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Mikhail S. Novikov - One of the best experts on this subject based on the ideXlab platform.
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Isomerization of 5-(2H-Azirin-2-yl)oxazoles: An Atom-Economic Approach to 4H-Pyrrolo[2,3-d]oxazoles.
Molecules (Basel Switzerland), 2021Co-Authors: Timur O Zanakhov, Ekaterina E. Galenko, Mikhail S. Novikov, Mariya A Kryukova, Alexander A KhlebnikovAbstract:An atom economical method for the preparation of variously substituted 4H-pyrrolo[2,3-d]oxazoles was developed on the basis of thermal isomerization of 5-(2H-azirin-2-yl)oxazoles. The latter were prepared by Rh2(oct)4 catalyzed reaction of 2-(3-aryl/heteroaryl)-2-diazoacetyl-2H-Azirines with a set of substituted acetonitriles, benzonitriles, acrylonitrile and fumaronitrile. According to DFT calculations the transformation of 5-(2H-azirin-2-yl)oxazole to 4H-pyrrolo[2,3-d]oxazole occurs through the nitrenoid-like transition state to give a 3aH-pyrrolo[2,3-d]oxazole intermediate, followed by 1,5-H-shift.
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buchner reaction Azirine modification approach toward cycloheptatriene containing nitrogen heterocyclic scaffolds
Journal of Organic Chemistry, 2021Co-Authors: Ekaterina E. Galenko, Mikhail S. Novikov, Mariya A Kryukova, Vladimir A Bodunov, Alexander F. KhlebnikovAbstract:The reaction conditions for the Buchner reaction of 2-(diazoacetyl)-2H-Azirines with benzene leading to 2-(cyclohepta-2,4,6-trien-1-yl)-2H-Azirines have been found. The Azirine fragment of these compounds was subsequently used to prepare 5-(cyclohepta-2,4,6-trien-1-yl)isoxazoles and α-(cyclohepta-2,4,6-triene-1-ylcarbonyl)-1H-pyrroles. NMR and DFT calculations showed that the cycloheptatriene-norcaradiene valence isomerization in the corresponding moieties of synthesized Azirines, isoxazoles, and pyrroles is very fast at room temperature. Cycloheptatriene valence isomer predominates in Azirines and pyrroles, while 5-(cycloheptatrienyl)isoxazoles exist in a pure cycloheptatriene form at 25 °C in chloroform solution. In accordance with the X-ray analysis, two of the synthesized pyrroles crystallized as norcaradiene isomers from a solution of equilibrium mixture of valence isomers. Reductive isoxazole ring opening using the Mo(CO)6/H2O reductive system afforded (Z)-3-amino-3-aryl-1-(cyclohepta-2,4,6-trien-1-yl)prop-2-en-1-ones, which are pure cycloheptatriene isomers. α-(Cycloheptatrieneylcarbonyl)-1H-pyrroles were transformed into the α-(benzylcarbonyl)-1H-pyrroles under cooperative TFA/Rh2(TFA)4 catalysis.
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2h Azirine 2 carbonyl azides preparation and use as n heterocyclic building blocks
Journal of Organic Chemistry, 2020Co-Authors: Liya D Funt, Mikhail S. Novikov, Yulia V Krivolapova, Olesya V Khoroshilova, Alexander F. KhlebnikovAbstract:2H-Azirine-2-carbonyl azides, new reactive heterocyclic building blocks, were synthesized in high yield by the reaction of sodium azide with 2H-Azirine-2-carbonyl chlorides, generated by the Fe(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-(Azidocarbonyl)-1H-pyrroles, prepared by the Ni(II)-catalyzed reaction of 2-(azidocarbonyl)-2H-Azirines with 1,3-diketones, easily undergo the Curtius rearrangement in boiling tBuOH to give Boc-protected α-aminopyrroles in high yield. Heating of 2-(azidocarbonyl)-1H-pyrroles for a short time in inert solvents leads to the high-yield formation of benzo- and hetero-fused 1H-pyrrolo[2,3-b]pyridin-6(7H)-ones, which are formed via a 6π electrocyclization involving the vicinal aryl or hetaryl substituent and the N═C bond of isocyanate, generated by the Curtius rearrangement of the azidocarbonyl group. The Pd-catalyzed cross-coupling reaction of 1-acetyl-2-methyl-3H-pyrrolo[2,3-c]isoquinolin-5-yl triflate, easily prepared from the corresponding pyrroloisoquinolone, leads to variously 5-substituted 3H-pyrrolo[2,3-c]isoquinolines in excellent yields.
