Cobaltocene-Induced Low-Temperature Radical Coupling Reactions in a Cobalt–Alkyne Series

Abstract

A novel method for the low-temperature generation of Co2(CO)6-complexed propargyl radicals is developed. It consists of an in situ preparation of the respective cationic species (−50 to −10 °C) and their rapid reduction with cobaltocene, Cp2Co, at −50 °C. The optimized experimental protocol is applied to both inter- and intramolecular reactions, affording topologically diverse α-aryl and α-napthyl, d,l- and meso-1,5-hexadiynes and 1,5-cyclodecadiynes. The d,l configuration is the most preferable steric arrangement in intermolecular radical C–C bond-forming reactions (d,l 69–92%), while a reversal of stereoselectivity is observed in intramolecular cyclizations (meso 79%). Under oxidizing conditions (Ce4+), decomplexation affords d,l-3,4-diaryl- and d,l-3,4-(1-/2-naphthyl)-1,5-hexadiynes in good to excellent yields (47–98%). An enhanced functional tolerance is showcased by introducing peripheral acid-sensitive functionalities, such as benzyloxy and methylenedioxy groups, and carrying out a five-step conversion schemefrom commercial aromatic aldehydes to radical dimersunder nonacidic conditions.

Acquiring a Prognostic Power in Co2(CO)6-Mediated, Cobaltocene-Induced Radical Dimerizations of Propargyl Triflates

“…The formation of the respective head-to-head dimers 3 served as an indirect proof that radicals 4 are in fact formed along the reaction coordinate. The new methodology that utilizes methyl propargyl ethers as substrates and triflic anhydride ( 5 ) as a reagent was originally optimized for α-phenyl derivative 6 , which converted to propargyl triflate 7 via ionic pair 8 (Scheme ). Experimentally, it was established that cobaltocene is capable of rapidly reducing propargyl triflate 7 even at −50 °C (10 min) and generating propargyl radicals 9 , which in turn dimerize to chromatographically separable stereoisomers ( d,l - 10 : meso - 10 , 62:38) …”

“…Cobalt-complexed propargyl ethers can act as precursors to triflates, which in turn can be reduced with cobaltocene to generate transient propargyl radicals . Synthetically, this new method represents a major enhancement to existing methodologies. , First, a new formatmethyl ether + triflic anhydrideallowed us to avoid the use of strong acids, such as HBF 4 and others, for generation of propargyl cations, thus making the methodology compatible with peripheral acid-sensitive functionalities.…”

“…Second, an in situ generation of propargyl triflates and α-C–OTf bond ionicity allowed for circumventing the laborious cation isolation step . Third, establishing an ability of cobaltocene to reduce propargyl triflates at temperatures as low as −50 °C substantially expanded the temperature domain for reduction reactions of the metal-stabilized carbocations. , Fourth, lower temperatures for cation generation and reduction allowed us to access propargyl cations of a higher level of conjugation, which are subject to rapid polymerization under standard conditions. , Chronologically, the first substrate successfully dimerized with a Tf 2 O–Cp 2 Co tandem contained a phenyl group in α-position to the metal core, Co 2 (CO) 6 . In this account, we present a systematic study on dimerization of propargyl triflates wherein the electronic effects of alpha substituents were varied to modulate the ionic nature of α-C–OTf bonds and hence their reducibility with cobaltocene.…”

Cobalt-Catalysed Bond Formation Reactions; Part 2

“…While most applications have concentrated on cobaltcarbonyl stabilised cations, reactions of propargyl radicals have also been described. In recent years, Melikyan reported in a series of publications the reduction of the Co 2 (CO) 6stabilised cations in the presence of zinc 214,215 or cobaltocene 216,217 for the in situ reduction and intra-as well as intermolecular dimerisation reactions (Scheme 62). After oxidative deprotection, 1,5-diynes were obtained in acceptable to good yields and moderate diastereoselectivities.…”

Crystal structures of (μ2-η2,η2-4-hydroxybut-2-yn-1-yl 2-bromo-2-methylpropanoate-κ4C2,C3:C2,C3)bis[tricarbonylcobalt(II)](Co—Co) and [μ2-η2,η2-but-2-yne-1,4-diyl bis(2-bromo-2-methylpropanoate)-κ4C2,C3:C2,C3]bis[tricarbonylcobalt(II)](Co—Co)

“…The novelty of these compounds, together with their close isolobal relationship to other members of the 'tetrahedrane series' (Hoffmann, 1982), spawned enormous interest in both the hexacarbonyls and their substituted derivatives. Applications include use in organic synthesis (Melikyan et al, 2012), as biological probes (Salmain & Jaouen, 1993) and in the stabilization of high-performance energetic materials (Windler et al, 2012). Their diverse redox properties (Robinson & Simpson, 1989) have also been exploited in the development of molecular wires (McAdam et al, 1996;Hore et al, 2000;Xie et al, 2012) where alkyne-hexacarbonyl-dicobalt cores are separated by electronically conducting spacers or connecting groups.…”