Catalytic allylic oxidation to generate vinylogous acyl sulfonates from vinyl sulfonates

Article abstract of DOI:10.1021/acs.orglett.9b00845

Regioselective formation of vinylogous acyl sulfonates was accomplished via the allylic oxidation of the corresponding vinyl sulfonates. The reaction progressed through the agency of catalytic iron(III) chloride catalysis with tert-Butyl hydroperoxide (TBHP) as the stoichiometric oxidant. Tolerance of other functional groups, including some other allylic and benzylic sites, was observed.

Full text of DOI:10.1021/acs.orglett.9b00845

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Catalytic Allylic Oxidation to Generate Vinylogous Acyl Sulfonates
from Vinyl Sulfonates
James K. Tucker and Matthew D. Shair*
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States
S
* Supporting Information
ABSTRACT: Regioselective formation of vinylogous acyl sulfonates was
accomplished via the allylic oxidation of the corresponding vinyl sulfonates.
The reaction progressed through the agency of catalytic iron(III) chloride
catalysis with tert-Butyl hydroperoxide (TBHP) as the stoichiometric oxidant.
Tolerance of other functional groups, including some other allylic and benzylic
sites, was observed.
a
inylogous acyl sulfonates are versatile intermediates for
organic synthesis, undergoing a variety of coupling and
Table 1. Experiments Concerning Catalyst Discovery
V
fragmentation processes.1 These substrates typically originate
from treatment of the corresponding 1,3-dicarbonyl with a
weak base and sulfonate electrophile (Figure 1A). In the case
entry
solvent
cat.
NMR yield of 2a (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
ACN
ACN
ACN
ACN
ACN
ACN
ACN
Acetone
ACN
ACN
ACN
ACN
ACN
PhH
Rh2cap4
Pd(OH)2/C
Na2CrO7
Cul
Cu(OAc)2
Fe(acac)3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl2
63
21
70
57
67
35
93
89
55
b
c
63
73
none
FeCl3
FeCl3
FeCl3
ca. 10
<5
d
Figure 1. Proposed utility of an oxidative approach to vinylogous acyl
sulfonates.
e
14
15
13
e
EtOAc
16
a
Reactions on 0.1 mmol of 1a; yields based on dimethylsulfone as an
b
c
d
e
of substrates lacking symmetrical substitution with respect to
the 1,3-dicarbonyl, a mixture of products results.2,3 Moreover,
the 1,3-dicarbonyl oxidation state must already be established,
limiting the range of vinylogous acyl sulfonates rapidly
accessible by this approach. A regioselective synthesis of
vinylogous acyl sulfonates via allylic oxidation of corresponding
vinyl sulfonates would thus increase the diversity of such
structures (Figure 1B).
To date, there are two examples of this oxidation, both of
which rely on superstoichiometric quantities of toxic reagents
while forming the product in moderate yield.4 We sought to
effect this transformation with greater facility under more
benign conditions.
internal standard. 40 °C. 5 equiv of TBHP. No TBHP. Percent
conversion by NMR to 2a without an internal standard.
oxidation system developed by Doyle, both known to effect
the oxidation of electron-deficient allylic sites, resulted in poor
conversion (ca. 20−30%) following extended reaction times.5
A preponderance of allylic oxidations in other settings are
catalytic in a transition metal species in acetonitrile or acetone,
with tert-Butyl-hydroperoxide (TBHP) as the stoichiometric
oxidant.6 We chose to evaluate a series of catalysts with these
parameters in place. Under the conditions described above
(Table 1), the efficiency of Rh2cap4 (entry 1) improved
markedly. Catalysis under these conditions based on simple
To study this transformation, we chose readily available vinyl
triflate 1a because it lacked a competing allylic site (Table 1).