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One-pot synthesis of 3-(pyridin-2-yl)-2,3-dihydroazetes via Rh(II)-catalyzed reaction of diazoesters with trimethylsilyl-protected 2-(pyridin-2-yl)-2H-Azirines
Chemistry of Heterocyclic Compounds, 2019Co-Authors: Alexander N. Koronatov, Nikolai V. Rostovskii, Alexander F. Khlebnikov, Mikhail S. NovikovAbstract:A one-pot method for the synthesis of 3-(pyridin-2-yl)-2,3-dihydroazetes was developed on the basis of Rh2(esp)2-catalyzed reaction of diazoesters with 3-aryl-2-(pyridin-2-yl)-2 H -Azirines. To prevent deactivation of the catalyst with the pyridine-containing Azirine reactant, the trimethylsilyl protection of pyridine nitrogen was used. The insertion and removal of the protecting group were carried out as a onepot synthesis. Reactions involving ethyl 2-diazo-3,3,3-trifluoropropanoate proceed stereoselectively with the formation of only the (2 RS ,3 SR )-isomer of the dihydroazete, which is due to the thermodynamic control of the process.
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Advances in 2H-Azirine chemistry: A seven-year update
Tetrahedron, 2019Co-Authors: Alexander F. Khlebnikov, Mikhail S. Novikov, Nikolai V. RostovskiiAbstract:Abstract 2H-Azirines are versatile building blocks for the preparation of various nitrogen-containing heterocycles. Seven years ago the comprehensive review on Azirine chemistry was published in Tetrahedron. Since then, there had been an explosion of research activities in the field of these strained molecules. This renaissance is primarily associated with the discovery of new reactivity of Azirines and in particular new catalytic and light-induced reactions, which made possible unusual transformations of this three-membered N-heterocycle into azole and azine derivatives as well as polyheterocyclic systems. The second reason for the progress of Azirine chemistry is the development of methods for the preparation of new Azirine derivatives. The third reason is the discovery of new synthetic equivalents of Azirines, which permitted avoiding the use of unstable Azirines in some modern catalytic procedures. In the present comprehensive review, we have placed particular emphasis on discussing the new developments in the synthesis and reactivity of Azirines for the period from 2012 until the end of 2018.
Alexander F. Khlebnikov - One of the best experts on this subject based on the ideXlab platform.
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buchner reaction Azirine modification approach toward cycloheptatriene containing nitrogen heterocyclic scaffolds
Journal of Organic Chemistry, 2021Co-Authors: Ekaterina E. Galenko, Mikhail S. Novikov, Mariya A Kryukova, Vladimir A Bodunov, Alexander F. KhlebnikovAbstract:The reaction conditions for the Buchner reaction of 2-(diazoacetyl)-2H-Azirines with benzene leading to 2-(cyclohepta-2,4,6-trien-1-yl)-2H-Azirines have been found. The Azirine fragment of these compounds was subsequently used to prepare 5-(cyclohepta-2,4,6-trien-1-yl)isoxazoles and α-(cyclohepta-2,4,6-triene-1-ylcarbonyl)-1H-pyrroles. NMR and DFT calculations showed that the cycloheptatriene-norcaradiene valence isomerization in the corresponding moieties of synthesized Azirines, isoxazoles, and pyrroles is very fast at room temperature. Cycloheptatriene valence isomer predominates in Azirines and pyrroles, while 5-(cycloheptatrienyl)isoxazoles exist in a pure cycloheptatriene form at 25 °C in chloroform solution. In accordance with the X-ray analysis, two of the synthesized pyrroles crystallized as norcaradiene isomers from a solution of equilibrium mixture of valence isomers. Reductive isoxazole ring opening using the Mo(CO)6/H2O reductive system afforded (Z)-3-amino-3-aryl-1-(cyclohepta-2,4,6-trien-1-yl)prop-2-en-1-ones, which are pure cycloheptatriene isomers. α-(Cycloheptatrieneylcarbonyl)-1H-pyrroles were transformed into the α-(benzylcarbonyl)-1H-pyrroles under cooperative TFA/Rh2(TFA)4 catalysis.
