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Catalytic Reductive Vinylidene Transfer Reactions Sudipta Pal, You-Yun Zhou, and Christopher Uyeda J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b05901 • Publication Date (Web): 14 Aug 2017 Downloaded from http://pubs.acs.org on August 14, 2017
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Journal of the American Chemical Society
Catalytic Reductive Vinylidene Transfer Reactions Sudipta Pal,‡ You-Yun Zhou,‡ and Christopher Uyeda* Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States
Supporting Information Placeholder ABSTRACT: Methylenecyclopropanes are important synthetic intermediates that possess strain energies exceeding those of saturated cyclopropanes by >10 kcal/mol. This report describes a catalytic reductive methylenecyclopropanation reaction of simple olefins, utilizing 1,1-dichloroalkenes as vinylidene precursors. The reaction is promoted by a dinuclear Ni catalyst, which is proposed to access Ni2(vinylidenoid) intermediates via C–Cl oxidative addition.
readily available and indefinitely stable 1,1-dihaloalkanes. In this context, we recently described a dinuclear Ni catalyst that promotes the cyclopropanation of alkenes using CH2Cl2 11 as a carbene source and Zn as a terminal reductant. Here, we report the reductive transfer of vinylidenes from 1,1dichloroalkenes (Figure 1). This method provides direct access to methylenecyclopropanes, a class of synthetic intermediates valued for their ability to engage in strain-induced 2d,2e,12 ring-opening reactions.
Vinylidenes (methylidene carbenes) are reactive intermediates comprising a divalent carbon atom incorporated into a 1 C=C double bond. Like their saturated carbene counterparts, vinylidenes undergo reactions that allow the valencedeficient carbon to increase its coordination number—for example, through cheletropic reactions with π-systems or 2 insertions into C–H bonds. Free vinylidenes are accessible from the decomposition of transiently generated diazo3 alkenes. Alternatively, (R2C=C)(M)(X) species (vinylidenoids) serve as R2C=C: surrogates, eliminating metal hal1d ides as stoichiometric byproducts. A key challenge associated with developing efficient transfer reactions of vinylidenes is their susceptibility to competing Fritsch–Buttenberg– Wiechell (FBW) rearrangements that form alkynes (Figure 4 1). The rate of the 1,2-shift varies as a function of the migrating group, but when one of the alkene substituents is an H 5 atom, the rearrangement becomes nearly barrierless. This process underlies the well-known Corey–Fuchs and Seyferth– 6 Gilbert alkyne syntheses. Transition metal catalysis may provide an avenue to address the instability of vinylidenes, allowing group transfer reactions to be favored over competing FBW rearrangement. Nevertheless, current carbene transfer catalysts are largely unsuitable for vinylidene transfer due to their reliance on 7 diazoalkane decomposition as an activation strategy. Diazoalkenes, the equivalent vinylidene precursors, are not known to be isolable and undergo N2 elimination spontaneously at 1d,3a room temperature. Transition metal-bound vinylidenes are accessible by an alternative route involving a metal8 induced isomerization of an alkyne. Buono described a Pdcatalyzed methylenecyclopropanation reaction that operates by this pathway and is effective for a range of norbornene9,10 derived substrates. Other classes of alkenes are not currently viable in catalytic vinylidene [2 + 1]-cycloadditions. Our group is interested in developing new modes of carbene generation based on the reductive dehalogenation of
Figure 1. Vinylidenes as reactive intermediates and design principles for a catalytic reductive vinylidene transfer reaction. In our initial studies, we arrived at an optimal set of conditions for a model methylenecyclopropanation reaction based 11 on our previously reported CH2 transfer method. The Ni2 13 catalyst 1 promotes the addition of 2 to styrene in 94% yield using Zn as a reductant (Table 1, entry 1). Of note, none of the 1,1-dichloroalkene is lost to polymerization, reductive dehalogenation, or FBW rearrangement, allowing the reaction to be conducted with near-equimolar quantities of the i-Pr two reaction partners. The [ NDI]Ni2Cl2 complex 4 is also a high-yielding catalyst, demonstrating efficient entry into the catalytic cycle from multiple oxidation states of the Ni2 complex (entry 2). The reaction is amenable to in situ catalyst
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Journal of the American Chemical Society i-Pr
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generation using the free NDI ligand (5, 5 mol%) and Ni(DME)Cl2 (10 mol%) in the place of preformed 1 (entry 3). Decreasing the steric profile of the imine aryl substituents leads to rapidly diminishing yields (entries 4–5). Finally, the importance of the dinuclear catalyst structure was assessed using a series of mononickel complexes bearing structurally related N-donor ligands. In these cases, there is significant consumption of the 1,1-dichloroalkene (2) but no productive vinylidene transfer to form 3 (entries 6–9). a
Table 1. Catalyst Structure–Activity Relationships
entry 1 2
catalyst [
i-Pr
[
i-Pr
NDI]Ni2(C6H6) (1)
E/Z ratio
94%
1:5
87%
1:5
b
i-Pr
92%
1:5
b
Et
50%
1:1
b
Me
3
4 5
NDI]Ni2Cl2 (4)
yield
NDI (5) + Ni(DME)Cl2
NDI (6) + Ni(DME)Cl2
