Photochemische Umsetzung von optisch aktiven 2-(1′-Methylallyl)anilinen mit Methanol

Photochemical Reaction of Optically Active 2-(1′-Methylallyl)anilines with Methanol It is shown that (?)-(S)-2-(1′-methylallyl)aniline ((?)-(S)- 4 ) on irradiation in methanol yields (?)-(2S, 3R)-2, 3-dimethylindoline ((?)-trans- 8 ), (?)-(1′R, 2′R)-2-(2′-methoxy-1′-methylpropyl)aniline ((?)-erythro- 9 ) as well as racemic (1′RS, 2′SR)-2-(2′-methoxy-1′-methylpropyl) aniline ((±)-threo- 9 ) in 27.1, 36.4 and 15.7% yield, respectively (see Scheme 3). By deamination and chemical correlation with (+)-(2R, 3R)-3-phenyl-2-butanol ((+)-erythro- 13 ; see Scheme 4) it was found that (?)-erythro- 9 has the same absolute configuration and optical purity as the starting material (?)-(S)- 4 . Comparable results are obtained when (?)-(S)-N-methyl-2-(1′-methylallyl)aniline ((?)-(S)- 7 ) is irradiated in methanol, i.e. the optically active indoline (+)-trans- 10 and the methanol addition product (?)-erythro- 11 along with its racemic threo-isomer are formed (cf. Scheme 3). These findings demonstrate that the methanol addition products arise from stereospecific, methanol-induced ring opening of intermediate, chiral trans, -(→(?)-erythro-compounds) and achiral cis-spiro [2.5]octa-4,6-dien-8-imines (→(±)-threo-compounds; see Schemes 1 and 2).     

Acid-Catalyzed [3,3]-Sigmatropic Rearrangements of N-Propargylanilines

The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)-, N-(1′-methylprop-2′-ynyl)-, and N-(1′-arylprop-2′-ynyl)-2,6-, 2,4,6-, 2,3,5,6-, and 2,3,4,5,6-substituted anilines in mixtures of 1N aqueous H₂SO₄ and ROH such as EtOH, PrOH, BuOH etc., or in CDCl₃ or CCl₄ in the presence of 4 to 9 mol-equiv. trifluoroacetic acid (TFA)has been investigated (cf. Scheme 12-25 and Tables 6 and 7). The rearrangement of N-(3′-X-1′,1′-dimethyl-prop-2′-ynyl)-2,6- and 2,4,6-trimethylanilines (X = Cl, Br, I) in CDCl₃/TFA occurs already at 20° with τ_1/2 of ca. 1 to 5 h to yield the corresponding 6-(1-X-3′-methylbuta-1,2′-dienyl)-2,6-dimethyl- or 2,4,6-trimethylcyclohexa-2,4-dien-1-iminium ions (cf. Scheme 13 and Footnotes 26 and 34) When the 4 position is not substituted, a consecutive [3,3]-sigmatropic rearrangement takes place to yield 2,6-dimethyl-4-(3′-X-1′,1′-dimethylprop-2′-ynyl)anilines (cf. Footnotes 26 and 34). A comparable behavior is exhibited by N-(3′-chloro-1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ( 45 ., cf. Table 7). The acid-catalyzed rearrangement of the anilines with a Cl substituent at C(3′) in 1N aqueous H₂SO₄/ROH at 85-95°, in addition, leads to the formation of 7-chlorotricyclo[3.2.1.0^2,7]oct-3-en-8-ones as the result of an intramolecular Diels-Alder reaction of the primarily formed iminium ions followed by hydrolysis of the iminium function (or vice versa; cf. Schemes 13,23, and 25 as well as Table 7). When there is no X substituent at C(1′) of the iminium-ion intermediate, a [1,2]-sigmatropic shift of the allenyl moiety at C(6) occurs in competition to the [3,3]-sigmatropic rearrangement to yield the corresponding 3-allenyl-substituted anilines (cf. Schemes 12,14–18, and 20 as well as Tables 6 and 7). The rearrangement of (?)?(S)-N-(1′-phenylprop-2′-ynyl)-2,6-dimethylaniline ((?)- 38 ; cf. Table 7) in a mixture of 1N H₂SO₄/PrOH at 86° leads to the formation of (?)-(R)-3-(3′-phenylpropa-1′,2′-dienyl)-2,6-dimethylaniline ((?)- 91 ), (+)-(E)- and (?)-(Z)-6-benzylidene-1,5-dimethyltricyclo[3.2.1.0^2′7]oct-3-en-8-one ((+)-(E)- and (?)-(Z)- 92 , respectively), and (?)-(S)-2,6-dimethyl-4-( 1′-phenylprop-2′-ynyl)aniline((?)- 93 ). Recovered starting material (10%) showed a loss of 18% of its original optical purity. On the other hand, (+)-(E)- and (?)-(Z)- 92 showed the same optical purity as (minus;)- 38 , as expected for intramolecular concerted processes. The CD of (+)-(E)- and (?)-(Z)- 92 clearly showed that their tricyclic skeletons possess enantiomorphic structures (cf. Fig. 1). Similar results were obtained from the acid-catalyzed rearrangement of (?)-(S)-N-(3′-chloro-1′phenylprop-2′-ynyl)-2,6-dimethylaniline ((?)- 45 ; cf. Table 7). The recovered starting material exhibited in this case a loss of 48% of its original optical purity, showing that the Cl substituent favors the heterolytic cleavage of the N–C(1′) bond in (?)- 45. A still higher degree (78%) of loss of optical activity of the starting aniline was observed in the acid-catalyzed rearrangement of (?)-(S)-2,6-dimethyl-N-[1′-(p-tolyl)prop-2′-ynyl]aniline ((?)- 42 ; cf. Scheme 25). N-[1′-(p-anisyl)prop-2-ynyl]-2,4,6-trimethylaniline( 43 ; cf. Scheme 25) underwent no acid-catalyzed [3,3]-sigmatropic rearrangement at all. The acid-catalyzed rearrangement of N-(1′,1′-dimethylprop-2′-ynyl)aniline ( 25 ; cf. Scheme 10) in 1N H₂SO₄/BuOH at 100° led to no product formation due to the sensitivity of the expected product 53 against the reaction conditions. On the other hand, the acid-catalyzed rearrangement of the corresponding 3′-Cl derivative at 130° in aqueous H₂SO₄ in ethylene glycol led to the formation of 1,2,3,4-tetrahydro-2,2-dimethylquinolin-4-on ( 54 ; cf. Scheme 10), the hydrolysis product of the expected 4-chloro-1,2-dihydro-2,2-dimethylquinoline ( 56 ). Similarly, the acid-catalyzed rearrangement of N-(3′-bromo-1′-methylprop-2′-ynyl)-2,6-diisopropylaniline ( 37 ; cf. Scheme 21) yielded, by loss of one i-Pr group, 1,2,3,4-tetrahydro-8-isopropyl-2-methylquinolin-4-one ( 59 ).     

