Iron-promoted difunctionalization of alkenes by phenylselenylation/1,2-aryl migration

Article abstract of DOI:10.1021/acs.orglett.7b02751

Iron-promoted difunctionalization of α,α-diaryl and α-aryl-α-alkyl allylic alcohols has been efficiently achieved by means of N-(phenylseleno)phthalimide (N-PSP) under mild conditions. An in situ generated phenylselenium cation (PhSe+) was added to the ol

Full text of DOI:10.1021/acs.orglett.7b02751

Letter
pubs.acs.org/OrgLett
Iron-Promoted Difunctionalization of Alkenes by Phenylselenylation/
1,2-Aryl Migration
Ping Wu,†,‡ Kaikai Wu,† Liandi Wang,† and Zhengkun Yu*,†,§
†Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. China
‡University of Chinese Academy of Sciences, Beijing 100049, P. R. China
§State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354
Fenglin Road, Shanghai 200032, P. R. China
S
* Supporting Information
ABSTRACT: Iron-promoted difunctionalization of α,α-diaryl and α-
aryl-α-alkyl allylic alcohols has been efficiently achieved by means of N-
(phenylseleno)phthalimide (N-PSP) under mild conditions. An in situ
generated phenylselenium cation (PhSe+) was added to the olefinic
CC bond to initiate the regioselective phenylselenylation with
concomitant 1,2-aryl migration, following a migration preference
contrary to the well-known radical pathway. Hydrazonation of the resultant alkene difunctionalization products, that is, α-
aryl-β-phenylselenyl ketones, and subsequent copper-catalyzed dehydroselenylation efficiently afforded functionalized 2-
pyrazoline derivatives.
Scheme 1. Difunctionalization of Allylic Alcohols
icinal difunctionalization of alkenes has been used as a high
Vatom and step-efficiency strategy to simultaneously
introduce two functional groups to saturate an olefinic carbon−
carbon double bond in organic synthesis.1,2 In this context,
transition-metal-catalyzed difunctionalization of functionalized
allylic alcohols has recently been paid much attention. Cu(I)-
catalyzed trifluoromethylation of α,α-diaryl allylic alcohols with
concomitant radical 1,2-aryl migration was realized to form β-
trifluoromethyl-α-aryl ketones.3a The same strategy was applied
for the establishment of α-quaternary carbonyl structures from
the tandem trifluoromethylation/semipinacol rearrangement of
allylic alcohols.3b An Fe(II)-catalyzed radical procedure was also
used for the same purpose.3c In these cases, trifluoromethyl
radical addition to the olefinic CC bond initiated the tandem
reactions. Under oxidative conditions, such reactions can also
occur. Cu(II) salt-catalyzed cyanomethylation of allylic alcohols
with alkyl nitriles was achieved with oxidative radical 1,2-aryl
migration.4a Ni(0)-catalyzed oxidative α-C(sp3)−H functional-
ization of N,N-dialkyl-substituted amides with α,α-diaryl allylic
alcohols underwent a similar pathway.4b Pd(0)-catalyzed cross-
couplingofα-bromocarbonylswithallylicalcohols formed α-aryl-
dicarbonyls via the acyl radical intermediates.4c Metal-free
oxidative radical 1,2-alkylarylation of α,α-diaryl allylic alcohols
was also realized by functionalization of the C(sp3)−H bonds in
alkanes,4d,e acetonitriles,4e,f simple ethers,4g alkyl ketones, and
analogs.4h Ag(I)-mediated radical phosphinylation/1,2-arylation
of α,α-diaryl allylic alcohols was reported.5a A tandem oxidative
radical silylation and 1,2-aryl migration was reported for α,α-
diaryl allylic alcohols under Cu(I) catalysis, yielding β-silyl
ketones.5b Visible-light photoredox catalysis has also been
documented for the radical 1,2-alkylarylation4d,6a,b and acylar-
ylation6c of allylic alcohols. For the radical difunctionalization of
α,α-diaryl allylic alcohols, a radical is initially added to the olefinic
CC bond, and then the relatively electron-deficient α-aryl
group with lower aromaticity preferentially migrates (Scheme
1a). It is noted that distal 1,n-cyano,7a heteroaryl,7b and alkynyl7c
migrations have recently been reported in unactivated alkenes by
Zhu’s group.
