1,5‐Dipolar Electrocyclizations of Thiocarbonyl Ylides Bearing CN Groups: Reactions of N‐[(Dimethylamino)methylene]thiobenzamide and 2‐(Dimethylhydrazono)‐1‐phenylethane‐1‐thione with Diazo Compounds

The reactions of thiobenzamide 8 with diazo compounds proceeded via reactive thiocarbonyl ylides as intermediates, which underwent either a 1,5‐dipolar electrocyclization to give the corresponding five membered heterocycles, i.e., 4‐amino‐4,5‐dihydro‐1,3‐thiazole derivatives (i.e., 10a, 10b, 10c , cis‐ 10d , and trans‐ 10d ) or a 1,3‐dipolar electrocyclization to give the corresponding thiiranes as intermediates, which underwent a S_Ni′‐like ring opening and subsequent 5‐exo‐trig cyclization to yield the isomeric 2‐amino‐2,5‐dihydro‐1,3‐thiazole derivatives (i.e., 11a, 11b, 11c , cis‐ 11d , and trans‐ 11d ). In general, isomer 10 was formed in higher yield than isomer 11 . In the case of the reaction of 8 with diazo(phenyl)methane ( 3d ), a mixture of two pairs of diastereoisomers was formed, of which two, namely cis‐ 10d and trans‐ 10d , could be isolated as pure compounds. The isomers cis‐ 11d and trans‐ 11d remained as a mixture. In the reactions of the thioxohydrazone 9 with diazo compounds 3b and 3d , the main products were the alkenes 18 and 23 , respectively. Their formation was rationalized by a 1,3‐dipolar electrocyclization of the corresponding thiocarbonyl ylide and subsequent desulfurization of the intermediate thiiran. As minor products, 2,5‐dihydro‐1,3‐thiazol‐5‐amines 21 and 24 were obtained, which have been formed by 1,5‐dipolar electrocyclization of the thiocarbonyl ylide, followed by a 1,3‐shift of the dimethylamino group.     

Synthesis of Multifunctionalized 1,2,3,4‐Tetrahydropyridines, 2,3‐Dihydropyridin‐4(1H)‐ones,and Pyridines from Tandem Reactions Initiated by [5+1] Cycloaddition of N‐Formylmethyl‐Substituted Enamides to Isocyanides: Mechanistic Insight and Synthetic Application

Tandem reactions for the efficient synthesis of multifunctionalized 1,2,3,4‐tetrahydropyridines, 2,3‐dihydropyridin‐4(1H)‐ones, and pyridine derivatives have been developed and reaction mechanisms have been investigated. Synthetic cascades are initiated by the Zn(OTf)₂‐mediated [5+1] cycloaddition of N‐formylmethyl‐substituted tertiary enamides to isocyanides, thus leading to the versatile heterocyclic enamino imine intermediates. Interception of the intermediates by diastereoselective reduction of imine functionality with Me₄NBH(OAc)₃ afforded 1,6‐disubstituted trans‐3‐hydroxy‐4‐arylamino‐ or ‐alkylamino‐1,2,3,4‐tetrahydropyridines, whereas acylation of the imino group followed by acidic hydrolysis produced 1,6‐disubstituted 3‐acyloxy‐2,3‐dihydropyridin‐4(1H)‐ones. Aerobic oxidation led to the aromatization followed by intermolecular acyl‐group transfer from the pyridinium nitrogen to the 3‐hydroxy moiety, thereby yielding substituted 3‐acyloxy‐4‐aminopyridines. Synthetic potentials of the resulting products have been demonstrated by expedient and highly stereoselective synthesis of cis,cis‐4,5‐dihydroxy‐2‐phenylpiperidine and trans,trans‐4‐amino‐5‐hydroxy‐2‐phenylpiperidine compounds, which are important in medicinal chemistry, through simple and practical reduction reactions.     

