Catalytic Radical-Polar Crossover Reactions of Allylic Alcohols

Article abstract of DOI:10.1021/jacs.8b12075

Radical-polar crossover hydrofunctionalizations of tertiary allylic alcohols are described. Depending on the structure of the catalyst, corresponding epoxides or semipinacol rearrangement products are selectively obtained in good yields. Experimental evidence points to the participation of alkylcobalt complexes as electrophilic intermediates.

Full text of DOI:10.1021/jacs.8b12075

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Communication
Catalytic radical-polar crossover reactions of allylic alcohols
Eric E. Touney, Nicholas J. Foy, and Sergey V. Pronin
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 27 Nov 2018
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Journal of the American Chemical Society
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Catalytic radical-polar crossover reactions of allylic alcohols
Eric E. Touney, Nicholas J. Foy, and Sergey V. Pronin*
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Department of Chemistry, University of California, Irvine, California 92697-2025, United States
Supporting Information Placeholder
O
Me
catalyst 4
catalyst 7
ABSTRACT: Radical-polar crossover hydrofunctional-
izations of tertiary allylic alcohols are described. De-
pending on the structure of the catalyst, corresponding
epoxides or semipinacol rearrangement products are
selectively obtained in good yields. Experimental evi-
dence points to the participation of alkylcobalt complex-
es as electrophilic intermediates.
R2
OH
R2
O
R1
silane &
oxidant
silane &
oxidant
R1
R1
R2
Me
Me
[Co]
OH
catalysis by alkylcobalt(IV)
complexes leads to
ligand-dependent outcomes
via
R1
R2
Figure 1. Reactivity of alkylcobalt(IV) complexes allows
for catalyst control in radical-polar crossover reactions.
We sought to explore the reactivity of tertiary allylic
alcohols12 that could arise from the formal protonation
of the double bond to generate carbocations or other
highly electrophilic species in the β-position to the hy-
droxy group. In this setting, multiple reaction pathways
are available, including epoxide formation and
semipinacol rearrangements. Direct protonation of the
alkene fragment is hindered by the competing ionization
of the tertiary alcohol moiety, but the corresponding
radical-polar crossover process is expected to bypass
this complication. We discovered that treatment of a so-
lution of alcohol 1 in acetone with cobalt complex 4 in
the presence of methylphenylsilane and N-
fluoropyridinium oxidant 3 yielded a mixture of prod-
ucts 2a and 2b favoring the epoxide (Table 1, entry 1).
Changing the structure of the salen ligand produced in-
structive trends. Catalyst 5 provided lower selectivity for
epoxide 2a and complex 6 proved to be less efficient
(entries 2–3). Strikingly, performing the reaction in the
presence of cobalt complex 7 and under otherwise iden-
tical conditions led to a reversal of selectivity and pref-
erential formation of semipinacol rearrangement product
2b (entry 4). Improvement in production of ketone 2b
was observed with catalyst 8, which bears a different
salen backbone (entry 5). Application of complex 9 with
a 1,2-cyclohexanediamine salen backbone resulted in the
preferential formation of epoxide 2a, but loss of effi-
ciency was observed (entry 6). Performing the reaction
with catalyst 4 at a lower temperature resulted in an in-
crease in selectivity of the epoxide formation and a
higher yield of product 2a was obtained (entry 7), and a
higher temperature led to a lower ratio of compound 2a
to 2b (entry 8). A similar trend was observed in the case
Metal hydride-mediated radical reactions provide a
highly chemoselective means for hydrofunctionalization
of alkenes with Markovnikov selectivity.1,2 The inter-
mediate alkyl radicals or their equivalents can react with
a variety of atom and group transfer reagents,3 undergo
addition into multiple bonds,4 and engage in cross-
coupling reactions5 to introduce new functionalities and
connectivity patterns. Recent reports demonstrate that
the radical formation can be combined with subsequent
oxidation to generate the corresponding electrophilic
intermediates, which can be captured with oxygen and
nitrogen nucleophiles to produce cyclic and acyclic
ethers, lactones and saturated nitrogen heterocycles.6–9
The radical-polar crossover nature of these processes
can be expected to considerably expand the scope of the
radical hydrofunctionalizations and offer the advantage
of chemoselectivity when compared to the correspond-
ing acid-catalyzed reactions. Although the exact mecha-
nism remains unclear, existing proposals suggest partici-
pation of carbocations as electrophilic intermediates.6,8
This pathway renders the carbon-heteroatom bond for-
mation largely devoid of catalyst control, which has had
a tremendous impact on the utility of other metal-
catalyzed processes.10 Similar limitations are inherent to
the majority of processes that proceed through radical
intermediates.11 Here we show cobalt-catalyzed reac-
tions that are uniquely capable of converting tertiary
allylic alcohols into epoxides or semipinacol rearrange-
ment products (Figure 1). The outcome of these radical-
polar crossover processes is under strong catalyst control
and points to the participation of alkylcobalt complexes
as electrophilic intermediates.