In order to explore the diversity of difunctionalization of
alkenes, such a radical 1,2-aryl migrating preference should be
circumvented by altering the reaction pathway. Organoselenium
compounds have demonstrated potential applications in organic
synthesis.8 However, selenylation-initiated difunctionalization of
Received: September 4, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02751
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a b
,
alkenes has not yet been documented although diverse alkene
difunctionalization methods have recently been established.
During the ongoing investigation of organoselenium chemistry
in organic synthesis,9 we reasonably envisioned that N-
(phenylseleno)phthalimide (N-PSP)10 might be used to initiate
the difunctionalization reactions of allylic alcohols by its ready
generation of phenylselenium cation (PhSe+) under mild
conditions. The strategy includes addition of the PhSe+ cation
to an olefinic CC bond to yield an episelenonium ion
intermediate which thus renders a cationic group migration.11
Due to the advantages of a simple iron salt as the catalyst or
promotor over other transition-metal compounds,12 we utilized
anironsalttopromotethegenerationofthePhSe+ cationfromN-
PSP to initiate the designed difunctionalization reactions of
alkenes. Herein, we disclose an iron-promoted tandem phenyl-
selenylation/1,2-aryl migration of allylic alcohols under mild
conditions (Scheme 1b).
Scheme 2. Scope of α,α-Diaryl Allylic Alcohols (1)
Initially, thereactionofα,α-diphenylallylicalcohol(1a)andN-
PSP (2) was conducted to optimize the reaction conditions for
the formation of α-phenyl-β-phenylselenyl ketone (3a). The
reaction conditions were optimized to a molar ratio of 1a:2 = 1:1,
10 mol % FeBr3 as the catalyst, THF as the solvent, 25 °C, and 0.5
h in air (see the Supporting Information (SI) for details). Under
theoptimalconditions, thescopeofallylicalcohols1wasexplored
(Scheme 2). Symmetrical α,α-diaryl allylic alcohols (1a−1h)
were applied to undergo the reactions with 2 on a 0.5 mmol scale,
affording the target products of type 3. Thus, α-phenyl-β-
phenylselenyl ketone 3a was obtained in 84% yield, and α,α-di(4-
methylphenyl) allylic alcohol (1b) reacted to form 3b in a
comparative yield (81%). An obvious negative electronic effect
from 4-methoxy on the aryl moiety led to inefficient formation of
3c (62%). Unexpectedly, a 4-phenoxy substituent did not exhibit
a detrimental impact on the reaction efficiency as 4-methoxy did,
and the desired reaction gave 3d in 73% yield by using 20 mol %
FeBr3. α,α-Di(haloaryl)allylic alcohols exhibited good reactivity
with 2, affording 3e−3g in 70−77% yields, and only a 4-
fluorophenyl-bearing substrate reacted less efficiently to form 3h
(60%). It should be noted that a 4-CF3 substituent on the aryl
moiety deprived the reactivity of the allylic alcohol. In the cases of
using unsymmetrical α,α-diaryl allylic alcohols, two kinds of
products, that is, ketones 3 and 3′, could be obtained. Formation
ofcompounds3isattributedtotheregioselective1,2-migrationof
the α-aryl group bearing a relatively electron-rich substituent,
while1,2-migrationoftheα-arylgroupbearingalesselectron-rich
or relatively electron-poor (deficient) substituent resulted in
productsoftype3′. Radical-initiateddifunctionalization reactions
of α,α-diaryl allylic alcohols formed compounds of type 3′ as the
major products.3−6 However, compounds 3 were the only or
dominant products in our cases. α-Phenyl-α-tolyl allylic alcohols
efficiently reacted with 2, giving the target products 3j−3l in 73−
84%yieldswithpreferential 1,2-migration ofthetolylgroups. The