Enzyme‐Mediated Preparation of (+)‐ and (−)‐β‐Irone and (+)‐ and (−)‐cis‐γ‐Irone from Irone alpha®

The (−)‐ and (+)‐β‐irones ((−)‐ and (+)‐ 2 , resp.), contaminated with ca. 7 – 9% of the (+)‐ and (−)‐trans‐α‐isomer, respectively, were obtained from racemic α‐irone via the 2,6‐trans‐epoxide (±)‐ 4 (Scheme 2). Relevant steps in the sequence were the LiAlH₄ reduction of the latter, to provide the diastereoisomeric‐4,5‐dihydro‐5‐hydroxy‐trans‐α‐irols (±)‐ 6 and (±)‐ 7 , resolved into the enantiomers by lipase‐PS‐mediated acetylation with vinyl acetate. The enantiomerically pure allylic acetate esters (+)‐ and (−)‐ 8 and (+)‐ and (−)‐ 9 , upon treatment with POCl₃/pyridine, were converted to the β‐irol acetate derivatives (+)‐ and (−)‐ 10 , and (+)‐ and (−)‐ 11 , respectively, eventually providing the desired ketones (+)‐ and (−)‐ 2 by base hydrolysis and MnO₂ oxidation. The 2,6‐cis‐epoxide (±)‐ 5 provided the 4,5‐dihydro‐4‐hydroxy‐cis‐α‐irols (±)‐ 13 and (±)‐ 14 in a 3 : 1 mixture with the isomeric 5‐hydroxy derivatives (±)‐ 15 and (±)‐ 16 on hydride treatment (Scheme 1). The POCl₃/pyridine treatment of the enantiomerically pure allylic acetate esters, obtained by enzymic resolution of (±)‐ 13 and (±)‐ 14 , provided enantiomerically pure cis‐α‐irol acetate esters, from which ketones (+)‐ and (−)‐ 22 were prepared (Scheme 4). The same materials were obtained from the (9S) alcohols (+)‐ 13 and (−)‐ 14 , treated first with MnO₂, then with POCl₃/pyridine (Scheme 4). Conversely, the dehydration with POCl₃/pyridine of the enantiomerically pure 2,6‐cis‐5‐hydroxy derivatives obtained from (±)‐ 15 and (±)‐ 16 gave rise to a mixture in which the γ‐irol acetates 25a and 25b and 26a and 26b prevailed over the α‐ and β‐isomers (Scheme 5). The (+)‐ and (−)‐cis‐γ‐irones ((+)‐ and (−)‐ 3 , resp.) were obtained from the latter mixture by a sequence involving as the key step the photochemical isomerization of the α‐double bond to the γ‐double bond. External panel olfactory evaluation assigned to (+)‐β‐irone ((+)‐ 2 ) and to (−)‐cis‐γ‐irone ((−)‐ 3 ) the strongest character and the possibility to be used as dry‐down note.     

Fused‐ring nitrogen and sulfur heterocycles by a tandem SN2‐michael addition reaction

A tandem S_N2‐Michael addition reaction has been developed for the synthesis of cis‐ and trans‐fused nitrogen and sulfur heterocycles from the cis and trans isomers of ethyl (±)‐(2E)‐3‐[2‐(iodomethyl)cyclo‐hexyl]‐2‐propenoate. Octahydro‐1H‐isoindole‐1‐acetic acid and octahydrobenzo[c]thiophene‐1‐acetic acid derivatives have been prepared and their stereochemistries elucidated using NMR and X‐ray crystallo‐graphic methods. Cyclization substrates for both the cis‐ and the trans‐fused rings are readily available in four steps from known compounds. Yields for the cyclization range from 80‐85% and stereochemical selec‐tivities with respect to the side chain vary from 12.5‐16:1 for the cis‐fused structures to 6‐7.5:1 for the trans‐fused structures. Steric interactions in the transition states for ring closure are proposed to rationalize the observed preferences.     

