1,3-Dipolare Cycloadditionen eines Carbonyl-ylids mit 1,3-Thiazol-5(4H)-thionen und Thioketonen

1,3-Dipolar Cycloadditions of a Carhonyl-ylide with 1,3-Thiazole-5(4H)-thiones and Thioketones Inp-xylene at 150°, 3-phenyloxirane-2,2-dicarbonitrile ( 4b ) and 2-phenyl-3-thia-1-azaspiro[4.4]non-1-ene-4-thione ( 1a ) gave the three 1:1 adduets trans- 3a , cis- 3a , and 13a in 61, 21, and 3% yield, respectively (Scheme 3). The stereoisomers trans- 3a and cis- 3a are the products of a regioselective 1,3-dipolar cycloaddition of carbonylylide 2b , generated thermally by an electrocyclic ring opening of 4b (Scheme 6), and the C?S group of 1a . Surprisingly, 13a proved not to be a regioisomeric cycloadduct of 1a and 2b , but an isomer formed via cleavage of the O? C(3) bond of the oxirane 4b . A reaction mechanism rationalizing the formation of 13a is proposed in Scheme 6. Analogous results were obtained from the reaction of 4b and 4,4-dimethyl-2-phenyl-1,3-thiazole-5 (4H)-thione ( 1b , Scheme 3). The thermolysis of 4b in p-xylene at 130° in the presence of adamantine–thione ( 10 ) led to two isomeric 1:1 adducts 15 and 16 in a ratio of ca. 2:1, however, in low yield (Scheme 4). Most likely the products are again formed viathe two competing reaction mechanisms depicted in Scheme 6. The analogous reactions of 4b with 2,2,4,4-tetramethylcyclobutane-1,3-thione ( 11 ) and 9H-xanthene-9-thione ( 12 ) yielded a single 1:1 adduct in each case (Schemes). In the former case, spirocyclic 1,3-oxathiolane 17 , the product of the 1,3-dipolar cycloaddition with 2a corresponding to 3a , was isolated in only 11 % yield. It is remarkable that no 2:1 adduct was formed even in the presence of an excess of 4b. In contrast, 4b and 12 reacted smoothly to give 18 in 81 % yield; no cycloadduct of the carbonylylide 2a could be detected. The structures of cis- 3a , 13a , 15 , and 18 , as well as the structure of 14 , which is a derivative of trans- 3a , have been established by X-ray crystallography (Figs. 1–3, Table).     

Asymmetric Synthesis of 3-Hydroxyprolines by Photocyclization of C(1′)-Substituted N-(2-Benzoylethyl)glycine Esters

The chiral N-(2-benzoylethyl)-N-tosylglycine esters 5a–h and the α-amino-γ-keto ester 6 were prepared from γ-(tosylamino) alcohols 7a–h . Irradiation of compounds 5a–c, e gave cis-3-hydroxyproline esters 20–23 (Scheme 6), partly with complete asymmetric induction by the C(1′)-substituent, whereas 6 gave enantiomerically pure 4-hydroxy-4-phenyl-L -proline esters 24 in good yield but low de (Scheme 6). The de of the photocyclization depended on the nature and/or size of the C(1′)-substituents. Irradiation of ketones 5d and 5f , bearing H-atoms at C(γ) with respect to the keto function, gave cyclobutanols (Scheme 9) in low yields besides the preferred Norrish-type-II cleavage product. Cyclopentanol 25 was a by-product of the photocyclization of 5c as a result of H? C(δ) abstraction from the t-Bu group. The structure of products 20, 22 , and 24a, b was established by NMR or X-ray analyses.     

A Flexible Stereoselective Synthesis of the Spirosesquiterpenes (±)-β-Acorenol, (±)-β-Acoradiene, (±)-Acorenone-B and (±)-Acorenone via an Intramolecular Ene-Reaction

