rs in C4 should be smaller than that between Ar3 and
Rl in C2. These considerations also match the
observed trend that the enantioselectivity gradually
decreased with the increase of the size of the Rs
substituent of (E)-3 (Table 2, entries 1, 9, and 10).
This trend can be explained by the increasing steric
repulsion between Ar3 and Rs in C1.
8
1a
54
73
9[e]
1b
1b
75
67
81
71
10[e]
[a] Reaction conditions for hydroboration: 1 (0.35 mmol), (9-BBN-H)2 (0.17 mmol;
1/B 1.05:1); 608C, 1 h. 2 (0.34 mmol) was used without purification. Reaction
conditions for enantioselective coupling reaction: (E)-3 (0.2 mmol), 2 (0.34 mmol),
EtOK (0.3 mmol), [CuOTf·(toluene)0.5] (10 mol%), L4 (10 mol%), THF/CH2Cl2 (1:3,
0.8 mL); 158C, 20 h. [b] Yield of the isolated product. [c] Constitutional isomer ratio
g/a>20:1 (determined by 1H NMR analysis of the crude reaction mixture). [d] The
enantiomeric excess was determined by HPLC analysis. [e] Constitutional isomer
ratio g/a>10:1. [f] Diastereomeric ratio (1:1). THP=tetrahydropyran, TIPS=trii-
sopropylsilyl.
In summary, we have developed an SN2’-type
enantioselective allylic cross-coupling between alkyl-
9-BBN reagents and g,g-disubstituted primary allyl
chlorides under the catalysis of a CuI/DTBM-MeO-
coordinatively saturated upon alkene coordination.[12] There-
fore, the reaction should proceed through an addition/b-
elimination sequence with the neutral organocopper(I) spe-
cies B. The enantioselection would occur at the transition
1
ꢀ
ꢀ
state of the R Cu addition across the C C double bond of
(E)-3 [C!D-TS!(E!) A + 4 + 9-BBN-OEt]. During this
addition/elimination step, 9-BBN-OEt may act as a Lewis
acid to assist the elimination of the chloride leaving group.[5,6c]
The formation of the a-coupling product in the reaction
with (R)-DTBM-BINAP (L2) or (R)-DTBM-SEGPHOS
(L3) might be due to the formation of alkyl(ethoxo)cuprate
species upon dissociation of one or two P atoms of the chiral
ligands. Such cuprate species would undergo oxidative
addition with 3 to form an isomeric mixture of ([s + p]-
Figure 1. A possible catalytic cycle.
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[2] For reviews on copper-catalyzed enantioselective allylic substi-
tutions with organomagnesium, organozinc, or organoaluminum
reagents, see: a) A. H. Hoveyda, A. W. Hird, M. A. Kacprzynski,
Chem. Commun. 2004, 1779 – 1785; b) C. A. Falciola, A. Alex-
akis, Eur. J. Org. Chem. 2008, 3765 – 3780; c) A. Alexakis, J. E.
Bꢁckvall, N. Krause, O. Pꢂmies, M. Diꢃguez, Chem. Rev. 2008,
108, 2796 – 2823; d) S. R. Harutyunyan, T. den Hartog, K.
Geurts, A. J. Minnaard, B. L. Feringa, Chem. Rev. 2008, 108,
2824 – 2852; for an enantioselective construction of all-carbon
quaternary stereogenic centers through copper-catalyzed allylic
substitutions with alkyllithium reagents, see: e) M. FaÇanꢄs-
Mastral, M. Pꢃrez, P. H. Bos, A. Rudolph, S. R. Harutyunyan,
B. L. Feringa, Angew. Chem. 2012, 124, 1958 – 1961; Angew.
Chem. Int. Ed. 2012, 51, 1922 – 1925.
[3] For a review on transition metal catalyzed allylic substitutions
with organoboron compounds, see: F. C. Pigge, Synthesis 2010,
1745 – 1762.
Figure 2. Proposed models for enantiodiscrimination. Rl and Rs are the
larger and smaller g-substituents, respectively, of 3. Ar1–Ar4 are the P-
substituents of L4. The biaryl scaffold of L4 is simplified with
a polygonal line.
