Cobalt-Catalyzed Silylcarbonylation of Unactivated Secondary Alkyl Tosylates at Low Pressure

Article abstract of DOI:10.1021/acs.orglett.7b02117

A catalytic preparation of silyl enol ethers from unactivated secondary alkyl tosylates is reported. An inexpensive cobalt catalyst is used under mild conditions with low pressures of carbon monoxide. Nucleophilic, anionic cobalt carbonyls facilitate the catalytic activation of a range of alkyl tosylates. The silylcarbonylation offers a practical approach to synthetically valuable silyl enol ethers from simple starting materials.

Full text of DOI:10.1021/acs.orglett.7b02117

Letter
pubs.acs.org/OrgLett
Cobalt-Catalyzed Silylcarbonylation of Unactivated Secondary Alkyl
Tosylates at Low Pressure
Joan E. Roque Pena and Erik J. Alexanian*
̃
Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
S
* Supporting Information
ABSTRACT: A catalytic preparation of silyl enol ethers from
unactivated secondary alkyl tosylates is reported. An
inexpensive cobalt catalyst is used under mild conditions
with low pressures of carbon monoxide. Nucleophilic, anionic
cobalt carbonyls facilitate the catalytic activation of a range of
alkyl tosylates. The silylcarbonylation offers a practical
approach to synthetically valuable silyl enol ethers from simple starting materials.
enol ether products. These transformations required elevated
CO pressures (50 atm CO) and high temperatures, however.
In previous studies, we developed low-pressure alkoxycarbo-
nylations of secondary alkyl bromides using palladium
catalysis.6 As this system involved carbon-centered radical
intermediates formed from single-electron processes, it was
ineffective with alkyl sulfonates. We therefore became
interested in developing an alternative system for low pressure,
carbonylative transformations of alkyl sulfonates. Herein, we
report our initial studies in this area which involve a cobalt-
catalyzed silylcarbonylation of alkyl sulfonates providing
valuable silyl enol ethers under mild conditions.
atalytic carbonylations of organohalides and sulfonates are
Cimportant processes for the preparation of a range of
valuable chemotypes.1 Recent studies have developed carbon-
ylations2 and carboxylations3 of alkyl electrophiles, which have
been much less studied than aryl or vinyl substrates. These
catalytic transformations are proposed to involve radical
intermediates produced from the activation of alkyl halide
substrates. There are few reports involving carbonylations of
aliphatic alcohol derivatives (e.g., sulfonates), which are unlikely
to participate in single electron processes and require a different
approach.4,5
A previous report demonstrated the utility of cobalt catalysts
in the carbonylation of alkyl sulfonates, but the use of iodide
salts suggests the reaction proceeds via alkyl iodides formed in
situ (Figure 1).4 A general approach to the carbonylation of
substrates containing C−O bonds was developed by Murai
using a catalytic system involving Co2(CO)8 and silanes under a
CO atmosphere.5 The impressive scope of this catalytic system
extended to the reactions of esters and lactones to afford silyl
Our studies began by investigating the cobalt-catalyzed
silylcarbonylation of secondary alkyl tosylate 1 (Table 1).
Table 1. Cobalt-Catalyzed Silylcarbonylation of an
a
Unactivated Secondary Alkyl Tosylate
b
entry
variation from standard conditions above
yield (%)
1
2
3
4
5
6
7
8
9
none
77
78
15
70
52
16
0
10 mol % K[Co(CO)4] instead of 5 mol % Co2(CO)8
40 °C instead of 80 °C
8 atm of CO instead of 2 atm of CO
2 equiv of K3PO4 instead of 2 equiv of Et3N
1 atm of Ar instead of 2 atm of CO
no Et3SiH
no Co2(CO)8
0
c
no Et3N
28(13)
a
b
Reactions were performed with [substrate]0 = 0.5 M. Yields
determined by 1H NMR spectroscopy of crude reaction mixture using
HMDS as the internal standard. Yield of aldehyde derivative.
c
Figure 1. Cobalt-catalyzed carbonylations of alkyl acetates and
sulfonates.
Received: July 11, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02117
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Commercially available Co2(CO)8 (5 mol %) successfully
catalyzed the silylcarbonylation using 2 equiv of Et3SiH in
toluene to afford silyl enol ether 2 in 77% yield (entry 1).
Potassium tetracarbonylcobaltate catalyzed the reaction with
comparable efficiency to the carbonyl dimer (78% yield, entry
2). Lowering the reaction temperature to 40 °C resulted in a
significant decrease in product yield (15% yield, entry 3).
Increasing the CO pressure from 2 to 8 atm slightly lowered
the reaction yield (70%, entry 4), demonstrating that lower CO
pressures are preferred for this transformation. The inorganic
base K3PO4 could also be used, albeit in lower yield (52%, entry
5). In the absence of CO, the reaction provides product 2 in
low yield (16%, entry 6). Both Et3SiH (entry 7) and Co2(CO)8
(entry 8) are required for the reaction to proceed. Finally, in
the absence of base a mixture of silyl enol ether 2 (28% yield)
