Highly Selective Lithium—Amine Reducing Systems. The Selective Reduction of Aromatic Compounds by Lithium in Mixed Amine Solvents<sup>1a</sup>

Benkeser, Robert A.; Agnihotri, Ram K.; Burrous, Merwyn L.; Kaiser, Edwin M.; Mallan, J. M.; Ryan, Patrick W.

doi:10.1021/jo01029a010

Cited by 16 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is similar to the Benkeser reduction without alcohol (Fig. 1B) ( 15 – 17 , 52 – 54 ). Although the addition of an alcohol under the Benkeser-type conditions gave Birch-type products ( 4 , 18 , 55 ), these findings have not garnered widespread use.…”

supporting

confidence: 86%

“…For example, the Benkeser group used lithium and neat ethylamine, ethylenediamine, or a mixture of primary and secondary amines, providing a mixture of over-reduced products, and did not use any other solvents (Fig. 1B) ( 15 – 17 ). Arenes could be reduced to the Birch-type products with lithium in a mixture of methylamine and isopropanol, but overreduction appeared inevitable ( 18 ).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran

Burrows

Kamo

Koide

2021

Science

View full text Add to dashboard Cite

Easy aryl reductions The Birch reduction has been widely used for more than half a century to achieve partial reduction of aryl rings by alkali metals at just two diametrically opposed carbon sites. However, the conditions require condensation of caustic gaseous ammonia. A variation developed soon afterward by Benkeser used safer liquid ethylene diamine but was prone to overreduction. By diluting ethylene diamine in tetrahydrofuran solvent, Burrows et al . now obtain selectivities comparable to Birch conditions but without the need for condensed ammonia. —JSY

show abstract

supporting

confidence: 86%

mentioning

confidence: 99%

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran

Burrows

Kamo

Koide

2021

Science

View full text Add to dashboard Cite

show abstract

“…11,12 Recently the Koide group demonstrated that ammonia could be replaced by ethylene diamine (e.g. Benkesser modification [13][14][15] ) to further enhance practicality. 16 Although some of these studies enabled practical and scalable Birch reduction, the chemoselectivity was revealed to be analogous to conventional Birch reduction.…”

Section: Main Textmentioning

confidence: 99%

Chemoselective, Metal-free, (Hetero)Arene Electroreduction Enabled by Rapid Alternating Polarity

Hayashi

Griffin

Harper

et al. 2022

Preprint

View full text Add to dashboard Cite

Arene semi-reduction remains a challenge when multiple re-ductively labile functional groups are present or when using heteroarene substrates. Conventional chemical and even elec-trochemical Birch-type reductions suffer from a lack of chemoselectivity due to a reliance on alkali metals or harshly reducing conditions. This study reveals that a simpler avenue is available for such reductions by simply altering the wave-form of current delivery, namely rapid alternating polarity (rAP). The developed method, which proceeds in protic sol-vent and can be easily scaled up, does not require any metal additives or stringently anhydrous conditions. The scope of this dearomatization is broad, tolerating numerous functional groups and providing rapid access to previously challenging molecules. While the mechanism has not been fully deci-phered, the key feature of the rAP reduction is that the main competing process, namely proton reduction, can be sup-pressed. As such, unique arene reductions can be accom-plished even outside solvent electrochemical window or in the presence of Brønsted acids.

show abstract

“… 15 , 16 While there have been several efforts to produce an ammonia-free Birch reduction, the methodologies have only been demonstrated on small scales 17 − 19 and in some cases, they led to over-reduction of the Birch-type products. 20 − 22 A recent report by Koide and co-workers demonstrated that a Birch reduction could be achieved by replacing ammonia with ethylenediamine in THF and lithium metal as the reducing agent. 15 They scaled up this methodology to 61 g scale in batch.…”

Section: Introductionmentioning

confidence: 99%

“… The traditional synthetic methodology of this reaction requires the use of alkali metals (typically Li, Na, or K) dissolved in liquid NH 3 which, in turn, necessitates cooling (typically <−33 °C) to maintain its liquid state . The harsh and challenging conditions of this methodology mean that it is not favored in industrial settings as it presents several safety challenges with copious amounts of ammonia required upon scale-up. , While there have been several efforts to produce an ammonia-free Birch reduction, the methodologies have only been demonstrated on small scales − and in some cases, they led to over-reduction of the Birch-type products. − A recent report by Koide and co-workers demonstrated that a Birch reduction could be achieved by replacing ammonia with ethylenediamine in THF and lithium metal as the reducing agent . They scaled up this methodology to 61 g scale in batch.…”

Section: Introductionmentioning

confidence: 99%

High-Productivity Single-Pass Electrochemical Birch Reduction of Naphthalenes in a Continuous Flow Electrochemical Taylor Vortex Reactor

Lee

Love

Mansouri

et al. 2022

Org. Process Res. Dev.

View full text Add to dashboard Cite

We report the development of a single-pass electrochemical Birch reduction carried out in a small footprint electrochemical Taylor vortex reactor with projected productivities of >80 g day –1 (based on 32.2 mmol h –1 ), using a modified version of our previously reported reactor [ Org. Process Res. Dev. 2021 , 25 , 7, 1619–1627], consisting of a static outer electrode and a rapidly rotating cylindrical inner electrode. In this study, we used an aluminum tube as the sacrificial outer electrode and stainless steel as the rotating inner electrode. We have established the viability of using a sacrificial aluminum anode for the electrochemical reduction of naphthalene, and by varying the current, we can switch between high selectivity (>90%) for either the single ring reduction or double ring reduction with >80 g day –1 projected productivity for either product. The concentration of LiBr in solution changes the fluid dynamics of the reaction mixture investigated by computational fluid dynamics, and this affects equilibration time, monitored using Fourier transform infrared spectroscopy. We show that the concentrations of electrolyte (LiBr) and proton source (dimethylurea) can be reduced while maintaining high reaction efficiency. We also report the reduction of 1-aminonaphthalene, which has been used as a precursor to the API Ropinirole. We find that our methodology produces the corresponding dihydronaphthalene with excellent selectivity and 88% isolated yield in an uninterrupted run of >8 h with a projected productivity of >100 g day –1 .

show abstract

Highly Selective Lithium—Amine Reducing Systems. The Selective Reduction of Aromatic Compounds by Lithium in Mixed Amine Solvents^1a

Cited by 16 publications

References 0 publications

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran

Chemoselective, Metal-free, (Hetero)Arene Electroreduction Enabled by Rapid Alternating Polarity

High-Productivity Single-Pass Electrochemical Birch Reduction of Naphthalenes in a Continuous Flow Electrochemical Taylor Vortex Reactor

Contact Info

Product

Resources

About

Highly Selective Lithium—Amine Reducing Systems. The Selective Reduction of Aromatic Compounds by Lithium in Mixed Amine Solvents1a

Cited by 16 publications

References 0 publications

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran

Chemoselective, Metal-free, (Hetero)Arene Electroreduction Enabled by Rapid Alternating Polarity

High-Productivity Single-Pass Electrochemical Birch Reduction of Naphthalenes in a Continuous Flow Electrochemical Taylor Vortex Reactor

Contact Info

Product

Resources

About

Highly Selective Lithium—Amine Reducing Systems. The Selective Reduction of Aromatic Compounds by Lithium in Mixed Amine Solvents^1a