[4] For enantioselective constructions of all-carbon quaternary
stereogenic centers through copper-catalyzed allylic substitu-
tions with aryl-, alkenyl-, allenyl-, and allylboron nucleophiles,
see: a) P. Zhang, H. Le, R. E. Kyne, J. P. Morken, J. Am. Chem.
Soc. 2011, 133, 9716 – 9719; b) R. Shintani, K. Takatsu, M.
Takeda, T. Hayashi, Angew. Chem. 2011, 123, 8815 – 8818;
Angew. Chem. Int. Ed. 2011, 50, 8656 – 8659; c) B. Jung, A. H.
Hoveyda, J. Am. Chem. Soc. 2012, 134, 1490 – 1493; d) F. Gao,
J. L. Carr, A. H. Hoveyda, Angew. Chem. 2012, 124, 6717 – 6721;
Angew. Chem. Int. Ed. 2012, 51, 6613 – 6617.
BIPHEP system to deliver enantioenriched chiral products
containing quaternary carbon stereogenic centers bearing
three sp3-alkyl groups and a vinyl group. This protocol
allowed the use of terminal alkenes as nucleophile precursors,
thus representing a formal reductive allylic cross-coupling of
terminal alkenes. Efforts to expand the utility of this reaction
and mechanistic works are ongoing in our laboratory.
[5] Y. Shido, M. Yoshida, M. Tanabe, H. Ohmiya, M. Sawamura, J.
Am. Chem. Soc. 2012, 134, 18573 – 18576.
[6] For copper-catalyzed g-selective and stereospecific allylic sub-
stitutions of secondary allylic phosphates with alkyl-9-BBN
reagents, see: a) H. Ohmiya, U. Yokobori, Y. Makida, M.
Sawamura, J. Am. Chem. Soc. 2010, 132, 2895 – 2897; b) K.
Nagao, H. Ohmiya, M. Sawamura, Synthesis 2012, 1535 – 1541;
c) K. Nagao, U. Yokobori, Y. Makida, H. Ohmiya, M. Sawamura,
J. Am. Chem. Soc. 2012, 134, 8982 – 8987; see also: d) A. M.
Whittaker, R. P. Rucker, G. Lalic, Org. Lett. 2010, 12, 3216 –
3218; e) H. Ohmiya, U. Yokobori, Y. Makida, M. Sawamura,
Org. Lett. 2011, 13, 6312 – 6315.
[7] For copper-catalyzed enantioselective conjugate addition with
alkyl-9-BBN reagents, see: a) M. Yoshida, H. Ohmiya, M.
Sawamura, J. Am. Chem. Soc. 2012, 134, 11896 – 11899; See
also: b) H. Ohmiya, M. Yoshida, M. Sawamura, Org. Lett. 2011,
13, 482 – 485; c) H. Ohmiya, Y. Shido, M. Yoshida, M. Sawa-
mura, Chem. Lett. 2011, 40, 928 – 930.
[8] Fu and co-workers reported the nickel-catalyzed enantioselec-
tive cross-couplings between alkyl-9-BBN and secondary alkyl
halides. The methodology has not been expanded yet to the
enantioselective construction of all-carbon quaternary stereo-
genic centers. See: a) B. Saito, G. C. Fu, J. Am. Chem. Soc. 2008,
130, 6694 – 6695; b) N. A. Owston, G. C. Fu, J. Am. Chem. Soc.
2010, 132, 11908 – 11909; c) Z. Lu, A. Wilsily, G. C. Fu, J. Am.
Chem. Soc. 2011, 133, 8154 – 8157; d) S. L. Zultanski, G. C. Fu, J.
Am. Chem. Soc. 2011, 133, 15362 – 15364; e) A. Wilsily, F.
Tramutola, N. A. Owston, G. C. Fu, J. Am. Chem. Soc. 2012, 134,
5794 – 5797.
Experimental Section
Typical procedure for copper-catalyzed enantioselective allylic cross-
coupling with alkylboranes (Table 1, entry 6). 3,4-Dimethoxy-1-
allylbenzene (1a; 93.4 mL, 0.54 mmol) and (9-BBN-H)2 (64.2 mg,
0.26 mmol) were placed in a vial containing a magnetic stirring bar.
The vial was sealed with a Teflonꢀ-coated silicon rubber septum and
the vial was evacuated and filled with argon. THF (0.3 mL) was added
to the vial, and then the mixture was stirred at 608C for 1 h to prepare
an
alkylborane.
