Cobalt catalyzed functionalization of unactivated alkenes: Regioselective reductive C-C bond forming reactions

Article abstract of DOI:10.1021/ja904856k

(Chemical Equation Presented) The cobalt catalyzed hydroaldoximation and hydrocyanooximation of unactivated alkenes is reported. Secondary and tertiary aldoximes and oximonitriles are synthesized with excellent regioselectivity under mild conditions, and conversion of the products to valuable intermediates is documented. The reactions expand the arsenal of reductive carbon-carbon bond forming reactions as well as regioselective functionalizations of unactivated double bonds.

Full text of DOI:10.1021/ja904856k

Published on Web 08/28/2009
Cobalt Catalyzed Functionalization of Unactivated Alkenes: Regioselective
Reductive C-C Bond Forming Reactions
Boris Gaspar and Erick M. Carreira*
Laboratorium fu¨r Organische Chemie, ETH Zürich, CH-8093 Zu¨rich, Switzerland
Received June 14, 2009; E-mail: carreira@org.chem.ethz.ch
Table 1. Examination of Various Phenyl Sulfonyl Oximes 1 in the
Cobalt Catalyzed Functionalization of 4-Phenylbutene (2)
The chemistry of oximes and oxime ethers is rich and well described
in the literature.1 They can be transformed into carbonyl and nitro
compounds, amines, hydroxylamines, or nitriles rather easily. Oximes
are also present in a number of compounds with a wide spectrum of
biological activities.2 Although many methods for the synthesis of
oximes have been developed, none involves direct synthesis from
unactivated alkenes. The ability to prepare oximes from olefins would
not only expand the range of functionalization reactions of alkenes
but also open up new strategic approaches in the synthesis of complex
molecules.3,4 Herein, we report a novel olefin functionalization reaction
which homologates olefins to afford aldoximes (X ) H) and oxi-
monitriles (X ) CN) (eq 1). The transformation is enabled by carrying
out in tandem an olefin hydrocobaltation reaction followed by reaction
of the organocobalt species with sulfonyl oximes 1.
entry
reagent
timea [h]
yield [%]
1
2
3
4
5
6
7
1a (R ) Bn, X ) H)
3
3
3
2.5
2
99
0
0
61
37
0
1b (R ) Bn, X ) Me)
1c (R ) Bn, X ) CF3)
1d (R ) Bn, X ) CO2Et)
1e (R ) BnCO, X ) CO2Me)
1f (R ) H, X ) CO2Me)
1g (R ) Bn, X ) CN)
3
2
95
a The reaction time refers to complete consumption of the alkene. In
cases where no desired product was observed, the starting olefin underwent
reduction and/or double bond migration to form the internal alkene.
We have documented a mild Co-catalyzed hydrocyanation of olefins
with p-toluenesulfonyl cyanide and phenylsilane that operates under
mild conditions and avoids handling of HCN at elevated pressures
and temperatures.5,6 We have been interested in expanding the nature
of reagents that can intercept the organocobalt intermediate, leading
to the formation of new C-C bonds. In this respect, we sought
alternatives to the more common transformations involving olefin
hydrocyanation, -formylation, and -carboxylation reactions. Thus, we
have examined various sulfonyl oxime ethers 1a-g and their utility
and compatibility with the hydrocobaltation reaction. We speculated
that these could display reactivity similar to that observed with tosyl
cyanide, by undergoing nucleophilic attack at C (and not S) and
subsequently ejecting the p-toluenesulfonyl group. A selection of
phenyl sulfonyl oximes 1a-d have been shown to participate in
reactions with radicals generated from alkyl iodides, alkyl allyl sulfones,
or alkyl phenyl tellurides.7 Yet, their reaction with olefins and in the
presence of organometallic reagents is unprecedented. Thus at the outset
of our investigations it was unclear whether the putative organocobalt
intermediates generated would be compatible with reagents 1 or the
end products present in the reaction mixture.
We commenced our studies by mixing 4-phenylbutene (2) with various
phenyl sulfonyl oximes 1 in the presence of Co catalyst 3 and phenylsilane
