3-(Dimethylamino)-2,2-dimethyl-2H-azirin als Aib-Äquivalent: Synthese von Aib-Oligopeptiden

3-(Dimethylamino)-2,2-dimethyl-2H-azirine as an Aib Equivalent; Synthesis of Aib Oligopeptides 3-(Dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) reacts with carboxylic acids at 0–25° to give 2-acylamino-N,N,2-trimethylpropionamides ( = 2-acylamino-N,N-dimethylisobutyramide, acyl-Aib-NMe₂) in excellent yields (Scheme 2 and 3). Examples of α-amino-, α-hydroxy-, and α-mercapto-carboxylic acids are given. On treatment with HCl in toluene, the terminal dimethylamide group is selectively converted to the corresponding carboxylic acid (→acyl-Aib) via an amide cleavage (Scheme 4 and 5); 1,3-oxazol-5(4H)-ones are intermediates of this amide hydrolysis. This reaction sequence has been used for the extension of peptide chains (Scheme 6). The synthesis of Aib-oligopeptides using this methodology is described (Scheme 8).     

Synthese von 1, 3, 4-Oxadiazolen und 4, 5-Dihydro-1, 2, 4-triazinen aus 3-Dimethylamino-2, 2-dimethyl-2 H-azirin und Carbohydraziden

Synthesis of 1,3,4-Oxadiazoles and 4,5-Dihydro-l,2,4-triazines from 3-Dimethylamino-2,2-dimethyl-2 Hazirine and Carbohydrazides 3-Dimethylamino-2, 2-dimethyl-2 H-azirine ( 1 ) reacts with aromatic carbohydrazides to give 2-(1-amino-1-methylethyl)-5-aryl-1, 3, 4-oxadiazoles ( 7 , 10 , 11 ). With ethyl carbazate the azirine 1 forms the aminoester 15 , which is easily cyclized to the 4, 5-dihydro-1, 2, 4-triazin-3 (2H)-one 16 . From the reaction of 1 with oxamohydrazide ( 17 ) and oxalodihydrazide 19 the 4, 5-dihydro-1, 2, 4-triazin-3-carboxamide 18 and the symmetric compound 20 , respectively, have been isolated. Reactions supporting the structures of the new compounds are described.     

Herstellung und Reaktionen der valenzpolaromeren Verbindung (4,4-Dimethyl-2-thiazolin-5-dimethyliminium)-2-thiolat ⇌ (1-Dimethylthiocarbamoyl-1-methyl-äthyl)-isothiocyanat aus 3-Dimethyl-amino-2,2-dimethyl-2H-azirin und Schwefelkohlenstoff

Synthesis and reactions of the valence polaromeric compound (4,4-dimethyl-2-thiazoline-5-dimethyliminium)-2-thiolate ? 1-dimethylthiocarbamoyl-1-methyl-ethyl isothiocyanate from 3-dimethylamino-2,2-dimethyl-2H-azirine and carbon disulfide. 3-Dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) reacts with carbon disulfide to give crystals which have the dipolar structure 3a [(4,4-dimethyl-2-thiazoline-5-dimethyliminium)-2-thiolate, Scheme 1]. In solution, the non-dipolar (charge-free) isomeric form 3b (1-Dimethyl-thiocarbamoyl-1-methyl-ethyl isothiocyanate) is almost exclusively populated. Reaction products are derived from both forms: Derivatives of 3a are the hydrolysis product 6 , the sodium borohydride reduction product 7 and the methylation products 9 and 10 , respectively (Scheme 2). The isothiocyanate form 3b is responsible for the various reaction products with amines (Scheme 3). One of the reaction products with ammonia, namely 20 , is also obtained by the reaction of 1 with thiocyanic acid. Thermolysis of the azirine/carbon disulfide adduct 3 leads to 2-dimethylamino-4,4-dimethyl-2-thiazoline-5-thione ( 17 ) in high yield. A possible mechanism is outlined in Scheme 4. The same compound is also formed by rearrangement of 3 under the catalytic influence of dimethylamine. Its structure has been established by X-ray crystallography (section 4). Again a rearrangement is involved in the reductive (NaBH₄) conversion of 17 to 7 , the direct reduction product of the dipolar species 3a (Scheme 5). The isothiocyanate form 3b is able to react with a second molecule of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) to yield compound 25 , which in the crystalline or dissolved state appears to be almost entirely populated by the carbodiimide form with structure 25b (Scheme 7), though all reaction products of 25 (reduction with sodium borohydride, addition of water or hydrogen sulfide, Schemes 7 and 8) are derived from the dipolar form 25a , not detectable as such; here again therefore there is a dynamic equilibrium 25a ? 25b . The two forms of adduct 3 , namely 3a and 3b , are obviously very easily interconverted at room temperature and therefore can be considered as valence polaromeric forms (section 5). A classification of the dipolar (zwitterionic) form is given, which allows a comparison of various dipolar species and gives as indication of charge stabilization by delocalization. The versatile reactivity of the 3-dimethylamino-2,2-dimethyl-2H-azirine/carbon disulfide adduct is demonstrated by the fact that with simple reagents approximately 25 derivatives have been obtained, most of them being new heterocyclic compounds.     