Mechanismus der photochemischen Methanol-Addition an 2-allylierte Aniline

Mechanism of the Photochemical Addition of Methanol to 2-Allylated Anilines We studied in methanol the photoreaction of the 2-allylated anilines, given in Scheme 3 (cf. also [ 1 ]). Irradiation of N-methyl-2-(1′-methylallyl)aniline ( 15 ) with a high pressure mercury lamp yielded trans- and cis-1,2,3-trimethylindoline (trans- and (cis- 34 ) as well as erythro- and threo-2-(2′-methoxy-1′-methylpropyl)-N-methylaniline (erythro- and threo- 35 ; Scheme 7). When the corresponding aniline d₃- 15 , specifically deuterated in the 1′-methyl group, was irradiated in methanol, a mixture of trans- and cis-d₃- 34 , and of erythro- and threo-d₃- 35 was obtained. Successive dehydrogenation of the mixture of cis/trans-d₃- 34 by Pd/C in boiling xylene and by MnO₂ in boiling benzene lead to the corresponding indole d₃- 36 (cf. Scheme 9), the ¹H- and ²H-NMR. spectra of which showed that both cis-d₃- and trans-d₃- 34 had bound the deuterium labeled methyl group exclusively at C(3). The ¹H- and ²H-NMR. analyses of the separated methanol addition products revealed that erythro-d₃- 35 contained the deuterium label to at least 95% in the methyl group at C(1′), and threo-d₃- 35 to 50% in CH₃? C(1′) and to 50% in CH₃? C(2′) (cf. Scheme 9). To confirm these results 2-(1′-ethylallyl)aniline ( 16 ) was irradiated in methanol, whereby a complex mixture of at least 6 products was obtained (cf. Scheme 11). Two products were identified as trans- and cis-3-ethyl-2-methylindoline (trans- and cis- 37 ). The four other products represented erythro- and threo-2-(1′-ethyl-2′-methoxypropyl)aniline (erythro- and threo- 39 ) as major components, and erythro- and threo-2-(2′-methoxy-1′-methylbutyl)aniline (erythro- and threo- 40 ). These results clearly demonstrate that the methanol addition products must arise from spirodienimine intermediates of the type of trans- 9 and cis- 11 (R¹ = CD₃ or C₂H₅, R² = CH₃ or H; Scheme 2) which are opened solvolytically with inversion of configuration by methanol. Thus, cis- 11 (R¹ = CD₃, R² = CH₃) must lead to a 1:1 mixture of threo- 13 and threo- 14 (i.e.) a 1:1 distribution of the deuterium labelled methyl group between C(1′) and C(2′) in threo- 35 ) The formation of erythro-d₃- 35 with at least 95% of the deuterium label in the methyl group at C(1′) indicates that trans- 9 (R¹ = CD₃, R² = CH₃) reacts with methanol regioselectively (> 95%) at the C(2), C(3) bond. Similarly, the formation of the methanol addition products in the photoreaction of 16 (Scheme 11) can be explained. Since the indolines, formed in both photoreactions, show no alteration in the position of the subsituent at C(1′) with respect to the starting material we suppose that the diradical 7 (R¹ = CD₃ or C₂H₅, R² = CH₃ or H; Scheme 2) is a common intermediate which undergoes competetive 1.3 and 1.5 ring closure yielding the spirodienimines and the indolines. This conception is supported by irradiation experiments with N, 3,5-trimethyl-2-(1′-methylally)aniline ( 17 ) and 2-(2′-cyclohexenyl)-N-methylaniline ( 18 ) in methanol. In the former case the formation of spirodienimines is hindered by the methyl group at C(3) for steric reasons, thus leading to a ratio of the indoline to the methoxy compounds of about 6.3 as compared with ca. 1.0 for 15 (cf. Scheme 12). On the other hand, no methoxy compounds could be detected in the reaction mixture of 18 (cf. Scheme 13) which indicates that in this case the 1.3 ring closure cannot compete with the 1.5 cyclization in the corresponding cyclic diradical of the type 7 (R¹–C(1′)–C(2′) is part of a six-membered ring; Scheme 2). We suppose that the diradicals of type 7 are formed by proton transfer in an intramolecular electron-donor-acceptor (EDA) complex arising from the excited single state of the aniline chromophor and the allylic side chain. This idea is supported by the fluorescence specta of 2-allylated N-methylanilines (cf. Fig.1-4) which show pronounced differences with respect to the corresponding 2-alkylated anilines. Furthermore, the anilines 18 and 20 when irradiated in methanol in the presence of an excess of trans-1,3-pentadiene undergo preferentially an intermolecular addition to the diene, thus yielding the N-(1′-methyl-2′-butenyl)anilines 52 and 51 , respectively (Scheme 15), i.e. as one would expect the diene with its low lying LUMO is a better partner for an EDA complex than the double bond of the allylic side chain.     