Novel Synthesis of 2‐Aryl‐4,5,6,7‐tetrahydro‐1,2‐benzisothiazol‐3(2H)‐ones and Their S‐Oxides

2‐Aryl‐4,5,6,7‐tetrahydro‐1,2‐benzisothiazol‐3(2H)‐ones 1a – e were synthesized by cyclocondensation of 2‐(thiocyanato)cyclohexene‐1‐carboxanilides 9 as a convenient new method. Their S‐oxides 10 were prepared by two routes, either by oxidation of 1 or dehydration of rac‐cis‐3‐hydroperoxysultims 11 . Furthermore, compounds 1 have been identified by HPLC? API‐MS‐MS as intermediates in the oxidation process of the salts 6 . The hydroperoxides 12b and rac‐trans‐ 11b have been unambiguously detected by HPLC? MS investigations and in the reaction of rac‐cis‐ 13b with H₂O₂ to the hydroperoxides rac‐trans‐ 11b and rac‐cis‐ 11b .     

1,3‐Thiazolidine‐dicarboxylates from Thioketones and Thermally Generated Azomethine Ylides

The reaction of 9H‐fluorene‐9‐thione ( 1 ) with the cis‐ and trans‐isomers of dimethyl 1‐(4‐methoxyphenyl)aziridine‐2,3‐dicarboxylate (cis‐ and trans‐ 2 , resp.) in xylene at 110° yielded exclusively the spirocyclic cycloadduct with trans‐ and cis‐configurations, respectively (trans‐ and cis‐ 3 , resp.; Scheme 1). Analogously, less‐reactive thioketones, e.g., thiobenzophenone ( 5 ), and cis‐ 2 reacted stereoselectively to give the corresponding trans‐1,3‐thiazolidine‐2,4‐dicarboxylate (e.g., trans‐ 8 ; Scheme 2). On the other hand, the reaction of 5 and trans‐ 2 proceeded in a nonstereoselective course to provide a mixture of trans‐ and cis‐substituted cycloadducts. This result can be explained by an isomerization of the intermediate azomethine ylide. Dimethyl 1,3‐thiazolidine‐2,2‐dicarboxylates 14 and 15 were formed in the thermal reaction of dimethyl aziridine‐2,2‐dicarboxylate 11 with aromatic thioketones (Scheme 3). On treatment of 14 and 15 with Raney‐Ni in refluxing EtOH, a desulfurization and ring‐contraction led to the formation of azetidine‐2,2‐dicarboxylates 17 and 18 , respectively (Scheme 4).     

Analogues of α‐Campholenal (= (1R)‐2,2,3‐Trimethylcyclopent‐3‐ene‐1‐acetaldehyde) as Building Blocks for (+)‐β‐Necrodol (= (1S,3S)‐2,2,3‐Trimethyl‐4‐methylenecyclopentanemethanol) and Sandalwood‐like Alcohols