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2h Azirine 2 carbonyl azides preparation and use as n heterocyclic building blocks
Journal of Organic Chemistry, 2020Co-Authors: Liya D Funt, Mikhail S. Novikov, Yulia V Krivolapova, Olesya V Khoroshilova, Alexander F. KhlebnikovAbstract:2H-Azirine-2-carbonyl azides, new reactive heterocyclic building blocks, were synthesized in high yield by the reaction of sodium azide with 2H-Azirine-2-carbonyl chlorides, generated by the Fe(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-(Azidocarbonyl)-1H-pyrroles, prepared by the Ni(II)-catalyzed reaction of 2-(azidocarbonyl)-2H-Azirines with 1,3-diketones, easily undergo the Curtius rearrangement in boiling tBuOH to give Boc-protected α-aminopyrroles in high yield. Heating of 2-(azidocarbonyl)-1H-pyrroles for a short time in inert solvents leads to the high-yield formation of benzo- and hetero-fused 1H-pyrrolo[2,3-b]pyridin-6(7H)-ones, which are formed via a 6π electrocyclization involving the vicinal aryl or hetaryl substituent and the N═C bond of isocyanate, generated by the Curtius rearrangement of the azidocarbonyl group. The Pd-catalyzed cross-coupling reaction of 1-acetyl-2-methyl-3H-pyrrolo[2,3-c]isoquinolin-5-yl triflate, easily prepared from the corresponding pyrroloisoquinolone, leads to variously 5-substituted 3H-pyrrolo[2,3-c]isoquinolines in excellent yields.
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One-pot synthesis of 3-(pyridin-2-yl)-2,3-dihydroazetes via Rh(II)-catalyzed reaction of diazoesters with trimethylsilyl-protected 2-(pyridin-2-yl)-2H-Azirines
Chemistry of Heterocyclic Compounds, 2019Co-Authors: Alexander N. Koronatov, Nikolai V. Rostovskii, Alexander F. Khlebnikov, Mikhail S. NovikovAbstract:A one-pot method for the synthesis of 3-(pyridin-2-yl)-2,3-dihydroazetes was developed on the basis of Rh2(esp)2-catalyzed reaction of diazoesters with 3-aryl-2-(pyridin-2-yl)-2 H -Azirines. To prevent deactivation of the catalyst with the pyridine-containing Azirine reactant, the trimethylsilyl protection of pyridine nitrogen was used. The insertion and removal of the protecting group were carried out as a onepot synthesis. Reactions involving ethyl 2-diazo-3,3,3-trifluoropropanoate proceed stereoselectively with the formation of only the (2 RS ,3 SR )-isomer of the dihydroazete, which is due to the thermodynamic control of the process.
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Advances in 2H-Azirine chemistry: A seven-year update
Tetrahedron, 2019Co-Authors: Alexander F. Khlebnikov, Mikhail S. Novikov, Nikolai V. RostovskiiAbstract:Abstract 2H-Azirines are versatile building blocks for the preparation of various nitrogen-containing heterocycles. Seven years ago the comprehensive review on Azirine chemistry was published in Tetrahedron. Since then, there had been an explosion of research activities in the field of these strained molecules. This renaissance is primarily associated with the discovery of new reactivity of Azirines and in particular new catalytic and light-induced reactions, which made possible unusual transformations of this three-membered N-heterocycle into azole and azine derivatives as well as polyheterocyclic systems. The second reason for the progress of Azirine chemistry is the development of methods for the preparation of new Azirine derivatives. The third reason is the discovery of new synthetic equivalents of Azirines, which permitted avoiding the use of unstable Azirines in some modern catalytic procedures. In the present comprehensive review, we have placed particular emphasis on discussing the new developments in the synthesis and reactivity of Azirines for the period from 2012 until the end of 2018.