Ringerweiterung von sechs- zu neungliedrigen Heterocyclen: Umsetzung von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin mit 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-on-1,1-dioxiden

Ring Enlargement of Six- to Nine-Membered Heterocycles: Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine with 3,4-Dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-Dioxides Reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and N-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazin-3-one 1,1-dioxides ( 4 ) in CHCl₃ yields 3-(dimethylamino)-4,5,6,7-tetrahydro-1,2,5,7-benzothiatriazonin-6-one 1,1-dioxides 5 , a novel nine-membered heterocyclic system, by ring enlargement (Schemes 2 and 4). In refluxing MeOH, the heterocycle 5a rearranges to give the N-[1-methyl-1-(1,1-dioxo-4H-1,2,4-benzothiadiazin-3-yl)ethyl]-N′, N′-dimethylurea 10 . The three isomeric 2-(methylamino)benzenesufonamides 8,9 , and 11 (Scheme 3) are obtained by naBH₄ reduction of 5a and 10 , respectively. Mechanisms for the thermal isomerization 5a → 10 and the NaBH₄ reduction of 5a are proposed in Schemes 5 and 6.     

15N-Markiertes 3-(Dimethylamino)-2,2-dimethyl-2H-azirin zur mechanistischen Untersuchung von Reaktionen mit NH-aciden Heterocyclen

₁₅N-Labelled 3-(Dimethylamino)-2,2-dimethyl-2H-azirine for Mechanistic Studies of Reactions with NH-Acidic Heterocycles The synthesis of 3-(dimethylamino)-2,2-dimethyl(1-¹⁵N)-2H-azirine ( 1 *) was accomplished via reaction of 1-chloro-N,N,2-trimethyl-1-propenylamine ( 9 ) and sodium (1-¹⁵N) azide (Scheme 3). The earlier reported reactions of 1 with saccharin ( 10 , Scheme 4), phthalimide ( 12 , Scheme 5), and 2H-1,3-benzoxazin-2,4(3H)-dione ( 16 , Scheme 6) were repeated with 1 *, and the position of the ¹⁵N-label in the products was determined by ¹⁵N-NMR spectroscopy. Whereas the postulated reaction mechanisms for 10 and 12 were confirmed by these experiments, the mechanism for the reaction of 16 had to be revised. With respect to the position of ¹⁵N in the products 17 and 18 , a new mechanism is formulated in Scheme 7. Treatment of 5,5-dimethyl-1,3-oxazolidine-2,4-dione ( 19 ) with 1 * led to 3,4-dihydro-2H-imidazol-2-on 20 in which only N(3) was labelled. The mechanism of a ring expansion and transannular ring contraction as shown in Scheme 8 is in agreement with this finding.     

Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen an Carbonsäurechloride. 35. Mitteilung über Photoreaktionen

