Cationic Co(I)-intermediates for hydrofunctionalization reactions: Regio- A nd enantioselective cobalt-catalyzed 1,2-hydroboration of 1,3-dienes

Article abstract of DOI:10.1021/jacs.8b13812

Much of the recent work on catalytic hydroboration of alkenes has focused on simple alkenes and styrene derivatives with few examples of reactions of 1,3-dienes, which have been reported to undergo mostly 1,4-additions to give allylic boronates. We find that reduced cobalt catalysts generated from 1,n-bis-diphenylphosphinoalkane complexes [Ph₂P-(CH₂)_n-PPh₂]CoX₂; n = 1-5) or from (2-oxazolinyl)phenyldiarylphosphine complexes [(G-PHOX)CoX₂] (G = 4-substituent on oxazoline ring) effect selective 1,2-, 1,4-, or 4,3-additions of pinacolborane (HBPin) to a variety of 1,3-dienes depending on the ligands chosen. Conditions have been found to optimize the 1,2-additions. The reactive catalysts can be generated from the cobalt(II)-complexes using trimethylaluminum, methyl aluminoxane, or activated zinc in the presence of sodium tetrakis[(3,5-trifluoromethyl)phenyl]borate (NaBARF). The complex, (dppp)CoCl₂, gives the best results (ratio of 1,2-to 1,4-addition >95:5) for a variety of linear terminal 1,3-dienes and 2-substituted 1,3-dienes. The [(PHOX)CoX₂] (X = Cl, Br) complexes give mostly 1,4-addition with linear unsubstituted 1,3-dienes, but, surprisingly, selective 1,2-additions with 2-substituted or 2,3-disubstituted 1,3-dienes. Isolated and fully characterized (X-ray crystallography) Co(I)-complexes, (dppp)₃Co₂Cl₂ and [(S,S)-BDPP]₃Co₂Cl₂, do not catalyze the reaction unless activated by a Lewis acid or NaBARF, suggesting a key role for a cationic Co(I) species in the catalytic cycle. Regio- A nd enantioselective 1,2-hydroborations of 2-substituted 1,3-dienes are best accomplished using a catalyst prepared via activation of a chiral phosphinooxazoline-cobalt(II) complex with zinc and NaBARF. A number of common functional groups, among them,-OBn,-OTBS,-OTs, N-phthalimido-groups, are tolerated, and er's > 95:5 are obtained for several dienes including 1-alkenylcycloalk-1-enes. This operationally simple reaction expands the realm of asymmetric hydroboration to provide direct access to a number of nearly enantiopure homoallylic boronates, which are not readily accessible by current methods. The resulting boronates have been converted into the corresponding alcohols, potassium trifluororoborate salts, N-BOC amines, and aryl derivatives by C-BPin to C-aryl transformation.

Full text of DOI:10.1021/jacs.8b13812

Article
Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
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Cationic Co(I)-Intermediates for Hydrofunctionalization Reactions:
Regio- and Enantioselective Cobalt-Catalyzed 1,2-Hydroboration of
1
,3-Dienes
‡
‡
‡
Krishnaja Duvvuri, Kendra R. Dewese, Mahesh M. Parsutkar, Stanley M. Jing, Milauni M. Mehta,
Judith C. Gallucci, and T. V. RajanBabu*
Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, United
States
*
S Supporting Information
ABSTRACT: Much of the recent work on catalytic hydro-
boration of alkenes has focused on simple alkenes and styrene
derivatives with few examples of reactions of 1,3-dienes, which
have been reported to undergo mostly 1,4-additions to give
allylic boronates. We find that reduced cobalt catalysts
generated from 1,n-bis-diphenylphosphinoalkane complexes
[
Ph P-(CH ) -PPh ]CoX ; n = 1−5) or from (2-oxazolinyl)-
2
2 n
2
2
phenyldiarylphosphine complexes [(G-PHOX)CoX ] (G = 4-
2
substituent on oxazoline ring) effect selective 1,2-, 1,4-, or 4,3-
additions of pinacolborane (HBPin) to a variety of 1,3-dienes
depending on the ligands chosen. Conditions have been found to optimize the 1,2-additions. The reactive catalysts can be
generated from the cobalt(II)-complexes using trimethylaluminum, methyl aluminoxane, or activated zinc in the presence of
sodium tetrakis[(3,5-trifluoromethyl)phenyl]borate (NaBARF). The complex, (dppp)CoCl , gives the best results (ratio of 1,2-
2
to 1,4-addition >95:5) for a variety of linear terminal 1,3-dienes and 2-substituted 1,3-dienes. The [(PHOX)CoX ] (X = Cl, Br)
2
complexes give mostly 1,4-addition with linear unsubstituted 1,3-dienes, but, surprisingly, selective 1,2-additions with 2-
substituted or 2,3-disubstituted 1,3-dienes. Isolated and fully characterized (X-ray crystallography) Co(I)-complexes,
(
dppp) Co Cl and [(S,S)-BDPP] Co Cl , do not catalyze the reaction unless activated by a Lewis acid or NaBARF,
3 2 2 3 2 2
suggesting a key role for a cationic Co(I) species in the catalytic cycle. Regio- and enantioselective 1,2-hydroborations of 2-
substituted 1,3-dienes are best accomplished using a catalyst prepared via activation of a chiral phosphinooxazoline-cobalt(II)
complex with zinc and NaBARF. A number of common functional groups, among them, -OBn, -OTBS, -OTs, N-phthalimido-
groups, are tolerated, and er’s > 95:5 are obtained for several dienes including 1-alkenylcycloalk-1-enes. This operationally
simple reaction expands the realm of asymmetric hydroboration to provide direct access to a number of nearly enantiopure
homoallylic boronates, which are not readily accessible by current methods. The resulting boronates have been converted into
the corresponding alcohols, potassium trifluororoborate salts, N-BOC amines, and aryl derivatives by C-BPin to C-aryl
transformation.