1
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Page 2 of 6
Table 1. Effect of reaction conditions on the radical-polar
crossover hydrofunctionalization of alcohol 1
retard the alkyl migration, and fluorinated epoxide 19a
is formed preferentially to cycloheptanone 19b irrespec-
tive of the catalyst. This effect is further enhanced in the
case of thiopyranone derivative 20a, where the corre-
sponding product of semipinacol rearrangement, ketone
20b, is not formed. The opposite scenario is observed
for epoxide 21a, which is not detected, and ketone 21b
is always the major product. A tetrahydropyran-based
substrate behaves similarly to the cyclohexanol deriva-
tive and epoxide 22a and ketone 22b are readily pre-
pared under standard conditions. Surprisingly, cyclopen-
tanol and cycloheptanol derivatives do not form the cor-
responding epoxides and only ring expansion products
23b–25b are isolated in good yields. In contrast, bicyclic
epoxides 26a and 27a are readily prepared using our
protocol with catalyst 4 while ketones 26b and 27b are
obtained in the presence of catalyst 7, which is superior
to catalyst 8 in these cases. Product 26b is formed as a
single diastereomer, but formation of its aza-analog 27b
is not diastereoselective. Acyclic allylic alcohols also
successfully participate in the cobalt-catalyzed hydro-
functionalizations. Thus, epoxide 28a and isopropyl me-
thyl ketone (28b) are selectively obtained from 2-
methyl-3-buten-2-ol in the presence of catalysts 5 and 7,
respectively. Only semipinacol rearrangement product
29b is obtained in the case of an acetophenone-derived
substrate, which is consistent with the high migratory
aptitude of the phenyl substituent, and epoxide 29a is
not formed.
1
2
3
4
5
6
7
8
5 mol% catalyst
3 equiv. 3
3 equiv. silane
Me
O
Me
O
OTf
Me
HO
Me
conditions
Me
N
F
3
N
N
N
Boc
Boc
1
Boc
2a
2b
catalyst
silane
conditionsa
1 (%)b 2a (%)b 2b (%)b
entry
9
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
PhSiH2Me
TMDS
(CH3)2CO, 0 ℃
(CH3)2CO, 0 ℃
(CH3)2CO, 0 ℃
(CH3)2CO, 0 ℃
(CH3)2CO, 0 ℃
(CH3)2CO, 0 ℃
1
2
4
5
6
7
8
9
4
4
8
8
4
8
4
8
<1
1
70
58
42
10
14
54
84
66
20
11
81
13
78
15
22
33
16
52
63
10
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
1
4
14
<1
21
<1
<1
<1
18
<1
24
<1
<1
5c
6
7d
8
(CH3)2CO, –40 ℃
(CH3)2CO, 23 ℃
(CH3)2CO, –40 ℃
(CH3)2CO, 23 ℃
CH2Cl2, –40 ℃
CH2Cl2, 0 ℃
26
51
53
14
45
7
9
10
11
12
13e
14e
(CH3)2CO, –40 ℃
(CH3)2CO, 0 ℃
TMDS
66
Ph
N
Ph
R3
R3
N
R1
R2
N
O
N
Co
Co
R
O
R
t-Bu
O
O
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
8 (R1 = R2 = R3 = Me)
9 (R1, R2 = (CH2)4; R3 = H)
4 (R = t-Bu)
5 (R = OMe)
6 (R = H)
7 (R = NO2)
a0.1 mmol of 1 (0.1 M), 3 equiv. of silane, 3 equiv. of
3, 2 h. bbased on internal standard and determined by 1H
NMR. cisolated 59% of 2b. disolated 73% of 2a. e12 h.
We also found that the structure of the catalyst had a
pronounced effect on the stereochemical outcome of the
semipinacol rearrangement of the 4-substituted cyclo-
hexanol derivatives. Thus, application of catalyst 7 led
to conversion of alcohol 30 to a nearly equimolar mix-
ture of diastereomeric products 11b and 11c (equation
2), which was in stark contrast to the highly diastereo-
of complex 8, although performing the reaction at a
higher temperature led to a lower yield of ketone 2b,
despite a marginal increase in the selectivity (entries 9–
10). We identified dichloromethane to be another suita-
ble solvent for the reaction (entries 11–12). 1,1,3,3-
Tetramethyldisiloxane (TMDS) could be used in place
of methylphenylsilane, but required increased reaction
times (entries 13–14).