The racemic spirosesquiterpenes β-acorenol ( 1 ), β-acoradiene ( 2 ), acorenone-B ( 3 ) and acorenone ( 4 ) (Scheme 2) have been synthesized in a simple, flexible and highly stereoselective manner from the ester 5 . The key step (Schemes 3 and 4), an intramolecular thermal ene reaction of the 1,6-diene 6 , proceeded with 100% endo-selectivity to give the separable and interconvertible epimers 7a and 7b . Transformation of the ‘trans’-ester 7a to (±)- 1 and (±)- 2 via the enone 9 (Scheme 5) involved either a thermal retro-ene reaction 10 → 12 or, alternatively, an acid-catalysed elimination 11 → 13 + 14 followed by conversion to the 2-propanols 16 and 17 and their reduction with sodium in ammonia into 1 which was then dehydrated to 2 . The conversion of the ‘cis’-ester 7b to either 3 (Scheme 6) or 4 (Scheme 7) was accomplished by transforming firstly the carbethoxy group to an isopropyl group via 7b → 18 → 19 → 20 , oxidation of 20 to 21 , then alkylative 1,2-enone transposition 21 → 22 → 23 → 3 . By regioselective hydroboration and oxidation, the same precursor 20 gave a single ketone 25 which was subjected to the regioselective sulfenylation-alkylation-desulfenylation sequence 25 → 26 → 27 → 4 .     

Stereospezifische Fragmentierungen in den Massenspektren von Cyclohexandiaminen und Bis(aminomethyl)cyclohexanen. 33. Mitteilung über massenspektrometrische Untersuchungen,,

Stereospecific Fragmentations in the Mass Spectra of Cyclohexanediamines and Bis(aminomethyl)cyclohexanes The mass spectral behaviour, especially loss of NH₃, of the six isomeric cyclohexanediamines 1--3 (cis and trans each, Scheme 1) as well as of the six isomeric bis(aminomethyl)cyclohexanes 4--6 (cis and trans each, Scheme 6) has been investigated. The cis- and trans-compounds of the 1,2-isomers 1 and 4 show very similar spectra, because of the ease of ring cleavage at C(1)–-C(2) and the similar geometrical relations in all ring conformations. The cis- and trans-compounds of both the 1,3- and 1,4-isomers 2, 3, 5 and 6 show striking differences in their mass spectra due to stereospecific elimination of NH₃ from the molecular ion.     

Insertion Reactions of [ReH(CO)5–n(PMe3)n] Complexes (n = 2–4) with aldehydes,CO2, and activated acetylenes

The complexes of the type [ReH(CO)_5–n(PMe₃)_n] (n = 4, 3) were reacted with aldehydes, CO₂, and RC?CCOOMe (R = H, Me) to establish a phosphine-substitutional effect on the reactivity of the Re–H bond. In the series 1–3 , benzaldehyde showed conversion with only 3 to afford a (benzyloxy)carbonyltetrakis(trimethylphosphine)rhenium complex 4 . Pyridine-2-carbaldehyde allowed reaction with all hydrides 1–3 . With 1 and 2 , the same dicarbonyl[(pyridin-2-yl)methoxy-O, N]bis(trimethylphosphine)rhenium 5b was formed with the intermediacy of a [(pyridin-2-yl)methoxy-O]-ligated species and extrusion of CO or PMe₃, respectively. The analogous conversion of 3 afforded the carbonyl[(pyridin-2-yl)methoxy-O,N]tris(trimethylphosphine)rhenium ( 1 ) 7b . While 1 did not react with CO₂, 2 and 3 yielded under relatively mild conditions the formato-ligated [Re(HCO₂)(CO)(L)(PMe₃)₃] species ( 8 (L = CO) and 9 (L = PMe₃)). Methyl propiolate and methyl butynoate were transformed, in the presence of 1 , to [Re{C(CO₂Me)?CHR}(CO)₃(PMe₃)₂] systems ( 10a (R = H), and 10b (R = Me)), with prevailing α-metallation and trans-insertion stereochemistry. Similarly, HC≡CCO₂Me afforded with 2 and 3 , the α-metallation products [Re{C(CO₂Me)?CH₂}(CO)(L)(PMe₃)₃] 11 (L = CO) and 12 (L = PMe₃). The methyl butyonate insertion into 2 resulted in formation of a mixture of the (Z)- and (E)-isomers of [Re{C(CO₂Me)?CHMe} (CO)₂(PMe₃)₃] ( 13a , b ). In the case of the conversion of 3 with MeC?CCO₂Me, a Re–H cis-addition product [Re{(E)-C(CO₂Me)?CHMe}(CO)(PMe₃)₄] ( 14 ) was selectively obtained. Complex 11 was characterized by an X-ray crystal-structure analysis.     

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.     

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.     