To complete our panorama in structure–activity relationships (SARs) of sandalwood‐like alcohols derived from analogues of α‐campholenal (= (1R)‐2,2,3‐trimethylcyclopent‐3‐ene‐1‐acetaldehyde), we isomerized the epoxy‐isopropyl‐apopinene (?)‐ 2d to the corresponding unreported α‐campholenal analogue (+)‐ 4d (Scheme 1). Derived from the known 3‐demethyl‐α‐campholenal (+)‐ 4a , we prepared the saturated analogue (+)‐ 5a by hydrogenation, while the heterocyclic aldehyde (+)‐ 5b was obtained via a Bayer‐Villiger reaction from the known methyl ketone (+)‐ 6 . Oxidative hydroboration of the known α‐campholenal acetal (?)‐ 8b allowed, after subsequent oxidation of alcohol (+)‐ 9b to ketone (+)‐ 10 , and appropriate alkyl Grignard reaction, access to the 3,4‐disubstituted analogues (+)‐ 4f,g following dehydration and deprotection. (Scheme 2). Epoxidation of either (+)‐ 4b or its methyl ketone (+)‐ 4h , afforded stereoselectively the trans‐epoxy derivatives 11a,b , while the minor cis‐stereoisomer (+)‐ 12a was isolated by chromatography (trans/cis of the epoxy moiety relative to the C₂ or C₃ side chain). Alternatively, the corresponding trans‐epoxy alcohol or acetate 13a,b was obtained either by reduction/esterification from trans‐epoxy aldehyde (+)‐ 11a or by stereoselective epoxidation of the α‐campholenol (+)‐ 15a or of its acetate (?)‐ 15b , respectively. Their cis‐analogues were prepared starting from (+)‐ 12a . Either (+)‐ 4h or (?)‐ 11b , was submitted to a Bayer‐Villiger oxidation to afford acetate (?)‐ 16a . Since isomerizations of (?)‐ 16 lead preferentially to β‐campholene isomers, we followed a known procedure for the isomerization of (?)‐epoxyverbenone (?)‐ 2e to the norcampholenal analogue (+)‐ 19a . Reduction and subsequent protection afforded the silyl ether (?)‐ 19c , which was stereoselectively hydroborated under oxidative condition to afford the secondary alcohol (+)‐ 20c . Further oxidation and epimerization furnished the trans‐ketone (?)‐ 17a , a known intermediate of either (+)‐β‐necrodol (= (+)‐(1S,3S)‐2,2,3‐trimethyl‐4‐methylenecyclopentanemethanol; 17c ) or (+)‐(Z)‐lancifolol (= (1S,3R,4Z)‐2,2,3‐trimethyl‐4‐(4‐methylpent‐3‐enylidene)cyclopentanemethanol). Finally, hydrogenation of (+)‐ 4b gave the saturated cis‐aldehyde (+)‐ 21 , readily reduced to its corresponding alcohol (+)‐ 22a . Similarly, hydrogenation of β‐campholenol (= 2,3,3‐trimethylcyclopent‐1‐ene‐1‐ethanol) gave access via the cis‐alcohol rac‐ 23a , to the cis‐aldehyde rac‐ 24 .     

Synthesis and structure of cycloalkane‐ and norbornane‐condensed 6‐aryl‐1,2,4,5‐tetrahydropyridazinones

The C=N double bond of certain cis‐ or trans‐cycloalkane and diexo‐ or diendo‐norbornane‐condensed pyridazinones was reduced with NaBH₃CN. The cis‐ or trans nature of the starting cycloalkane derivatives was always retained in the saturated products, with a high degree of diastereoselectivity: the hydrogen on the new stereocenter and the annelational hydrogen next to the carbonyl always exhibited the same steric orientation. The stereostructures were determined by means of nmr measurements and confirmed by molecular modelling.     

Unexpected Formation of Dimethylthioketene Cycloadducts in the Reaction of 1,3‐Diphenylaziridine‐2,2‐dicarboxylate with Cyclobutanethione Derivatives

The reaction of 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone ( 1 ) with cis‐1‐alkyl‐2,3‐diphenylaziridines 5 in boiling toluene yielded the expected trans‐configured spirocyclic 1,3‐thiazolidines 6 (Scheme 1). Analogously, dimethyl trans‐1‐(4‐methoxyphenyl)aziridine‐2,3‐dicarboxylate (trans‐ 7 ) reacted with 1 and the corresponding dithione 2 , respectively, to give spirocyclic 1,3‐thiazolidine‐2,4‐dicarboxylates 8 (Scheme 2). However, mixtures of cis‐ and trans‐derivatives were obtained in these cases. Unexpectedly, the reaction of 1 with dimethyl 1,3‐diphenylaziridine‐2,2‐dicarboxylate ( 11 ) led to a mixture of the cycloadduct 13 and 5‐(isopropylidene)‐4‐phenyl‐1,3‐thiazolidine‐2,2‐dicarboxylate ( 14 ), a formal cycloadduct of azomethine ylide 12 with dimethylthioketene (Scheme 3). The regioisomeric adduct 16 was obtained from the reaction between 2 and 11 . The structures of 6b , cis‐ 8a , cis‐ 8b, 10 , and 16 have been established by X‐ray crystallography.     