5 mol% 7
3 equiv. 3
3 equiv. PhSiH2Me
O
O
OH
Me
Me
(2)
(CH3)2CO, 0 ℃
63%, 11b:11c 1.5:1
Ph
Ph
Ph
30
11b
11c
The observed bifurcation of the radical-polar crosso-
ver pathways allows for selective transformation of var-
ious dialkyl(vinyl)carbinols to the corresponding epox-
ides and ketones. Thus, 1-vinylcyclohexan-1-ol and a
series of the 4-substituted derivatives are readily con-
verted to epoxides 10a–16a in synthetically useful yields
in the presence of catalyst 4 (Table 2). Switching the
catalyst to cobalt complex 8 allows for efficient produc-
tion of corresponding cycloheptanones 10b–16b. Nota-
bly, products 11b–16b are formed in a highly diastere-
oselective manner, with the preference for cis arrange-
ment of the substituents. 4,4-Disubstituted cyclohexanol
derivatives also participate in the radical-polar crossover
hydrofunctionalization and corresponding epoxides 17a–
19a and ketones 17b–19b are produced. The presence of
the strong electron-withdrawing substituents appears to
selective formation of ketone 11b in the presence of cat-
alyst 8 (see Table 2). Furthermore, analysis of the minor
rearrangement products formed during the synthesis of
epoxide 11a with catalyst 4 revealed a similarly low ra-
tio of diastereomers 11b and 11c. Interestingly, applica-
tion of epimeric starting material 31 resulted in a highly
diastereoselective formation of cycloheptanone 11c irre-
spective of the structure of catalyst (equation 3). Similar
dependence of the stereochemical outcome on the
5 mol% 4 or 7 or 8
3 equiv. 3
3 equiv. PhSiH2Me
O
O
OH
Me
Me
(3)
(CH3)2CO, 0 ℃
62–93%
Ph
Ph
11b:11c ≤ 1:19
Ph
31
11b
11c
2
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Journal of the American Chemical Society
Table 2. Preliminary Substrate Scope of the Cobalt-Catalyzed Epoxidationa,b and Semipinacol Rearrangementa,c
1
2
3
4
O
Me
5 mol% 4
5 mol% 7 or 8
R2
OH
R2
O
R1
3 equiv. 3
3 eqiuv. PhSiH2Me
(CH3)2CO, –40 ℃
3 equiv. 3
3 eqiuv. PhSiH2Me
(CH3)2CO, 0 ℃
R1
R1
R2
Me
5
6
7
8
Me
Me
Me
O
O
O
O
O
O
Me
O
Me
Me
Me
O
Me
9
Ph
t
-
Bu
n-Pent
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ph
t
-Bu
n
-
Pent
10a (52%)d
11a (52%)
12a (56%)
13a (54%)
10b (65%)d,e
11b (71%; d.r. 16:1)e
12b (66%, d.r. 18:1)e
13b (66%; d.r. 15:1)e
Me
Me
O
Me
O
Me
O
O
O
O
O
O
Me
Me
Me
Me
Me
Me
EtO2C
BnO
BocHN
Me Me
OBn
NHBoc
CO2Et
14a (50%)
15a (69%)
16a (51%)
17a (60%)d
14b (52%, d.r. 17:1)e
15b (58%, d.r. 17:1)e
16b (51%, d.r. 16:1)e
17b (60%)e
Me
O
O
Me
O
Me
O
Me
O
O
O
O
Me
Me
Me
Me
O
O
O
O
O
S
O
O
O
Me
S
O
O
F
F
Me
F
F
O
O
Me Me
18a (60%)
19a (55%)d
20a (42%)
21a (n/o)h
18b (72%)e
19b (30%)d,e,f
20b (n/o)g
21b (57%)e
Me
O
O
O
Me
O
Me
O
O
Me
O
O
Me
Me
Me
Me
O
O
23a (n/o)i
24a (n/o)j
25a (n/o)k
23b (70%)d,e
24b (59%)e
25b (66%)e
22a (58%)d
22b (59%)l
Me
Me
H
O
Me
Me
O
O
O
Me
Me
O
Me
Me
Ph
Me
O
O
O
Ph
BocN
O
Me
Me
Me
Me
Me
BocN
27a (53%)
O
26a (45%)
28a (41%)d,m
29a (n/o)n
26b (62%, d.r. > 19:1)l
27b (54%, d.r. 1:1)l
28b (55%)d,l
29b (54%)d,e
aunless noted otherwise, yields in parentheses correspond to isolated, analytically pure material. bunless noted other-
c
wise, ratio of epoxide to ketone is ≥3:1 (see SI for details). ratio of ketone to epoxide is ≥4:1 (see SI for details).
dbased on internal standard and determined by 1H NMR (see SI for additional details). ewith catalyst 8. fepoxide 19a is
the major product (48% by 1H NMR analysis). gepoxide 20a is the major product (32% by 1H NMR analysis). hketone
1
i
1
21b is the major product (48% by H NMR analysis). ketone 23b is the major product (90% by H NMR analysis).