Bestrahlung von 4-allylierten 2,6-Dimethylanilinen in Methanol

Irradiation of 4-Allylated 2,6-Dimethylanilines in Methanol 4-Allyl-, 4-(1′-methylallyl)-, 4-(2′-butenyl)-, and 4-(1′,1′-dimethylallyl)-2,6-dimethylaniline ( 14–17 ; cf. Scheme 3) were obtained by the acid catalysed, thermal rearrangement of the corresponding N-allylated anilines in good yields. Aniline 14 , when irradiated with a high pressure mercury lamp through quartz in methanol, yielded as main product 4-(2′-methoxypropyl)-2,6-dimethylaniline ( 22 ; cf. Scheme 4) and, in addition, 2,6-dimethyl-4-propylaniline ( 18 ) and 4-cyclopropyl-2,6-dimethylaniline ( 23 ). The analogous products, namely erythro- and threo-4-(2′-methoxy-1′-methylpropyl)-2,6-dimethylaniline (erythro- and threo- 24 ), 2,6-dimethyl-4-(1′-methylpropyl)aniline ( 19 ), trans- and cis-2,6-dimethyl-4-(2′-methylcyclopropyl)aniline (trans- and cis- 25 ), as well as small amounts of 4-ethyl-2,6-dimethylaniline ( 26 ), were formed by irradiation of 15 in methanol (cf. Scheme 5). When this photoreaction was carried out in O-deuteriomethanol, erythro- and threo- 24 showed an up-take of one deuterium atom in the side chain. The mass spectra of erythro- and threo- 24 revealed that in 50% of the molecules the deuterium was located at the methyl group at C(1′) and in the other 50% at the methyl group at C(2′) (cf. Scheme 6). This is a good indication that the methanol addition products arise from methanolysis of intermediate spiro[2.5]octa-4,7-dien-6-imines (cf. Scheme 7). This assumption is further supported by the photoreaction of 17 in methanol (cf. Scheme 8) which led to the formation of 4-(2′-methoxy-1′,2′-dimethylpropyl)-2,6-dimethylaniline ( 28 ) as main product. The occurrence of a rearranged side chain in 28 can again be explained by the intervention of a spirodienimine 31 (cf. Scheme 9). In comparison with 14, 15 and 17 , the 2′-butenylaniline 16 reacted only sluggishly on irradiation in methanol (cf. Scheme 10). It is suggested that all photoproducts - except for the cyclopropyl derivatives which are formed presumably via a triplet di-π-methane rearrangement - arise from an intramolecular singlet electron-donor-acceptor complex between the aniline and ethylene chromophor of the side chain. Protonation of this complex at C(3′) or C(2′) will lead to diradicals (e.g. 33 and 34 , respectively, in Scheme 11). The diradicals of type 33 undergo ring closure to the corresponding spirodienimine intermediates (e.g. 31 ) whereas the diradicals of type 34 take up two hydrogen atoms to yield the photo-hydrogenated compounds (e.g. 21 ) or undergo to a minor extent fragmentation to side chain degraded products (e.g. 30 ; see also footnote 7).–Irradiation of 4-ally-2,6-dimethylaniline ( 14 ) in benzene or cyclohexane yielded the corresponding azo compound 38 (cf. Scheme 12), whereas its N,N-dimethyl derivative 41 was transformed into the cyclopropyl derivative 42 . The allyl moiety in 14 is not necessary for the formation of azo compounds since 2,4,6-trimethylaniline ( 39 ) exhibited the same type of photoreaction in benzene solution.     