INTRODUCTION
lective hydroborations of di- and trisubstituted 1,3-diene
substrates have not been reported. There are several reports
of 1,4/4,1-additions of boranes to various acyclic 1,3-dienes.
■
1
Regio- and enantioselective hydrofunctionalization of prochiral
,3-dienes, which are among the most readily available starting
5
materials for organic synthesis, can provide intermediates with
multiple latent functionalities for further synthetic elabo-
ration. As one of the most useful hydrofunctionalization
Yet, except for one report of selective additions of catechol
borane to (E)-penta-1,3-diene (Figure 1A), examples of 1,2-
6
1
(
anti-Markovnikov) hydroborations of substituted 1,3-dienes
reaction, metal-catalyzed vicinal hydroboration of alkenes has a
7
8
are limited to two substrates, myrcene and isoprene. While
2
,3
long history. However, enantioselective hydroboration of
,3-dienes to produce chiral intermediates from even the least
enantioselective Pt-catalyzed 1,2- and 1,4-diborations of acyclic
1
1j,9
1
,3-dienes are known, documented cases of useful levels of
complex among these substrates, monosubstituted (E)-1,3-
dienes (1, R = H, R = H, R = H, R = alkyl), presents a
regioselectivity and enantioselectivity in 1,2-hydroboration in
acyclic 1,3-dienes are limited to a publication describing a Cu-
catalyzed addition of bis-pinacolborane, which just appeared
1
2
3
4
significant challenge because of the possibility of 1,2- and 1,4-
additions leading to chiral and achiral products, and geo-
metrical isomers of the residual double bond in some of the
4
products (eq 1). Additional substituents, for example, at C −
3
Received: December 27, 2018
1
C positions further exacerbate this problem, and enantiose-
©
XXXX American Chemical Society
A
DOI: 10.1021/jacs.8b13812
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Journal of the American Chemical Society
Article
catalysts for highly efficient regio- and enantioselective
1h,12
codimerizations of prototypical 1,3-dienes and ethylene.
The Zn/NaBARF-mediated reactions also work for hetero-
1d
dimerization of 1,3-dienes and acrylates. Isolated Co(I)
complex (dppp) Co Br in the absence of an activator does not
3
2
2
catalyze these dimerization reactions. However, in the presence
of activators like NaBARF or (C F ) B a quantitative reaction
6
5 3
1d
ensues. We wondered if these catalyst systems would also
effect selective hydroboration reactions of 1,3-dienes. The
studies that followed revealed several novel aspects of this
venerable reaction (Figure 1C), including a possible role of a
cationic Co(I)-catalyst, the details of which are reported here.
RESULTS AND DISCUSSION
■
Selective 1,2-Hydroboration of 1,3-Dienes. Our early
studies concentrated on the reaction between a prototypical
1
,3-diene, (E)-1,3-nonadiene (1a), and pinacolborane (HBPin,
Pin = 2,3-dimethylbutane-2,3-dioxy) in the presence of 5 mol
of (L)CoCl [L = bis-1,n-diphenylphosphinoalkane, n = 1−
%
5
2
, Figure 2) and various activators/reducing agents at room
temperature to give two major products 2a (a 1,2-adduct) and
3
a (a 1,4-adduct), along with 0−5% of an isomerization
13
product 4a (eq 4, Table 1).
In sharp contrast to
6
catecholborane, HBPin showed no reactivity with dienes in
the presence of Co(II)-complexes without an activator such as
trimethylaluminum (TMA) or methylaluminoxane (MAO)
(eq 4, Table 1, entries 1−3 vs entries 4 and 5). A quick
Figure 1. Selectivity in hydroboration of 1,3-dienes.
1
0
(
2
Figure 1B, eq 3), and our own preliminary disclosure in
11
13
017 (Figure 1C).
Our interest in this problem had its origin in the cobalt
optimization of activators and solvents (Table 1) revealed
that, for the formation of the 1,2- and 1,4-adducts (2a and 3a),
methyl aluminoxane (MAO) in methylene chloride or ether
was the most suitable solvent (entries 4 and 5), with the latter
giving slightly better regioselectivity (2a:3a = 95:5) for the 1,2-
catalysis of enantioselective diene−alkene heterodimerization
reactions. During these investigations we identified what
appeared to be a Co(I)-species, generated by treatment of
13
(
L−L)CoX [(L−L) = 1,n-bis-diphenylphosphinoalkane)]
addition.
2
1d
either with trimethylaluminum or with zinc and NaBARF
Compared to MAO, TMA gave lower selectivity (entry 4 vs
entry 8). 1,2-Dimethoxyethane and THF were acceptable
(
BARF = tetrakis-[(3,5-bis-trifluoromethyl)phenyl]borate), as
Figure 2. Ligands and Co(I) complex used in scouting experiments (Tables 1 and 2).