jketone 24b is the major product (71% by 1H NMR analysis). kketone 25b is the major product (70% by 1H NMR anal-
ysis). lwith catalyst 7. mwith catalyst 5 (18% of ketone 28b was also observed by 1H NMR analysis). nketone 29b is the
major product (73% by 1H NMR analysis, isolated yield 66%). n/o: not observed.
structure of the precatalyst and the configuration of the
starting material was observed for the 4-alkylsubstituted
cyclohexanol derivatives.
degree of inversion of the stereochemical configura-
tion.16–18 Formation of alkylcobalt(III) complexes via
Scheme 1. Proposed Participation of Alkylcobalt In-
termediates
The catalyst control over the bifurcation of the radical-
polar crossover pathways and the stereochemical out-
come of the semipinacol rearrangements points to the
participation of alkylcobalt complexes as electrophilic
intermediates (Scheme 1). Halpern and co-workers pre-
viously demonstrated that relevant cobalt(III) complexes
undergo oxidation to the corresponding cationic spe-
cies.13 The resulting so-called alkylcobalt(IV) intermedi-
ates14,15 were found to undergo facile displacement with
various nucleophiles, which could proceed with a high
Me
[Co]
OH
R2
Me
[Co]
OH
R2
[Co-H]
OH
R2
radical pair
collapse
R1
HAT
R1
R1
oxidation
O
Me
[Co]
OH
R2
Me
R2
or
O
R1
displacement
or semipinacol
R1
R1
R2
Me
3
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hydrogen atom transfer (HAT)19,20 followed by the radi-
Page 4 of 6
the relevant, previously described semipinacol rear-
rangements is limited to strained ring systems such as
cyclopropanol and cyclobutanol derivatives.30–32 The
outcome of the hydrofunctionalizations is under strong
catalyst control, which is associated with the participa-
tion of alkylcobalt complexes as electrophilic intermedi-
ates. This pathway may also be operable in the other
radical-polar crossover hydrofunctionalizations. Togeth-
er with the stereoinvertive nature of the nucleophilic
displacement of alkylcobalt(IV) intermediates and the
established utility of chiral cobalt complexes in enanti-
oselective synthesis,33 these findings may provide a
starting point for the development of asymmetric pro-
cesses.
1
2
3
4
5
6
7
8
cal pair collapse was previously implicated in hydro-
formylations21 and more recently in cobalt-catalyzed
isomerizations and hydroarylations of alkenes,22 where
participation of alkylcobalt(IV) complexes in the
transmetalation event was also suggested.23 We propose
that the radical-polar crossover hydrofunctionalizations
of the tertiary allylic alcohols with catalysts 4 and 7 in-
volve alkylcobalt(IV) complexes as electrophilic inter-
mediates.24 The preference for the epoxidation in the
presence of catalyst 4 and the semipinacol rearrange-
ment in the case of catalyst 7 can be explained based on
the different leaving group abilities associated with the
nature of the arene fragments in the corresponding al-
kylcobalt(IV) intermediates where the nitro-substituted
complex would serve as a better nucleofuge. Similar
trends were previously observed in relevant Lewis acid-
catalyzed reactions of the derivatives of unsaturated 1,2-
diols.25 We also found the stereochemical outcome of the
semipinacol rearrangements of substrates 30 and 31 in
the presence of catalysts 4 and 7 to be closely aligned
with the distribution of cycloheptanones 11b and 11c
obtained upon treatment of the corresponding bromohy-
drins with a silver(I) salt, which activates the alkyl bro-
mide towards the migratory displacement.26
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ASSOCIATED CONTENT
Experimental procedures and spectroscopic data for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
spronin@uci.edu
Notes
The authors declare no competing financial interest.
The highly diastereoselective production of ketones
11b–16b in the presence of catalyst 8 is reminiscent of
the stereochemical outcome of the semipinacol rear-
rangements of related bromohydrins induced by electro-
philic iodine(I) reagents, which proceed via the interme-
diacy of the corresponding carbocations.27 The sterically
hindered nature of the salen backbone of catalyst 8 is
expected to retard the radical pair collapse and destabi-
lize the corresponding alkylcobalt(IV) intermediates
towards homolysis of the carbon-cobalt bond relative to
the derivatives of complexes 4 and, particularly, 7.28,29
We therefore propose that the ring expansions in the
presence of catalyst 8 proceed largely via direct oxida-
tion of the corresponding radical intermediates (equation
4), but the involvement of alkylcobalt complexes cannot
ACKNOWLEDGMENT
Acknowledgment is made to the Donors of the American
Chemical Society Petroleum Research Fund for partial
support of this research (PRF 58063-DNI1). Funding from
the School of Physical Sciences at the University of Cali-
fornia Irvine and the Chao Family Comprehensive Cancer
Center is also gratefully acknowledged. We thank Profes-
sors Larry Overman and Chris Vanderwal for providing
routine access to their instrumentation and helpful discus-
sions. Dedicated to the memory of Professor Jack Halpern.