New Studies on [2+3] Cycloadditions of Thermally Generated N‐Isopropyl‐ and N‐(4‐Methoxyphenyl)‐Substituted Azomethine Ylides

The thermal reaction of 1‐substituted 2,3‐diphenylaziridines 2 with thiobenzophenone ( 6a ) and 9H‐fluorene‐9‐thione ( 6b ) led to the corresponding 1,3‐thiazolidines (Scheme 2). Whereas the cis‐disubstituted aziridines and 6a yielded only trans‐2,4,5,5‐tetraphenyl‐1,3‐thiazolidines of type 7 , the analogous reaction with 6b gave a mixture of trans‐ and cis‐2,4‐diphenyl‐1,3‐thiazolidines 7 and 8 . During chromatography on SiO₂, the trans‐configured spiro[9H‐fluorene‐9,5′‐[1,3]thiazolidines] 7c and 7d isomerized to the cis‐isomers. The substituent at N(1) of the aziridine influences the reaction rate significantly, i.e., the more sterically demanding the substituent the slower the reaction. The reaction of cis‐2,3‐diphenylaziridines 2 with dimethyl azodicarboxylate ( 9 ) and dimethyl acetylenedicarboxylate ( 11 ) gave the trans‐cycloadducts 10 and 12 , respectively (Schemes 3 and 4). In the latter case, a partial dehydrogenation led to the corresponding pyrroles. Two stereoisomeric cycloadducts, 15 and 16 , with a trans‐relationship of the Ph groups were obtained from the reaction with dimethyl fumarate ( 14 ; Scheme 5); with dimethyl maleate ( 17 ), the expected cycloadduct 18 together with the 2,3‐dihydropyrrole 19 was obtained (Scheme 6). The structures of the cycloadducts 7b, 8a, 15b , and 16b were established by X‐ray crystallography.     

Synthese und spektroskopische Charakterisierung einiger Pentacarbonylwolfram(0)‐Komplexe mit monound bicyclischen Phosphiran‐Liganden: Kristallstruktur von [{(Me3Si)2HCPC(H)H–C(H)Ph}W(CO)5]

Synthesis and Spectroscopic Characterisation of some Pentacarbonyltungsten(0) Complexes with Mono‐ and Bicyclic Phosphirane Ligands: Crystal Structure of [{(Me₃Si)₂HCPC(H)H–C(H)Ph}W(CO)₅] The tungsten(0) complex [{(Me₃Si)₂HCPC(Ph)=N}W(CO)₅] ( 1 ) reacts upon heating with alkene derivatives 2 , 6 , 8 , and 10 in toluene to form benzonitrile and the complexes [{(Me₃Si)₂HCPC(R¹,R²)–C(R³,R⁴}W(CO)₅] ( 4 , 7 a , b , 9 a , b , 11 a , b ) ( 4 (trans): R¹,R³ = Ph, R²,R⁴ = H, 7 a , b (cis, meso and rac): R¹,R³ = Ph, R²,R⁴ = H, 9 a , b (RR und SS): R¹ = Ph, R²,R³,R⁴ = H, 11 a , b : R¹=R³ = (CH₂)₄, R²,R⁴ = H). Spectroscopic and mass spectrometric data are discussed. The structure of the complex 9 a was determined by X‐ray single crystal structure analysis showing characteristic data for the phosphirane ring such as a narrow angle at phosphorus (49,2(2)°), different P–C distances (P–C(6) 182,1(5) and P–C(7) 185,2(4) pm) and 152,9(6) pm for the basal C–C bond.     

1H and 13C NMR studies of some germacrones and isogermacrones

The ¹H and ¹³C NMR spectra of the trans,trans-, cis,cis- and cis-C-3–C-4, trans-C-7–C-8-germacrones and of the cis-C-2–C-3, trans-C-7–C–8, trans-C-2–C-3, cis-C-7–C-8- and cis,cis-isogermacrones are analysed. The last two isogermacrones are new compounds. The C-2–C-3 double bond in the previously described isogermacrone is found to be of cis configuration, contrary to the hitherto accepted trans arrangement.     

