References
Citation from Seeburger et al:
Homogeneous azidophenylselenylation of glycals using TMSN3–Ph2Se2–PhI(OAc)2
Mironov, Y. V.; Sherman, A. A.; Nifantiev, N. E. Tetrahedron Lett. 2004, 45, 9107-9110.
Homogeneous azidophenylselenylation of glycals using TMSN3–Ph2Se2–PhI(OAc)2
Mironov, Y. V.; Sherman, A. A.; Nifantiev, N. E. Tetrahedron Lett. 2004, 45, 9107-9110.
2-Azido-4,6-O-benzylidene-2-deoxy-3-levulinoyl-D-galactopyranoside-N-phenyl-trifluoroacetimidate(molecule 18) can be synthesized from phenyl-2-azido-4,6-O-benzylidene-2-deoxy-1-selanyl-α-D-galactopyranoside (molecule 17) using a simple two step mechanism that involves nucleophilic addition to a (amide) and lone-pair-assisted ionization among others. The purpose of synthesizing Molecule 18 is so that it might be used to form complex carbohydrate chains with other glycoprotein and glycolipid conjugate. Molecule 18 is a derivative of the 2-amino-2-deoxy-alpha-D-galactopyranoside which is synthesized using appropriately substituted 2-azido-2-deoxy-galactosyl donors. A common example of this is the azidonitration of triacetylgalactal.
However, this particular synthesis requires multiple steps and produces many unwanted byproducts before the final desired compound (molecule 2 in the diagram above) is created. A new synthesis scheme for the anti-Markovnikov azidophenylselenylation (addition of azide and selenium phenyl groups – APS) was explored in the Mironov et al. This mechanism involves a one-step azidophenylselenylation of olefins such as galactal 1 (see diagram above) by treatment with NaN3, PhI(OAc)2, and Ph2Se2. Selenoglycosides such as molecule 2 (a derivative of molecules 17 and 18 from the Seeburger paper) are efficient glycosyl donors which are needed for needed for the synthesis of 2-amino-2-deoxy-alpha-D-galactopyranosides so this new synthesis procedure is very promising for the field of carbohydrate synthesis. Mironov commented that his team's attempts to reproduce previously published protocols for this reaction were unsuccessful so in order to improve the efficiency of the reaction, Mironov replaced NaN3 with a more DCM-soluble azide donor such as TMSN3. This increased the yield of APS from 88% to 91% while cutting down the overall reaction time from 48 hours to 4 hours. Using TMSN3 also guaranteed the production of the anti-Markovnikov addition product whereas NaN3 produced a mixture of the Markovnikov and the anti-Markovnikov products.
Synthesis using NaN3:
Synthesis using TMSN3:
Further experiments with different functional groups on the cyclic ether also have shown that the use of TMSN3 as an azide donor was more effective for APS reactions of benzyl-containing compounds; this is relevant to our reaction because both molecules 17 and 18 contain a benzyl group. In short, the use of TMSN3 as an azide donor in azidophenylselenylation reactions provides shorter reaction times, higher yields and more stereospecificity in the products.
Articles that Cited Homogeneous azidophenylselenylation of glycals using TMSN3–Ph2Se2–PhI(OAc)2
.
Reference 1:
Metalated heterocycles in organic synthesis: recent applications
Chinchilla, R.; Najera, C.; Yus, M. ARKIVOC. 2007, 1, 152-231.
The paper reviews the generation and synthetic uses of organometallics that are formed by metalation of a heterocyclic ring. Its main focus is talking about how metalated heterocycle plays a key role in synthetic organic chemistry. The papers introduce the types of metals and subdivide the types of melated heterocycle, including its methods for their preparation and the synthetic uses. This paper give references on reaction in cyclic molecules, which in our part, gives an idea how certain donor is used to make cyclic ether, the product that we use for our group section, more stable and effectively, providing shorter reaction time and higher yield.
Reference 2:
Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars
Bongat, A. F. G.; Demchenko, A. V. Carbohydr. Res.. 2007, 342, 374-406.
The synthesis of glycosides has given scientists much difficulty due to the need for stereoselectivity in the product. This paper discusses various methods of synthesis for 2-amino-2-deoxyglycosides, such as a nucleophilic displacement at carbon C-2, the introduction of an amine protecting group, cycloaddition reactions, and the amidation of glycals, among many others. The synthesis of a product similar to molecule 17 from Seeburger et al. is attributed to the introduction of 2-azido moiety to glycals via the radical mechanism.
Reference 3:
Organic azides: An exploding diversity of a unique class of compounds
Brase, S.; Gil, C.; Knepper, K.; Zimmermann V. Angew.Chem. Int. Ed.. 2005, 44, 5188-5240.
This article discusses the importance of azide's unique regioselectivity in azidoselenation reactions. Azide attaches to the least substituted site on an alkene such as the one in galactal 1, referenced in Mironov et al. The affinity of the azide group for the less substituted location makes it useful in the synthesis of selenoglycosides such as molecule 2 from Mironov et al.