Application of Corey−Yu oxidation conditions and the
dirhodium tetracaprolatamate (Rh2cap4)-mediated allylic
Received: March 7, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00845
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
chromium and copper sources also converted 1a to an
acceptable extent. Interestingly, iron(III) acetylacetanoate
(iron(III) acac, entry 6) was capable of mediating the
transformation in this setting, albeit at a reduced efficiency.7
Use of iron(III) chloride (entry 7) improved upon the
efficiency of iron(III) acac and led to an overall superior
reaction outcome. Despite being a well-known agent for
oxidative C−C bond formation and a variety of allylic C−H
bond oxidations, iron(III) chloride is yet to be reported as a
catalyst for transformation of olefins to enones, to the best of
our knowledge.8 We chose to investigate the substrate scope
for iron(III) chloride catalysis, given the novelty of the catalyst
for this transformation and the improvement of iron over more
toxic or costly species often employed to effect allylic
oxidations.
displayed a window of chemoselectivity for the desired
oxidation over another olefin in cases 2p and 2q. Products
2e, 2f, and 2u were isolated despite containing benzylic
centers.9 Interestingly, the oxidation of six-membered rings
occurred with greater facility than that of analogous five-
membered rings as shown in the relative ease of formation of
2a versus 2h and 2o versus 2n. The method scaled well,
forming 2a on gram scale in 79% isolated yield. In many cases,
use of elevated catalyst loadings together with extended
reaction times at lower temperatures served to improve the
yield. The transformation worked best for structures with
quaternary centers immediately adjacent to the triflate.
Competitive oxidation of the remaining allylic site of
nonquaternary vinylogous acyl triflates was one issue. Addi-
tionally, as steric bulk adjacent to the triflate decreased, the
yield of vinylogous acyl triflate generally decreased because of
its hydrolysis under the reaction conditions. This is
unsurprising given the use of acidic iron(III) chloride in a
partially aqueous reaction mixture. Attempts to circumvent
these issues in studies of 2u formation such as buffering with
inorganic or amine bases, employing anhydrous reaction
conditions, substituting other catalysts, or changing the
sulfonate identity failed to improve the reaction outcome.10
While the system allowed for variance of R′′ from hydrogen in
case 2k, homoallylic steric bulk was tolerated poorly.11
Additionally, the process failed for linear substrates and
those containing nitrogeneous moieties.11
The scope for the oxidation of vinyl triflates is shown in
Scheme 1. Aryl ring halide and methoxy substitution as shown
for structures 2b−d and 2g was well tolerated. The system
a
Scheme 1. Vinyl Triflate Substrate Scope
Given the limitations observed with vinyl triflates, we turned
our attention to a survey of the oxidation of vinyl tosylates to
vinylogous acyl tosylates, and the results are shown in Scheme
2. The transformation progressed under slightly gentler
Scheme 2. Brief Survey of Vinyl Tosylates
conditions than in the case of vinyl triflates and delivered
the vinylogous acyl tosylate in a similar yield to that of the
analogous vinylogous acyl triflate. The slightly more forceful
conditions necessary for the oxidation of vinyl triflates might
be on account of the greater electron deficiency of vinyl
triflates relative to tosylates; typically, the chemical shift of the
vinylic proton on a vinyl triflate is slightly downfield that of the
analogous vinyl tosylate. Hydrolysis and overoxidation of the
desired products were the issues as steric bulk immediately
adjacent to the tosylate decreased.
As a demonstration of the proposed utility of this method,
we generated vinylogous acyl nonaflate 7 selectively from vinyl
nonaflate 8 in 54% yield (Scheme 3A). Conditions employed
a
Method A: 5 mol % FeCl3, 60 °C. Method B: 10 mol % FeCl3, 40
°C. Method C: 20 mol % FeCl3, 30 °C.
B
DOI: 10.1021/acs.orglett.9b00845
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
illustration of the utility of vinylogous acyl sulfonates for
diverse derivitization.