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2H‑Azirines as C–C Annulation Reagents in Cu-Catalyzed Synthesis of Furo[3,2‑c]quinolone Derivatives
2019Co-Authors: Pavel A. Sakharov, Nikolai V. Rostovskii, Alexander F. Khlebnikov, Taras L. Panikorovskii, Mikhail S. NovikovAbstract:A method of furo-annulation of 4-hydroxy-2-oxoquinoline-3-carboxylates with 3-arylAzirines under Cu(II) catalysis was developed to synthesize a variety of 2,3-dihydrofuro[3,2-c]quinolones bearing a carbamate group at the C2 position. The reaction involves an Azirine ring opening across the N–C2 bond and formation of a dihydrofuran ring with the inclusion of two Azirine carbon atoms, accompanied by a shift of the ester group to the nitrogen. The discovered reaction is the first example of the use of 2H-Azirines for furo-annulation
Silvia Kanzler - One of the best experts on this subject based on the ideXlab platform.
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[(2H‐Azirin‐2‐yl)methyl]phosphonate: Darstellung aus allylischen α‐ und γ‐Hydroxyphosphonaten und Anwendung zur diastereoselektiven Synthese von substituirten [(Aziridin‐2‐yl)methyl]phosphonsäureestern
Liebigs Annalen der Chemie, 1994Co-Authors: Elisabeth Öhler, Silvia KanzlerAbstract:[(2H-Azirin-2-yl)methyl]phosphonates: Synthesis from Allylic α- and γ-Hydroxyphosphonates and Application to Diastereoselective Formation of Substituted [(Aziriden-2-yl)methyl]phosphonates Various substituted (3-azido-1-alkenyl)phosphonates 3 (R3 = alkyl) or their equilibrium mixtures with the regioisomeric α-azidophosphonates 4 (R3 = Ph) have been synthesized from allylic α- or γ-hydroxyphosphonates 2 or 1 by Mitsunobu reaction with TPP/DEAD/HN3, and converted into the new [(2H-azirin-2yl)methyl]phosphonates 6 upon heating in toluene with DBU catalysis. The transformation 3/46 proceeds via base-catalyzed rearrangement to the (3-azido-2-alkenyl)-phosphonates 5 and subsequent thermolysis. Reduction of the 2H-Azirines 6 with NaBH4 in methanol at 5°C results in the predominant formation of the disubstituted aziridines cis-7. Addition of trimethylsilyl cyanide to compounds 6 yields stereoselectively the highly functionalized aziridines trans-8, while NaOCH3-catalyzed addition of dimethyl phosphite proceeds with even higher selectivity to yield the bisphosphonates trans-9 with excellent yields.
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2h azirin 2 yl methyl phosphonate darstellung aus allylischen α und γ hydroxyphosphonaten und anwendung zur diastereoselektiven synthese von substituirten aziridin 2 yl methyl phosphonsaureestern
European Journal of Organic Chemistry, 1994Co-Authors: Elisabeth Öhler, Silvia KanzlerAbstract:[(2H-Azirin-2-yl)methyl]phosphonates: Synthesis from Allylic α- and γ-Hydroxyphosphonates and Application to Diastereoselective Formation of Substituted [(Aziriden-2-yl)methyl]phosphonates Various substituted (3-azido-1-alkenyl)phosphonates 3 (R3 = alkyl) or their equilibrium mixtures with the regioisomeric α-azidophosphonates 4 (R3 = Ph) have been synthesized from allylic α- or γ-hydroxyphosphonates 2 or 1 by Mitsunobu reaction with TPP/DEAD/HN3, and converted into the new [(2H-azirin-2yl)methyl]phosphonates 6 upon heating in toluene with DBU catalysis. The transformation 3/46 proceeds via base-catalyzed rearrangement to the (3-azido-2-alkenyl)-phosphonates 5 and subsequent thermolysis. Reduction of the 2H-Azirines 6 with NaBH4 in methanol at 5°C results in the predominant formation of the disubstituted aziridines cis-7. Addition of trimethylsilyl cyanide to compounds 6 yields stereoselectively the highly functionalized aziridines trans-8, while NaOCH3-catalyzed addition of dimethyl phosphite proceeds with even higher selectivity to yield the bisphosphonates trans-9 with excellent yields.