1,3-Oxathiole and Thiirane Derivatives from the Reactions of Azibenzil and α-diazo amides with thiocarbonyl compounds

The reactions of α-diazo ketones 1a,b with 9H-fluorene-9-thione ( 2f ) in THF at room temperature yielded the symmetrical 1,3-dithiolanes 7a,b , whereas 1b and 2,2,4,4-tetramethylcyclobutane-1,3-dithione ( 2d ) in THF at 60° led to a mixture of two stereoisomeric 1,3-oxathiole derivatives cis- and trans- 9a (Scheme 2). With 2-diazo-1,2-diphenylethanone ( 1c ), thio ketones 2a–d as well as 1,3-thiazole-5(4H)-thione 2g reacted to give 1,3-oxathiole derivatives exclusively (Schemes 3 and 4). As the reactions with 1c were more sluggish than those with 1a,b , they were catalyzed either by the addition of LiClO₄ or by Rh₂(OAc)₄. In the case of 2d in THF/LiClO₄ at room temperature, a mixture of the monoadduct 4d and the stereoisomeric bis-adducts cis- and trans- 9b was formed. Monoadduct 4d could be transformed to cis- and trans- 9b by treatment with 1c in the presence of Rh₂(OAc)₄ (Scheme 4). Xanthione ( 2e ) and 1c in THF at room temperature reacted only when catalyzed with Rh₂(OAc)₄, and, in contrast to the previous reactions, the benzoyl-substituted thiirane derivative 5a was the sole product (Scheme 4). Both types of reaction were observed with α-diazo amides 1d,e (Schemes 5–7). It is worth mentioning that formation of 1,3-oxathiole or thiirane is not only dependent on the type of the carbonyl compound 2 but also on the α-diazo amide. In the case of 1d and thioxocyclobutanone 2c in THF at room temperature, the primary cycloadduct 12 was the main product. Heating the mixture to 60°, 1,3-oxathiole 10d as well as the spirocyclic thiirane-carboxamide 11b were formed. Thiirane-carboxamides 11d–g were desulfurized with (Me₂N)₃P in THF at 60°, yielding the corresponding acrylamide derivatives (Scheme 7). All reactions are rationalized by a mechanism via initial formation of acyl-substituted thiocarbonyl ylides which undergo either a 1,5-dipolar electrocyclization to give 1,3-oxathiole derivatives or a 1,3-dipolar electrocyclization to yield thiiranes. Only in the case of the most reactive 9H-fluorene-9-thione ( 2f ) is the thiocarbonyl ylide trapped by a second molecule of 2f to give 1,3-dithiolane derivatives by a 1,3-dipolar cycloaddition.     

Mono- and Dialkylation of Derivatives of (1R, 2S)-2-Hydroxycyclopentanecarboxylic Acid and -cyclohexanecarboxylic acid via bicyclic dioxanones: Selective generation of three contiguous stereogenic centers on a cyclohexane ring

Ethyl (1R, 2S)-2-hydroxycyclopentanecarboxylate and -cyclohexanecarboxylate ( 1a and 2a , respectively) obtained in 40 and 70% yield by reduction of 3-oxocyclopentanecarboxylate and cyclohexanecarboxylate, respectively (Scheme 2), with non-fermenting yeast, are converted to bicyclic dioxanone derivatives 3 and 4 with formaldehyde, isobutyraldehyde, and pivalaldehyde (Scheme 3). The Li-enolates of these dioxanones are alkylated (→ 5a – 5i , 5j , 6a – 6g ), hydroxyalkylated (→ 51, m, 6d, e ), acylated (→ 5k, 6c ) and phenylselenenylated (→ 7 – 9 ) with usually high yields and excellent diastereoselectivities (Scheme 3, Tables and 2). All the major isomers formed under kinetic control are shown to have cis-fused bicyclic structures. Oxidation of the seleno compounds 7–9 leads to α, β-unsaturated carbonyl derivatives 10 – 13 (Scheme 3) of which the products 12a – c with the C?C bond in the carbocyclic ring (exocyclic on the dioxanone ring) are most readily isolated (70–80% from the saturated precursors). Michael addition of Cu(I)-containing reagents to 12a – c and subsequent alkylations afford dioxanones 14a – i and 16a – d with trans-fused cyclohoxane ring (Scheme 4). All enolate alkylations are carried out in the presence of the cyclic urea DMPU as a cosolvent. The configuration of the products is established by NMR measurements and chemical correlation. Some of the products are converted to single isomers of monocyclic hydroxycyclopentane ( 17 – 19 ) and cyclohexane derivatives ( 20 – 23 ; Scheme 5). Possible uses of the described reactions for EPC synthesis are outlined. The observed steric course of the reactions is discussed and compared with that of analogous transformations of monocyclic and acyclic derivatives.     

