[{"doi":"10.1021/acs.oprd.1c00442","volume":26,"type":"journal_article","quality_controlled":"1","month":"02","article_type":"original","publication_identifier":{"issn":["1083-6160"],"eissn":["1520-586X"]},"publication":"Organic Process Research & Development","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"author":[{"first_name":"Julia","last_name":"Reisenbauer","full_name":"Reisenbauer, Julia","id":"51d862e9-36ee-11f0-86d3-8534c85a5496"},{"last_name":"Bhawal","first_name":"Benjamin N.","full_name":"Bhawal, Benjamin N."},{"first_name":"Nicola","last_name":"Jelmini","full_name":"Jelmini, Nicola"},{"last_name":"Morandi","first_name":"Bill","full_name":"Morandi, Bill"}],"OA_place":"repository","date_published":"2022-02-15T00:00:00Z","day":"15","main_file_link":[{"open_access":"1","url":"https://www.research-collection.ethz.ch/entities/publication/4ed5123f-eb11-4a4d-b06c-f50edcec38b8"}],"article_processing_charge":"No","publisher":"American Chemical Society","citation":{"ama":"Reisenbauer J, Bhawal BN, Jelmini N, Morandi B. Development of an operationally simple, scalable, and HCN-free transfer hydrocyanation protocol using an air-stable nickel precatalyst. <i>Organic Process Research &#38; Development</i>. 2022;26(4):1165-1173. doi:<a href=\"https://doi.org/10.1021/acs.oprd.1c00442\">10.1021/acs.oprd.1c00442</a>","ista":"Reisenbauer J, Bhawal BN, Jelmini N, Morandi B. 2022. Development of an operationally simple, scalable, and HCN-free transfer hydrocyanation protocol using an air-stable nickel precatalyst. Organic Process Research &#38; Development. 26(4), 1165–1173.","ieee":"J. Reisenbauer, B. N. Bhawal, N. Jelmini, and B. Morandi, “Development of an operationally simple, scalable, and HCN-free transfer hydrocyanation protocol using an air-stable nickel precatalyst,” <i>Organic Process Research &#38; Development</i>, vol. 26, no. 4. American Chemical Society, pp. 1165–1173, 2022.","chicago":"Reisenbauer, Julia, Benjamin N. Bhawal, Nicola Jelmini, and Bill Morandi. “Development of an Operationally Simple, Scalable, and HCN-Free Transfer Hydrocyanation Protocol Using an Air-Stable Nickel Precatalyst.” <i>Organic Process Research &#38; Development</i>. American Chemical Society, 2022. <a href=\"https://doi.org/10.1021/acs.oprd.1c00442\">https://doi.org/10.1021/acs.oprd.1c00442</a>.","short":"J. Reisenbauer, B.N. Bhawal, N. Jelmini, B. Morandi, Organic Process Research &#38; Development 26 (2022) 1165–1173.","mla":"Reisenbauer, Julia, et al. “Development of an Operationally Simple, Scalable, and HCN-Free Transfer Hydrocyanation Protocol Using an Air-Stable Nickel Precatalyst.” <i>Organic Process Research &#38; Development</i>, vol. 26, no. 4, American Chemical Society, 2022, pp. 1165–73, doi:<a href=\"https://doi.org/10.1021/acs.oprd.1c00442\">10.1021/acs.oprd.1c00442</a>.","apa":"Reisenbauer, J., Bhawal, B. N., Jelmini, N., &#38; Morandi, B. (2022). Development of an operationally simple, scalable, and HCN-free transfer hydrocyanation protocol using an air-stable nickel precatalyst. <i>Organic Process Research &#38; Development</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acs.oprd.1c00442\">https://doi.org/10.1021/acs.oprd.1c00442</a>"},"issue":"4","intvolume":"        26","abstract":[{"text":"Hydrocyanation reactions enable access to synthetically valuable nitriles from readily available alkene precursors. However, hydrocyanation reactions using hydrogen cyanide (HCN) or similarly toxic reagents on laboratory scale can be particularly challenging due to their hazardous nature. In addition, such processes typically require air- and temperature-sensitive Ni(0) precatalysts, further reducing the operational simplicity of this transformation. Herein, we report a HCN-free transfer hydrocyanation of alkenes and alkynes that employs commercially available aliphatic nitriles as sacrificial HCN donors in combination with a catalytic amount of air-stable and inexpensive NiCl2 as a precatalyst and a cocatalytic Lewis acid. The scalability and robustness of the catalytic process were demonstrated by the hydrocyanation of α-methylstyrene on a 100 mmol scale (11.4 g of product obtained) using 1 mol % of the Ni catalyst. In addition, the feasibility of the dehydrocyanation protocol using the air-stable Ni(II) precatalyst and norbornadiene as a sacrificial acceptor was showcased by the selective conversion of an aliphatic nitrile into the corresponding alkene.","lang":"eng"}],"oa":1,"date_created":"2025-12-09T14:24:58Z","extern":"1","title":"Development