REFERENCES
(1) For pioneering work on relevant hydrofunctionalizations see:
Mukaiyama, T.; Yamada, T. Recent advances in aerobic oxygenation.
Bull. Chem. Soc. Jpn. 1995, 68, 17 and references therein.
O
Me
(2) For an excellent review see: Crossley, S. W. M.; Martinez, R.
M.; Obradors, C.; Shenvi, R. A. Mn, Fe, and Co-catalyzed radical
hydrofunctionalizations of olefins. Chem. Rev. 2016, 116, 8912.
(3) For selected examples see: (a) Waser, J.; Nambu, H.; Carreira,
E. M. Cobalt-catalyzed hydroazidation of olefins: convenient access
to alkyl azides. J. Am. Chem. Soc. 2005, 127, 8294. (b) Gaspar, B.;
Carreira, E. M. Mild cobalt-catalyzed hydrocyanation of olefins with
tosyl cyanide. Angew. Chem. Int. Ed. 2007, 46, 4519. (c) Gaspar, B.;
Carreira, E. M. Catalytic hydrochlorination of unactivated olefins
with para-toluenesulfonyl chloride. Angew. Chem. Int. Ed. 2008, 47,
5758. (d) Gaspar, B.; Carreira, E. M. Cobalt catalyzed functionaliza-
tion of unactivated alkenes: regioselective reductive C−C bond form-
ing reactions. J. Am. Chem. Soc. 2009, 131, 13214. (e) Girijaval-
labhan, V.; Alvarez, C.; Njoroge, F. G. Regioselective cobalt-
catalyzed addition of sulfides to unactivated alkenes. J. Org. Chem.
2011, 76, 6442. (f) Baker, T.; Boger, D. L. Fe(III)/NaBH4‑Mediated
free radical hydrofluorination of unactivated alkenes. J. Am. Chem.
Soc. 2012, 134, 13588. (g) Leggans, E. K.; Barker, T. J.; Duncan, K.
K.; Boger, D. L. Iron(III)/NaBH4-Mediated additions to unactivated
alkenes: synthesis of novel 20′-vinblastine analogues. Org. Lett. 2012,
oxidation
R2
OH
R2
(4)
OH
R2
R1
R1
then
semipinacol
R1
Me
be ruled out at this point. In a similar vein, the extent of
contribution of the alkylcobalt-based pathways in the
presence of catalysts 4 and 7 likely varies from substrate
to substrate, and current data do not exclude participa-
tion of the alkyl radical-based pathways.
In summary, we disclose new radical-polar crossover
hydrofunctionalizations of tertiary allylic alcohols that
can selectively produce either the corresponding epox-
ides or semipinacol rearrangement products. Notably,
the direct conversion of the tertiary allylic alcohols to
the corresponding epoxides is without precedent in the
realm of currently available methods, and the scope of
4
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Journal of the American Chemical Society
14, 1428. (h) Shigehisa, H.; Nishi, E.; Fujisawa, M.; Hiroya, K. Co-
heterocycles by hydrofunctionalization of unactivated olefins: unpro-
tected and protected strategies J. Am. Chem. Soc. 2016, 138, 10597.
(9) A radical-polar crossover pathway is also proposed in a relevant
hydroarylation of alkenes: Shigehisa, H.; Ano, T.; Honma, H.; Ebisa-
wa, K.; Hiroya, K. Co-Catalyzed hydroarylation of unactivated ole-
fins Org. Lett. 2016, 18, 3622.
(10) For examples and an excellent discussion see: Surry, D. S.;
Buchwald, S. L. Biaryl phosphane ligands in palladium-catalyzed
amination. Angew. Chem. Int. Ed. 2008, 47, 6338.
balt-catalyzed hydrofluorination of unactivated olefins: a radical ap-
proach of fluorine transfer. Org. Lett. 2013, 15, 5158. (i) Iwasaki, K.;
Wan, K. K.; Oppedisano, A.; Crossley, S. W. M.; Shenvi, R. A. Sim-
ple, chemoselective hydrogenation with thermodynamic stereocontrol.
J. Am. Chem. Soc. 2014, 136, 1300. (j) King, S. M.; Ma, X.; Herzon,
S. B. A method for the selective hydrogenation of alkenyl halides to
alkyl halides. J. Am. Chem. Soc. 2014, 136, 6884. (k) Ma, X. S.; Her-
zon, S. B. Non-classical selectivities in the reduction of alkenes by
cobalt-mediated hydrogen atom transfer. Chem. Sci. 2015, 6, 6250. (l)
Zheng, J.; Wang, D.; Cui, S. Fe-Catalyzed reductive coupling of un-
activated alkenes with β-nitroalkenes. Org. Lett. 2015, 17, 4572. (m)
Crossley, S. W. M.; Martinez, R. M.; Guevara-Zuluaga, S.; Shenvi, R.