(E)‐,(Z)‐Parallel Preparative Methods for Stereodefined β,β‐Diaryl‐ and α,β‐Diaryl‐α,β‐unsaturated Esters: Application to the Stereocomplementary Concise Synthesis of Zimelidine

Parallel and practical methods for the preparation of both (E)‐ and (Z)‐β‐aryl¹‐β‐aryl²‐α,β‐unsaturated esters 1 and (E)‐ and (Z)‐α‐aryl¹‐β‐aryl²‐α,β‐unsaturated esters 2 are described. These methods involve accessible, robust, stereocomplementary N‐methylimidazole (NMI)‐mediated enol tosylations (14 examples, 70–99 % yield), as well as stereoretentive Suzuki–Miyaura cross‐couplings (36 examples, 64–99 % yield). The highlighted feature of the present protocol is the use of parallel and stereocomplementary approaches to obtain highly (E)‐ and (Z)‐pure products 1 and 2 by utilizing sequential enol tosylations and cross‐coupling reactions. An expeditious and parallel synthesis of (E)‐ and (Z)‐zimelidine ( 3 ), which is a highly representative selective serotonin reuptake inhibitor (SSRI), was performed by utilizing the present methods.     

Asymmetric Synthesis of the cis‐ and trans‐3,4‐Dihydro‐2,4,8‐trihydroxynaphthalen‐1(2H)‐ones

A short and efficient protocol for the asymmetric synthesis of cis‐ and trans‐3,4‐dihydro‐2,4,8‐trihydroxynaphthalen‐1(2H)‐one ( 1 and 2 , resp.) is described, with a phthalide annulation as the key step. Introduction of a OH substituent at position 2 was performed by Sharpless dihydroxylation of a silyl enol ether or by means of an N‐sulfonyloxaziridine. The absolute configuration of each isomer was determined via Mosher‐ester derivatives. By comparison with previously recorded CD spectra of our natural sample, we established that the natural trans‐ and cis‐isomers from Ceratocystis fimbriata sp. platani were the (?)‐(2S,4S)‐isomer (?)‐ 2 and the (+)‐(2S,4R)‐isomer (+)‐ 1 , respectively.     

Reactions of Sterically Hindered ‘Thiocarbonyl Ylides' with 1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile: Isolation of a Cyclic Seven‐Membered Ketene Imine

When ‘thiocarbonyl ylide' 1A (=(2,2,4,4‐tetramethyl‐3‐oxocyclobutylidenesulfonio)methanide) is generated from the dihydrothiadiazole 5A by N₂ extrusion at 40° in the presence of 2,3‐bis(trifluoromethyl)fumaronitrile ((E)‐ 10 ), a cyclic seven‐membered ketene imine 11 and trans‐thiolane 12 are formed (81 : 19). The reaction of 1A with (Z)‐ 10 furnishes 11, 12 , and cis‐thiolane 25 in the ratio of 82 : 12 : 6. The strained ketene imine 11 is crystalline and storable as a consequence of the stabilizing ‘perfluoroalkyl effect'. The ketene imine group is stereogenic; 11 has a transoid structure with respect to the CF₃ groups, and there is no evidence for the cisoid diastereoisomer. Ketene imine 11 adds H₂O, MeOH, and PhNH₂. In solution at 60°, 11 undergoes an irreversible ring contraction, furnishing the thiolanes 12 / 25 98 : 2. The rate constant of this first‐order rearrangement increases 850‐fold, as the solvent polarity rises from cyclohexane to CD₃CN, in accordance with a zwitterionic intermediate. It is the same intermediate that is initially formed from 1A and 10 , and its intramolecular N‐ and C‐alkylation give rise to 11 and 12 + 25 , respectively. In contrast to 1A , thiocarbonyl ylide 27 , which harbors the sterically less‐demanding adamantylidene group, reacts with (E)‐ 10 to give trans‐thiolane 29 , but no ketene imine. The precursor 26 catalyzes the (Z)/(E) isomerization of 10 ((E)/(Z) ca. 95 : 5 at equilibrium), thus obviating conclusions on steric course and mechanism of this cycloaddition.     