Scheme 3. Adavntages Associated with an Oxidative
Approach to Vinylogous Acyl Sulfonates
Preliminary mechanistic investigations are underway. Sub-
stitution of iron(III) chloride with iron(II) chloride or a
variety of other transition metal sources still allowed the
reaction to proceed (Table 1). Based on these results, we
propose an iron II/III catalytic cycle operating with analogy to
the canonical Fenton oxidation pathway first discussed by
Haber and Weiss (Scheme 5A).16 Performance of the reaction
Scheme 5. Mechanistic Proposal
in the literature from 1,3-dicarbonyl 5 gave an isomeric mix of
products. In fact, these conditions favored vinylogous acyl
nonaflate 6 (54% yield) over formation of desired product 7
(20% yield).2 A second advantage of this oxidation was
demonstrated in the two-pot synthesis of 1,3-dicarbonyl
compound 10 from ketone 9, representing an improvement
over lengthier sequences typical in the literature (Scheme
3B).12 Product 2a underwent the addition/fragmentation
process described by Dudley et al. to generate products
11a−b in good yield (Scheme 4).13 Sterically demanding
couplings of 2a in Sonogashira and Suzuki reactions formed 12
and 13 in high yield.14,15 Additionally, formation of alcohol 14
in a hydride-mediated reductive ring opening was achieved in
58% yield.13 The formation of 11−14 serves as a brief
Scheme 4. Representative Derivitization of Vinylogous Acyl
a
Triflate Products
under conditions free from atmospheric oxygen had no effect
on the yield of the desired product. Analysis of the gas formed
by this reaction following its completion by a glowing splint
test offered evidence that an oxidizing gas had been generated.
Production of oxygen from tert-butyl peroxy radicals (Scheme
5B) might explain the formation of an oxidizing atmosphere.17
Therefore, we propose that intermediate A may combine with
either molecular oxygen or tert-butyl peroxy radical to generate
intermediate B or C en route to the vinylogous acyl sulfonate.
Given the highly reactive tert-butoxy radical postulated by this
mechanism, the window of chemoselectivity for the desired
transformation over alternative allylic and benzylic positions is
surprising.
We have accomplished the regioselective formation of
vinylogous acyl sulfonates through an iron(III) chloride
mediated oxidation of the corresponding vinyl sulfonates.
The most favorable vinyl sulfonates for this transformation
contained quaternary centers immediately adjacent to the vinyl
sulfonate, although other classes of products were isolated at
lower yields. The vinylogous acyl sulfonates produced were
useful for an assortment of subsequent transformations. Future
studies will improve the process for less sterically protected
vinyl sulfonates, achieve the oxidation of linear substrates, and
address substrates with steric hindrance around the allylic site.
a
Conditions: (a) Li−X, THF, −78 to −10 °C over 1 h; then, 60 °C,
30 min; (b) (Ph3P)4Pd0, CuI, triisopropylsilylacetylene, iPr2NEt/
THF 1:1, 70 °C; (c) (Ph3P)4Pd0, PhB(OH)2, aq Na2CO3, 3:1 PhMe/
EtOH, rt; (d) LiHBEt3, −78 °C to rt.
C
DOI: 10.1021/acs.orglett.9b00845
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Lett. 2007, 17, 2289−2292. (b) Cole, K. P.; Hsung, R. P. Org. Lett.
2003, 5, 4843−4846.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00845.
■
S
(13) Kamijo, S.; Dudley, G. B. J. Am. Chem. Soc. 2006, 128, 6499−
6507.
(14) Nakatsuji, H.; Ueno, K.; Misaki, T.; Tanabe, Y. Org. Lett. 2008,
10, 2131−2134.
(15) Luo, Y.; Carnell, A. J. Angew. Chem., Int. Ed. 2010, 49, 2750−
General experimental information; details regarding
catalyst discovery, optimization, and limitations; 1H
and 13C NMR spectra (PDF)
2754.
(16) Haber, F.; Weiss, J. Proc. R. Soc. London, Ser. A 1934, 147, 332−
351.
(17) Combination of organic peroxy radicals to generate oxygen:
(a) Bartlett, P. D.; Guenther, P. J. Am. Chem. Soc. 1966, 88, 3288−
3294. (b) Kirsch, L. J.; Parkes, D. A. J. Chem. Soc., Faraday Trans. 1
1981, 77, 293−307.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: shair@chemistry.harvard.edu.
ORCID
James K. Tucker: 0000-0002-7731-2294
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We acknowledge Jennifer Wang (Harvard University) for
assistance with mass spectrometry characterization.
■
REFERENCES
■
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DOI: 10.1021/acs.orglett.9b00845
Org. Lett. XXXX, XXX, XXX−XXX