steric effect from the methyl substituent in the tolyl moiety
remarkably affected the regioisomer selectivity of the target
products. For the allylic alcohol substrates bearing two α-aryls
with significantly different or opposite electronic properties, their
reactionswith2exclusivelyaffordedtheregioselectiveproductsof
type 3. Thus, 3m (77%), 3n (82%), 3o (80%), and 3p (71%) were
exclusively produced. Such a 1,2-aryl migration preference is
contrary to the well-known radical 1,2-aryl migration in the
difunctionalization of α,α-diaryl allylic alcohols (Scheme 1a).3−6
Following such a 1,2-aryl migration preference, product 3q (79/
21) was obtained in 73% yield, demonstrating the steric effect on
the regioisomer selectivity. Compound 3r (86/14) was formed in
a
Conditions: 1 (0.5 mmol), 2 (0.5 mmol), FeBr3 (0.05 mmol), THF
b
(5 mL), 25 °C, 0.5 h. Isolated yields refer to 3 and its isomer. Only
the major products are shown with the ratio of 3 to its isomer 3′ given
in parentheses through the 1H NMR determination of the crude
c
product. Using 20 mol % FeBr3, 2 h.
82% yield, and the two chloro substituents featured the electron-
withdrawing property. Unexpectedly, α-phenyl-α-(4-fluorophen-
yl) allylic alcohol reacted with 2 to produce 3s (65%) as a 1:1
mixture of the regioisomers of types 3 and 3′, while 3- and 2-F
substituents differentiated the product selectivities for 3t (90/10)
and 3u (86/14). α,α-Di(4-CF3-phenyl) allylic alcohol did not
react with 2 under the stated conditions. The preference of aryl
migration depends on the electron-donating capability of the
chloro and methoxy substituents, and the order 4-OMe > 4-Cl >
2-Cl was unambiguously observed in the formation of 3w (73%,
74/26) and 3x (78%, 64/36).
Next, the reactions of α-alkyl-α-aryl allylic alcohols (1′) with 2
were investigated to further extend the substrate scope (Scheme
3). Under the standard conditions, α-methyl-α-phenyl allylic
alcohol (1a′) reacted with 2 to form α-phenyl-β-phenylselenyl
alkyl ketone 4a in 70% yield with regioselective 1,2-migration of
the phenyl group. This migration phenomenon was similar to
those radical 1,2-aryl migrations as previously reported.3a,4d The
4-tolyl analog reacted with 2 more efficiently to yield 4b (76%).
However, both α-methyl-α-(3-tolyl) and α-methyl-α-(2-tolyl)
allylic alcohols exhibited lower reactivity and required 20 mol %
FeBr3 to form 4c (50%) and 4d (52%), respectively. α-Methyl-α-
(4-methoxyphenyl) allylic alcohol also reacted well to produce 4e
B
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a b
,
a
Scheme 3. Scope of α-Aryl-α-alkyl Allylic Alcohols (1′)
Table 1. Hydrazonation and Dehydroselenylation
a
Conditions: 1′ (0.5 mmol), 2 (0.5 mmol), FeBr3 (0.05 mmol), THF
b
c
(5 mL), 25 °C, air, 0.5 h. Yields refer to the isolated products. Using
20 mol % FeBr3, 0.5 h. Using 20 mol % FeBr3, 2 h.
d
(53%). However, α-methyl-α-(4-bromophenyl) allylic alcohol
exhibited a poor reactivity to form 4f in 23% yield. Unexpectedly,
α-ethyl-α-phenyl allylic alcohol could efficiently react with 2 to
afford 4g (86%). α-Cyclopropyl-α-phenyl allylic alcohol reacted
to produce 4h in a moderate yield (55%), while two types of
products including the 1,2-cyclopropyl migration product were
obtained in its radical-initiated difunctionalization.4c The α-
methylallylic alcohol bearing electron-deficient 4-CF3-phenyl did
not undergo the reaction. 1-Vinylcyclobutanol also reacted with 2
to yield the ring-expansion product 4i (50%), but transformation
of 1-vinylcyclopentanol to cyclohexanone could not be realized,
and α,α-dimethyl allylic alcohol could not react to form 4j either.