and aldehyde (13% yield) forms, suggesting that base plays an
important role in the silyl enol ether formation (entry 9).
With our optimized conditions in hand, we applied the
silylcarbonylation to a range of secondary alkyl tosylates (Table
2). Importantly, the reaction tolerates ether and ester
functionality, which underwent cleavage in previous catalytic
silylcarbonylations (entries 3−5).5 The silylcarbonylation of β-
alkoxy substrate 13 delivered silyl enol ether 14 in 56% yield,
although an increase in the amount of Et3SiH to 5 equiv was
required (entry 7). Silylcarbonylation of the primary chloride
15 proceeded chemoselectively to afford product 16 in 48%
yield. Reactions involving more sterically hindered linear
tosylates also delivered product, albeit in somewhat decreased
yields (entries 9−10). Cyclic substrates were also well tolerated,
as cyclopentyl and cycloheptyl tosylates (entries 11−12) as well
as 2-norbornyl tosylate (entry 13) were successfully converted
to silyl enol ether products.
Table 2. Low-Pressure Silylcarbonylations of Alkyl
Tosylates
a
The silylcarbonylation facilitates the efficient synthesis of a
variety of products through elaboration of the versatile silyl enol
ether functionality. Representative examples are shown in
Scheme 1. In these transformations, the crude product from the
silylcarbonylation is directly used in the second step.
Desilylation with KF provides aldehyde 27 in 56% yield over
two steps. Reduction produces branched alcohol 28 in 71%
yield. Bromination of the silyl enol ether provides direct access
to α-bromo aldehyde 29. Other manipulations of the silyl enol
ether are easily envisioned.7
We next performed experiments aimed at probing the
reaction mechanism of the silylcarbonylation. A major question
was the potential intermediacy of an aldehyde prior to silyl enol
ether formation. In order to test this possibility, we submitted
2-methylpentanal to the optimized reaction conditions (eq 1).
a
See Table 1 for conditions. For ratios of stereoisomers, see the
b
c
Supporting Information. Isolated yields. 5 equiv of Et3SiH.
d
Determined by 1H NMR spectroscopy of the crude reaction mixture
using HMDS as the internal standard.
Scheme 1. Functionalization of Silyl Enol Ether Products
The 1H NMR analysis of the crude reaction mixture indicated a
15% yield of silyl enol ether (31), which is substantially lower
than the silylcarbonylation of similar substrates in Table 2 (i.e.,
entry 6). However, when the aldehyde was submitted to the
optimized reaction conditions in the absence of base, a 53% yield
of silyl enol ether 31 was obtained (eq 2). These results suggest
that under our standard conditions in the presence of base, free
aldehyde is not a major reaction intermediate, as silyl enol ether
formation from aldehydes is inefficient in these reactions.
Based upon our experiments and prior studies, a plausible
catalytic cycle for the silylcarbonylation of alkyl tosylates is
B
DOI: 10.1021/acs.orglett.7b02117
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
depicted in Scheme 2. The reaction begins by substitution of
the alkyl tosylate by a cobaltate nucleophile.8,9 This is followed
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Scheme 2. Plausible Catalytic Cycle for the
Silylcarbonylation
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(11) The silylcarbonylation of octyl tosylate under the standard
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the Supporting Information for details.
by CO insertion to afford an acyl cobalt complex. Oxidative
addition of Et3SiH is then followed by a 1,3-silantropic shift to
deliver a cobalt carbene intermediate.8,10 A subsequent 1,2-
hydride shift is then followed by β-hydride elimination to
deliver the silyl enol ether product. Interestingly, the reaction
performs poorly with primary alkyl tosylates,11 which is
potentially a result of the decreased rate of β-hydride
elimination of alkyl cobalt species with less substitution.5
In conclusion, we have developed a cobalt-catalyzed, low
pressure transformation of unactivated alkyl tosylates providing
silyl enol ethers. This process is a rare example of the catalytic
activation of secondary alkyl tosylates. The reaction proceeds
under mild conditions and displays a broad substrate scope in
the production of synthetically versatile silyl enol ethers.
Mechanistic studies are consistent with the direct formation of
product without the presence of aldehyde intermediates.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b02117.
Experimental procedures and spectral data for all new
compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: eja@email.unc.edu.
ORCID
Erik J. Alexanian: 0000-0002-0256-2133
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by Award No. R01 GM107204 from
the National Institute of General Medical Sciences.
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DOI: 10.1021/acs.orglett.7b02117
Org. Lett. XXXX, XXX, XXX−XXX