Highly Regioselective Benzylic Deprotonation of Some (η ⁶ ‐Tetralin)‐ and (η ⁶ ‐ trans ‐Octahydroanthracene)Cr(CO) ₃ Derivatives: Is the Regioselectivity Stereoelectronically Controlled?

Abstract

The regioselectivity of benzylic deprotonation of a number of conformationally restricted (arene)Cr(CO)3 complexes has been examined in order to ascertain whether stereoelectronic effects play a role in such reactions. The complexes rac‐5, rac‐6, rac‐7, rac‐8 and rac‐9 were diastereoselectively synthesized from the corresponding C2‐symmetric ligands (2,3‐disubstituted trans‐1,2,3,4‐tetrahydronaphthalene and trans‐1,2,3,4,4a,9,9a,10‐octahydroanthracene derivatives). Due to the desymmetrization caused by the Cr(CO)3 complexation, all four benzylic protons could be distinguished by 1H NMR and were assigned in all cases by a combination of H,H‐COSY spectra and the observation of H/D exchange at both exo positions (tert‐BuOK/[D6]DMSO). Deprotonation (n‐butyllithium)/deuteration (D2O or CF3CO2D) experiments revealed a very high, unforeseen regioselectivity in the cases of rac‐5 and rac‐7, while the other substrates showed a low selectivity (rac‐6) or could not be deuterated at all under these conditions (rac‐8, rac‐9). In the case of rac‐5, the regioselectivity of the deprotonation was further confirmed by acylation (AcCl) or alkylation (MeI) of the lithiated intermediate. These results clearly rule out the notion that the regioselectivity is due to the preferred abstraction of pseudoaxially oriented benzylic hydrogen atoms. The crystal structures of rac‐1, rac‐5 and rac‐7 suggest a possible link between the preferred conformation of the Cr(CO)3 tripod and the regioselectivity of the benzylic deprotonation. In analogy to a commonly accepted picture often used to explain the regioselectivity of nucleophile additions to (arene)Cr(CO)3 complexes, it was anticipated that those benzylic positions which are activated by an eclipsed CO ligand should be preferentially deprotonated (kinetically controlled). This (new) stereoelectronic model was corroborated by experiments using complexes rac‐60 and rac‐62, which were regioselectively deprotonated at the predicted position. In summary, it has been shown for the first time that the preferred conformation of the Cr(CO)3 tripod may have a directing influence on the regioselectivity of benzylic deprotonation in (arene)Cr(CO)3 complexes, at least in conformationally unambiguous situations where no obvious electronic effects are operative.

Regiochemistry in Aryl Radical Cyclization onto Methylenecycloalkanes

“…Radical Cyclization of 6 with Bu 3 SnH at a 0.1 M Concentration. To a solution of 6 , (92.2 mg, 0.360 mmol) in benzene (3.5 mL) were added Bu 3 SnH (115 mg, 0.396 mmol) and AIBN (9.7 mg, 0.040 mmol), and the mixture was heated under reflux for 9 h. After workup, the crude material was chromatographed on silica gel (hexane). The first fraction gave an oily mixture of 7 , , 18 , and the recovered 6 (52.1 mg) in a ratio of ca.…”

“…To a solution of 6 , (92.2 mg, 0.360 mmol) in benzene (3.5 mL) were added Bu 3 SnH (115 mg, 0.396 mmol) and AIBN (9.7 mg, 0.040 mmol), and the mixture was heated under reflux for 9 h. After workup, the crude material was chromatographed on silica gel (hexane). The first fraction gave an oily mixture of 7 , , 18 , and the recovered 6 (52.1 mg) in a ratio of ca. 7:1:2: 1 H NMR (500 MHz) δ 1.00−1.10 ( 7 / 10 × 2 H, m, for 7 ), 1.23 ( 1 / 10 × 3 H, s, for 18 ), 1.23−1.90 [( 2 / 10 × 6 + 7 / 10 × 8 + 1 / 10 × 8) H, m], 2.05−2.13 [( 2 / 10 + 1 / 10 ) H, m], 2.35 ( 2 / 10 H, dt, J = 13.1, 3.8 Hz, for 6 ), 2.40−2.50 [( 2 / 10 + 7 / 10 ) × 2 H, m], 2.66 ( 1 / 10 H, dd, J = 15.1, 7.3 Hz, for 18 ), 2.72 ( 2 / 10 H, dd, J = 14.1, 8.8 Hz, for 6 ), 2.78 ( 7 / 10 × 2 H, dd, J = 15.5, 4.0 Hz, for 7 ), 2.89 ( 1 / 10 H, dd, J = 15.1, 7.3 Hz, for 18 ), 3.08 ( 2 / 10 H, dd, J = 14.1, 5.6 Hz, for 6 ), 4.60 ( 2 / 10 H, s, for 6 ), 4.70 ( 2 / 10 H, s, for 6 ), 7.00−7.30 [(3 + 8 / 10 ) H, m], 7.53 ( 2 / 10 H, d, J = 6.9 Hz, for 6 ).…”

Metal‐catalysed hydrogen isotope exchange labelling: a brief overview

“…Similar results were obtained by dedeuteration studies with deuterated toluene ligands 49. The exchange of the benzylic protons of η 6 ‐tetralin and trans ‐ η 6 ‐(octahydroanthracene)Cr(CO) 3 complexes has also been studied, and the conformation of the tricarbonylchromium tripod has been shown to determine the orientation of the exchange 50…”

Lithiation/Electrophilic Quench Sequence of “Benzylic” Position of (η5-Methylcyclohexadienyl)Mn(CO)3 Complexes

“…Having discovered the lithiation/electrophilic quench sequence methodology that allows substitution of the ring protons of (η 5 -cyclohexadienyl)Mn(CO) 3 complexes, we wondered whether this reaction could be applied to functionalize “benzylic” positions, i.e., positions α to the η 5 -π system of such complexes. Indeed, the study of the benzylic position has already been reported for the cationic [(η 6 -arene)Mn(CO) 3 ] + series and has been well developed in the (η 6 -arene)Cr(CO) 3 series . In the early 1990s, Eyman et al and then Gladfelter et al investigated the generality of deprotonation of organometallic complexes at a benzylic position using a large excess of strong base−such as potassium hydride or potassium tert -butoxide−and worked on different [(η 6 -alkylarene)Mn(CO) 3 ] + complexes.…”