227622-58-4Relevant academic research and scientific papers
The Cyclization of Allenyl-Substituted Hydroxylamines to 1,2-Oxazines: an Experimental and Computational Study
Jasiński, Marcin,Reissig, Hans-Ulrich,Utecht-Jarzyńska, Greta,Würthwein, Ernst-Ulrich
, p. 6740 - 6748 (2020)
To gain a deeper understanding of the formation of the synthetically important 3,6-dihydro-2H-1,2-oxazines, the 6-endo-trig cyclization of allenyl-substituted hydroxylamines was experimentally investigated in detail employing a model compound. The solvent effect was moderate with respect to the rate, but crucial to suppress side-product formation. Surprisingly, acids or bases had no big influence on the cyclization rate. With O-deuterated allenyl hydroxylamine a high primary isotope effect was found, indicating that the proton transfer is crucial in the rate-determining step. DFT calculations evidence that the allenyl-substituted hydroxylamine is converted into an energetically similar zwitterionic intermediate with an allyl cation subunit. It cyclizes to the 1,2-oxazine as the most stable species. Alternative pathways starting from the zwitterion were computationally investigated. Interestingly, it can also undergo a fragmentation to give a pentadiene derivative and a nitroso compound. The hetero Diels–Alder reaction of these components may also deliver the 1,2-oxazine. To evaluate an alternative mechanistic scenario, calculations of the protonated allenyl-substituted hydroxylamine were also performed.
Internally protected amino sugar equivalents from enantiopure 1,2-oxazines: Synthesis of variably configured carbohydrates with C-branched amino sugar units
Pfrengle, Fabian,Reissig, Hans-Ulrich
scheme or table, p. 11915 - 11925 (2011/01/12)
A stereodivergent synthesis of differently configured C2-branched 4-amino sugar derivatives was accomplished. The Lewis acid mediated rearrangement of phenylthio-substituted 1,2-oxazines delivered glycosyl donor equivalents that can directly be employed in glycosidation reactions. Treatment with methanol provided internally protected amino sugar equivalents that have been transformed into the stereoisomeric methyl glycosides 28, ent-28, 29, ent-29 and 34 in two simple reductive steps. Reaction with natural carbohydrates or bicyclic amino sugar precursors allowed the synthesis of homo-oligomeric di- and trisaccharides 44, 46 and 47 or a hybrid trisaccharide 51 with natural carbohydrates. Access to a bivalent amino sugar derivative 54 was accomplished by reaction of rearrangement product 10 with 1,5-pentanediol. Alternatively, when a protected L-serine derivative was employed as glycosyl acceptor, the glycosylated amino acid 60 was efficiently prepared in few steps. In this report we describe the synthesis of unusual amino sugar building blocks from enantiopure 1,2-oxazines that can be attached to natural carbohydrates or natural product aglycons to produce new natural product analogues with potential applications in medicinal chemistry. Make it simple: A Lewis acid mediated rearrangement of 1,2-oxazines delivers internally protected amino sugar equivalents that can be incorporated into oligosaccharides. Deprotection of the amino sugar precursors by simple reductive steps provides new natural product analogues having C2-branched 4-amino sugar units with different absolute and relative configurations.
Stereodivergent syntheses of highly substituted enantiopure 4-alkoxy-3,6-dihydro-2H-1,2-oxazines by addition of lithiated alkoxyallenes to carbohydrate-derived aldonitrones
Helms, Matthias,Schade, Wolfgang,Pulz, Robert,Watanabe, Toshiko,Al-Harrasi, Ahmed,Fisera, Lubor,Hlobilova, Iva,Zahn, Gernot,Reissig, Hans-Ulrich
, p. 1003 - 1019 (2007/10/03)
Additions of lithiated alkoxyallenes to D-glyceraldehyde-based nitrones 1 and 2 did not provide the expected hydroxylamine derivatives. Instead, a novel [3+3] cyclization process furnished 4-alkoxy-3,6-dihydro-2H-1,2-oxazines 9-14 with excellent syn selectivities and in moderate to good yields. Through precomplexation of the nitrones the corresponding anti-configured 1,2-oxazines 9, 10 and 13 could be obtained with high stereoselectivity. The reactions of nitrones 3-6, derived from D-erythrose or D-threose, generally proceeded less diastereoselectively, but reasonable yields of anti-configured 1,2-oxazines such as anti-17 and anti-19 could be obtained under Lewis acid promotion conditions. This was also the case for reactions of the D-arabinose-derived nitrone 7, which provided the anti-1,2-oxazines 23 and 24 with excellent diastereoselectivity and in good yields. Bisnitrone 8 and lithiated methoxyallene furnished a mixture of six compounds, among which the major component was the C2-symmetric syn/syn-1,2-oxazine 29. The diastereoselectivities of these reactions are interpreted on the basis of Dondoni's model for reactions between organolithium compounds and nitrones. The mechanisms for formation of 1,2-oxazines and of side products are discussed. The method introduced here seems to be of broad applicability and an excellent tool for diastereoselective chain elongation of carbohydrate derivatives, affording stereodefined precursors of aminopolyols and other highly functionalized compounds. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
New polyhydroxylated pyrrolidines derived from enantiopure 3,6-dihydro-2H-1,2-oxazines
Pulz, Robert,Al-Harrasi, Ahmed,Reissig, Hans-Ulrich
, p. 2353 - 2355 (2007/10/03)
(Matrix Presented) Diastereoselective hydroborations of enantiopure 3,6-dihydro-2H-1,2-oxazines led to dihydroxy-substituted 1,2-oxazines. Samarium diiodide-induced N-O bond cleavage generated 1,4-amino alcohols which were recyclized to polyhydroxylated pyrrolidines which are potential glycosidase inhibitors.
A new diastereoselective synthesis of enantiomerically pure 1,2-oxazine derivatives by addition of lithiated methoxyallene to chiral nitrones
Schade, Wolfgang,Reissig, Hans-Ulrich
, p. 632 - 634 (2007/10/03)
Addition of lithiated methoxyallene 2 to nitrones provided hydroxylamine derivatives which usually undergo very fast cyclization to 3,6-dihydro-2H- 1,2-oxazines. Chiral nitrones 5, 8, or 10 which furnished 1,2-oxazines 6, 9, and 11 with excellent syn diastereoselectivities are of particular interest. By precomplexation of nitrone 5b with diethylaluminum chloride 1,2-oxazine 6b was produced with excellent anti selectivity. The resulting 3,6-dihydro-2H- 1,2-oxazines are versatile starting materials for stereoselective syntheses of polyfunctional compounds.