Photoreaktionen von 1-Alkylbenztriazolen

The irradiation of benzotriazoles (cf. Scheme 2) with light of 225–325 nm in protic and in aromatic solvents was investigated. In aqueous 0.1N H₂SO₄ benzotriazole ( 5 ) and 1-methyl-benzotriazole ( 6 ) yielded 2-amino- and 2-methylaminophenol ( 25 and 26 ), respectively (Scheme 3). In 2-propanol 6 , 5-chloro- and 6-chloro-1-methyl-benzotriazole ( 14 and 15 ) were reduced to N-methylaniline, 4-chloro- and 3-chloro-N-methyl-aniline ( 27 , 28 and 29 ), respectively (Scheme 4). When the benzotriazoles were irradiated in aromatic solvents only C, C coupling products were observed (cf. Scheme 6 and Tables 1–4). It is of importance that 5-chloro-1-methyl-benztriazole ( 14 ) when decomposed photolytically in benzene solution yielded only 4-chloro-2-phenyl-N-methyl-aniline ( 49 ) and its 6-chloro isomer only 5-chloro-2-phenyl-N-methyl-aniline ( 50 ), i.e. the intervention of benzo-1H-azirine intermediates (e.g. 53 , Scheme 8) can be excluded. The substitution patterns which are observed when 6 is irradiated in toluene, anisole, fluoro-, chloro-, bromobenzene and benzonitrile (cf. Table 4) can best be explained by assuming that 6 , after loss of nitrogen, forms a diradical intermediate in the singlet state with highly zwitterionic character. 1-(1′-Alkenyl)-benzotriazoles (cf. Table 7) form on irradiation in cyclohexane solution indoles by intramolecular ring closure of the diradical intermediate and proton shift. After irradiation of 1-decyl-benzotriazole ( 8 ) in a glassy matrix at 77K a 7-line ESR. spectrum characteristic of a triplet radical is observed. This is in agreement with the fact that the lowest lying state of intermediates of type 2 (Scheme 1) should be a triplet state (cf. [21] [26]).     

Stereochemical Analysis of an Aromatic Triplet Di-π-methane Rearrangement

It is shown that (−)-(S)-N,N-dimethyl-2-(1′-methylallyl)aniline ((−)-(S)- 4 ), on direct irradiation in MeCN at 20°, undergoes in its lowest-lying triplet state an aromatic di-π-methane (ADPM) rearrangement to yield (−)-(1′R,2′R)- and (+)-(1′R,2′S)-N,N-dimethyl-2-(2-methylcyclopropyl)aniline ((−)-trans- and (+)-cis- 7 ) in an initial trans/cis ratio of 4.71 ± 0.14 and in optical yields of 28.8 ± 5.2% and 15 ± 5%, respectively. The ADPM rearrangement of (−)-(S)- 4 to the trans- and cis-configurated products occurs with a preponderance of the path leading to retention of configuration at the pivot atom (C(1′) in the reactant and C(2′) in the products) for (−)-trans- 7 and to inversion of configuration for (+)-cis- 7 , respectively. The results can be rationalized by assuming reaction paths which involve the occurrence of discrete 1,4- and 1,3-diradicals (cf. Schemes 10, 12, and 13). A general analysis of such ADPM rearrangements which allows the classification of these photochemical reactions in terms of borderline cases is presented (Scheme 14). It is found that the optical yields in these ‘step-by-step’ rearrangements are determined by the first step, i.e. by the disrotatory bond formation between C(2) of the aromatic moiety and C(2′) of the allylic side chain leading to the generation of the 1,4-diradicals. Moderation of the optical yields can occur in the ring closure of the 1,3-diradicals to the final products, which may take place with different trans/cis-ratios for the individual 1,3-diradicals. Compounds (−)-trans- 7 as well as (+)-cis- 7 easily undergo the well-known photochemical trans/cis-isomerization. It mainly leads to racemization. However, a small part of the molecules shows trans/cis-isomerization with inversion of configuration at C(1′), which is best explained by a photochemical cleavage of the C(1′)–C(3′) bond.     