trans‐Selective Insertional Dihydroboration of a cis‐Diborene: Synthesis of Linear sp3‐sp2‐sp3‐Triboranes and Subsequent Cationization

The reaction of aryl‐ and amino(dihydro)boranes with dibora[2]ferrocenophane 1 leads to the formation 1,3‐trans‐dihydrotriboranes by formal hydrogenation and insertion of a borylene unit into the B=B bond. The aryltriborane derivatives undergo reversible photoisomerization to the cis‐1,2‐μ‐H‐3‐hydrotriboranes, while hydride abstraction affords cationic triboranes, which represent the first doubly base‐stabilized B₃H₄⁺ analogues.     

Synthesis and transformations of stereoisomeric ethyl 2‐isothiocyanato‐1‐cyclopentanecarboxylatesm

Ethyl vis‐ and trans‐2‐isothiocyanato‐1‐cyclopentanecarboxylates 2 and 7 were prepared by the reaction of the corresponding alicyclic ethyl 2‐amino‐1‐carboxylates and thiophosgene. The cis‐isothiocyanato compound 2 underwent ring closure with amines in one or two steps, resulting in 3‐substituted‐cis‐2‐thioxocyclopenta[d]pyrimidin‐4‐ones 3a‐g. The trans isomer 7 failed to cyclize, but gave carboxamide 8a,b or thiourea ester derivatives 9a,b.     

Photocyclization reactions. Part 8. Synthesis of 2‐quinolone,quinoline and coumarin derivatives using trans‐cis isomerization by photoreaction

2‐Quinolone 2 , quinoline 3 , coumarin (2H‐1‐benzopyran‐ 2 ‐one) 5 , and 2H‐1‐benzopyran hemiacetal 6 were synthesized by photocyclization reaction of traans‐o‐aminocinnamoyl derivatives trans‐ 1 and trans‐o‐hydroxycinnamoyl derivatives trans‐ 4 . The reaction proceeds through trans‐cis isomerization followed by intramolecular cyclization.     

Synthesis and 1H and 13C NMR structural analysis of cis‐ and trans‐2‐imino‐1,3‐ and ‐3,1‐perhydrobenzoxazines and their 3‐ and 1‐N‐methyl derivatives

cis‐ and trans‐2‐imino‐1,3‐ and ‐3,1‐perhydrobenzoxazines and the N‐methyl derivatives of the latter were synthesized from the corresponding cyclic 1,3‐amino alcohol with cyanogen bromide. The configurations of the studied compounds were confirmed by ¹H and ¹³C NMR spectra. All trans‐fused compounds exist in biased chair–chair conformations as expected, whereas the cis‐fused 1,3‐benzoxazines attain exclusively the O‐in conformations. The cis‐fused 3,1‐benzoxazines, especially the 1‐methyl‐substituted derivatives, tend to favor the N‐out form, obviously owing to the favorable axial orientation of this N‐methyl. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of 6‐Aminoindolo[2,1‐a]isoquinoline‐5‐carbonitriles by the Cu‐Catalyzed Reaction of 2‐(2‐Bromophenyl)‐1H‐indoles with CH2(CN)2

A series of 6‐aminoindolo[2,1‐a]isoquinoline‐5‐carbonitriles 4 have been prepared by treatment of 2‐(2‐bromophenyl)‐1H‐indoles 1 , available from 1‐(2‐bromophenyl)ethanones or 1‐(2‐bromophenyl)propan‐1‐ones by using Fischer indole synthesis, with propanedinitrile in the presence of a catalytic amount of CuBr and an excess of K₂CO₃ in DMSO at 100°.     