Chiral Salan Aluminium Ethyl Complexes and Their Application in Lactide Polymerization

Synthetic routes to aluminium ethyl complexes supported by chiral tetradentate phenoxyamine (salan‐type) ligands [Al(OC₆H₂(R‐6‐R‐4)CH₂)₂{CH₃N(C₆H₁₀)NCH₃}‐C₂H₅] ( 4 , 7 : R=H; 5 , 8 : R=Cl; 6 , 9 : R=CH₃) are reported. Enantiomerically pure salan ligands 1–3 with (R,R) configurations at their cyclohexane rings afforded the complexes 4 , 5 , and 6 as mixtures of two diastereoisomers ( a and b ). Each diastereoisomer a was, as determined by X‐ray analysis, monomeric with a five‐coordinated aluminium central core in the solid state, adopting a cis‐(O,O) and cis‐(Me,Me) ligand geometry. From the results of variable‐temperature (VT) ¹H NMR in the temperature range of 220–335 K, ¹H–¹H NOESY at 220 K, and diffusion‐ordered spectroscopy (DOSY), it is concluded that each diastereoisomer b is also monomeric with a five‐coordinated aluminium central core. The geometry is intermediate between square pyramidal with a cis‐(O,O), trans‐(Me,Me) ligand disposition and trigonal bipyramidal with a trans‐(O,O) and trans‐(Me,Me) disposition. A slow exchange between these two geometries at 220 K was indicated by ¹H–¹H NOESY NMR. In the presence of propan‐2‐ol as an initiator, enantiomerically pure (R,R) complexes 4 – 6 and their racemic mixtures 7 – 9 were efficient catalysts in the ring‐opening polymerization of lactide (LA). Polylactide materials ranging from isotactically biased (P_m up to 0.66) to medium heterotactic (P_r up to 0.73) were obtained from rac‐lactide, and syndiotactically biased polylactide (P_r up to 0.70) from meso‐lactide. Kinetic studies revealed that the polymerization of (S,S)‐LA in the presence of 4 /propan‐2‐ol had a much higher polymerization rate than (R,R)‐LA polymerization (k_SS/k_RR=10.1).     

Hydroalumination and Hydrogallation Reactions with Tri(ethynyl)silanes – Generation of Compounds with up to Three Coordinatively Unsaturated Aluminium Atoms

Hydroalumination or hydrogallation of tri(ethynyl)silanes, RSi(C≡C‐Ar)₃ ( 1a , R = Ph, Ar = Ph; 1b , R = Me, Ar = Ph; 1c , R = Me, Ar = C₆H₄Me), with the element hydrides H‐EtBu₂ (E = Al, Ga) in stoichiometric ratios of 1:1 to 1:3 at ambient temperature yielded the addition products (PhC≡C)₂(R)Si[(tBu₂E)C=C(H)Ph] ( 2 , R = Ph, E = Ga; 3a , R = Me, E = Al; 3b , R = Me, E = Ga), (PhC≡C)(Me)Si[(tBu₂E)C=C(H)Ph]₂ ( 4a , E = Al, 4b , E = Ga) and (Me)Si[(tBu₂Al)C=C(H)Ar]₃ ( 5 , Ar = Ph; 6 , Ar = C₆H₄Me). Compounds 2 – 4 show a relatively close interaction between the coordinatively unsaturated aluminium or gallium atoms and one of the C_α(≡C) atoms of unreacted alkyne substituents [245 (E = Al) and 266 pm (E = Ga)] that stabilises the kinetically favoured cis addition products with E and hydrogen on the same side of the resulting C=C double bonds. In the absence of these stabilising effects the compounds were found to isomerise to the thermodynamically favoured trans isomers.     