Die thermische Umlagerung von 2-(Buta-1′,3′-dienyl)-phenolen in 2-Alkyl-2H-chromene; Beispiele für aromatische [1,7a]- und [1,5s]sigmatropische Wasserstoffverschiebungen

2-(1′-cis,3′-cis-)- and 2-(1′-cis,3′-trans-Penta-1′,3′-dienyl)-phenol (cis, cis- 4 and cis, trans- 4 , cf. scheme 1) rearrange thermally at 85–110° via [1,7 a] hydrogen shifts to yield the o-quinomethide 2 (R ? CH₃) which rapidly cyclises to give 2-ethyl-2H-chromene ( 7 ). The trans formation of cis, cis- and cis, trans- 4 into 7 is accompanied by a thermal cis, trans isomerisation of the 3′ double bond in 4. The isomerisation indicates that [1,7 a] hydrogen shifts in 2 compete with the electrocyclic ring closure of 2 . The isomeric phenols, trans, trans- and trans, cis- 4 , are stable at 85–110° but at 190° rearrange also to form 7 . This rearrangement is induced by a thermal cis, trans isomerisation of the 1′ double bond which occurs via [1, 5s] hydrogen shifts. Deuterium labelling experiments show that the chromene 7 is in equilibrium with the o-quinomethide 2 (R ? CH₃), at 210°. Thus, when 2-benzyl-2H-chromene ( 9 ) or 2-(1′-trans,3′-trans,-4′-phenyl-buta1′,3′-dienyl)-phenol (trans, trans- 6 ) is heated in diglyme solution at >200°, an equilibrium mixture of both compounds (～ 55% 9 and 45% 6 ) is obtained.     

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).     

