[{"article_type":"letter_note","year":"2019","oa_version":"Published Version","date_updated":"2023-02-21T10:10:23Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","publication_identifier":{"issn":["1083-6160"],"eissn":["1520-586X"]},"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."}],"_id":"11984","date_published":"2019-12-20T00:00:00Z","issue":"12","article_processing_charge":"No","volume":23,"publication_status":"published","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1021/acs.oprd.9b00456"}],"day":"20","author":[{"last_name":"Guberman","first_name":"Mónica","full_name":"Guberman, Mónica"},{"id":"93e5e5b2-0da6-11ed-8a41-af589a024726","orcid":"0000-0001-8689-388X","last_name":"Pieber","first_name":"Bartholomäus","full_name":"Pieber, Bartholomäus"},{"first_name":"Peter H.","full_name":"Seeberger, Peter H.","last_name":"Seeberger"}],"type":"journal_article","citation":{"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>","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>","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>.","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.","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>."},"title":"Safe and scalable continuous flow azidophenylselenylation of galactal to prepare galactosamine building blocks","language":[{"iso":"eng"}],"doi":"10.1021/acs.oprd.9b00456","extern":"1","month":"12","date_created":"2022-08-25T11:30:33Z","page":"2764-2770","quality_controlled":"1","publication":"Organic Process Research and Development","status":"public","intvolume":"        23","publisher":"American Chemical Society"},{"volume":20,"status":"public","intvolume":"        20","quality_controlled":"1","publication":"Organic Process Research and Development","publisher":"American Chemical Society","publication_status":"published","_id":"11985","date_published":"2016-02-19T00:00:00Z","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."}],"date_created":"2022-08-25T11:34:28Z","extern":"1","month":"02","issue":"2","article_processing_charge":"No","page":"376-385","doi":"10.1021/acs.oprd.5b00370","publication_identifier":{"issn":["1083-6160"],"eissn":["1520-586X"]},"date_updated":"2023-02-21T10:10:26Z","language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","year":"2016","oa_version":"None","author":[{"id":"93e5e5b2-0da6-11ed-8a41-af589a024726","orcid":"0000-0001-8689-388X","last_name":"Pieber","first_name":"Bartholomäus","full_name":"Pieber, Bartholomäus"},{"first_name":"D. Phillip","full_name":"Cox, D. Phillip","last_name":"Cox"},{"last_name":"Kappe","first_name":"C. Oliver","full_name":"Kappe, C. Oliver"}],"type":"journal_article","day":"19","article_type":"original","title":"Selective olefin reduction in thebaine using hydrazine hydrate and O₂ under intensified continuous flow conditions","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>","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>","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>.","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>.","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.","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."}}]