Irradiation of 2, 3-diphenyl-2H-azirine ( 1a ) and 1-azido-1-phenyl-propene, the precursor of 2-methyl-3-phenyl-2H-azirine ( 1b ), in benzene, with a high pressure mercury lamp (pyrex filter) in the presence of acid chlorides yields the oxazoles 5a–d (Scheme 2). Photolysis of 2, 2-dimethyl-3-phenyl-2H-azirine ( 1c ) under the same conditions gives after methanolysis the 5-methoxy-2, 2-dimethyl-4-phenyl-3-oxazolines 7a, b, d , while hydrolysis of the reaction mixture leads to the formation of the 1, 2-diketones 8a, c, d (Scheme 4). The suggested reaction path for all these reactions is a 1, 3-dipolar cycloaddition of the photochemically generated benzonitrilemethylides 2 to the carbonyl double bond of the acid chlorides to give the intermediates 4 , followed by either elimination of hydrogen chloride or solvolysis (Schemes 2 and 4). Irradiation of 1c in the presence of acetic acid anhydride leads via the intermediate 9 to the 5-hydroxy-3-oxazoline 10 and the 5-methylidene-3-oxazoline 11 (Scheme 5).     

Reaktion von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit 6-Methyluracil; Kristallstruktur der Reaktionsprodukte

Reaction of 3-Dimethylamino-2,2-dimethyl-2H-azirine with 6-Methyluracil; Crystal Structure of the Products The reaction of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) with 6-methyl-uracil ( 4 ) in 2-propanol at 80° yields the 4H-imidazoje derivative 5 as the main product. This reaction is similar to the previously reported ones with heterocyclic compounds containing the sequence NH? CO? NH? CO. In the presence of water, 5 is easily hydrolyzed to 6 . The structures of 5 and 6 have been established by X-ray crystallography.     

3-(Dimethylamino)-2,2-dimethyl-2H-azirin als α-Aminoisobuttersäure(Aib)-Äquivalent: Cyclische Depsipeptide durch direkte Amid-Cyclisierung

3-(Dimethylamino)-2,2-dimethyl-2H,-azirine as an α-Aminoisobutyric-Acid (Aib) Equivalent: Cyclic Depsipeptides via Direct Amid Cyclization In MeCN at room temperature, 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) and α-hydroxycarboxylic acids react to give diamides of type 8 (Scheme 3). Selective cleavage of the terminal N,N-dimethylcarboxamide group in MeCN/H₂O leads to the corresponding carboxylic acids 13 (Scheme 4). In toluene/Ph SH , phenyl thioesters of type 11 are formed (see also Scheme 5). Starting with diamides 8 , the formation of morpholin-2,5- diones 10 has been achieved either by direct amide cyclization via intermediate 1,3-oxazol-5(4H)-ones 9 or via base-catalyzed cyclization of the phenyl thioesters 11 (Scheme 3). Reaction of carboxylic acids with 1 , followed by selective amide hydrolysis, has been used for the construction of peptides from α-hydroxy carboxylic acids and repetitive α-aminoisobutyric-acid (Aib) units (Scheme 4). Cyclization of 14a, 17a , and 20a with HCI in toluene at 100° gave the 9-, 12-, and 15-membered cyclic depsipeptides 15, 18 , and 21 , respectively.     

Reaktionen von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit. NH-aciden Heterocyclen; Synthese von 4H-imidazolen

Reactions of 3-Dimethylamino-2,2-dimethyl-2H-azirine with NH-Acidic Heterocycles; Synthesis of 4H-Imidazoles In this paper, reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) with heterocyclic compounds containing the structure unit CO? NH? CO? NH are described. 5,5-Diethylbarbituric acid ( 5 ) reacts with 1 in refluxing 2-propanol to give the 4H-imidazole derivative 6 (Scheme 2) in 80% yield. The structure of 6 has been established by X-ray crystallography. Under similar conditions 1 and isopropyl uracil-6-carboxylate ( 7 ) yield the 4H-imidazole 8 (Scheme 3), the structure of which is deduced from spectral data and the degradation reactions shown in Scheme 3. Hydrolysis of 8 with 3N HCl at room temperature leads to the α-ketoester derivative 9 , which in refluxing methanol gives dimethyl oxalate and 5-dimethyl-amino-2,4,4-trimethyl-4H-imidazole ( 10 ). On hydrolysis the latter is converted to the known 2,4,4-trimethyl-2-imidazolin-5-one ( 11 ) [6]. Quinazolin-2,4 (1H, 3H)-dione ( 12 ) and imidazolidinetrione (parabanic acid, 14 ) undergo with 1 a similar reaction to give the 4H-imidazoles 13 and 15 , respectively (Schemes 4 and 5). In Scheme 6 two possible mechanisms for the formation of 4H-imidazoles from 1 and heterocycles of type 16 are formulated. The zwitterionic intermediate f corresponds to b in Scheme 1. Instead of dehydration as in the case of the reaction of 1 with phthalohydrazide [3], or ring expansion as with saccharin and cyclic imides [1] [2], f , undergoes ring opening (way A or B). Decarboxylation then leads to the 4H-imidazoles 17 .     