Synthesis of 5‐[2‐(guanin‐9‐yl)‐ and 5‐[2‐(2‐aminopurin‐9‐yl)ethyl]‐2‐D‐ribo‐(1,2′,3′,4′‐tetrahydroxybutyl)‐1,3‐dioxane

Stereoselective synthesis of 5‐[2‐(guanin‐9‐yl)‐ and 5‐[2‐(2‐aminopurin‐9‐yl)ethyl]‐2‐D‐ribo‐(1′,2′,3′,4′‐tetrahydroxybutyl)‐1,3‐dioxane, 2‐5, as potential prodrugs of penciclovir, has been accomplished in six steps from readily available 2,3,4,5‐tetra‐O‐acetyl‐aldehydo‐D‐ribose ( 6 ) and the 1,3‐diol 7 . It has been demonstrated that the use of boron trifluoride diethyl etherate (BF₃·Et₂O) in dichloromethane along with excess anhydrous copper(II) sulfate was crucial for the efficient formation of cyclic acetal 8 . In addition, the chromatographic separation of cis and trans isomers of the cyclic acetal at the bromide stage 10 was feasible, which was requisite for the successful stereoselective synthesis of the ribosyl derivatives 2–5 .     

Hydrogen‐bonding patterns in enaminones: (2Z)‐1‐(4‐bromophenyl)‐2‐(pyrrolidin‐2‐ylidene)ethanone and its piperidin‐2‐ylidene and azepan‐2‐ylidene analogues

The title compounds, namely (2Z)‐1‐(4‐bromophenyl)‐2‐(pyrrolidin‐2‐ylidene)ethanone, C₁₂H₁₂BrNO, (I), (2Z)‐1‐(4‐bromophenyl)‐2‐(piperidin‐2‐ylidene)ethanone, C₁₃H₁₄BrNO, (II), and (2Z)‐2‐(azepan‐2‐ylidene)‐1‐(4‐bromophenyl)ethanone, C₁₄H₁₆BrNO, (III), are characterized by bifurcated intra‐ and intermolecular hydrogen bonding between the secondary amine and carbonyl groups. The former establishes a six‐membered hydrogen‐bonded ring, while the latter leads to the formation of centrosymmetric dimers. Weak C—H...Br interactions link the individual molecules into chains that run along the [011], [101] and [101] directions in (I)–(III), respectively. Additional weak Br...O, C—H...π and C—H...O interactions further stabilize the crystal structures.     

Thermal [2+3]‐Cycloadditions of trans‐1‐Methyl‐2,3‐diphenylaziridine with CS and CC Dipolarophiles: An Unexpected Course with Dimethyl Dicyanofumarate

The thermal reaction of trans‐1‐methyl‐2,3‐diphenylaziridine (trans‐ 1a ) with aromatic and cycloaliphatic thioketones 2 in boiling toluene yielded the corresponding cis‐2,4‐diphenyl‐1,3‐thiazolidines cis‐ 4 via conrotatory ring opening of trans‐ 1a and a concerted [2+3]‐cycloaddition of the intermediate (E,E)‐configured azomethine ylide 3a (Scheme 1). The analogous reaction of cis‐ 1a with dimethyl acetylenedicarboxylate ( 5 ) gave dimethyl trans‐2,5‐dihydro‐1‐methyl‐2,5‐diphenylpyrrole‐3,4‐dicarboxylate (trans‐ 6 ) in accord with orbital‐symmetry‐controlled reactions (Scheme 2). On the other hand, the reactions of cis‐ 1a and trans‐ 1a with dimethyl dicyanofumarate ( 7a ), as well as that of cis‐ 1a and dimethyl dicyanomaleate ( 7b ), led to mixtures of the same two stereoisomeric dimethyl 3,4‐dicyano‐1‐methyl‐2,5‐diphenylpyrrolidine‐3,4‐dicarboxylates 8a and 8b (Scheme 3). This result has to be explained via a stepwise reaction mechanism, in which the intermediate zwitterions 11a and 11b equilibrate (Scheme 6). In contrast, cis‐1,2,3‐triphenylaziridine (cis‐ 1b ) and 7a gave only one stereoisomeric pyrrolidine‐3,4‐dicarboxylate 10 , with the configuration expected on the basis of orbital‐symmetry control, i.e., via concerted reaction steps (Scheme 10). The configuration of 8a and 10 , as well as that of a derivative of 8b , were established by X‐ray crystallography.