Highly Functionalized Cyclohexenes Derived from Benzene: Sequential Tandem Addition Reactions Promoted by Tungsten

Abstract

The dihapto-coordination of benzene to the πbasic fragment {TpW(NO)(PMe 3 )} (Tp = hydridotris-(pyrazolyl)-borate) enhances the basicity of the arene ligand to the point that it can be protonated with a mild Brønsted acid (diphenylammonium triflate; pK a ∼ 1). The resulting η 2benzenium complex reacts with a wide range of nucleophiles including protected enolates, cyanide, amines, methoxide, and aromatic nucleophiles to form 5-substituted 3,4-η 2 -1,3-cyclohexadiene complexes in good yield (42−70%). These coordinated dienes were successfully taken through a second protonation and nucleophilic addition with a similar scope of nucleophiles (54− 80%). The resulting cis-3,4-and cis-3,6-disubstituted η 2 -cyclohexene complexes were prepared with high regio-and stereocontrol, as governed by the asymmetric nature of π-allyl intermediates. In some cases, a diene linkage isomerization from 3,4-η 2 to 1,2-η 2 could be effected with a redox catalyst, and reactions of the latter species led to cis-3,5-disubstituted cyclohexene products exclusively. Oxidative decomplexation afforded the free cyclohexene products in moderate yield (37−68%). Additionally, when a single enantiomer of the chiral dearomatization agent was used, the elaborated cyclohexenes were able to be synthesized in enantioenriched forms (86−90% enantiomeric excess). Full characterization of 40 new compounds is provided that includes two-dimensional NMR, IR, electrochemical and in some cases crystallographic data.

Hydroamination of Dihapto‐Coordinated Benzene and Diene Complexes of Tungsten: Fundamental Studies and the Synthesis of γ‐Lycorane

“…In this case, the metal activates the aromatic ligand toward protonation to form an η 3 ‐ or η 2 ‐arenium intermediate ( reaction IV ) [14] . Our previous work has demonstrated that this intermediate reacts with carbon nucleophiles to generate substituted cyclohexadienes [15,16] . Strikingly, we found that addition of methylamine resulted in the hydroamination of the benzene ring to form the aminodiene ( reaction IV ) [15] .…”

“…Our previous work has demonstrated that this intermediate reacts with carbon nucleophiles to generate substituted cyclohexadienes [15,16] . Strikingly, we found that addition of methylamine resulted in the hydroamination of the benzene ring to form the aminodiene ( reaction IV ) [15] . This result was surprising because not only was addition of the amine competitive with deprotonation of the arenium ligand, but the resulting complex was kinetically stable with respect to elimination, provided that it was kept in a basic environment.…”

“…For the η 2 ‐benzenium system, this equilibrium in solution is approximately 10 : 1 ( 1 H‐NMR), favoring isomer 2 in its distal conformer ( 2D ). Under Curtin–Hammett conditions, addition of the amine is not necessarily dictated by the dominant species in solution, but in the case of methylamine, addition occurs smoothly at the anticipated carbon providing the distal aminodiene 4D with a >96 : 4 selectivity ( Scheme 2 ) [15] . As is typical for these arenium species, [13] nucleophilic addition occurs strictly anti to the ring face bound by the metal [15] .…”

“…Under Curtin–Hammett conditions, addition of the amine is not necessarily dictated by the dominant species in solution, but in the case of methylamine, addition occurs smoothly at the anticipated carbon providing the distal aminodiene 4D with a >96 : 4 selectivity ( Scheme 2 ) [15] . As is typical for these arenium species, [13] nucleophilic addition occurs strictly anti to the ring face bound by the metal [15] . The selectivity becomes even more impressive when the arene contains an electron‐withdrawing group.…”

Asymmetric organic synthesis with stoichiometric transition metal complexes

“…trifluoromethyl benzene) that stabilize the  complexes by significant metal to ligand -back bonding, 55 selective dearomatization of benzene, proved to be quite challenging. 56 The challenge has been effectively addressed using the chiral-at-tungsten, enantiopure complexes that added sequentially first a proton, and then a nucleophile, across the uncoordinated double bond distal to the phosphine ligand, both from the face opposite to the metal fragment. After decomplexation, the protocol produced cis-disubstituted cyclohexenes in a high enantiomeric purity (Scheme 29).…”