Meanwhile,
[CuOTf·(toluene)0.5
]
(7.8 mg,
0.03 mmol), (R)-DTBM-MeO-BIPHEP (L4) (35.5 mg, 0.03 mmol),
and EtOK (39.9 mg, 0.45 mmol) were placed in another vial. This vial
was sealed with a Teflonꢀ-coated silicon rubber septum and then
evacuated and filled with argon. After CH2Cl2 (0.9 mL) was added to
the vial, the mixture was stirred at 258C for 1 h. Next, the alkylborane
solution was transferred to the vial containing the CuI/L4 complex.
Next, (E)-3a (58.5 mg, 0.3 mmol) was added. After 20 h of stirring at
158C, diethyl ether was added to the mixture. The mixture was
filtered through a short plug of silica gel, and was then washed with
diethyl ether. After the solvent was removed under reduced pressure,
flash chromatography on silica gel (0–3% EtOAc/hexane) provided
4aa (66.0 mg, 0.20 mmol) at 81% ee in 65% yield.
Received: February 13, 2014
Published online: March 25, 2014
[9] For discussion on the effect of the DTBM groups in the
enantioselective copper-catalyzed hydrosilylation of aryl
ketones, see: B. H. Lipshutz, K. Noson, W. Chrisman, A.
Lower, J. Am. Chem. Soc. 2003, 125, 8779 – 8789.
[10] For Tables 1 and 2, and Eq. (2), small amounts of dechlorinated
compounds which stemmed solely from the allyl chloride (3)
were detected in the crude reaction mixture after removal of the
catalyst.
Keywords: allylic compunds · asymmetric catalysis · boron ·
.
copper · synthetic methods
[11] The absolute configuration of 4ha was determined by trans-
forming it to a known compound. See the Supporting Informa-
tion for details. Absolute configurations of 4aa and the other
[1] a) J. P. Das, I. Marek, Chem. Commun. 2011, 47, 4593 – 4623;
b) I. Marek, Y. Minko, M. Pasco, T. Mejuch, N. Gilboa, H.
Chechik, J. P. Das, J. Am. Chem. Soc. 2014, 136, 2682 – 2694.
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products listed in Table 2 were assigned by consideration of the
stereochemical pathway.
of Table 1, decreased the product yield (14% yield) with the
regioselectivity and enantioselectivity unchanged (g/a > 20:1,
83% ee). The use of tBuOK resulted in no reaction.
[15] a) N. Yoshikai, S.-L. Zhang, E. Nakamura, J. Am. Chem. Soc.
2008, 130, 12862 – 12863; b) M. Yamanaka, S. Kato, E. Naka-
mura, J. Am. Chem. Soc. 2004, 126, 6287 – 6293; For a review,
see: c) N. Yoshikai, E. Nakamura, Chem. Rev. 2012, 112, 2339 –
2372.
[16] Liu and co-workers proposed an SN2-type substitution of
arylcuparate species with primary alkyl (pseudo)halides in the
copper-catalyzed cross-coupling reaction with arylboronate
reagents. See: C.-T. Yang, Z.-Q. Zhang, Y.-C. Liu, L. Liu,
Angew. Chem. 2011, 123, 3990 – 3993; Angew. Chem. Int. Ed.
2011, 50, 3904 – 3907.
[12] Rapid and quantitative formation of a tetravalent borate (2’) was
confirmed by 11B NMR spectroscopy. Treatment of 2a with
EtOK in THF/CH2Cl2 (1:3) at 258C for 10 min caused a complete
disappearance of the signal for 2a (d = 69.6 ppm, RT), and a new
signal appeared at the higher magnetic field (d = ꢀ3.1 ppm),
which was assigned to 2aꢀ.[6a] Subsequent mixing of the borate
with one equiv of CuOTf·(toluene)0.5/(R)-DTBM-MeO-
BIPHEP (L4) at 258C for 15 min formed 9-BBN-OEt (d =
55.6 ppm, RT). See the Supporting Information for details of
the NMR studies.
[13] X. Sun, L. Zhou, W. Li, X. Zhang, J. Org. Chem. 2008, 73, 1143 –
1146.
[14] EtOK was optimal among the bases screened. The use of MeOK
instead of EtOK under the reaction conditions used for entry 4
4958 www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 4954 –4958