A. Synthesis of the privileged 8-arylmenthol class by radical arylation
of isopulegol. Org. Lett. 2016, 18, 2620. (n) Ma, X.; Herzon, S. B.
Intermolecular hydropyridylation of unactivated alkenes J. Am. Chem.
Soc. 2016, 138, 8718.
(4) For selected examples see: (a) Wang, L.-C.; Jang, H.-Y.; Roh,
Y.; Lynch, V.; Schultz, A. J.; Wang, X.; Krische, M. J. Diastereose-
lective cycloreductions and cycloadditions catalyzed by Co(dpm)2-
silane (dpm = 2,2,6,6-tetramethylheptane-3,5-dionate):ꢀ mechanism
and partitioning of hydrometallative versus anion radical pathways. J.
Am. Chem. Soc. 2002, 124, 9448. (b) Waser, J.; Carreira, E. M. Con-
venient synthesis of alkylhydrazides by the cobalt-catalyzed hydrohy-
drazination reaction of olefins and azodicarboxylates. J. Am. Chem.
Soc. 2004, 126, 5676. (c) Smith, D. M.; Pulling, M. E.; Norton, J. R.
Tin-free and catalytic radical cyclizations. J. Am. Chem. Soc. 2007,
129, 770. (d) Lo, J. C.; Yabe, Y.; Baran, P. S. A practical and catalyt-
ic reductive olefin coupling. J. Am. Chem. Soc. 2014, 136, 1304. (e)
Lo, J. C.; Gui, J.; Yabe, Y.; Pan, C.-M.; Baran, P. S. Functionalized
olefin cross-coupling to construct carbon–carbon bonds. Nature 2014,
516, 343. (f) Crossley, S. W. M.; Barabé, F.; Shenvi, R. A. Simple,
chemoselective, catalytic olefin isomerization. J. Am. Chem. Soc.
2014, 136, 16788 (g) Kuo, J. L.; Hartung, J.; Han, A.; Norton, J. R.
Direct generation of oxygen-stabilized radicals by H• transfer from
transition metal hydrides. J. Am. Chem. Soc. 2015, 137, 1036. (h) Gui,
J.; Pan, C.-M.; Jin, Y.; Qin, T.; Lo, J. C.; Lee, B. J.; Spergel, S. H.;
Mertzman, M. E.; Pitts, W. J.; La Cruz, T. E.; Schmidt, M. A.; Dar-
vatkar, N.; Natarajan, S.; Baran, P. S. Practical olefin hydroamination
with nitroarenes. Science 2015, 348, 886. (i) Dao, H. T.; Li, C.;
Michaudel, Q.; Maxwell, B. D.; Baran, P. S. Hydromethylation of
unactivated olefins. J. Am. Chem. Soc. 2015, 137, 8046. (j) Zheng, J.;
Qi, J.; Cui, S. Fe-Catalyzed olefin hydroamination with diazo com-
pounds for hydrazone synthesis. (k) Lo, J. C.; Kim, D.; Pan, C.-M.;
Edwards, J. T.; Yabe, Y.; Gui, J.; Qin, T.; Gutiérrez, S.; Giacoboni, J.;
Smith, M. W.; Holland, P. L.; Baran, P. S. Fe-catalyzed C–C bond
construction from olefins and radicals. J. Am. Chem. Soc. 2017, 139,
2484. (l) Saladrigas, M.; Bosch, C.; Saborit, G. V.; Bonjoch, J.; Brad-
shaw, B. Radical cyclization of alkene-tethered ketones initiated by
hydrogen-atom transfer. Angew. Chem. Int. Ed. 2018, 57, 182. (m)
Saladrigas, M.; Loren, G.; Bonjoch, J.; Bradshaw, B. Hydrogen atom
transfer (HAT)-triggered iron-catalyzed intra- and intermolecular
coupling of alkenes with hydrazones: access to complex amines. ACS
Catal. 2018, 8, 11699.
1
2
3
4
5
6
7
8
(11) For a unique case of catalyst control in relevant alkene isomer-
izations see reference (4)(f).
9
(12) For examples of relevant metal hydride-mediated reactions of
allylic alcohols see references (3)(i), (3)(l), (4)(b),(h),(i),(j). For appli-
cations in synthesis see: (a) Cherney, E. C.; Lopchuk, J. M.; Green, J.
C.; Baran, P. S. A unified approach to ent-atisane diterpenes and re-
lated alkaloids: synthesis of (–)-methyl atisenoate, (–)-isoatisine, and
the hetidine skeleton. J. Am. Chem. Soc. 2014, 136, 12592. (b) Zhu,
D.; Yu, B. Total synthesis of linckosides A and B, the representative
starfish polyhydroxysteroid glycosides with neuritogenic activities. J.
