Atmosphere Effects on Arene Reduction with Lithium and Ethylenediamine in THF

Abstract

Birch reductions employing lithium metal have been performed mostly under argon due to concerns about forming metal nitrides from the reduction of dinitrogen if performed under nitrogen. Although it is generally understood that inert atmospheres are standard for Birch and Birch-type (lithium, ethylenediamine, t-BuOH, THF) reductions, the atmosphere effect on Birch reduction has not been studied. Herein, we report the reduction of model substrates using lithium metal and ethylenediamine in THF under various atmospheric conditions. The reductions under argon and nitrogen atmospheres afforded essentially the same yields. Surprisingly, oxygen not only perturbed the yields in some cases but also controlled regioselectivity for a subset of naphthalenes. We propose a mechanism underlying the unexpected oxygen-dependent regioselectivity for the Birch-type reduction of naphthalenes. This work shows that the Birch-type reduction may be performed under a nitrogen atmosphere and may account for a fraction of oxygen-sensitive Birch-type reductions.

Figure 1

Previous work and current work. (a) Previous Birch reduction reactions were performed under argon or, occasionally, nitrogen atmosphere. Concerns regarding nitride formation were not experimentally addressed. (b) Current work shows that Birch-type reduction can be employed under an argon, nitrogen, air, or oxygen atmosphere. In the presence of oxygen, regioisomers may be produced from naphthalenes.

Figure 2

Reduction of naphthalene (8) measured over time. Reaction condition: 8 (3.0 mmol), lithium (9.0 mmol), ethylenediamine (18 mmol), t-BuOH (7.5 mmol), THF (10 mL), 0 °C, indicated atmosphere (1 atm), 1 h. Aliquots (0.1 mL) of the reaction mixture were taken at 0, 5, 10, 15, 30, 45, and 60 min for analysis. (a) Reduction of 8 under an argon atmosphere. (b) Reduction of 8 under an oxygen atmosphere. Percent yields were determined by ¹H NMR using 1-methoxyadamantane as an internal standard. (c) The reduction of naphthalene with two competing pathways.

Scheme 1. Reduction Pathway for Naphthalene (8) under Lithium-Ethylenediamine-THF Condition^,

R = −(CH₂)₂NH₂ under lithium-ethylenediamine-THF condition. R′ = t-Bu under lithium-ethylenediamine-THF condition.

Figure 3

Substrate scope of polyaromatic reduction under alternative atmospheres. Reaction condition A: arene (2.0 mmol), lithium (10 mmol), ethylenediamine (20 mmol), t-BuOH (10 mmol), THF (6.7 mL), 0 °C, atmosphere (1 atm), 1 h. Reaction condition B: arene (2.0 mmol), lithium (6.0 mmol), ethylenediamine (12 mmol), t-BuOH (6.0 mmol), THF (6.7 mL), 0 °C, atmosphere (1 atm), 1 h. ^aFollowing condition A using 6.0 mmol of t-BuOH. ^bPercent yield determined by ¹H NMR may not be accurate due to peak overlaps. ^ct-BuOH was not used. ^dReduction was performed on a 20 mmol scale. ^eUsing the same condition as 30. Percent yields were determined by ¹H NMR comparison to 1-methoxyadamantane or 1,3,5-trimethoxybenzene as an internal standard. For more details, see the Supporting Information.