B
DOI: 10.1021/jacs.8b13812
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Journal of the American Chemical Society
Article
a
Table 1. Effect of Activators, Solvents on (dppp)Co(I)-Catalyzed Hydroboration of (E)-1,3-Nonadiene (1a)
entry
catalyst (mol %)
activator (equiv)
Zn (equiv)
solvent
time
44 h
44 h
conv (%)
2a:3a:4a
1
2
3
4
5
6
7
8
9
0
10
0
5
5
5
5
10
5
5
0
0
0
0
0
0
0
0
0
0
0
1
1
0
1
1
0
0
0
−
ether
ether
0
0
0
−
−
−
MAO (2)
MAO (2)
MAO (2)
MAO (2)
MAO (2)
TMA (0.3)
MAO (2)
CH Cl2
2.5 h
2
CH Cl2
5 min
5 min
20 h
18 h
15 min
20 h
30 min
2 h
30 min
30 min
24 h
5 min
45 min
24 h
100
100
100
100
100
0
100
100
88
100
<5
100
100
0
90:10:0
95:5:0
94:6:0
95:5:0
46:54:0
−
82:14:4
68:32:0
82:13:5
73:19:7
−
2
ether
DME
THF
b
CH Cl2
2
PhCH3
ether
ether
ether
ether
ether
10
11
12
13
14
15
16
17
18
NaBARF (0.1)
5
5
5
AgSbF (0.1)
6
NaBARF (0.1)
InBr (0.1)
3
5
0
c
Co(I): 5a
Co(I): 5a
Co(I): 5a
NaBARF (0.04)
NaBARF (0.04), −20 °C
CH Cl2
83:14:3
89:11:0
−
2
c
CH Cl2
2
c
0
CH Cl2
2
d
5
Various
CH Cl2
0.5−2 h
0
−
2
a
See eqs 4 (entries 1−9) and 5 (entries 10−17) for typical procedures (see Supporting Information, p S16 for details). Catalyst (dppp)CoCl used
2
b
c
unless otherwise noted (entries 15−17). See Supporting Information for further details. Me Al at −10 °C. Recrystallized Co(I) complex
Co (dppp) Cl (5a) used (1 mol %). (dppp)CoCl with AlCl , Et Al, EtAlCl , Et AlCl, Me AlCl, EtMgBr, or NaB(H)Et (all at rt). See Table S2
3
d
2
3
2
2
3
3
2
2
2
3
(
p S19) for further details.
Table 2. Effect of Ligands on Regioselectivity of Hydroboration of (E)-1,3-Nonadiene (1a)a,b
c
entry
catalyst (5 mol %)
activator (equiv)
MAO (2)
MAO (2)
MAO (2)
MAO (2)
MAO (2)
MAO (2)
solvent
time
4 h
3 h
15 min
3 h
20 h
3 h
24 h
24 h
25 min
25 min
conv (%)
2a:3a:4a
1
2
3
4
5
6
(dppm)CoCl2
(dppe)CoCl2
(dppp)CoCl2
(dppb)CoCl2
(dpppent)CoCl2
(dppf)CoCl2
(i‑PrPDI)CoCl2
(ImPy)CoCl2
[PHOX]CoBr2
Et O
100
100
99
6:82:12
2
Et O
15:70:15
>95:5:0
71:19:10
100:0:0
58:21:21
41:59:0
2
Et O
2
Et O
100
2
d
Et O
80
2
Et O
100
2
b
d
7
b
NaBHEt (0.3)
Et O
56
57
3
2
d
8
NaBHEt (0.2)
THF
32:68:10
3
e
9
Zn (1), NaBARF (0.1)
Zn (1), NABARF (0.1)
Et O
2
100
100
30:70:0
9:89:1
1
0
[L5a]CoBr (R = Ph)
Et O
2
2
a
b
See eq 4 (entries 1−8) and eq 5 (entries 9, 10) and Supporting Information for details and a more complete set of Co(II)-complexes. See eqs 4
c
d
and 5 and Figures 2 and 4 for structures of ligands. Determined by GC where baseline separations of the isomers were observed. Remaining
material was reduction or isomerization of starting diene. In 24 h the ratio changed to 40:36:24.
e
(
entries 6 and 7; see also Table S1, p S19 in Supporting
product 4a increases progressively with time, suggesting that it
is indeed a secondary (isomerization) product. Replacement of
Information). But the reaction rate was significantly lower (up
to 18 h for complete reaction versus 5 min for ether or CH Cl
under otherwise similar conditions). Several other aluminum
NaBARF with AgSbF (0.1 equiv) led to a slow reaction (2 h)
2
2
6
giving a ratio of 68:32 for 2a to 3a (entry 11). While Zn alone
(in the absence of NaBARF) is not capable of effecting the
reaction (entry 14), surprisingly, NaBARF (in the absence of
Zn) appears to give the products in a relatively slow, yet clean
reaction (entry 12), with presumably HBPin acting as a
salts, Grignard reagents, and NaB(H)Et , commonly used for
3
activation of Co(II) complexes in catalytic hydrofunctionaliza-
tion reactions, were ineffective (entry 18; see also Table S2, p
S20). When there was no hydroboration, minor products
resulting from isomerization and/or reduction of the starting
material were observed.
8a,b
reducing agent to produce a competent Co(I)-catalyst.
InBr can be used as a replacement for NaBARF, with some
3
We also discovered that a more functional-group tolerant
catalyst system that effected heterodimerization of 1,3-dienes
deterioration of regioselectivity (entry 13).
In order to verify the role of a cationic Co(I)-intermediate in
these processes, we synthesized and fully characterized (X-ray
crystallography) a Co(I)-complex (dppp) Co Cl (5a, Figure
1
d
and alkyl acrylates was competent to effect the regioselective
hydroboration reactions of 1,3-dienes (eq 5 and Table 1,
entries 10−17), even though the 1,2:1,4-selectivity is slightly
3
2
2
13
2) and used this isolated complex for hydroboration studies.
1
3
lower (∼82:14) compared to the MAO-activated catalysts.