Untersuchungen über aromatische Amino-Claisen-Umlagerungen

Investigations on Aromatic Amino-Claisen Rearrangements The thermal and acid catalysed rearrangement of p-substituted N-(1′,1′-dimethylallyl)anilines (p-substituent=H (5) , CH₃ (6) , iso-C₃H₇ (7) , Cl (8) , OCH₃ (9) , CN (10) ), of N-(1′,1′-dimethylallyl)-2,6-dimethylaniline (11) , of o-substituted N-(1′-methylallyl)anilines (o-substituent=H (12) , CH₃ (13) , t-C₄H₉ (14) , of (E)- and (Z)-N-(2′-butenyl)aniline ((E)- and (Z)- 16 ), of N-(3′-methyl-2′-butenylaniline (17) and of N-allyl- (1) and N-allyl-N-methylaniline (15) was investigated (cf. Scheme 3). The thermal transformations were normally conducted in 3-methyl-2-butanol (MBO), the acid catalysed rearrangements in 2N -0,1N sulfuric acid. - Thermal rearrangements. The N-(1′,1′-dimethylallyl)anilines rearrange in MBO at 200-260° with the exception of the p-cyano compound 10 in a clean reaction to give the corresponding 2-(3′-methyl-2′-butenyl)anilines 22–26 (Table 2 and 3). The amount of splitting into the anilines is <4% ( 10 gives ? 40% splitting). The secondary kinetic deuterium isotope effect (SKIDI) of the rearrangement of 5 and its 2′,3′,3′-d₃-isomer 5 amounts to 0.89±0.09 at 260° (Table 4). This indicates that the partial formation of the new s?-bond C(2), C(3′) occurs already in the transition state, as is known from other established [3,3]-sigmatropic rearrangements. The rearrangement of the N-(1′-methylallyl)anilines 12–14 in MBO takes place at 290–310° to give (E)/(Z)-mixtures of the corresponding 2-(2′-Butenyl)anilines ((E)- and (Z)- 30,-31 , and -32 ) besides the parent anilines (5–23%). Since a dependence is observed between the (E)/(Z)-ratio and the bulkiness of the o-substituent (H: (E)- 30 /(Z)- 30 =4,9; t-C₄H₉: (E)- 32 /(Z)- 32 =35.5; cf. Table 6), it can be concluded, that the thermal amino-Claisen rearrangement occurs preferentially via a chair-like transition state (Scheme 22). Methyl substitution at C(3′) in the allyl chain hinders the thermal amino-Claisen-rearrangement almost completely, since heating of (E)-and (Z)- 16 , in MBO at 335° leads to the formation of the expected 2-(1′-methyl-allyl) aniline (33) to an extent of only 12 and 5%, respectively (Scheme 9). The main reaction (?60%) represents the splitting into aniline. This is the only observable reaction in the case of 17 . The inversion of the allyl chain in 16 - (E)- and (Z)- 30 cannot be detected - indicated that 33 is also formed in a [3, 3]-sigmatropic process. This is also true for the thermal transformation of N-allyl- (1) and N-allyl-N-methylaniline (15) into 2 and 34 , respectively, since the thermal rearrangement of 2′, 3′, 3′-d₃- 1 yields 1′, 1′, 2′-d₃- 2 exclusively (Table 8). These reaction are accompanied to an appreciable extent by homolysis of the N, C (1′) bond: compound 1 yields up to 40% of aniline and 15 even 60% of N-methylaniline ((Scheme 10 and 11). The activation parameters were determined for the thermal rearrangements of 1, 5, 12 and 15 in MBO (Table 22). All rearrangements show little solvent dependence (Table 5, 7 and 9). The observed ΔH^≠ values are in the range of 34-40 kcal/mol and the ΔS^≠ values very between -13 to -19 e.u. These values are only compatible with a cyclic six-membered transition state of little polarity. - Acid catalysed rearrangements. - The rearrangement of the N-(1′, 1′-dimethylallyl) anilines 5-10 occurs in 2N sulfuric acid already at 50-70° to give te 2-(3′-methyl-2′-butenyl)anilines 22-27 accompanied by their hydrated forms, i.e. the 2-(3′-hydroxy-3′-methylbutyl) anilines 35-40 (Tables 10 and 11). The latter are no more present when the rearrangement is conducted in 0.1 N sulfuric acid, whilst the rate of rearrangement is practically the same as in 2 N sulfuric acid (Table 12). The acid catalysed rearrangements take place with almost no splitting. The SKIDI of the rearrangement of 5 and 2′, 3′, 3′-d₃- 5 is 0.84±0.08 (2 N H₂SO₄, 67, 5°, cf. Table 13) and thus in accordance with a [3,3]-sigmatropic process which occurs in the corresponding anilinium ions. Consequently, the rearrangement of a 1:1 mixture of 2′, 3′, 3′-d₃- 5 and 3, 5-d₂- 5 in 2 N sulfuric acid at 67, 5° occurs without the formation of cross-products (Scheme 13). In the acid catalysed rearrangement of the N-1′-methylallyl) anilines 12-14 at 105-125° in 2 N sulfuric acid the corresponding (E)- and (Z)-anilines are the only products formed (Table 14 and 15). Again no splitting is observed. Furthermore, a dependence of the observed (E)/(Z) ratio and the bulkiness of the o-substituent ( H : (E)/(Z)- 30 = 6.5; t- C ₄ H ₉: (E)- 32 /(Z)- 32 = 90; cf. Table 15) indicates that also in the ammonium-Claisen rearrangement a chair-like transition state is preferentially adopted. In contrast to the thermal rearrangement the acid catalysed transformation in 2 N-O, 1 N sulfuric acid (150-170°) of (E)- and (Z)- 16 as well as of 1 and 15 , occurs very cleanly to yield the corresponding 2-allylated anilines 33, 2 and 34 (Scheme 15 and 18). The amounts of the anilines formed by splitting are <2%. During longer reaction periods hydration of the allyl chain of the products occurs, and in the case of the rearrangement of (E)- and )Z)- 16 the indoline 45 is formed (Scheme 15 and 18). All transformations occur with inversion of the allyl chain. This holds also for the rearrangement of 1 , since 3′, 3′-d₂- 1 gives only 1′, 1′-d₂- 2 (Scheme 17). The activation parameters were determined for the acid catalysed rearrangement of 1, 5, 12 and 15 in 2 N sulfuric acid (Table 22). The ΔH^≠ values of 27-30 kcal-mol and the ΔS^≠ values of +9 to -12 e.u. are in agreement with a [3, 3]-sigmatropic process in the corresponding anilinium ions. The acceleration factors (k_H+/k_Δ) calculated from the activation parameters of the acid catalysed and thermal rearrangements of the anilines are in the order of 10⁵ - 10⁷. They demonstrate that the essential driving force of the ammonium-Claisen rearrangement is the ‘delocalisation of the positive charge’ in the transition state of these rearrangements (cf. Table 23). Solvation effects in the anilinium ions, which can be influenced sterically, also seem to play a role. This is impressively demonstrated by N-(1′, 1′-dimethylallyl)-2, 6-dimethylaniline (11) : its rearrangement into 4-(1′, 1′-dimethylallyl)-2, 6-dimethylaniline (43) cannot be achieved thermally, but occurs readily at 30° in 2 N sulfuric acid. From a preparative standpoint the acid catalysed rearrangement in 2 N-0, 1 N sulfuric acid of N-allylanilines into 2-allylanilines, or if the o-positions are occupied into 4-allylanilines, is without doubt a useful synthetic method (cf. also [17]).     

