---
_id: '11984'
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.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Mónica
full_name: Guberman, Mónica
last_name: Guberman
- first_name: Bartholomäus
full_name: Pieber, Bartholomäus
id: 93e5e5b2-0da6-11ed-8a41-af589a024726
last_name: Pieber
orcid: 0000-0001-8689-388X
- first_name: Peter H.
full_name: Seeberger, Peter H.
last_name: Seeberger
citation:
ama: Guberman M, Pieber B, Seeberger PH. Safe and scalable continuous flow azidophenylselenylation
of galactal to prepare galactosamine building blocks. Organic Process Research
and Development. 2019;23(12):2764-2770. doi:10.1021/acs.oprd.9b00456
apa: Guberman, M., Pieber, B., & Seeberger, P. H. (2019). Safe and scalable
continuous flow azidophenylselenylation of galactal to prepare galactosamine building
blocks. Organic Process Research and Development. American Chemical Society.
https://doi.org/10.1021/acs.oprd.9b00456
chicago: Guberman, Mónica, Bartholomäus Pieber, and Peter H. Seeberger. “Safe and
Scalable Continuous Flow Azidophenylselenylation of Galactal to Prepare Galactosamine
Building Blocks.” Organic Process Research and Development. American Chemical
Society, 2019. https://doi.org/10.1021/acs.oprd.9b00456.
ieee: M. Guberman, B. Pieber, and P. H. Seeberger, “Safe and scalable continuous
flow azidophenylselenylation of galactal to prepare galactosamine building blocks,”
Organic Process Research and Development, 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.
mla: Guberman, Mónica, et al. “Safe and Scalable Continuous Flow Azidophenylselenylation
of Galactal to Prepare Galactosamine Building Blocks.” Organic Process Research
and Development, vol. 23, no. 12, American Chemical Society, 2019, pp. 2764–70,
doi:10.1021/acs.oprd.9b00456.
short: M. Guberman, B. Pieber, P.H. Seeberger, Organic Process Research and Development
23 (2019) 2764–2770.
date_created: 2022-08-25T11:30:33Z
date_published: 2019-12-20T00:00:00Z
date_updated: 2023-02-21T10:10:23Z
day: '20'
doi: 10.1021/acs.oprd.9b00456
extern: '1'
intvolume: ' 23'
issue: '12'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1021/acs.oprd.9b00456
month: '12'
oa: 1
oa_version: Published Version
page: 2764-2770
publication: Organic Process Research and Development
publication_identifier:
eissn:
- 1520-586X
issn:
- 1083-6160
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Safe and scalable continuous flow azidophenylselenylation of galactal to prepare
galactosamine building blocks
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2019'
...
---
_id: '11985'
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.
article_processing_charge: No
article_type: original
author:
- first_name: Bartholomäus
full_name: Pieber, Bartholomäus
id: 93e5e5b2-0da6-11ed-8a41-af589a024726
last_name: Pieber
orcid: 0000-0001-8689-388X
- first_name: D. Phillip
full_name: Cox, D. Phillip
last_name: Cox
- first_name: C. Oliver
full_name: Kappe, C. Oliver
last_name: Kappe
citation:
ama: Pieber B, Cox DP, Kappe CO. Selective olefin reduction in thebaine using hydrazine
hydrate and O₂ under intensified continuous flow conditions. Organic Process
Research and Development. 2016;20(2):376-385. doi:10.1021/acs.oprd.5b00370
apa: Pieber, B., Cox, D. P., & Kappe, C. O. (2016). Selective olefin reduction
in thebaine using hydrazine hydrate and O₂ under intensified continuous flow conditions.
Organic Process Research and Development. American Chemical Society. https://doi.org/10.1021/acs.oprd.5b00370
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.” Organic Process Research and Development. American Chemical
Society, 2016. https://doi.org/10.1021/acs.oprd.5b00370.
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,”
Organic Process Research and Development, 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.
mla: Pieber, Bartholomäus, et al. “Selective Olefin Reduction in Thebaine Using
Hydrazine Hydrate and O₂ under Intensified Continuous Flow Conditions.” Organic
Process Research and Development, vol. 20, no. 2, American Chemical Society,
2016, pp. 376–85, doi:10.1021/acs.oprd.5b00370.
short: B. Pieber, D.P. Cox, C.O. Kappe, Organic Process Research and Development
20 (2016) 376–385.
date_created: 2022-08-25T11:34:28Z
date_published: 2016-02-19T00:00:00Z
date_updated: 2023-02-21T10:10:26Z
day: '19'
doi: 10.1021/acs.oprd.5b00370
extern: '1'
intvolume: ' 20'
issue: '2'
language:
- iso: eng
month: '02'
oa_version: None
page: 376-385
publication: Organic Process Research and Development
publication_identifier:
eissn:
- 1520-586X
issn:
- 1083-6160
publication_status: published
publisher: American Chemical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Selective olefin reduction in thebaine using hydrazine hydrate and O₂ under
intensified continuous flow conditions
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2016'
...