As expected, the isolated complex 5a (0.01 equiv) in the
presence of NaBARF (0.04 equiv) proceeded to give an
exceptionally clean, fast reaction (entry 15). Even at −20 °C
this complex (1 mol %) effected quantitative hydroboration of
the diene in ∼45 min (entry 16). The Co(I) complex 5a in the
absence of NaBARF showed no activity for several hours (entry
Thus, a combination of (dppp)CoCl (0.05 equiv), 1 equiv of
2
activated Zn, and 0.1 equiv of NaBARF gave a mixture of 2a,
3
a, and 4a in a ratio of 82:14:4 (entry 10; for further details,
see also Tables S4−S7 in Supporting Information, p S22).
Under these conditions, the proportion of the isomerization
C
DOI: 10.1021/jacs.8b13812
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Journal of the American Chemical Society
7). Among hydrocarbon solvents, toluene was unsuitable,
Article
1
leading to a complex reaction; hexane gave the three products
in a ratio of 85:12:2.
Ligand Effects. Further studies revealed that the
regioselectivity of the reaction is strongly dependent on the
nature of the ligand. In several instances significantly more of a
vinylboronate 4a, resulting from isomerization of the initial
adducts, is also formed, especially with ligands dppm, dppe,
dppb, and dppf (Table 2; see also Table S3 for a more
complete list, p S21). The reaction with ligands with a narrow
bite angle (dppm and dppe) gave a 1,4-adduct (3a) as the
major product (Table 2, entries 1 and 2). The iminopyridine
ligands (see Figure 2 for the structures of the ligands) were
included in this study (entries 7 and 8), since they have been
previously used in both Co- and Fe-catalyzed hydroboration
2
b,5c,7,14
reactions.
In the event, reduced cobalt complexes of
these imine ligands promoted only relatively sluggish non-
selective reactions (entries 7 and 8). Yet another imine-type
ligand we tested, phosphino-oxazoline, PHOX, and a phenyl-
15
substituted analog L5a (see Figure 2 and Figure 4 for
structures of ligands) also gave predominantly the 1,4-
hydroboration product upon activation by Zn and NaBARF
(
entries 9 and 10).
The scope of the reaction for a series of dienes was
explored under the optimized reaction conditions [eq 4, Table
, entry 5: (dppp)CoCl /MAO/ether/rt], and the results are
4b
1
2
shown in Figure 3. In most cases the reaction was complete
with 5 mol % catalyst in ether (0.1 M) as the solvent within 60
min leading to the terminal boronate (2) resulting from 1,2-
hydroboration. Higher proportions of the 1,4-adducts were
obtained in substrates carrying a relatively bulky 4-substituent
(2d:3d = 46:54; 2g:3g = 80:20). 3,4-Dialkyl 1,3-diene also
gave higher amounts of the 1,4-adduct (e.g., 2i:3i = 77:23).
The product distribution from isoprene and myrcene, two
dienes with 2-substituents, is particularly noteworthy for the
ligand dependence on the ratio of the 1,2- vs 1,4-adducts. With
Figure 3. Scope of regioselective 1,2-hydroboration of 1,3-dienes. See
Figure S1 (Supporting Information, p S6) for structures of precursor
1,3-dienes.
(
dppp)CoCl , isoprene gave a ratio of 2h:3h = 78:22, whereas
Scheme 1. 1,2-Hydroboration of Substituted 1,3-Dienes
2
myrcene gave a ratio of 2j:3j = 72:28. Both these substrates
gave an uncommonly high selectivity for the 1,4-adduct (2h:3h
=
2:98; 2j:3j = 2:98) with the phosphinooxazoline ligand L5d.
The reaction works well with 1-vinylcycloalkenes giving a high
proportion of the 1,2-hydroboration products (e.g., 2k, 2l,
2
m). The reaction was tolerant of common functional groups,
among them, the following groups: TBS-ether (2e), N-
phthalimido group (2f), and di- and trisubstituted alkene
(2g, 2j, 2l). We also noticed that the regioselectivity of the
reaction was dependent on the geometric isomeric purity of
the starting diene. For example, isomerically pure (3E)-(6R)-
impressive array of chiral intermediates generically represented
by 8 and 9 (X = -OR, -NHR, -alkyl, -alkenyl, -aryl, -halogen).
Our studies started with a preliminary evaluation of cobalt-
catalyzed hydroboration of three prototypical 2-substituted
6
,10-dimethyl)undeca-1,3−9-triene gave the product 2g:3g
with >80:20 selectivity for the 1,2:1,4-additions; however, for a
mixture of geometric isomers of (3E)-[(6R)]- and (3Z)-(6R)-
triene (44:56), a lower selectivity for the adducts was observed.
1
,3-dienes, 10a−c (Scheme 2), using the protocols outlined in
1,2-Hydroboration of 2-Substituted Dienes. Next our
eq 4 (LCoX , MAO activation) and eq 5 (LCoX , Zn/
2
2
attention turned to how we might exploit the novel
regioselectivity afforded by the cobalt catalysts for an
enantioselective reaction. We reasoned that, among the various
prochiral dienes, the novel and most impactful for this purpose
would be 2,4-disubstituted 1,3-dienes (6), which can option-
ally include a 3-substituent (Scheme 1). Such a substitution
pattern would also include R and R substituents as parts of a
carbocyclic or heterocyclic ring system. The products that
could be derived from resulting boronate (7) will include an
NaBARF activation). Of these, we chose the 2-ethyl diene 10b
for a detailed optimization for high selectivities for the
formation of the major chiral 1,2-adduct (11b), since this
substrate proved the most challenging. Like the other 2-
substituted dienes, 10b gave one major boronate regioisomer
(up to 97% of the mixture of boronates), 11b, along with two
minor products, 12b and 13b, corresponding to 1,2-, 1,4-, and
4,3-addition of HBPin to the diene (Scheme 2). A selection of
the most pertinent results from these studies are shown in
3
4
D
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Journal of the American Chemical Society
Article
Scheme 2. Selective 1,2-Hydroboration of 2-Substituted 1,3-
Dienes
were converted into the corresponding alcohols by oxidation
with H O for further analysis and identification.