Facile Preparation of (±)-12-Epiprostaglandins from 7-Oxabicyclo[2.2.1]hept-5-en-2-one via an all-cis-formyllactone related to Corey lactone

The bicyclic monoselenoacetal 7 , easily obtained from (±)-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 6 ) via a radical addition-acyl migration sequence, was converted to racemic 12-epiprostaglandins 3 and 4 . The key intermediate was the all-cis-formyllactone 2b related to Corey lactone (see 12 ; Scheme 1). The presence of a (tert-butyl)-dimethylsilyl protective group for the 11-OH substituent (prostaglandin numbering) was found to be crucial in avoidingβ -elimination and epimerization during the Wittig-Horner reaction (Scheme 2). Epimerization at C(12) at the formyllactone stage (see 2b ) was also possible and gave the known precursor 1b of naturally occurring prostaglandins and analogs.     

Reaktion von Phenyldiazomethan mit 1,3-Thiazol-5(4H)-thionen: Basenkatalysierte Ring-Öffnung des Primäradduktes

Reaction of Phenyldiazomethane with 1,3-Thiazole-5(4H)-thiones: Base-Catalyzed Ring Opening of the Primary Adduct Reaction of 1,3-thiazole-5(4H)-thiones 1 and phenyldiazomethane ( 2a ) in toluene at room temperature yields the thiiranes trans- and cis-1,4-dithia-6-azaspiro[2.4]hept-5-enes (trans- and cis- 4 ; Scheme 2). With Ph₃P in THF at 70°, these thiiranes are transformed stereospecifically into (E)- and (Z)-5-benzylidene-4,5-dihydro-1,3-thiazoles 5 , respectively. In the presence of DBU, 1 and 2a react to give 1,3,4-thiadiazole derivatives 6 or 7 via base-catalyzed ring opening of the primary cycloadduct (Scheme 3). In the case of 2-(alkylthio)-substituted 1,3-thiazole-5(4H)-thiones 1c and 1d , this ring opening proceeds by elimination of the corresponding alkylthiolate, yielding isothiocyanate 7 . The structures of (Z)- 5c and 6b have been established by X-ray crystallography.     

Spirocoleone: Synthese und Charakterisierung von vier diastereomeren Spiro (methylcyclopropan)-Substrukturen; Revision der Konfiguration an C(12) und C(15) von Coleon P und Derivaten sowie von Coleon-Z-Derivaten; Röntgenstrukturanalysen von Lanugon J und weiteren Spirocoleonen

Spirocoleons: Synthesis and Characterization of Four Diastereomeric Spiro (methylcyclopropane) Substructures; Revision of the Configuration at C(12) and C(15) of Coleon P and Derivatives and Coleon-Z Derivatives; X-Ray Analysis of Lanugon J and of Further Spirocoleons X-ray analyses show the correctness of the previously published structure of coleon Q (1) , establish the structure of lanugon J (4a) , and necessitate a revision of the configuration at C(12) and C(15) in coleon P (3a) and its derivatives 3b and 3c , and furthermore of the coleon Z derivatives 11a–11d . Two further diastereomeric spiro (methylcyclopropane) substructures have been generated by photoisomerization of lanugon J (4a) and 12-O-desacetylcoleon N (8) ; they represent the novel cis-type B with (12R, 13R, 15S)- and the novel trans-type D with (12R, 13R, 15R)-configuration (Scheme 1). The structures of the photoproducts 5a ((12R, 13R, 15R)-lanugon J) and 7a ((12R, 13R, 15S)-lanugon J) were established by X-ray analysis. So far, only two of the eight possible diastereomers of the spiro-(methylcyclopropane) substructure I have been detected in nature, i.e. the trans-type A with (12R, 13S, 15S)- and the cis-type C with (12R, 13S, 15R)-configuration. The four diastereomers A-D , all possessing (12R)-configuration, show very similar properties. However, careful comparison of spectral and chiroptical data allow a differentiation, even in the case of functionalization of H₃C(17). The (12S)-counter-parts could not yet be prepared.     

Stereochemistry of the Robinson Anellation: Studies on the Mode of Formation of the Intermediate Hydroxy Ketones

The stereochemical outcome of the base-catalyzed cyclization of diketones 5 – 8 has been investigated under protic conditions (Scheme 3). The more stable trans-fused ketols are preferentially formed in kinetically controlled aldol reactions, when the incipient angular substituent R = H (6 → 10a ) or CN ( 7 → 11a , 8a → 12a ). For R = Me (as in 5 ), axial attack of the side-chain enolate double bond on the ring C?O group results in the rather selective formation of cis- 9b. It is assumed that these cyclizations are controlled by relative product stabilities (product-like transition state) and steric effects. The competition between fused (e.g. 9 ) and bridged ketol (e.g. 13 ) formation in these cyclizations is discussed. The cis-fused (‘steroid’) ketols were readily equilibrated with their trans-counterparts (9b ? 9a, 10b ? 10a, 11b ? 11a) under aprotic conditions (5 mol-% of LDA, THF, 0°), thus, allowing assessments of relative stabilities.     