Zur Photochemie von 1H- und 2H-Indazolen in saurer Lösung

On the Photochemistry of 1H- and 2H-Indazoles in Acidic Solution It is shown that 1H- and 2H-indazoles (cf. Scheme 2) on protonation (0, 1N H₂SO₄ in water or alcoholic solution) give analogous indazolium ions (see Fig. 1 and 2) which on irradiation undergo heterolytic cleavage of the N (1), N (2) bond whereby aromatic nitrenium ions in the singlet ground state are formed (cf. Scheme 13). If the para position of these nitrenium ions is not occupied by a substituent (e.g. a methyl group) they are readily trapped by nucleophiles present (e.g. water, alcohols, chloride ions) to yield the corresponding 5-substituted 2-amino-benzaldehydes or acetophenones (cf. Schemes 4–10). Photolysis of indazole ( 4 ) and 3-methyl-indazole ( 5 ) in 0,75N H₂SO₄ in alcoholic solutions gives in addition minor amounts of the corresponding 3-substituted 2-amino-benzaldehydes and acetophenones, respectively (cf. Schemes 6 and 8 and Table 2). Phenylnitrenium ions carrying a methyl group in the para position give in aqueous sulfuric acid mainly the reduction products, i.e. 2-amino-5-methyl-benzaldehydes (cf. Schemes 11 and 12 and Table 3). In methanolic sulfuric acid, in addition to the reduction products, 6-methoxy substituted benzaldehydes are found (cf. Schemes 11 and 12 and Table 3) which are presumably formed by an addition-elimination mechanism (cf. Scheme 18). It is assumed that precursors of the reduction products are the corresponding nitrenium ions in the triplet ground state. Singlet-triplet conversion of the nitrenium ions may become efficient when addition of nucleophiles to the singlet nitrenium ions is reversible (cf. Scheme 22) thus, enhancing the probability of conversion or when conjugation in the singlet nitrenium ions is disturbed by steric effects (cf. Scheme 20) thus, destabilizing the singlet state relative to the triplet state.     

Umlagerungsreaktionen von (2′-Propinyl)cyclohexadienolen und -semibenzolen

Rearrangements of (2′-Propinyl)cyclohexadienols and -semibenzenes The acid-catalyzed dienol-benzene rearrangement of 3- and 5-methyl-substituted (2′-propinyl)cyclohexadienols has been investigated. Treatment of the dienols with CF₃COOH in CCl₄ yields allenyl- and (2′-propinyl)benzenes via [3,4]- and [1,2]-sigmatropic rearrangements, respectively. The reaction with H₂SO₄ in Et₂O leeds to a mixture of allenyl-, 2′-propinyl-, 3′-butinyl- and (2′,3′-butadienyl)benzenes (Scheme 3). The latter are products of a thermal semibenzene-benzene rearrangement (cf. Scheme 9). The corresponding semibenzenes have been prepared by dehydration of the cyclohexadienols with H₂SO₄ or POCl₃ (Schemes 6 and 7). Under acidic conditions, the p-(2′-propinyl)semibenzenes 33–35 (Scheme 8) undergo [3,4]- and [1,2]-sigmatropic rearrangements to give again allenyl- and (2′-propinyl)benzenes, whereas the thermal rearrangements to the 3′-butinyl- and (2′,3′-butadienyl)benzenes (Scheme 9) involves a radical mechanism. In contrast, the o-(2′-propinyl)semibenzene b (Scheme 7) leads to (2′,3′-butadienyl)benzene 32 via a thermal [3,3]-sigmatropic rearrangement.     

Säurekatalysierte Umlagerung von 4-Allyl-cyclohex-2-en-1-olen; Beispiele für ladungskontrollierte [3s, 4s]-Umlagerungen von cyclischen Allylkationen

The acid-catalysed rearrangement of the cyclohex-2-en-1-ols 15 , d₃- 15 , 16 , 17 and 19 , the cyclohexa-2,5-dien-1-ols 20 and 21 , and also the allyl alcohols 22 and 23 (Scheme 3), using 98-percent sulfuric acid/acetic anhydride 1:99 at room temperature, was investigated. From the rearrangement of 4-allyl-4-phenyl-cyclohex-2-en-1-ol ( 15 ), with reaction times greater than 2 hours a single product is obtained, 4-allyl-biphenyl ( 50 ) in 33% yield (Scheme 9). With reaction times below 2 hours the acetate 53 from 15 was isolated, and this could be converted into 50 . The reaction of 2′,3′,3′-d₃-15 in Ac₂O/H₂SO₄ lead to 1′,1′,2′-d₃-50 (Scheme 11). The rearrangement of 4-allyl-4-methyl-cyclohex-2-en-1-ol (16) (Scheme 14) yielded 39% of the corresponding acetate 60 and 30% of 4-allyl-toluene ( 6 ), which also resulted by a rearrangement of 60 under the reaction conditions. These rearrangements are all [3s,4s]-sigmatropic reactions, which proceed via the cyclohexenyl cation a (Scheme 12, R = C₆H₅, CH₃). In Ac₂O/H₂SO₄ the allyl-cyclohexadienes primarely formed subsequently undergo dehydrogenation to yield the benzene derivatives 6 , 50 and d₃- 50 . From the rearrangement of 4,4-diphenyl-cyclohex-2-en-1-ol ( 19 ) at 0° a reaction mixture is obtained which consists of the acetate 55 , 2,3-diphenyl-cyclohexa-1,4-diene ( 57 ) and o-terphenyl ( 56 ) (Scheme 10). Both 55 and 57 are converted under the reaction conditions to o-terphenyl ( 56 ). No 4-(1′-methylallyl)-biphenyl is obtained from the rearrangement of 4-crotyl-4-phenyl-cyclohex-2-en-1-ol ( 17 ). In this case, apart from the corresponding acetate 64 , a single product 5-(1′-acetoxyethyl)-1-phenyl-bicyclo[2.2.2]oct-2-ene ( 65 ) (Scheme 16) was obtained; under the reaction conditions the acetate 64 rearranges to 65 . The rearrangement of 4-allyl-4-phenyl-cyclohexa-2,5-dien-1-ol ( 20 ) gives, as expected, not only 4-allyl-biphenyl ( 50 ) but also 2- and 3-allyl-biphenyl ( 51 and 52 ) and biphenyl (Scheme 13). 4-Benzyl-4-methyl-cyclohexa-2,5-dien-1-ol (syn- and anti- 21 ) gave in Ac₂O/H₂SO₄ at 10° as rearrangement products 93% of 2-benzyltoluene ( 97 ) and 7% of 4-benzyl-toluene ( 98 ) (Scheme 21). Hence [1,4]-rearrangements in cyclohexadienyl cations, seems to occur only to a limited extent. The alicyclic alcohols 22 and 23 (Scheme 18) gave, in Ac₂O/H₂SO₄, as main product the corresponding acetates 73 and 75 , as well as small amounts of olefins 74 and 76 formed by dehydration i.e. [3,4]-rearrangements occur in these systems. Also no [3,4]-rearrangements were observed in solvents reactions of either 4,4-dimethyl-hepta-1, 6-dien-3-yl tosulate (79; see Scheme 19) or its corresponding alcohol 24.     