2
2
The best results were obtained from activation of the
(
dppp)CoCl by reduction with zinc (1 equiv) in the presence
2
of NaBARF (10 mol %, Table 3, entry 1). Use of isolated
recrystallized) Co(I)-complex (dppp) Co Cl (5a, Figure 2)
(
3
2
2
in the presence of NaBARF resulted in the fastest and cleanest
reaction (5 min, 1 mol % Co(I) catalyst vs 25 min, 5 mol % in
situ generated Co(I) catalyst, entry 1 vs entry 2) under
otherwise identical conditions to give comparable selectivity
for the major isomer 11b (see also entry 15, Table 1 for a
similar reaction with (E)-nona-1,3-diene). The Co(II)-
complex derived from the achiral PHOX ligand (Figure 4)
was also found (entry 3) to be slightly more selective for the
production of the 1,2-adduct (11b:12b:13b = 97:3:0). This
surprising finding is in sharp contrast to the corresponding
reaction between HBPin and 1,3-dienes with no substituents at
C such as (E)-1,3-nonadiene (1a) where the cobalt complex
2
of this ligand led to a nonselective reaction with formation of a
1
,4-adduct as the major product (Table 2, entry 9).
Enantioselective 1,2-Hydroboration of 2-Substituted
Dienes. Enantioselective hydroboration of 10b was further
explored under the newly developed protocols (Scheme 2)
using various chiral ligands, and the results are shown in entries
4
−16 in Table 3. Structures of some of the chiral ligands and
that of a fully characterized (X-ray crystallography) Co(I)-
1
6
Table 3. The Supporting Information contains a more
elaborate table, Table S8 (p S24), with extensive details of
optimization of ligands, activators, and reaction parameters for
high selectivity for the formation of the 1,2-hydroboration
product, 11b. These experiments revealed that among the
achiral 1,n-bis-diphenylphosphino-ligands (Figure 4 for struc-
complex, [[(S,S)-BDPP] Co Cl ], used in this study are shown
3
2
2
17
in Figure 4. The products 11b, 12b, and 13b resulting from
the 1,2-, 1,4-, and 4,3-hydroborations (Scheme 2) were
oxidized to the corresponding alcohols (14b, 15b, and 16b).
Enantioselectivity for the major chiral alcohol products 14b
and 16b (the latter mostly seen only in entries 4 and 5) were
determined by chiral stationary phase gas chromatography
(CSP GC). In cases where these alcohols showed poor
resolution on CSP GC, chiral stationary phase liquid
chromatography (CSP HPLC) of the corresponding 2-
17
tures of various ligands ) only 1,3-bis-diphenylphosphinopro-
pane (dppp) gave preparatively useful levels of regioselectivity
(
1
11b: 92−95%) between the three isomers (11b, 12b, and
1
8,19
3b).
Isolation of the boronates resulted in some losses on
19
the column, and the isolated yields are sometimes lower than
the assays by GC or NMR. Consequently, the crude products
naphthoate esters was used for the er determination. The
absolute configurations among these series of alcohols were
a
Table 3. Optimization of Regio- and Enantioselectivity in Hydroboration of 10b
b
b
c
entry
[L]Co-complex (mol %)
activator (mol %)
Zn (mol %)
time (min)
conv (%)
11b:12b:13b
er 14b (S)
1
2
3
4
5
6
7
8
9
(dppp)CoCl (5)
NaBARF (10)
NaBARF (4)
NaBARF (10)
NaBARF (10)
NaBARF (4)
NaBARF (10)
NaBARF (10)
NaBARF (10)
MAO (200)
NaBARF (10)
NaBARF (10)
0
100
0
100
100
0
100
100
100
0
100
0
25
5
25
2 × 60
20
100
100
100
100
100
100
75
92:1:4
95:2:3
97:3:0
63:0:37
65:0:35
97:1:2
57:43:0
90:10:0
93:4:3
96:0:4
93:3:4
−
50:50
50:50
50:50
2
5a: (dppp) Co Cl (1) (recrystallized)
3
2
2
(PHOX)CoBr (5)
2
d
(S,S)-(BDPP)CoBr (5)
5b:[(S,S)-(BDPP)] Co Cl (1) (recrystallized)
92:8
93:7
2
d
3
2
2
e
(L4a)CoCl (5)
60
60
90:10
2
(L4b)CoBr (5)
70:30
80:20
78:22
93:7
92:8
−
94:6
94:6
62:38
53:47
2
(L4c)CoBr (5)
24 × 60
7.5 × 60
25
6 × 60
24 × 60
30
6 × 60
20
45
15
2
(L5a)CoCl (5)
100
100
100
0
100
100
100
100
2
10
11
12
13
14
15
16
(L5a)CoCl (5)
2
(L5a)CoCl (5)
2
(L5a)CoCl (5)
0
2
(L5c)CoBr (5)
NaBARF (10)
NaBARF (10)
NaBARF (10)
NaBARF (10)
100
100
100
100
94:0:5
97:0:2
91:2:7
95:5:0
2
(L5d)CoBr (5)
2
(L6c)CoBr (5)
2
(L7)CoBr (5)
2
a
See Scheme 2 and Supporting Information (SI) for experimental details and analytical data. A more elaborate table (Table S8, p S24) with
b
1
c
additional ligands and procedures can also be found in the SI. Determined by GC and confirmed by H NMR. For 11b. Determined by CSP GC
of the alcohols (14b) prepared by oxidation (basic H O ) of the boronates 11b. Configuration confirmed by comparison of optical rotation of 14b
2
2
d
that of an authentic sample. See Supporting Information for details. Selectivities for the minor product (13b): entry 4 (er = 98:2, S major); entry 5
e
(
er = 98:2, S major). See Supporting Information for details. In this case, the absolute configuration of the major product is (R).