The applicability of the resultant α-aryl-β-phenylselenyl
ketones 3 and 4 was investigated. Treatment of 3 or 4 with 2,4-
dinitrophenylhydrazine (5) in the presence of boron trifluoride
etherate13 in refluxing methanol resulted in hydrazones 6 (42−
88%) (Table 1). Compounds 3 and 4 were liquid at ambient
temperature, and it is impossible to determine their solid-state
molecular structures. To our delight, the hydrazine derivatives of
3 and 4 were solid at ambient temperature and the single crystals
of hydrazones 6e and 6g were successfully obtained for the X-ray
structural determinations (see the SI for details). It is
unambiguously demonstrated that in the reactions of α,α-diaryl
allylic alcohols 1 with 2 to form compounds 3m and 3p (Scheme
2), the relatively electron-rich aryl groups (4-MeO-phenyl vs
phenyl and 2-F-phenyl) preferentially underwent the 1,2-
migration.
Removal of phenylselenyl moiety from compounds 6 was
attempted by means of m-chloroperoxybenzoic acid (m-CPBA),
H2O2, and tri-n-butyltin hydride (nBu3SnH).9 Unfortunately, no
dephenylselenylation reaction occurred. To our delight, Cu-
(OAc)2·H2O could efficiently catalyze the dehydrophenylsele-
nylation of compounds 6 in DMSO at 120 °C, affording 2-
pyrazoline derivatives 7a−7g (71−90%) and 7i (85%),
respectively (Table 1, entries 1−7 and 9). In the case of using
3r the target product 7h was obtained in a relatively low yield
(59%) (Table 1, entry 8). Starting from the mixture of
regioisomers 3s and 3s′ (50/50), a mixture product of 7i and
7i′ with the unchanged molar ratio 50:50 was obtained (Table 1,
entry 9). In a similar fashion, the mixture product of 7j and 7j′ was
also obtained (Table 1, entry 10). It is noteworthy that the
corresponding hydrazones 6k−6n of ketones, 4a, 4g, 4h, and 4i
were also prepared (73−86%), but they could not undergo the
catalytic dehydrophenylselenylation reactions (see the SI).
a
Conditions A: 3 or 4 (0.2 mmol), 5 (0.2 mmol), BF3·OEt2 (0.4
mmol), MeOH (2 mL), 65 °C; Conditions B: 6 (0.1 mmol),
Cu(OAc)2·H2O (0.01 mmol), DMSO (1 mL), 120 °C, air, 0.5 h.
Yields refer to the isolated products. Ar′ = 2,4-(O2N)2C6H3.
Pyrazolines are important five-membered azaheterocycles
which can act as useful synthetic building blocks,14 and the
pyrazoline motif exists in many biologically active compounds.15
Although diverse methods have been reported for their
synthesis,16,17 the present synthetic method provides an
alternative route to functionalized pyrazoline derivatives.
To explore the reaction mechanism, the reaction of 1a and 2
was conducted in the presence of 2 equiv of a radical scavenger
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or 2,6-di-tert-
butyl-4-methylphenol (BHT), and the target product 3a was
obtained in 78−82% yields. These results excluded a radical
Scheme 4. Proposed Mechanism for Tandem
Phenylselenylation/1,2-Aryl Migration of Allylic Alcohols
C
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Zhang, F. M.; Wang, S. H. Chem. Commun. 2015, 51, 749. (d) Yu, Y.;
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pathway. Thus, a plausible reaction mechanism is proposed in
Scheme 4.8c Interaction of Lewis acid FeBr3 with2 initially
generates the phenylselenium cation (PhSe+) as well as anion A.