of an operationally simple, scalable, and HCN-free transfer hydrocyanation protocol using an air-stable nickel precatalyst","_id":"20764","status":"public","date_updated":"2025-12-16T12:02:59Z","scopus_import":"1","oa_version":"Submitted Version","page":"1165-1173","publication_status":"published","OA_type":"green","year":"2022"},{"oa_version":"Published Version","scopus_import":"1","date_updated":"2023-02-21T10:10:23Z","year":"2019","page":"2764-2770","publication_status":"published","_id":"11984","status":"public","title":"Safe and scalable continuous flow azidophenylselenylation of galactal to prepare galactosamine building blocks","extern":"1","abstract":[{"lang":"eng","text":"Differentially protected galactosamine building blocks are key components for the synthesis of human and bacterial oligosaccharides. The azidophenylselenylation of 3,4,6-tri-O-acetyl-d-galactal provides straightforward access to the corresponding 2-nitrogenated glycoside. Poor reproducibility and the use of azides that lead to the formation of potentially explosive and toxic species limit the scalability of this reaction and render it a bottleneck for carbohydrate synthesis. Here, we present a method for the safe, efficient, and reliable azidophenylselenylation of 3,4,6-tri-O-acetyl-d-galactal at room temperature, using continuous flow chemistry. Careful analysis of the transformation resulted in reaction conditions that produce minimal side products while the reaction time was reduced drastically when compared to batch reactions. The flow setup is readily scalable to process 5 mmol of galactal in 3 h, producing 1.2 mmol/h of product."}],"oa":1,"date_created":"2022-08-25T11:30:33Z","author":[{"first_name":"Mónica","last_name":"Guberman","full_name":"Guberman, Mónica"},{"first_name":"Bartholomäus","last_name":"Pieber","full_name":"Pieber, Bartholomäus","orcid":"0000-0001-8689-388X","id":"93e5e5b2-0da6-11ed-8a41-af589a024726"},{"full_name":"Seeberger, Peter H.","first_name":"Peter H.","last_name":"Seeberger"}],"publication":"Organic Process Research and Development","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"issue":"12","intvolume":"        23","publisher":"American Chemical Society","citation":{"ama":"Guberman M, Pieber B, Seeberger PH. Safe and scalable continuous flow azidophenylselenylation of galactal to prepare galactosamine building blocks. <i>Organic Process Research and Development</i>. 2019;23(12):2764-2770. doi:<a href=\"https://doi.org/10.1021/acs.oprd.9b00456\">10.1021/acs.oprd.9b00456</a>","ista":"Guberman M, Pieber B, Seeberger PH. 2019. Safe and scalable continuous flow azidophenylselenylation of galactal to prepare galactosamine building blocks. Organic Process Research and Development. 23(12), 2764–2770.","chicago":"Guberman, Mónica, Bartholomäus Pieber, and Peter H. Seeberger. “Safe and Scalable Continuous Flow Azidophenylselenylation of Galactal to Prepare Galactosamine Building Blocks.” <i>Organic Process Research and Development</i>. American Chemical Society, 2019. <a href=\"https://doi.org/10.1021/acs.oprd.9b00456\">https://doi.org/10.1021/acs.oprd.9b00456</a>.","ieee":"M. Guberman, B. Pieber, and P. H. Seeberger, “Safe and scalable continuous flow azidophenylselenylation of galactal to prepare galactosamine building blocks,” <i>Organic Process Research and Development</i>, vol. 23, no. 12. American Chemical Society, pp. 2764–2770, 2019.","short":"M. Guberman, B. Pieber, P.H. Seeberger, Organic Process Research and Development 23 (2019) 2764–2770.","mla":"Guberman, Mónica, et al. “Safe and Scalable Continuous Flow Azidophenylselenylation of Galactal to Prepare Galactosamine Building Blocks.” <i>Organic Process Research and Development</i>, vol. 23, no. 12, American Chemical Society, 2019, pp. 2764–70, doi:<a href=\"https://doi.org/10.1021/acs.oprd.9b00456\">10.1021/acs.oprd.9b00456</a>.","apa":"Guberman, M., Pieber, B., &#38; Seeberger, P. H. (2019). Safe and scalable continuous flow azidophenylselenylation of galactal to prepare galactosamine building blocks. <i>Organic Process Research and Development</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acs.oprd.9b00456\">https://doi.org/10.1021/acs.oprd.9b00456</a>"},"date_published":"2019-12-20T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1021/acs.oprd.9b00456","open_access":"1"}],"day":"20","article_processing_charge":"No","type":"journal_article","doi":"10.1021/acs.oprd.9b00456","volume":23,"publication_identifier":{"eissn":["1520-586X"],"issn":["1083-6160"]},"article_type":"letter_note","quality_controlled":"1","month":"12"},{"article_type":"original","extern":"1","abstract":[{"lang":"eng","text":"Hydrocodone, a