Abstract
The regio- and diastereoselectivity of transformations of nine-membered lactams with a Z double bond in the cyclic tether towards building blocks for medicinal chemistry was evaluated. To this end, 3-aminohexahydrooxazoninones were synthesized using a standard ring-closing metathesis (RCM) approach of easily available O,N-bisallylated serine derivatives. The obtained Z double bond in the medium sized lactam was used as a handle to evaluate the stereoselectivity of electrophile induced transformations. It was shown that dibromination and electrophilic activation by NBS followed by attack of O-nucleophiles proceeded in a diastereoselective manner. Cyclization of obtained bromohydrins and face-selective epoxidation gave access to both diastereomers of the epoxidized lactams. Finally, a Heck-reaction of a bromobenzyl moiety at the lactam N-atom with the Z-double bond resulted in the diastereoselective formation of bicyclic bridged nine-membered lactams.
| Original language | English |
|---|---|
| Pages (from-to) | 36-40 |
| Number of pages | 5 |
| Journal | European Journal of Organic Chemistry |
| Volume | 2019 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 10 Jan 2019 |
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Keywords
- Cyclization
- Diastereoselectivity
- Heck reaction
- Medium-ring compounds
- Metathesis
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Regio‐and Diastereoselective Functionalization of 3‐Amino‐hexahydrooxazoninones. / Schurgers, Ben; Wouters, Johan; De Blieck, Ann; Van Lommen, Guy; Menet, Christel; Verniest, Guido.
In: European Journal of Organic Chemistry, Vol. 2019, No. 1, 10.01.2019, p. 36-40.Research output: Contribution to journal › Article
TY - JOUR
T1 - Regio‐and Diastereoselective Functionalization of 3‐Amino‐hexahydrooxazoninones
AU - Schurgers, Ben
AU - Wouters, Johan
AU - De Blieck, Ann
AU - Van Lommen, Guy
AU - Menet, Christel
AU - Verniest, Guido
PY - 2019/1/10
Y1 - 2019/1/10
N2 - The regio- and diastereoselectivity of transformations of nine-membered lactams with a Z double bond in the cyclic tether towards building blocks for medicinal chemistry was evaluated. To this end, 3-aminohexahydrooxazoninones were synthesized using a standard ring-closing metathesis (RCM) approach of easily available O,N-bisallylated serine derivatives. The obtained Z double bond in the medium sized lactam was used as a handle to evaluate the stereoselectivity of electrophile induced transformations. It was shown that dibromination and electrophilic activation by NBS followed by attack of O-nucleophiles proceeded in a diastereoselective manner. Cyclization of obtained bromohydrins and face-selective epoxidation gave access to both diastereomers of the epoxidized lactams. Finally, a Heck-reaction of a bromobenzyl moiety at the lactam N-atom with the Z-double bond resulted in the diastereoselective formation of bicyclic bridged nine-membered lactams.
AB - The regio- and diastereoselectivity of transformations of nine-membered lactams with a Z double bond in the cyclic tether towards building blocks for medicinal chemistry was evaluated. To this end, 3-aminohexahydrooxazoninones were synthesized using a standard ring-closing metathesis (RCM) approach of easily available O,N-bisallylated serine derivatives. The obtained Z double bond in the medium sized lactam was used as a handle to evaluate the stereoselectivity of electrophile induced transformations. It was shown that dibromination and electrophilic activation by NBS followed by attack of O-nucleophiles proceeded in a diastereoselective manner. Cyclization of obtained bromohydrins and face-selective epoxidation gave access to both diastereomers of the epoxidized lactams. Finally, a Heck-reaction of a bromobenzyl moiety at the lactam N-atom with the Z-double bond resulted in the diastereoselective formation of bicyclic bridged nine-membered lactams.
KW - Cyclization
KW - Diastereoselectivity
KW - Heck reaction
KW - Medium-ring compounds
KW - Metathesis
UR - http://www.scopus.com/inward/record.url?scp=85052652007&partnerID=8YFLogxK
U2 - 10.1002/ejoc.201800409
DO - 10.1002/ejoc.201800409
M3 - Article
VL - 2019
SP - 36
EP - 40
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
SN - 1434-193X
IS - 1
ER -