E
DOI: 10.1021/jacs.8b13812
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Journal of the American Chemical Society
Article
entry 17), there was no reaction in the absence of NaBARF.
Selectivities of 2,2′-biaryl-bis-diphenylphosphine-Co(II) com-
plexes (L4a, L4b, and L4c) depend on the structures of the
ligands, with the BINAP-ligand giving overall the best regio-
and enantioselectivities [97% 1,2-HB with er = 90:10 (entry
1
7
6
)]. The segphos complex gave a significantly larger
proportion of the 1,4-adduct and exhibited only moderate
enantioselectivity for the 1,2-adduct 11b (entry 7, 11b:12b =
5
7:43; er for 11b: 70:30).
Achiral and chiral phosphino-oxazoline ligands are by far
15
the best ligands for obtaining the highest regio- and
enantioselectivities in the formation of the 1,2-hydroboration
product 11b (entries 3 and 9−14). Among the chiral ligands,
the (R)-4-(phenyloxazolinyl)-diphenylphosphino-ligand L5a
(
entry 10) and a corresponding bis-(3,5-dimethylphenyl)
ligand L5c (entry 13) are the best, the latter giving the er
value 94:6 for the 1,2-adduct, 11b. A structurally analogous bis-
(
3,5-bis-trifluoromethylphenyl) ligand L5d is equally good,
even though the reaction is slower (entry 14). Activation by Zn
and NaBARF appears to be superior to MAO (entry 9 vs 10).
Other ligands in this class (L5b, L6a−d, L7) all gave poor
16
results.
From a practical perspective, the enantioselective 1,2-
hydroboration of a 2-substituted diene using HBPin is best
carried out using the reduced (L5a)CoX (X = Cl, Br), a
catalyst generated by in situ reduction of the corresponding
(
(
L5a)CoX complex with Zn in the presence of NaBARF
Scheme 3; see SI p S17, procedure D for details). This
2
Scheme 3. Regio- and Enantioselective Hydroboration of
Prochiral 1,3-Dienes
protocol is broadly applicable as illustrated by examples shown
in Figure 5. Even though the isolated Co(I)-complex activated
with a near-equivalent amount of NaBARF is significantly
more active (typically the reaction is complete within 5 min
with 1 mol % catalyst), the in situ reduction procedure avoids
the isolation of the sensitive Co(I)-complex. The reactions are
easily scaled up to gram scales with no loss of selectivity.
Figure 4. Achiral and chiral ligands and a chiral Co(I) complex for
regio- and enantioselective hydroboration of prochiral 1,3-diene.
4b
In addition to the products from simple 1,3-dienes with
primary or secondary alkyl substituents at C and/or C
2
4
established by comparison of specific rotations with those of
authentic samples (see Supporting Information).
positions of the diene (products 11a−11f), various other
derivatives, a TBS ether (11g), a benzyl ether (11h), a tosylate
(11i), and even a phthalimido group tolerated these mild
reaction conditions to give excellent regio- and enantioselec-
tivities (er generally >94:6) for the 1,2-hydroboration
products. 1-Alkenylcycloalkenes gave products (11k−11n)
with an exocyclic chiral center, and a latent endocyclic double
bond for further elaboration. A trisubstituted alkene derived
from (S)-perrilaldehyde gave a product (11o) with excellent
diastereoselectivity (96:4).
Among the initially studied cobalt complexes, [(S,S)-
1
m
BDPP]CoBr2 (5 mol %) in the presence of Zn (1 equiv)
and NaBARF (10 mol %) was found to be an efficient catalyst
for the enantioselective reaction, giving exclusively the chiral
products, the 1,2-adduct 11b (63%), and the 4,3-adduct 13b
21
(
37%) in very good to excellent enantioselectivities (er = 92:8
20
and 98:2, respectively, for the two adducts, entry 4). The
corresponding prereduced Co(I)-complex 5b [{[(S,S)-
BDPP] Co Cl }], 1 mol %, Figure 4] in the presence of 4
Cyclohexa-1,3-diene, the only endocyclic 1,3-diene in our
study, with the bis-(3,5-ditrifluoromethylphenyl)-PHOX ligand
3
2
2
mol % NaBARF was also an exceptional catalyst exhibiting
similar regio- and enantioselectivities (entry 5). As expected
from earlier results on the hydroboration of (E)-1,3-nonadiene
using the isolated Co(I) complex (dppp) Co Cl (Table 1,
22
L5d, gave a 1,4-adduct (R)-12p with er >95:5 (1,2:1,4-adduct
1l
3:97). [(R)-BINAP]CoBr gave mostly the 1,2-adduct (11p)
2
in a surprisingly low er of 69:31. An examination of the
3
2
2
F
DOI: 10.1021/jacs.8b13812
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Journal of the American Chemical Society
Article
Figure 5. Scope of enantioselective 1,2-hydroboration of substituted 1,3-dienes. See Supporting Information for details including the structures of
the starting 1,3-dienes (Figure S2, p S6). For typical procedure, see procedure D (p S17, Supporting Information). Column under each compound
1l
shows isolated yields, regioselectivity and enantioselectivity (er) in that order. Boronates (S)-11p (a 1,2-adduct, formed with ent-L4a as the
22
ligand) and (R)-12p (formed with L5d as the ligand) have been reported before. See Supporting Information for details.