high value active pharmaceutical ingredient (API), is usually produced in a semisynthetic pathway from morphine, codeine or thebaine. The latter alkaloid is an attractive precursor as it is not used as a remedy itself. The key step in this production route is a selective olefin reduction forming 8,14-dihydrothebaine which can be subsequently hydrolyzed to yield hydrocodone. Unfortunately, standard hydrogenation procedures cannot be applied due to severe selectivity problems. A transfer hydrogenation using in situ generated diimide is the only known alternative to achieve a selective transformation. The most (atom) economic generation of this highly unstable reducing agent is by oxidizing hydrazine hydrate (N2H4·H2O) with O2. In the past, this route was “forbidden” on an industrial scale due to its enormous explosion potential in batch. A continuous high-temperature/high-pressure methodology allows an efficient, safe, and scalable processing of the hazardous reaction mixture. The industrially relevant reduction was achieved by using four consecutive liquid feeds (of N2H4·H2O) and residence time units, resulting in a highly selective reduction within less than 1 h."}],"quality_controlled":"1","date_created":"2022-08-25T11:34:28Z","month":"02","status":"public","_id":"11985","title":"Selective olefin reduction in thebaine using hydrazine hydrate and O₂ under intensified continuous flow conditions","publication_identifier":{"issn":["1083-6160"],"eissn":["1520-586X"]},"doi":"10.1021/acs.oprd.5b00370","volume":20,"type":"journal_article","date_published":"2016-02-19T00:00:00Z","day":"19","article_processing_charge":"No","publication_status":"published","page":"376-385","year":"2016","issue":"2","intvolume":"        20","publisher":"American Chemical Society","citation":{"ama":"Pieber B, Cox DP, Kappe CO. Selective olefin reduction in thebaine using hydrazine hydrate and O₂ under intensified continuous flow conditions. <i>Organic Process Research and Development</i>. 2016;20(2):376-385. doi:<a href=\"https://doi.org/10.1021/acs.oprd.5b00370\">10.1021/acs.oprd.5b00370</a>","chicago":"Pieber, Bartholomäus, D. Phillip Cox, and C. Oliver Kappe. “Selective Olefin Reduction in Thebaine Using Hydrazine Hydrate and O₂ under Intensified Continuous Flow Conditions.” <i>Organic Process Research and Development</i>. American Chemical Society, 2016. <a href=\"https://doi.org/10.1021/acs.oprd.5b00370\">https://doi.org/10.1021/acs.oprd.5b00370</a>.","ieee":"B. Pieber, D. P. Cox, and C. O. Kappe, “Selective olefin reduction in thebaine using hydrazine hydrate and O₂ under intensified continuous flow conditions,” <i>Organic Process Research and Development</i>, vol. 20, no. 2. American Chemical Society, pp. 376–385, 2016.","ista":"Pieber B, Cox DP, Kappe CO. 2016. Selective olefin reduction in thebaine using hydrazine hydrate and O₂ under intensified continuous flow conditions. Organic Process Research and Development. 20(2), 376–385.","short":"B. Pieber, D.P. Cox, C.O. Kappe, Organic Process Research and Development 20 (2016) 376–385.","mla":"Pieber, Bartholomäus, et al. “Selective Olefin Reduction in Thebaine Using Hydrazine Hydrate and O₂ under Intensified Continuous Flow Conditions.” <i>Organic Process Research and Development</i>, vol. 20, no. 2, American Chemical Society, 2016, pp. 376–85, doi:<a href=\"https://doi.org/10.1021/acs.oprd.5b00370\">10.1021/acs.oprd.5b00370</a>.","apa":"Pieber, B., Cox, D. P., &#38; Kappe, C. O. (2016). Selective olefin reduction in thebaine using hydrazine hydrate and O₂ under intensified continuous flow conditions. <i>Organic Process Research and Development</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acs.oprd.5b00370\">https://doi.org/10.1021/acs.oprd.5b00370</a>"},"publication":"Organic Process Research and Development","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","language":[{"iso":"eng"}],"date_updated":"2023-02-21T10:10:26Z","author":[{"id":"93e5e5b2-0da6-11ed-8a41-af589a024726","orcid":"0000-0001-8689-388X","full_name":"Pieber, Bartholomäus","last_name":"Pieber","first_name":"Bartholomäus"},{"full_name":"Cox, D. Phillip","last_name":"Cox","first_name":"D. Phillip"},{"first_name":"C. Oliver","last_name":"Kappe","full_name":"Kappe, C. Oliver"}],"oa_version":"None","scopus_import":"1"}]