Am. Chem. Soc. 2015, 137, 15098.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(13) Abley, P.; Dockal, E. R.; Halpern, J. Oxidative cleavage of
cobalt-carbon bonds in organobis(dimethylg1yoximato)cobalt com-
pounds J. Am. Chem. Soc. 1972, 94, 659.
(14) (a) Halpern, J.; Chan, M. S.; Hanson, J.; Roche, T. S.; Topich,
J. A. Detection and characterization of radical cations produced by
one-electron chemical and electrochemical oxidations of organocobalt
compounds J. Am. Chem. Soc. 1975, 97, 1606. (b) Halpern, J.;
Topich, J.; Zamaraev, K. I. Electron paramagnetic resonance spectra
and electronic properties of organobis(dimethylglyoximato)cobalt(IV)
complexes. Inorganica Chim. Acta 1976, 20, L21. (c) Topich, J.;
Halpern, J. Organobis(dioximato)cobalt(IV) complexes: electron
paramagnetic resonance spectra and electronic structures Inorg.
Chem. 1979, 18, 1339. (d) Halpern, J.; Chan, M. S.; Roche, T. S.;
Tom,
G.
M.
Redox
chemistry
of
organo-
bis(dimethylglyoximato)cobalt complexes. Acta Chem. Scan. A 1979,
33, 141.
(15) Formation of relevant inner-sphere complexes between cation-
ic cobalt(III) species and alkyl radicals has also been proposed:
Lande, S. S.; Kochi, J. K. Formation and oxidation of alkyl radicals
by cobalt(III) complexes. J. Am. Chem. Soc. 1968, 90, 5196.
(16) Anderson, S. N.; Ballard, D. H.; Chrzastowski, J. Z.; Dodd,
D.; Johnson, M. D. Inversion of configuration in the nucleophilic
displacement of cobalt from alkylcobalt( IV) complexes and its rele-
vance to the halogenation of the corresponding alkylcobalt(III) com-
plexes J. Chem. Soc., Chem. Commun. 1972, 0, 685.
(17) Magnuson, R. H.; Halpern, J.; Levitin, I. Ya.; Vol’pin, M. E.
Stereochemistry of the nucleophilic cleavage of cobalt-carbon bonds
in organocobalt(IV) compounds J. Chem. Soc., Chem. Commun.
1978, 0, 44.
(18) For a discussion of alternative mechanisms of displacement
see: Vol’pin, M. E.; Levitin, I. Ya.; Sigan, A. L.; Halpern, J.; Tom, G.
M. Reactivity of organocobalt(IV) chelate complexes toward nucleo-
philes: diversity of mechanisms. Inorg. Chim. Acta 1980, 41, 271.
(19) Radical pair formation via the HAT: Sweany, R. L.; Halpern,
J. Hydrogenation of α-methylstyrene by hydridopentacarbonylmanga-
nese(I). Evidence for a free-radical mechanism. J. Am. Chem. Soc.
1977, 99, 8335.
(20) For the proposed involvement of the HAT as the initial step in
relevant metal hydride-mediated hydrogenations see references (3)(i)
and (3)(j). For similar mechanistic considerations see: (a) Eisenberg,
D. C.; Norton, J. R. Hydrogen-atom transfer reactions of transition-
metal hydrides. Isr. J. Chem. 1991, 31, 55. (b) Ishikawa, H.; Colby,
D. A.; Seto, S.; Va, P.; Tam, A.; Kakei, H.; Rayl, T. J.; Hwang, I.;
Boger, D. L. Total synthesis of vinblastine, vincristine, related natural
products, and key structural analogues J. Am. Chem. Soc. 2009, 131,
4904.
(5) (a) Green, S. A.; Matos, J. L. M.; Yagi, A.; Shenvi, R. A.
Branch-selective hydroarylation: iodoarene–olefin cross-coupling J.
Am. Chem. Soc. 2016, 138, 12779. (b) Green, S. A.; Vásquez-
Céspedes, S.; Shenvi, R. A. Iron–nickel dual-catalysis: a new engine
for olefin functionalization and the formation of quaternary centers J.
Am. Chem. Soc. 2018, 140, 11317.
(6) Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya,
K. Hydroalkoxylation of unactivated olefins with carbon radicals and
carbocation species as key intermediates. J. Am. Chem. Soc. 2013,
135, 10306.
(7) Shigehisa, H.; Koseki, N.; Shimizu, N.; Fujisawa, M.; Niitsu,
M.; Hiroya, K. Catalytic hydroamination of unactivated olefins using
a Co catalyst for complex molecule synthesis. J. Am. Chem. Soc.
2014, 136, 13534.
(21) Ungvávy, F.; Markó, L. Reaction of HCo(CO)4 and CO with
styrene.