SubsequentadditionofPhSe+ cationtotheolefinicCCbondin
allylic alcohol 1 forms episelenium ion B8a which undergoes
intramolecular ring-opening by the nucleophilic attack of the α-
aryl group to yield dearomatic cation C. 1,2-Aryl migration is thus
established to yield protonated ketone intermediate D.
Deprotonation by anion A affords the target product 3 or 4
with regeneration of FeBr3.
In conclusion, iron-promoted phenylselenylation with con-
comitant 1,2-aryl migration of allylic alcohols was efficiently
realized under mild conditions. In contrast to the radical 1,2-aryl
migration in the difunctionalization of α,α-diaryl allylic alcohols,
the PhSe+-initiated process has demonstrated an opposite
preference for 1,2-aryl migration. The present method provides
a new difunctionalization strategy of alkenes and offers an
alternative route to functionalized pyrazoline derivatives.
ASSOCIATED CONTENT
* Supporting Information
■
S
TheSupportingInformationisavailablefreeofchargeontheACS
Publications website at DOI: 10.1021/acs.orglett.7b02751.
(10) (a) Armstrong, A.; Emmerson, D. P. G. Org. Lett. 2011, 13, 1040.
(b) Tang, E.; Wang, W. L.; Zhao, Y. J.; Zhang, M.; Dai, X. Org. Lett. 2016,
18, 176.
(11) (a) Chretien, F.; Chapleur, Y. J. Org. Chem. 1988, 53, 3615.
(b) Denmark, S. E.; Collins, W. R.; Cullen, M. D. J. Am. Chem. Soc. 2009,
131, 3490. (c) Sun, K.; Wang, X.; Lv, Y. H.; Li, G.; Jiao, H. Z.; Dai, C. W.;
Li, Y. Y.; Zhang, C.; Liu, L. Chem. Commun. 2016, 52, 8471.
Experimental materials and procedures, NMR of com-
pounds, and X-ray crystallographic analysis for compounds
6e and 6g (PDF)
Crystallographic data for compounds 6e and 6g (CIF)
AUTHOR INFORMATION
■
(12) (a) Bauer, I.; Knolker, H. J. Chem. Rev. 2015, 115, 3170.
̈
Corresponding Author
*E-mail: zkyu@dicp.ac.cn.
ORCID
(b) Lindhorst, A. C.; Haslinger, S.; Kuhn, F. E. Chem. Commun. 2015, 51,
̈
17193. (c) Saa, C. Angew. Chem., Int. Ed. 2016, 55, 10960. (d)Furstner, A.
́
̈
ACS Cent. Sci. 2016, 2, 778. (e) Shang, R.; Ilies, L.; Nakamura, E. Chem.
Rev. 2017, 117, 9086.
(13) Stefane, B.; Polanc, S. Synlett 2004, 698.
Ping Wu: 0000-0003-2650-9043
Kaikai Wu: 0000-0003-1950-5343
Liandi Wang: 0000-0003-4996-3687
Zhengkun Yu: 0000-0002-9908-0017
Notes
̌
(14) Yang, W. J.; Sun, W.; Zhang, C.; Wang, Q. J.; Guo, Z. Y.; Mao, B.
M.; Liao, J. N.; Guo, H. C. ACS Catal. 2017, 7, 3142.
(15) Hock, K. J.; Mertens, L.; Metze, F. K.; Schmittmann, C.; Koenigs,
R. M. Green Chem. 2017, 19, 905.
(16)Chen, J. R.;Dong, W.R.;Candy,M.;Pan,F.F.;Jorres, M.;Bolm,C.
̈
The authors declare no competing financial interest.
J. Am. Chem. Soc. 2012, 134, 6924.
(17) Wei, Q.; Chen, J. R.; Hu, X. Q.; Yang, X. C.; Lu, B.; Xiao, W. J. Org.
Lett. 2015, 17, 4464.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (21472185) and the National Basic Research Program of
China (2015CB856600) for support of this research.
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