Ringschlussreaktionen mit 2-(β-Styryl)benzylaminen 5-Phenyl-1H-2-benzazepine. 23. Mitteilung über siebengliedrige Heterocyclen

Cyclization reactions with 2-(β-styryl)benzylamines 5-Phenyl-1H-2-benzazepines Cyclization of the urea derivative 3 with POCl₃ to give 2-(4-methyl-1-piperazinyl)-4-phenylquinoline ( 4 ) was carried out in analogy to the quinoline synthesis of Foulds & Robinson. This reaction was used for the preparation of 2-benzazepines. The trisubstituted ureas 6 and 8 , derived from the 2-(β-styryl)-benzylamines 5 , were cyclized with POCl₃ to yield the 3-amino-5-phenyl-1H-2-benzazepines 7 and 9 , respectively. Similarly, cyclization of the corresponding acetyl-derivatives 10 gave the 3-methyl-5-phenyl-1H-2-benzazepines 12 . On the other hand, the disubstituted urea 15 , cyclized under the same conditions to the 1-methyl-1-phenylisoindoline derivative 16 , and 2-(β-styryl)benzylamine ( 5a ) on treatment with phosgene gave the isoindoline 17 in an analogous manner.     

4(And 5)-cyclopropylamino-5(and 4)halo-3(2H)pyridazinones. Formation and characterization of isomers

The reactions of 4,5-dihalo-3(2H)pyridazinones with ammonia and amines gave mixtures of 5-amino-4-halo- and 4-amino-5-halo-3(2H)pyridazinones separated by chromatography. Structures were elucidated by means of retention values (R_f) and confirmed by independent synthesis.     

Die Struktur des Adduktes aus 3-Dimethylamino-2,2-dimethyl-2H-azirin und 3-Methyl-2,4-diphenyl-1,3-oxazolium-5-olat. Vorläufige Mitteilung

Structure of the adduct from 3-dimethylamino-2,2-dimethyl-2H-azirine and 3-methyl-2,4-diphenyl-1,3-oxazolium-5-olate 3-Dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) reacts with 3-methyl-2,4-diphenyl-1,3-oxazolium-5-olate ( 5a ) to give a 1:1 adduct ( 7 ) in a 88% yield. Its crystal structure has been determined by X-ray analysis (direct methods) and refined with 1056 structure amplitudes to R = 0,032. The crystal system is monoclinic, space group P2₁/c, with unit cell dimensions a = 10.663, b = 9,828, c = 18,592 Å, and β = 90,63°. It is obvious that 4-dimethylamino-5,5-dimethyl-2-[α-(N-methyl-benzamido)benzyliden]-Δ³-1,3-oxazoline ( 7 ) arises from an addition of 1 to the valence-polaromeric ketene form 5b of the mesoionic oxazolone 5a (Scheme 3).     

Reaktion von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit Barbitursäure

Reaction of 3-Dimethylamino-2,2-dimethyl-2H-azirine with Barbituric Acid The reaction of 3-dimethylamino-2,2-dimethyl-2H-azirine (1) with barbituric acid (4) in dimethyl formamide at room temperature yields a mixture of several compounds. The two main products 5 and 6 have been isolated in 40 and 10% yield, respectively, and their structures established by X-ray analysis. In Schemes 4–6 reaction mechanisms for the formation of 5 and 6 are postulated, the first step beeing either a C- or an N-alkylation of barbituric acid. Reduction of 5 and 6 with NaBH₄ in ethanol at room temperature yields 6,6-dimethyl-1,5,6,7-tetrahydro-pyrrolo[2,3-d]pyrimidin-2,4(3H)-dione (7) and 3,3-dimethyl-2,3-dihydro-imidazo[1,2-c]pyrimidin-5,7(1H, 6H)-dione (8) in 38 and 48% yield, respectively. Treatment of 6 with 3N aqueous NaOH at room temperature gives 3,3-dimethyl-imidazo[1,2-c]pyrimidin-2,5,7 (1H, 3H, 6H)-trione (9) in 51% yield (Scheme 3).     

Synthesis of 2-(2′,3′-dihydroxypropyl)-5-amino-2H-1,2,4-thiadiazol-3-one and 3-(2′,3′-dihydroxypropyl)-5-amino-3H-1,3,4-thiadiazol-2-one

The synthesis of two new acyclic nucleoside analogs, 2-(2′,3′-dihydroxypropyl)-5-amino-2H-1,2,4-thiadiazol-3-one (1) and 3-(2′,3′-dihydroxypropyl)-5-amino-3H-1,3,4-thiadiazol-2-one (2), is reported. The first compound, 1, was obtained by reaction of 3-chloro-1,2-propanediol with the sodium salt of 5-amino-2H-1,2,4-thiadiazol-3-one (3) in anhydrous dimethylformamide. Similarly, 5-amino-3H-1,3,4-thiadiazol-2-one (4) reacted with 3-chloro-1,2-propanediol to give 2. The thiadiazole 4 was prepared by condensation-cyclization of hydrazothiodicarbonamide (9).     

Synthese und Reaktionen 8-gliedriger Heterocyclen aus 3-Dimethylamino-2,2-dimethyl-2H-azirin und Saccharin bzw. Phthalimid

Synthesis and Reactions of 8-membered Heterocycles from 3-Dimethylamino-2,2-dimethyl-2H-azirine and Saccharin or Phthalimide 3-Dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) reacts at 0-20° with the NH-acidic compounds saccharin ( 2 ) and phthalimide ( 8 ) to give the 8-membered heterocycles 3-dimethylamino-4,4-dimethyl-5,6-dihydro-4 H-1,2,5-benzothiadiazocin-6-one-1,1-dioxide ( 3a ) and 4-dimethylamino-3,3-dimethyl-1,2,3,6-tetrahydro-2,5-benzodiazocin-1,6-dione ( 9 ), respectively. The structure of 3a has been established by X-ray (chap. 2). A possible mechanism for the formation of 3a and 9 is given in Schemes 1 and 4. Reduction of 3a with sodium borohydride yields the 2-sulfamoylbenzamide derivative 4 (Scheme 2); in methanolic solution 3a undergoes a rearrangement to give the methyl 2-sulfamoyl-benzoate 5 . The mechanism for this reaction as suggested in Scheme 2 involves a ring contraction/ring opening sequence. Again a ring contraction is postulated to explain the formation of the 4H-imidazole derivative 7 during thermolysis of 3a at 180° (Scheme 3). The 2,5-benzodiazocine derivative 9 rearranges in alcoholic solvents to 2-(5′-dimethylamino-4′,4′-dimethyl-4′H-imidazol-2′-yl) benzoates ( 10 , 11 ), in water to the corresponding benzoic acid 12 , and in alcoholic solutions containing dimethylamine or pyrrolidine to the benzamides 13 and 14 , respectively (Scheme 5). The reaction with amines takes place only in very polar solvents like alcohols or formamide, but not in acetonitrile. Possible mechanisms of these rearrangements are given in Scheme 5. Sodium borohydride reduction of 9 in 2-propanol yields 2-(5′-dimethylamino-4′,4′-dimethyl-4′H-imidazol-2′-yl)benzyl alcohol ( 15 , Scheme 6) which is easily converted to the O-acetate 16 . Hydrolysis of 15 with 3N HCl at 50° leads to an imidazolinone derivative 17a or 17b , whereas hydrolysis with 1N NaOH yields a mixture of phthalide ( 18 ) and 2-hydroxymethyl-benzoic acid ( 19 , Scheme 6). The zwitterionic compound 20 (Scheme 7) results from the hydrolysis of the phthalimide-adduct 9 or the esters 11 and 12 . Interestingly, compound 9 is thermally converted to the amide 13 and N-(1′-carbamoyl-1′-methylethyl)phthalimide ( 21 , Scheme 7) whose structure has been established by an independent synthesis starting with phthalic anhydride and 2-amino-isobutyric acid. However, the reaction mechanism is not clear at this stage.     

Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen mit kumulierten Doppelbindungen. Vorläufige Mitteilung

Irradiation of 2-methyl- ( 1c ) and 2,2-dimethyl-3-phenyl-2H-azirine ( 1d ) in benzene solution in the presence of carbon dioxide yields 2-methyl-4-phenyl- ( 3c ) and 2,2-dimethyl-4-phenyl-3-oxazolin-5-one ( 3d ), respectively. Similar cycloadducts are observed (see table) when 2,3-diphenyl-2H-azirine ( 1b ) and 1d are irradiated in the presence of phenylisocyanate, o-tolylisocyanate, phenylisothiocyanate or di-o-tolyl-carbodiimide.     

Zur Photodimerisierung von 3-Phenyl-2H-azirinen. Vorläufige Mitteilung

Irradiation of 3-phenyl-2H-azirine ( 2 ) in benzene solution with a high-pressure mercury lamp yields 4,5-diphenyl-1,3-diazabicyclo[3,1,0]hex-3-ene ( 4 ) and not 3-phenylimino-4-phenyl-1-azabicyclo[2,1,0]pentane ( 1 ), as had been reported previously by others [2]. 2-Methyl-3-phenyl-2H-azirine ( 3 ) yields on irradiation a 2:1 mixture of 2-exo, 6-exo- and 2-exdo, 6-exo-dimethyl-4,5-diphenyl-1,3-diazabicyclo[3,1,0]hex-3-ene (2-exo,6-exo- and 2-endo, 6-exo- 5 ). Irradiation of 2,3-diphenyl-2H-azirine ( 8 ) leads to the formation of 2,4,5-triphenyl-imidazole ( 9 ) and tetra-phenylpyrazine ( 10 ). The suggested reaction path for the generation of 9 and 10 is shown in Scheme 2.     

Photoreaktionen des 3-(2-Thienyl)-2,2-dimethyl-2H-azirins

Synthesis and Photochemistry of 3-(2-Thienyl)-2,2-dimethyl-2H-azirine The synthesis of 3-(2-thienyl)-2,2-dimethyl-2 H-azirine (1) is described. UV. irradiation of 1 in benzene solution generates the nitrile isopropylide 2 which reacts in a regiospecific manner with activated C, C and C, O double bonds to give 1-pyrrolines and 3-oxazolines, respectively. With chelidonic acid diethyl ester the cycloaddition of 2 to the C, C double bond is preferred.     

Heterocyclole als Zwischenprodukte einer neuen, überraschenden Umlagerung bei der Reaktion von 3-(Dimethylamino)-2,2-dimethyl-2H-azirin mit monosubstituierten Parabansäuren. Vorläufige Mitteilung

Cyclols as Intermediates in the Reaction of 3-(Dimethylamino)-2,2-dimethyl-2H-azirine with Monosubstituted Parabanic Acids; a New and Unexpected Rearrangement The reaction of 3-(dimethylamino)-2,2-dimethyl-2H-azirine ( 1 ) with N-methylparabanic acid ( 4 ) in 2-propanol at room temperature gives the cyclol 5 in 97% yield. In acetonitrile solution 5 rearranges to the imidazoline derivative 6 (Scheme 2). The structures of the unexpected products 5 and 6 have been established by X-ray crystallography.     

Optisch aktive 3-Amino-2H-azirine als Bausteine für enantiomerenreine α,α-disubstituierte α-Aminosäuren: Synthese des α-Methylphenylalanin-Synthons and Einbau in Modell-Peptide

Optically Active 3-Amino-2H-azirines as Synthons for Enantiomerically Pure αα-Disubstituted α-Amino Acids: Synthesis of the α-Methylphenylalanine Synthons and Some Model Peptides The synthesis of a novel 2-benzyl-2-methyl-3-amino-2H-azirine derivative with a chiral amino group is described. Chromatographic separation of the diastereoisomer mixture yielded the pure diastereoisomers 9a and 9b (Scheme 4) which are the D - and L -2-methylphenylalanine ((α-Me)Phe) synthons, respectively. The reaction of 9a and 9b with thiobenzoic acid and with Z-leucine yielded the monothiodiamides 10a and 10b (Scheme 5) and the dipeptide derivatives 11a and 11b (Scheme 6), respectively. Methanolysis of 11b yielded 12b . The absolute configuration of 10a was established by X-ray crystallography. The absolute configuration of (α-Me)Phe in 12b has been deduced from the known configuration of L -leucine.