Mechanism
of
(α-phenylpropiony1)-
and
(β-
(8) Shigehisa, H.; Hayashi, M.; Ohkawa, H.; Suzuki, T.; Okayasu,
H.; Mukai, M.; Yamazaki, A.; Kawai, R.; Kikuchi, H.; Satoh, Y.;
Fukuyama, A.; Hiroya, K. Catalytic synthesis of saturated oxygen
phenylpropionyl)cobalt tetracarbony1 formation. Organometallics
1982, 1, 1120.
(22) References (4)(f) and (5)(a).
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(23) Shevick, S. L.; Obradors, C.; Shenvi, R. A. Mechanistic inter-
rogation of Co/Ni-dual catalyzed hydroarylation. J. Am. Chem. Soc.
2018, 140, 12056.
to cyclobutanones. J. Org. Chem. 1980, 45, 2874. For relevant ring
expansions of allenylcyclopropanols see: (b) Kleinbeck, F.; Toste, F.
D. Gold(I)-catalyzed enantioselective ring expansion of allenylcyclo-
propanols. J. Am. Chem. Soc. 2009, 131, 9178.
1
2
3
4
5
6
7
8
(24) We evaluated the absolute majority of the cases (12 out of 14
total) where the pronounced bifurcation of pathways was observed
and found that application of catalyst 7 always resulted in preferential
formation of the semipinacol rearrangement product when application
of catalyst 4 led in preferential formation of the epoxide.
(25) Zhu, L.-L.; Li, X.-X.; Zhou, W.; Li, X.; Chen, Z. Divergent
synthetic routes for ring expansion or cyclization from 1,4-allylic diol
derivatives via gold(I) catalysis or zinc(II) mediation J. Org. Chem.
2011, 76, 8814.
(31) (a) Clark, G. R.; Thiensathit, S. A palladium-catalyzed rear-
rangement of 1-vinyl-1-cyclobutanols. Tetrahedron Lett. 1985, 26,
2503. (b) Bernard, A. M.; Frongia, A.; Secci, F.; Piras, P. P. 2,2-
Dimethyl cyclopentanones by acid catalyzed ring expansion of iso-
propenylcyclobutanols. A short synthesis of (±)-α-cuparenone and
(±)-herbertene. Chem. Commun. 2005, 0, 3853. (c) Masarwa, A.;
Weber, M.; Sarpong, R. Selective C–C and C–H bond activa-
tion/cleavage of pinene derivatives: synthesis of enantiopure cyclo-
hexenone scaffolds and mechanistic insights. J. Am. Chem. Soc. 2015,
137, 6327. For relevant ring expansions of allenylcyclobutanols see:
(d) Yao, L.-F.; Wei, Y.; Shi, M. Silver- and gold-catalyzed intramo-
lecular rearrangement of propargylic alcohols tethered with meth-
ylenecyclopropanes: stereoselective synthesis of allenylcyclobutanols
and 1-vinyl-3-oxabicyclo[3.2.1]octan-8-one derivatives. J. Org.
Chem. 2009, 74, 9466.
9
(26) See Supporting Information for details.
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(27) Tsuji, N.; Kobayashi, Y.; Takemoto, Y. Electrophilic iodine(I)
compounds induced semipinacol rearrangement via C–X bond cleav-
age Chem. Commun. 2014, 50, 13691.
(28) Samsel, E. G.; Kochi, J. K. Radical chain mechanism for alkyl
rearrangement in organocobalt complexes. J. Am. Chem. Soc. 1986,
108, 4790.
(29) For a discussion of the strength of carbon-cobalt bond in rele-
vant complexes see: Chiang, L.; Allan, L. E. N.; Alcantara, J.; Wang,
M. C. P.; Storr, T.; Shaver, M. P. Tuning ligand electronics and pe-
ripheral substitution on cobalt salen complexes: structure and
polymerisation activity. Dalton Trans. 2014, 43, 4295.
(30) (a) Wasserman, H. H.; Hearn, M. J.; Cochoy, R. E. Cyclopro-
panones. Formation of vinylcyclopropanols and their rearrangement
(32) For a relevant radical rearrangement of diaryl(vinyl)carbinols
see: Deng, Z.; Chen, C.; Cui, S. Fe(III)-mediated isomerization of
α,α-diarylallylic alcohols to ketones via radical 1,2-aryl migration
RSC Adv. 2016, 8, 93753.
(33) Pellissier, H.; Clavier, H. Enantioselective cobalt-catalyzed
transformations. Chem. Rev. 2014, 114, 2775 and references therein.
O
Me
[Co-H]
[Co-H]
R2
OH
R2
O
R1
[O]
[O]
R1
R1
R2
Me
Me
[Co]
OH
R2
catalyst-controlled synthesis
of epoxides and
semipinacol products
via
R1
6
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