a
Table 4. Role of Cationic Co(I)-Catalyst in Hydroboration of Dienes
entry
Co(I)-source (equiv)
Zn (equiv)
NaBARF (equiv)
MAO (equiv)
time (min)
conv (%)
1
2
3
4
5
6
7
(dppp)CoCl (0.05)
0
0
1
0
1
0
0
0
0
0
0
0
2
0
0
0
0
0
0
0
44 × 60
5
30
30
24 × 60
5
24 × 60
20
0
2
(dppp)CoCl (0.05)
100
100
88
0
100
0
2
(dppp)CoCl (0.05)
0.1
0.1
0
0.1
0
2
(dppp)CoCl (0.05)
2
(dppp)CoCl (0.05)
2
b
Co(I): Co (dppp) Cl (0.01)
2
3
2
b
Co(I) : Co (dppp) Cl (0.01)
Co(I) : Co [(S,S)-BDPP] Cl (0.01)
Co(I) : Co [(S,S)-BDPP] Cl (0.01)
2
3
2
c
b
8
9
0.04
0
100
0
2
3
2
b
24 × 60
2
3
2
a
b
c
See eq 6 and Supporting Information (R = H, Et). Recrystallized Co(I) complex 5a or 5b (see Figures 2 and 4 for structures). Substrate (E)-2-
ethyl-1,3-nonadiene, R = Et. (L5a)CoCl /Zn-mediated reactions also do not proceed without NaBARF. See Supporting Information (pp S284−
2
S286) for details.
dependence of the enantioselectivity on the enantiomeric
purity of the BINAP ligand showed that there is no nonlinear
effect on the selectivity in this reaction unlike what was seen in
a related Cu-catalyzed reaction (see Supporting Information
The key results that are pertinent to this discussion are
assembled in Table 4 and further discussed below (eq 6). In a
1
0a
for details). As for the limitations, a diene with a bulky 4-
substituent, 10q, gave a product with noticeably low er of
7
4:26 for the 1,2-adduct 11q in only 48% yield.
Role of Cationic Co(I) in Hydroboration of 1,3-Dienes
series of experiments with reducing agents and activators, we
find strong evidence that a cationic Co(I) may be involved as
an intermediate in the reaction, just as they played a key role in
the diene-acrylate dimerization, where we initially discovered
and a Possible Mechanism of the Reaction. Even though
we have not carried out any detailed mechanistic studies,
several observations made during the optimization studies
provide key insights into the mechanism of this reaction, for
which many details are already available in the literature for
1d
this. Even though (dppp)CoCl is known to be a catalyst,
2
albeit a poor one, for the hydroborations using catechol
3c,7,8,23
6
both the Cu- and Co-catalyzed versions.
borane, this complex does not effect the reactions of HBPin in
G
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Figure 6. A plausible mechanism of the hydroboration of 1,3-dienes, which accounts for ligand, counterion, and solvent effects and configuration of
products.
the absence of an activator/reducing agent such as MAO or Zn
and NaBARF (entries 1 vs 2 and 3). The Zn/NaBARF-
activation works best when 1 equiv of Zn and 0.1 equiv of
NaBARF are employed (entry 3). Surprisingly, while Zn alone
is not competent to effect (apparently the ZnBr2 that is
produced is an inefficient Lewis acid to promote the reaction)
the hydroboration (entry 5), NaBARF alone does activate the
Co(II)-salts in a slow reaction (entry 4). In this reaction,
NaBARF presumably plays a dual role, one, to promote the
reduction of the Co(II) salt by HBPin, and, two, to generate a
Co(I)-cationic species from the reduced cobalt salt thus
generated. Support for such a hypothesis comes from the fact
that independently synthesized, and fully characterized (X-ray
crystallography), Co(I)-complexes (dppp) Co Cl (5a, Figure
as THF and DME), also give some clues about the cationic
nature of the putative intermediates in the reaction. In
addition, several alternate well-defined Co(I) species prepared
1d
during our studies on diene-acrylate dimerization, e.g.,
3
3
[(S,S)-BDPP]Co(η -cyclooctenyl), (S)-BINAP]Co(η -cyclo-
3
octenyl), (dppp)Co(η -cyclooctenyl), when activated by
[H (OEt ) [BARF] , are also superb catalysts for this
+
−
2
2
hydroboration, yielding similar selectivities. Based on our
observations and literature precedents, we propose the
mechanism outlined in Figure 6 for this reaction.
In this proposal, the reaction starts with the generation of
the Co(I) species 17 by reduction of the (P−P)CoX or (P−
2
N)CoX by Zn. This process may be assisted by NaBARF that
2
is added to the reaction mixture. The fact that a sluggish
reaction occurs even in the absence of Zn (but only in the
presence of NaBARF) suggests that HBPin may be competent
to performing this reduction under conditions where cationic
intermediates can be generated. Abstraction of the halide from
17 by NaBARF generates a cationic species 18, possibly
stabilized by the 1,3-diene. Subsequent events are as yet
uncertain, but it is reasonable to speculate that addition of
HBPin followed by insertion of the terminal alkene into the
Co−H bond in 19 in a 1,2-fashion (LCo[B] on C , H, on C )
3
2
2
2
) and [(S,S)-BDPP] Co Cl (5b, Figure 4) are not catalysts
3 2 2
in themselves for the hydroboration (entries 7 and 9).
However, upon addition of NaBARF the reaction is almost
instantaneous (entries 6 and 8), a situation reminiscent of the
Lewis acid activation of Rh(I)-catalyzed hydroboration of
23d
alkenes observed by Crudden.