Light-Induced Cycloaddition of Furan and addition of methanol to a 4-thiacyclohex-2-enone ( = 2,3-dihydro-4H-thiin-4-one) and a 4-thiacyclopent-2-enone ( = thiophen-3(2H)-one)

Irradiation of newly synthesized 2,2-dimethyl-2,3-dihydro-4H-thiin-4-one ( 1 ) in furan affords the two [4 + 2] cycloadducts 3 and 4 and the [2 + 2] cycloadduct 5 in a 5:4:1 ratio (Scheme 1). Irradiation of 1 in MeOH gives a 3:2 mixture of 5- and 6-methoxy-2,2-dimethylthian-4-ones 6 and 7 . Irradiation in CD₃OD affords the same (deuterated) adducts with the CD₃O and D groups trans to each other, results compatible with cis-addition of MeOH to a trans -configurated ground-state enone. Irradiation of the same enone in furan/MeOH 1:1 gives only the furan cycloadducts 3–5 and no MeOH adducts, suggesting that furan interacts with the (excited) triplet enone before the deactivation of this species to a ground-state (E)-cyclohexenone, which then reacts with MeOH. On irradiation in furan, the corresponding five-membered thiaenone, 2,2-dimethylthiophen-3(2H)-one ( 2 ) affords only one, cis-fused, [4 + 2] cycloadduct with ‘exo’-configuration, i.e. 8 , and 2 does not undergo solvent addition but rather cyclodimerization (→ 9 ) on irradiation in MeOH (Scheme 1).     

cis-trans-and Intramolecular enol-enolic equilibrium of β-ketoaldehydes

Tautomerism of aromatic β-ketoaldehydes p-XPhCOCH₂CHO ( 1 , X = NMe₂, OMe, Me, H, Br, NO₂), aliphatic β-ketoaldehydes and benzoylacetaldehyde RCOCH₂CHO ( 2 , R = Me, i-Bu, t-Bu, Ph), RCOCH(Me)CHO ( 3 , R = Me, Et, i-Pr) and methyl 2-formylpropionate MeOCOCH(Me)CHO ( 4 ) has been studied by the ¹H NMR technique. In basic solvents both cis- and trans-enol forms of these compounds co-exist. trans-Enolisation, which occurs exclusively at the formyl group, is most favoured in compound ( 4 ) and least favoured in compounds ( 1 ) and ( 2 ). The increasing electron-attracting property of the substituent X in the aromatic β-ketoaldehydes ( 1 ), as well as increasing solvent basicity in the series propanediol-1, 2-carbonate, acetone < dimethylformamide < dimethylacetamide < pyridine, also shifts the equilibrium towards the trans-enol form. The trans-enol form is absent in aprotic solvents of low basicity such as CCl₄, C₂HCl₃ and toluene. The thermodynamic parameters of the cis-trans-enol (C ? T) and cis-enol-enolic (C ? C') equilibria have been estimated from the temperature dependences. The transition from the cis-to the trans-enol form is accompanied by an entropy decrease of about 10 cal mol^?1 degree^?1. Nevertheless the trans-enol form is stabilised due to its lower enthalpy. The cis-trans-enol equilibrium is determined by the relative strength of the intramolecular hydrogen bond in the cis-enol form and the intermolecular hydrogen bonds with basic solvent molecules of the trans-enol form. The enthalpy difference of the two cis-enolic forms does not exceed 1.0 kcal/mol, in rough agreement with the data calculated by the CNDO/2 approximation. Polar solvents favour the hydroxymethyleneketone form (C) for both groups of compounds 2 and 3 . The content of the hydroxymethyleneketone form is about the same within series 2 where R = Me, i-Bu, Ph and is a little higher for the t-Bu derivative. A decrease of temperature only slightly shifts the equilibrium of compounds 1 and 2 to the hydroxymethyleneketone form, while in the case of 2-methyl-β-ketoaldehydes (3) this effect is markedly pronounced.