Heinz Heimgartner - One of the best experts on this subject based on the ideXlab platform.
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synthesis of poly aib oligopeptides and aib containing peptides via the Azirine oxazolone method and their crystal structures
Helvetica Chimica Acta, 2011Co-Authors: Ingeborg Danneckerdorig, Anthony Linden, Heinz HeimgartnerAbstract:The protected poly-Aib oligopeptides Z-(Aib)n-N(Me)Ph with n=2–6 were prepared according to the ‘Azirine/oxazolone method’, i.e., by coupling amino or peptide acids with 2,2,N-trimethyl-N-phenyl-2H-azirin-3-amine (1a) as an Aib synthon (Scheme 2). Following the same concept, the segments Z-(Aib)3-OH (9) and H-L-Pro-(Aib)3-N(Me)Ph (20) were synthesized, and their subsequent coupling with N,N′-dicyclohexylcarbodiimide (DCC)/ZnCl2 led to the protected heptapeptide Z-(Aib)3-L-Pro-(Aib)3-N(Me)Ph (21; Scheme 3). The crystal structures of the poly-Aib oligopeptide amides were established by X-ray crystallography confirming the 310-helical conformation of Aib peptides.
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Synthesis of a Regular 24-membered Cyclodepsipeptide by Direct Amide Cyclization
Zeitschrift für Naturforschung B, 2009Co-Authors: Peter Köttgen, Anthony Linden, Heinz HeimgartnerAbstract:The synthesis of a 24-membered cyclic depsipeptide with an alternating sequence of phenyllactic acid and α-aminoisobutyric acid (Aib) is described. The linear precursor was prepared via the ‘Azirine/oxazolone method’ using 2,2-dimethyl-3-amino-2H-Azirines as building blocks for the α,α-disubstituted α-amino acid Aib. The macrolactonization leading to the cyclodepsipeptide was achieved by the ‘direct amide cyclization’, i.e., by treatment of a solution of the linear precursor in toluene with HCl gas.
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A novel heterospirocyclic 2H-Azirin-3-amine as synthon for 3-Aminothiolane-3-carboxylic acid
HETEROCYCLES, 2007Co-Authors: Joelle L. Raber, Kathrin A. Brun, Heinz HeimgartnerAbstract:The heterospirocyclic 2H-azirin-3-amine (9), i.e., N-methyl-N-phenyl-5-thia-1-azaspiro[2.4]hept-1-en-2-amine, was prepared from the commercially available thiolane-3-one (10) via the corresponding 3-carbonitrile (11) and 3-thiocarboxamide (14). This Azirine reacted with thiobenzoic acid to give 3-benzoylamino-N-methyl-N-phenylthiolane-3-thiocarboxamide (15). With N-protected valine, the protected dipeptides (16) and (17), which contain a heterocyclic amino acid, were obtained as mixtures of diastereoisomers.
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introduction of the aib pro unit into peptides by means of the Azirine oxazolone method on solid phase
Tetrahedron, 2006Co-Authors: Simon Stamm, Heinz HeimgartnerAbstract:Abstract A method for the direct introduction of Aib-Pro into peptides on solid phase was developed. The Aib-Pro unit was introduced by means of the ‘Azirine/oxazolone method’ using allyl N-(2,2-dimethyl-2H-azirin-3-yl)- l -prolinate as the synthon. After the reaction of the resin-bound amino or peptide acid with allyl N-(2,2-dimethyl-2H-azirin-3-yl)- l -prolinate, the allyl protecting group of the resulting extended peptide could be removed by a mild Pd0-promoted procedure. Cleavage of the peptide from the resin was performed with UV light at 352 nm and yielded C-terminal protected peptides. The method found a successful application in the syntheses of different Aib-Pro containing peptaibol segments. Furthermore, a protected derivative of the peptide antibiotic Trichovirin I 1B was prepared by segment condensation.