Indeed the use of isolated
Co(I)- complexes in conjunction with NaBARF represent the
most efficient way of conducting this hydroboration reaction,
which we found especially valuable for carrying out the
enantioselective reactions (Table 3, Figure 5). Temperatures as
low as −20 °C can be used to effect the 1,2-hydroboration of a
1
2
would produce the intermediate 20a. Reductive eliminatio-
8a,23b,d
n
from this species would produce the 1,2-hydro-
1
,3-diene (Supporting Information, Table S7, p S23). The
boration product (2). Alternately, if the alkene inserts into the
2
3c
configurations of the 1,2- and 1,4-hydroboration products, (E
and Z) respectively, along with the remarkable solvent effects
Co−B bond in a 2,1-mode (LCo[H] on C ,B on C ) a
2
1
3
stabilized η -intermediate 20b would result. Reductive
elimination from 20b with C−H bond formation can result
(
e.g., significantly slower reaction in coordinating solvents such
H
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Article
in the 1,2- or 1,4-hydroboration product (2 and 4
respectively). The configuration of the resulting double
bond, (E), in the 1,2-adduct and (Z) in the 1,4-adduct is
consistent with this conjecture. For the catalytic cycle in
in 2-substituted dienes. The reactive catalysts can be generated
from the cobalt(II)-salts using trimethylaluminum, methyl
aluminoxane, or activated zinc in the presence of NaBARF.
The regioselectivity (1,2 vs 1,4) depends on the ligands and
8
23b,d
hydroboration, either an oxidative addition to Co(I)
or a
the diene, with (dppp)CoX giving the best results (1,2:1,4 =
2
7
,23a,c
σ-bond metathesis
has been invoked as a key step that
>95:5) for both linear terminal 1,3-dienes and 2-substituted
1,3-dienes. Isolated and fully characterized (X-ray crystallog-
raphy) Co(I)-complexes, (dppp) Co Cl and [(S,S)-
activates the B−H bond of HBPin. In this discussion we have
not considered alternatives involving the σ-bond metathesis.
Mechanistic studies to delineate these possibilities, and the
intriguing ligand effects [for example, why the major product
from (E)-1,3-nonadiene (1a) using dppp ligand is the 1,2-
adduct, whereas the Ph-PHOX (L5a) complex gives the 1,4-
adduct exclusively], are currently in progress and will be
reported in due course.
3
2
2
BDPP] Co Cl , do not catalyze the reaction unless activated
3
2
2
by a Lewis acid or NaBARF, suggesting a key role for a cationic
Co(I) species in the catalytic cycle. Regio- and enantioselective
1,2-hydroborations of 2-substituted 1,3-dienes are best
accomplished using a catalyst prepared via activation of a
chiral phosphine-oxazoline-cobalt(II) complex with zinc and
NaBARF. A number of common functional groups, among
them, -OBn, -OTBS, -OTs, N-phthalimido- groups, are
tolerated, and er’s up to >98:2 are observed for several dienes
including 1-alkenylcycloalk-1-enes.
Useful Transformations of the Homoallylic Boro-
nates. Boronates are versatile compounds that are readily
converted into other organic intermediates. In addition to the
well-known basic H O -mediated oxidation to the correspond-
2
2
ing alcohol, three other transformations of a prototypical
boronate are shown in Scheme 4. The homoallylboronates
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.8b13812.
■
*
S
Scheme 4. Derivatization of Chiral Pinacolboronates
Crystallographic information complex 5a (CIF)
Crystallographic information for complex 5b (CIF)
Experimental procedures, syntheses and isolation of all
intermediates, and tables with details of several
optimization studies; spectroscopic and gas chromato-
graphic data showing compositions of products under
various reaction conditions (PDF)
AUTHOR INFORMATION
Corresponding Author
E-mail: rajanbabu.1@osu.edu.
■
*
ORCID
Stanley M. Jing: 0000-0001-8952-4553
Milauni M. Mehta: 0000-0002-4597-2829
T. V. RajanBabu: 0000-0001-8515-3740
Author Contributions
‡
K.D., K.R.D., and M.M.P. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
have been converted into the corresponding alcohols,
Financial assistance for this research provided by the U.S.
National Institutes of Health (R01 GM108762) and the U.S.
National Science Foundation (CHE-1362095) is gratefully
acknowledged.
24
25
potassium trifluoroborate salts, N-BOC amines, and aryl
26
derivatives by C-BPin to C-aryl transposition by known
chemistry. Other examples of such compounds including
alcohols derived from achiral (2a−2m) and chiral (11a−11q)
boronates are included in the Supporting Information.
DEDICATION
■
This paper is dedicated to Prof. Dr. Gerhard Hilt (Universitat
Oldenburg) in recognition of his seminal contributions to the
applications of low-valent cobalt regents in organic synthesis.
̈
CONCLUSIONS
■
Among the myriad of possibilities for hydrofunctionalization
reactions of 1,3-dienes, 1,2-hydroboration is an uncommon
reaction. We find that reduced cobalt catalysts generated from
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16) See Supporting Information (Table S8, p S24) for more details.
(
17) A complete list of all ligands examined is shown in Supporting
Information (Figure S3, p S15).
(
18) The structures of the boronates were established by not only
HRMS and rigorous NMR analysis of the primary products, but also
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are readily separted on CSP-GC, enabling the determination of
enantioselectivity of the reaction.
(
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and chiral stationary phase chromatogarms.
(
20) Incidentally, with the (S, S)-BDPP and (S, S)-DIOP ligands,
unsubstituted 1,3-diene (E)-1,3-nonodiene (1a) also gave a significant
amount (∼16%) of a 4,3-hydroboration product, structurally
analogous 13, in er’s > 91:9.
K
DOI: 10.1021/jacs.8b13812
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX