Umamidierungsreaktionen an offenkettigen Amino-amid-Systemen. 1. Mitteilung über Umamidierungsreaktionen

Transamidation Reaction of Open Chaine Amino-amides Amino-amides of type 11 with a primary amino and a N, N-disubstituted amide group isomerize under base catalysis completely to amino-amides 16 with a secondary amino and a N-monosubstituted amide group (see Scheme 3). Amino-amides having a secondary instead of the primary amino group are under base catalysis in equilibrium with the corresponding isomeres (Scheme 4). The opening of the proposed tetrahedral intermediate 13 (Scheme 3) takes place under stereo-electronic control (Schemes 5 and 6).     

Die «Zip»-Reaktion: Eine neue Ringerweiterungsreaktion. Synthese von 17-, 21- und 25-gliedrigen Polyaminolactamen. 4. Mitteilung über Umamidierungsreaktionen

The Zip-reaction: A New Method for the Synthesis of Macrocyclic Polyaminolactams The 21- and 25-membered aminolactams 11 and 25 were synthesized from the 13-membered lactam 4 . To introduce the ring enlargement unit (a propylamino group) 4 was N-alkylated using acrylonitrile and the resulting product hydrogenated. Repetition of this reaction sequence gave 3 , which was converted in the presence of base in 90% yield to the ring-enlarged macrocyclic base 11 (Scheme 2). In a similar but stepwise synthesis consisting of two separate ring-enlargement reactions 4 was transformed to 11 via 13 (Scheme 4). Introducing three ringenlargement units into 4 the 25-membered aminolactam 25 was synthesized in 84% yield (Scheme 5). The mechanism of the ring-enlargement reaction is given in Scheme 3. In comparison to a zip-fastener or zipper this reaction is called “zipreaction”.     

Ringerweiterungsreaktionen von N-(2-Aminoäthyl)-, N-(4-Aminobutyl)-, N-(6-Amino-4-aza-hexyl)- und N-(8-Amino-4-aza-octyl)-lactamen. 7. Mitteilung über Umamidierungsreaktionen

Ring Enlargement Reactions of N -(2-Aminoethyl)- , N -(4-Aminobutyl)- , N -(6-Amino-4-aza-hexyl)- and N -(8-Amino-4-aza-octyl)-lactames The N-aminoalkyl-lactams 1 , 3 , 4 , 10 (Scheme 2) and 13 (Scheme 3) have been synthesized. In the presence of KAPA (potassium 3-aminopropylamide in 1,3-propanediamine) 1 is stable, whereas 3 , 4 and 10 rearrange under ring enlargement to 5 , 8 and 11 , respectively. The 4-aminobutyl derivate 13 rearranges in a fast reaction to 14 ; after a longer reaction time the 22membered ring 16 and the ring opened product 18 are formed. Hence it may be concluded that the 7membered lactam ring is more stable than the 10membered one, and the 11membered lactam ring is more stable than the 8 membered one. Moreover, the 5- and 6 membered ring intermediates of these transamidation reactions are prefered to the 7membered ring intermediates (cf. [10]).     

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.     

Repetierbare Ringerweiterungen durch [2,3]-sigmatropische Umlagerungen in cyclischen Allylsulfonium-allyliden; Synthese von mittleren und grossen Thiacyclen. Vorläufige Mitteilung

Repeatable ring expansions by [2,3]-sigmatropic shifts in cyclic allylsulfonium allylides; synthesis of medium- and large-sized thiacycles Allylation of a 2-vinyl thiacyclus with allyl bromide in 2,2,2-trifluoroethanol followed by ylide generation by use of aqueous potassium hydroxide results in a [2,3]-sigmatropic rearrangement with formation of a new 2-vinyl thiacyclus enlarged by three carbon atoms (Scheme 1). In this way, starting from the 5-membered ring 1 , a series of four ring enlargement sequences leads to the 17-membered thiacycles 9 and 10 via the 8-, 11- and 14-membered rings 4 , 7 and 8 (Scheme 2).     

The Carbon Zip Reaction: A Method for Expanding Carbocycles

A general method for enlargement of carbocyclic rings by the so called zip reaction is given. The Michael adducts of 2-nitrocycloalkanones with 3-oxo-4-pentenoates in the presence of tetrabutylammonium fluoride give in high yield compounds with the ring enlarged by four C-atoms. By this method 7-, 8-, and 12-membered cycloalkanones were converted respectively to 11-, 12-, and 16-membered functionalized carbocycles (see Scheme 2 and 3).     

Basenkatalysierte Cyclisierungen von 2-(2-Propinyl)oxybenzamiden

Base Catalysed Cyclizations of 2-(2-Propynyl)oxy-benzamide Systems 2-(2-Propynyl)oxy-benzamides were cyclized under base catalysis to 6- or 7-membered ring compounds, depending on the reaction conditions. Treatment of 2-(2-propynyl)oxy-benzamide ( 10 ) with sodium methylsulfinylmethanide (NaMSM) in DMSO gave two isomeric oxazepinons 11 (34%) and 12 (7%), while the transformation with sodium-2-propanolate in 2-propanol afforded the oxazinone 13 (34%) and with lithium cyclohexyl-isopropylamide (Li-CHIP) in N-methylpyrrolidone 11 (48%) exclusively (Scheme 4). N-Methyl-2-(2-propynyl)-oxy-benzamide ( 14 ) behaved similarly. In the reaction of 14 with sodium 2-propanolate in 2-propanol yielding the benzoxazinone 16 , the allenyloxy-benzamide 17 could be isolated as an intermediate (Scheme 5). The N-phenyl-compounds 18 and 22 treated with NaMSM/DMSO were converted to 3-anilino-2-methyl-benzo- and naphtho-pyran-4-ones, respectively (Schemes 6 and 7). The mechanisms for these reactions are discussed (Schemes 8, 9 and 10).     

3-Alkyl-1-benzoxepin-5-on-Derivate und 2-Alkyl-1, 4-naphthochinone aus 2-Acylaryl-propargyläthern

3-Alkyl-1-benzoxepin-5-one derivatives and 2-alkyl-1,4-naphtoquinones from 2-acylaryl propargyl ethers. It was found that 3-alkyl-1-benzoxepin-5(2H)-ones of type B can be synthesized by treating 2-acylaryl propargyl ethers of type A with sodium methylsulfinyl methide (NaMSM, dimesyl sodium) (Scheme 13). Oxepinone derivatives of type B undergo ring contraction with base (also NaMSM) to yield the quinol derivatives C which, oxidize (during work-up), if R² = H, to the 1,4-naphthoquinones D (Scheme 13). The propargyl ethers used are listed in Scheme 1. The naphthalene derivatives 1 and 3 give oxepinones (E- 9 and a mixture of 14/15 respectively), whereas the expected oxepinone from 2 is transformed directly into the quinone 11 (Scheme 2, 3 and 5). Isomerizations of 2-acetylphenyl propargyl ethers ( 4, 5 and 6 ) (Schemes 6, 7 and 8) are less successful because of side reactions. If however the acetyl group is replaced by a propionyl or substituted propionyl group (as in ethers 7 and 8 ) oxepinones are obtained again in good yield (Scheme 9). The mechanistic pathway for the transformation of naphthyl propargyl ethers (and phenyl derivatives) under influence of NaMSM is shown in Scheme 10. The base-catalysed conversion of 4-phenyl-l-benzoxepin-5(2H)-one,benzo[f]furo[2,3-c](10 H)-oxepin-4-oncsand 3-methoxy-G,11- dihydro-dibenzo[b, e]loxepin-11-oneinto thc corresponding quinones has been reported [13] [20] [21]. The conversion of 2-acylaryl propargyl others via the isolable benzoxepin-5-one derivativcs or directly into the specifically substituted 1,4-naphthoquinone derivatives is of synthetic interest.     

Studies on Reactions of Thioketones with Trimethyl(trifluoromethyl)silane Catalyzed by Fluoride Ions

Treatment of 2,2,4,4‐tetramethylcyclobutane‐1,3‐dione ( 6 ) in THF with CF₃SiMe₃ in the presence of tetrabutylammonium fluoride (TBAF) yielded the corresponding 3‐(trifluoromethyl)‐3‐[(trimethylsilyl)oxy]cyclobutanone 7 (Scheme 1) via nucleophilic addition of a CF anion at the CO group and subsequent silylation of the alcoholate. Under similar conditions, the ‘monothione' 1 reacted to give thietane derivative 8 (Scheme 2), whereas in the case of ‘dithione' 2 only the dispirodithietane 9 , the dimer of 2 , was formed (Scheme 3). A conceivable mechanism for the formation of 8 is the ring opening of the primarily formed CF₃ adduct A followed by ring closure via the S‐atom (Scheme 2). In the case of thiobenzophenones 4 , complex mixtures of products were obtained including diarylmethyl trifluoromethyl sulfide 10 and 1,1‐diaryl‐2,2‐difluoroethene 11 (Scheme 4). Obviously, competing thiophilic and carbophilic addition of the CF anion took place. The reaction with 9H‐fluorene‐9‐thione ( 5 ) yielded only 9,9′‐bifluorenylidene ( 14 ; Scheme 6); this product was also formed when 5 was treated with TBAF alone. Treatment of 4a with TBAF in THF gave dibenzhydryl disulfide ( 15 ; Scheme 7), whereas, under similar conditions, 1 yielded the 3‐oxopentanedithioate 17 (Scheme 9). The reaction of dithione 2 with TBAF led to the isomeric dithiolactone 16 (Scheme 8), and 3 was transformed into 1,2,4‐trithiolane 18 (Scheme 10).     

Aktivierte Chinone: Substitution von Azulenen,Benzofuran und Indolen durch 2-Methoxycarbonyl-1,4-benzochinon. Regiospezifische Synthesen von Polymethoxy-fluorenonen und eine neue Synthese des 2,6-Dihydro-naphtho[1,2,3-cd]indol-6-on-Systems

Activated quinones: substitution reactions by methoxy-carbonyl-1,4-benzoquinone of azulenes, benzofuran and indoles; regiospecific syntheses of polymethoxy-fluorenones; a new synthesis of the 2,6-dihydro-naphtho[1,2,3-cd]indol-6-one system. We present new electrophilic substitution reactions of azulenes and 5-membered heterocyclics by methoxy-carbonyl-1,4-benzoquinone. Hydroquinones 3a and 5 are prepared from azulene, and 3b from guaiazulene (see Scheme 1). Benzofuran undergoes α- and β-substitution (hydroquinones 9 10 ) (see Scheme 2). Only β-substitution is observed with indole (hydroquinone 20 ) (see Scheme 4). After methylation, saponification and intramolecular acylation of the substituted indoles 22c, 22d , derivatives of 2,6-dihydro-naphtho[1,2,3-cd]indol-6-one have been obtained. Spectral data prove the presence of the methylidenequinone tautomer. By protonation or alkylation at the carbonyl group of 23 , the violet, highly delocalized 16π-electron systems 25 are generated. Analogously, polymethoxy-fluorenones have been prepared from methoxylated diphenylquinones 15 (see Scheme 3). They also are transformed by protonation and alkylation to the highly coloured and delocalized 12 π-electron systems 18 . By contrast, anthracene is not substituted by methoxycarbonyl-1,4-benzoquinone, but undergoes cycloaddition to the triptycene derivative 1 (see Scheme 1). A summary is presented of previously described reactions of activated quinones.     

Amidine als Zwischenprodukte bei Umamidierungsreaktionen. 9. Mitteilung über Umamidierungsreaktionen

Amidines as Intermediates in Transamidation Reactions By loss of water in the presence of p-toluenesulfonic acid/xylole N-aminoalkyllactames form bicyclic amidines. The corresponding N-alkylaminoalkyl-lactames' react to bicyclic amidinium salts or to transamidated products, ring-enlarged by the N-alkylamino residue, respectively (s. Scheme 1). The bicyclic amidines and amidinium salts are partially hydrolyzed by KOH/H₂O to lactames (s. Scheme 2). Which of the two possible isomeric lactames are formed is discussed.     

Oligonucleosides with a Nucleobase‐Including Backbone,Part 4, A Convergent Synthesis of Ethynediyl‐Linked Adenosine Tetramers

Deprotection of the tetramer 24 , obtained by coupling the iodinated dimer 18 with the alkyne 23 gave the 8′,5‐ethynediyl‐linked adenosine‐derived tetramer 27 (Scheme 3). As direct iodination of C(5′)‐ethynylated adenosine derivatives failed, we prepared 18 via the 8‐amino derivative 17 that was available by coupling the imine 15 with the iodide 7 ; 15 , in its turn, was obtained from the 8‐chloro derivative 12 via the 4‐methoxybenzylamine 14 (Scheme 2). This method for the introduction of the 8‐iodo substituent was worked out with the N‐benzoyladenosine 1 that was transformed into the azide 2 by lithiation and treatment with tosyl azide (Scheme 1). Reduction of 2 led to the amine 3 that was transformed into 7 . 1,3‐Dipolar cycloaddition of 3 and (trimethylsilyl)acetylene gave 6 . The 8‐substituted derivatives 4a – d were prepared similarly to 2 , but could not be transformed into 7 . The known chloride 8 was transformed into the iodide 11 via the amines 9 and 10 . The amines 3 , 10 , and 16 form more or less completely persistent intramolecular C(8)N−H⋅⋅⋅O(5′) H‐bonds, while the dimeric amine 17 forms a ca. 50% persistent H‐bond. There is no UV evidence for a base‐base interaction in the protected and deprotected dimers and tetramers.     

4-Amino-1,5-dihydro-2H-pyrrol-2-one aus Bortrifluorid-katalysierten Umsetzungen von 3-Amino-2H-azirinen mit Carbonsäure-Derivaten

4-Amino-1,5-dihydro-2H-pyrrol-2-ones from Boron Trifluoride Catalyzed Reactions of 3-Amino-2H-azirines with Carboxylic Acid Derivatives Reaction of 3-amino-2H-azirines 1 with ethyl 2-nitroacetate ( 6a ) in refluxing MeCN affords 4-amino-1,5-dihydro-2H-pyrrol-2-ones 7 and 3,6-diamino-2,5-dihydropyrazines 8 , the dimerization product of 1 (Scheme 2). Thus, 6a reacts with 1 as a CH-acidic compound by C? C bond formation via C-nucleophilic attack of deprotonated 6a onto the amidinium-C-atom of protonated 1 (Scheme 5). The scope of this reaction seems to be rather limited as 1 and 2-substituted 2-nitroacetates do not give any products besides the azirine dimer 8 (see Table 1). Sodium enolates of carboxylic esters and carboxamides 11 react with 1 under BF₃ catalysis to give 4-amino-1,5-dihydro-2H-pyrrol-2-ones 12 in 50–80% yield (Scheme 3, Table 2). In an analogous reaction, 3-amino-2H-pyrrole 13 is formed from 1c and the Li-enolate of acetophenone (Scheme 4). A reaction mechanism for the ring enlargement of 1 involving BF₃ catalysis is proposed in Scheme 6.     

Synthese der Spermidin-Alkaloide (±)-Inandenin-10-ol,Inandenin-10-on und (±)-Oncinotin

Syntheses of the Spermidine Alkaloids (±)-Inandenin-10-ol, Inandenin-10-one, and (±)-Oncinotine New syntheses of the title compounds using two-ring-enlargement reactions are described. Starting from the aldehyde 1 , the corresponding 4′-aza derivative 15 could be obtained by reductive amination with the appropriate and protected spermidine derivative 14 (Scheme 4). Enlargement of the carbocyclic ring in 15 by five members gave, after further transformations, the hydroxylactam 18 . Transamidation of 18 , the second ring-enlargement step, led to (±)-inandenin-10-ol (7;22.9% overall yield) and, after oxidation, to inandenin-10-one ( 8 ; 22.5%, overall yield). (±)-Oncinotine 6 was synthesized by two pathways (Scheme 6): protection of the terminal NH₂ group by treatment with the Nefkens reagent and replacement of the OH group by Cl gave 24 , which by thermal transamidation followed by direct ring closure led to the oncinotine derivative 26 . The same intermediate could be obtained in higher yield via 28 by oxidation and protection of 18 followed by transamidation and reductive ring closure. Treatment of 26 with hydrazine finally gave (±)-oncinotine 6 in 15.9% overall yield.     

Über die Synthese von substituierten 2-Aminopyrrolinen, 2. Mitt.

Geminal dimethyl substituted N-acylaziridines react with diphenylacetonitrite (as anion), the course of the reaction depending on the nature of the acyl group. N-carbethoxy-2.2-dimethylaziridine undergoes abnormal aziridine ring opening at the gem.-substituted C atom and migration of the carbethoxy group accompanied by 5-membered ring closure to yield as major product N-2-carbethoxylamino-3.3-diphenyl-4.4-dimethylpyrroline-1 (1). In contrast, N-tosyl-2.2-dimethylaziridine undergoes normal ring opening at the less substituted C-atom with retention of the tosyl group on the original N-atom to form N-1-tosyl-2-imino-3.3-diphenyl-5.5-dimethylpyrrolidine (10). Deacylation of the N-carbethoxy- and N-tosyl derivatives yields the substituted 2-aminopyrrolines3, 9 and11.     

Experiments on the total synthesis of Lysolipin I. Part II. Michael addition of 1,3-cyclohexanedione to quinone acetals

Base-catalyzed reaction of 1,3-cyclohexanedione ( 3 ) with the quinone monoacetals 4 and 7 leads to the polycyclic products 5 and 8 , respectively, and in the case of 4 to variable amounts of dibenzofuranone 6 . The 2-arylcyclohexanedione 9 , on the other hand, is isolated from the reaction of 3 and bisacetal 11 catalyzed by ZnCl₂ (Scheme 2). Treatment of the adduct 8 with (CH₃O)₂SO₂/K₂CO₃ results in cleavage of teh heterocyclic ring by a retro-Michael reaction affording teh liable enone 23 which was further transformed to 24 by selective hydrogenation. The 8-acetoxydibenzofuranone 22 is obtainable from 8 by acid treatment and acetylation (Scheme 4). The reactions of the silylenol ethers 27 and 35 with quinone monoacetals were very complex (Scheme 6). The desired arylcyclohexanone derivatives 28 and 36 were formed in very low yields. Under certain conditions (elevated temperature or strong Lewis acids as catalysts), single-electron transfer or addition to the ene-acetal rather than to the enone function of the quinone monoacetals became predominant. In connection with this study, the sensitive 2-methoxy-p-benzoquinone monoacetals 15 (Scheme 3) and 29 (Scheme 6) have been prepared and characterized.     

Palladium‐Catalyzed Cascade Oligocyclizations Involving Competing Elementary Steps Such as Thermal [1,5]‐Acyl Shifts

Palladium(Pd)‐catalyzed oligocyclizations of 2‐bromotetradec‐1‐ene‐7,13‐diynes with an unsubstituted terminal acetylene moiety like 3 and 5 and 15‐bromohexadec‐15‐ene‐3,9‐diyn‐2‐ones like 4 and 6 afforded fulvene derivatives 20 and 21 (Scheme 7) and bis(cyclohexane)‐annulated methylenecyclopentene systems 16 and 18 (Schemes 5 and 6), respectively. These transformations constitute cascades of cyclizing carbopalladation steps with ensuing [1,5]‐sigmatropic H‐atom and acyl shifts, respectively (Scheme 8). In contrast, analogous substrates with one three‐atom and one four‐atom tether between the unsaturated C,C‐bonds, such as 1 and 2 , behave differently in that the Pd‐substituted hexa‐1,3,5‐triene intermediates 12 undergo a 6π‐electrocyclization instead of a 5‐exo‐trig carbopalladation followed by β‐hydride elimination to furnish tricyclic bis‐annulated benzene derivatives 13 and 14 (Scheme 4).     

1, 5, 6, 7-Tetrahydro-2H-[1,4]diazepin-5,7-dione aus Malonimiden und 3-Dimethylamino-2,2-dimethyl-2H-azirin

1, 5, 6, 7-Tetrahydro-2H-[1, 4]diazepin-5, 7-diones from Malonimides and 3-Dimethylamino-2, 2-dimethyl-2H-azirine Reaction of the aminoazirine 1 with malonimides of type 7 in 2-propanol at room temperature leads to the 1,4-diazepine derivatives of type 9 (Scheme 3). The structure of 6, 6-diethyl-3-dimethylamino-2,2-dimethyl-1,5,6, 7-tetrahydro-2H- [1,4] diazepin-5, 7-dione ( 9a ) has been proved by single crystal X-ray analysis (Chapter 4). Reduction of the 7-membered heterocycle 9a with sodium borohydride yields the perhydro-[1,4]diazepin-5, 7-dione 10 , while 9a in ethanol at 60° undergoes a ring contraction to the 4 H-imidazole derivative 11a (Scheme 4): Mechanisms of these two reactions are discussed in comparison with previously reported reactions (Chapter 5).     

Asymmetric Synthesis of the Alkaloids mayfoline and N(1)-acetyl-N(1)-deoxymayfoline

The total syntheses of the spermidine alkaloids (?)-mayfoline ( 11 ) and (+)-N(1)-acetyl-N(1)-deoxymayfoline ( 12 ) are described. These macrocyclic lactams belong to the most interesting conjugates of the polyamine derivatives very commonly found in nature. The enantioselective syntheses were achieved through resolution of the methyl 3-amino-3-phenylpropanoate ( 2 ) by recrystallization of its (+)-L -tartrate salt. Construction of the 13-membered ring ensued through condensation, reductive ring expansion (internal bond cleavage), and finally a transamidation reaction involving a second ring expansion.     

Reaction of Optically Active Oxiranes with Thiofenchone and 1‐Methylpyrrolidine‐2‐thione: Formation of 1,3‐Oxathiolanes and Thiiranes

The SnCl₄‐catalyzed reaction of (?)‐thiofenchone (=1,3,3‐trimethylbicyclo[2.2.1]heptane‐2‐thione; 10 ) with (R)‐2‐phenyloxirane ((R)‐ 11 ) in anhydrous CH₂Cl₂ at ?60° led to two spirocyclic, stereoisomeric 4‐phenyl‐1,3‐oxathiolanes 12 and 13 via a regioselective ring enlargement, in accordance with previously reported reactions of oxiranes with thioketones (Scheme 3). The structure and configuration of the major isomer 12 were determined by X‐ray crystallography. On the other hand, the reaction of 1‐methylpyrrolidine‐2‐thione ( 14a ) with (R)‐ 11 yielded stereoselectively (S)‐2‐phenylthiirane ((S)‐ 15 ) in 56% yield and 87–93% ee, together with 1‐methylpyrrolidin‐2‐one ( 14b ). This transformation occurs via an S_N2‐type attack of the S‐atom at C(2) of the aryl‐substituted oxirane and, therefore, with inversion of the configuration (Scheme 4). The analogous reaction of 14a with (R)‐2‐{[(triphenylmethyl)oxy]methyl}oxirane ((R)‐ 16b ) led to the corresponding (R)‐configured thiirane (R)‐ 17b (Scheme 5); its structure and configuration were also determined by X‐ray crystallography. A mechanism via initial ring opening by attack at C(3) of the alkyl‐substituted oxirane, with retention of the configuration, and subsequent decomposition of the formed 1,3‐oxathiolane with inversion of the configuration is proposed (Scheme 5).