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the Azirine oxazolone method on solid phase introduction of various α α disubstituted α amino acids
Helvetica Chimica Acta, 2006Co-Authors: Simon Stamm, Anthony Linden, Heinz HeimgartnerAbstract:Peptides containing various α,α-disubstituted α-amino acids, such as α-aminoisobutyric acid (Aib), 1-aminocyclopentane-1-carboxylic acid, α-methylphenylalanine, and 3-amino-3,4,5,6-tetrahydro-2H-pyran-3-carboxylic acid have been synthesized from the N- to the C-terminus by the ‘Azirine/oxazolone method’ under solid-phase conditions. In this convenient method for the synthesis of sterically demanding peptides on solid-phase, 2H-azirin-3-amines are used to introduce the α,α-disubstituted α-amino acids without the need for additional reagents. Furthermore, the synthesis of poly(Aib) sequences has been explored.
Elisabeth Öhler - One of the best experts on this subject based on the ideXlab platform.
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[(2H‐Azirin‐2‐yl)methyl]phosphonate: Darstellung aus allylischen α‐ und γ‐Hydroxyphosphonaten und Anwendung zur diastereoselektiven Synthese von substituirten [(Aziridin‐2‐yl)methyl]phosphonsäureestern
Liebigs Annalen der Chemie, 1994Co-Authors: Elisabeth Öhler, Silvia KanzlerAbstract:[(2H-Azirin-2-yl)methyl]phosphonates: Synthesis from Allylic α- and γ-Hydroxyphosphonates and Application to Diastereoselective Formation of Substituted [(Aziriden-2-yl)methyl]phosphonates Various substituted (3-azido-1-alkenyl)phosphonates 3 (R3 = alkyl) or their equilibrium mixtures with the regioisomeric α-azidophosphonates 4 (R3 = Ph) have been synthesized from allylic α- or γ-hydroxyphosphonates 2 or 1 by Mitsunobu reaction with TPP/DEAD/HN3, and converted into the new [(2H-azirin-2yl)methyl]phosphonates 6 upon heating in toluene with DBU catalysis. The transformation 3/46 proceeds via base-catalyzed rearrangement to the (3-azido-2-alkenyl)-phosphonates 5 and subsequent thermolysis. Reduction of the 2H-Azirines 6 with NaBH4 in methanol at 5°C results in the predominant formation of the disubstituted aziridines cis-7. Addition of trimethylsilyl cyanide to compounds 6 yields stereoselectively the highly functionalized aziridines trans-8, while NaOCH3-catalyzed addition of dimethyl phosphite proceeds with even higher selectivity to yield the bisphosphonates trans-9 with excellent yields.
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2h azirin 2 yl methyl phosphonate darstellung aus allylischen α und γ hydroxyphosphonaten und anwendung zur diastereoselektiven synthese von substituirten aziridin 2 yl methyl phosphonsaureestern
European Journal of Organic Chemistry, 1994Co-Authors: Elisabeth Öhler, Silvia KanzlerAbstract:[(2H-Azirin-2-yl)methyl]phosphonates: Synthesis from Allylic α- and γ-Hydroxyphosphonates and Application to Diastereoselective Formation of Substituted [(Aziriden-2-yl)methyl]phosphonates Various substituted (3-azido-1-alkenyl)phosphonates 3 (R3 = alkyl) or their equilibrium mixtures with the regioisomeric α-azidophosphonates 4 (R3 = Ph) have been synthesized from allylic α- or γ-hydroxyphosphonates 2 or 1 by Mitsunobu reaction with TPP/DEAD/HN3, and converted into the new [(2H-azirin-2yl)methyl]phosphonates 6 upon heating in toluene with DBU catalysis. The transformation 3/46 proceeds via base-catalyzed rearrangement to the (3-azido-2-alkenyl)-phosphonates 5 and subsequent thermolysis. Reduction of the 2H-Azirines 6 with NaBH4 in methanol at 5°C results in the predominant formation of the disubstituted aziridines cis-7. Addition of trimethylsilyl cyanide to compounds 6 yields stereoselectively the highly functionalized aziridines trans-8, while NaOCH3-catalyzed addition of dimethyl phosphite proceeds with even higher selectivity to yield the bisphosphonates trans-9 with excellent yields.