in ethanol at RT (Table 1). We were pleased to observe that phenylsul-
fonylmethanal O-benzyloxime (1a) (entry 1) undergoes reaction with 2
to provide product 4a in 99% yield. The methyl and trifluoromethyl
ketoximes 1b and 1c respectively (entries 2 and 3) failed to participate in
any reaction; we suspect that this is most likely a consequence of steric
congestion. Accordingly, changing to a somewhat smaller ethylester group
was beneficial, and reagent 1d (entry 4) gave product 4d in 61% yield.
Replacing the O-benzyl group with a phenylacetyl protecting group had
a detrimental effect on the reaction as reagent 1e (entry 5) furnished 4e in
merely 37% yield and free oxime 1f (entry 6) did not participate in the
reaction at all. We have also prepared N-(benzyloxy)-1-(phenylsulfonyl)-
methanimidoyl cyanide 1g (entry 7)8 and examined it in the reaction, where
it proved to efficiently afford the corresponding oximonitrile 4g in 95%
yield. This represents a convenient one-step preparation of this class of
compounds that have otherwise been assembled through multistep
sequences.9 Interestingly, reagent 1g is bench stable and easy to prepare,
yet, to the best of our knowledge, it has not been examined in radical
transfer processes.7
The scope of the new C-C forming reactions with the two most
efficient reagents 1a and 1g was examined next (Table 2). The reaction
displays excellent Markovnikov selectivity with both reagents, as only
the branched products were detected. This is most likely the consequence
of regioselective hydrocobaltation of the double bond, positioning cobalt
on the more substituted carbon.10 Simple alkenes (entries 1 and 2),
protected alcohols (entries 3, 4, and 6), esters (entries 8 and 9), and ketones
(entry 5) are well tolerated, and both sulfonyl oximes 1a and 1g give
comparable high yields. However, the conversion of the more challenging
trisubstituted alkenes (entry 11) or styrene derivatives (entries 12 and 13)
with sulphonyl oxime 1a was very low. Yet, the same substrates undergo
functionalization by 1g cleanly. Thus the corresponding products can be
isolated in good yields with the styrene derivatives (entries 12 and 13)
with complete selectivity for the formation of a benzylic C-C bond.
Reagent 1g also proved superior in the case of substrates with sensitive
functional groups such as an aldehyde (entry 10), which remained
untouched under the reductive conditions, selectively providing the desired
product in 86% yield. Even pyrrole and furan derived heterocycles (entries
14 and 15) were tolerated in the process giving the corresponding products
in good yields. However, R,ꢀ-unsaturated esters such as ethyl crotonate
failed to provide the desired aldoxime or oximonitrile compounds.
9
13214 J. AM. CHEM. SOC. 2009, 131, 13214–13215
10.1021/ja904856k CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Scope of the Cobalt Catalyzed Functionalization of
Alkenesa
In summary, we have documented a new cobalt-catalyzed C-C
bond forming reaction, which introduces an O-benzyloxime or
oximonitrile onto unactivated double bonds. The reaction is tolerant
to a range of functional groups and displays complete Markovnikov
selectivity. The reaction conditions are mild (EtOH, ambient temper-
atures), and the products can be further transformed into aldehydes as
well as amidoximes. Future work will be dedicated to study the
potential applications of these processes in the synthesis in more
complex settings as well as the development of asymmetric versions.
Acknowledgment. We thank the Swiss National Foundation for
support of this research (Grant 2-00020-119838).
Supporting Information Available: Experimental procedures and
spectral data for all products. This material is available free of charge via
the Internet at http://pubs.acs.org.
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a General procedure: catalyst 3 (2 mol %), alkene (0.5 mmol), reagent 1a
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