Die Geometrie des aktivierten Komplexes der thermischen und ladungsinduzierten aromatischen para → ortho - Claisen-Umlagerung

Pure 10β-(trans-2′-butenyl)-17β-hydroxy-estra-1,4-dien-3-one ( 6 ), 10-(trans-2′-butenyl)-2-oxo-Δ^1(9),3(4)-hexahydronaphthalene ( 13 ), trans-2′-butenyl 17β-hydroxy-3-estra-1,3,5-(10)-trienyl ether ( 12 ) and trans-2′-butenyl 5,6,7,8-tetrahydro-2-naphthyl ether ( 14 ) were prepared by direct C- and O-alkylation, respectively, of the corresponding phenols (cf. [3] [10]), namely estra-3, 17β-diol and 5,6,7,8-tetrahydro-2-naphthol. The Claisen rearrangement of the ether 14 (200°, 12 h) yielded 53% 1-(1′-methylallyl)- and 34% 3-(1′-methylallyl)-5,6,7,8-tetrahydro-2-naphthol ( 15 and 16 , respectively), whereas in the thermal (120°, 14 h) and in the acid-catalysed (boron trifluoride in ether, 20°, 20 min) reaction of the corresponding dienone 13 nearly equal amounts of 15 (53–54%) and 16 (46%) were formed by thermal and charge-induced aromatic [3s, 3s]-sigmatropic rearrangements [2]. The steroid dienone 6 , on heating at 120°, was rearranged by [3s, 3s]-sigmatropic processes to form 52% of 2-(1′-methylallyl)- and 48% of 4′-(1′-methylallyl)-3, 17β-dihydroxy-estra-1,3,5,(10)-triene ( 7 and 8 , respectively). The steroid phenols 7 and 8 were carefully separated; subsequent hydrogenation (Raney-Ni in alcohol) and ozonolysis yielded 2-methylbutyric acid ( 9 ): from 7 , S-(+)- 9 , and from 8 , R-(?)- 9 , obtained in 88,5 and 88,0% optical purity (cf. [4a]). This means (cf. scheme 2 and Table 2) that both phenols are formed to the extent of at least 94% via a chair-like activated complex, and of at most 6% via a both-like activated complex (ΔΔG = 2.15 kcal/mol). Similarly, the boron trifluoride-induced rearrangement of 6 (born trifluoride in ether, 0°, 45 min) yielded 7 and 8 , from which S-(+)- 9 and R-(?)- 9 were respectively obtained in 89% and 98% optical purity. For these induced rearrangements this corresponds to at least 94,5 and 99%, respectively, of the chair-like, and to only 5.5 and 1% of the boat-like activated complex (ΔΔG = 1.5–2.5 kcal/mol). These results demonstrate that the activated complexes of both [3s,3s]-sigmatropic processes, i.e. the pure thermal reaction at 120° and the charge-induced reaction occurring at 0°, must be very similar. Thus, the boron trifluoride accelerates the Cope-like reactions 6 → 7 + 8 , but does not influence the geometries of their transition states. The Claisen rearrangement of the steroid ether 12 (200°, 15 h), yielding 7 and 8 , was not influenced by the chiral steroid skeleton, because no optical induction was observed (both phenols, 7 and 8 , yielded on degradation racemic 2-methylbutyric acid (9)).     

Über Umlagerungen bei der Cyclialkylierung von Arylpentanolen zu 2,3‐Dihydro‐1H‐inden‐Derivaten, 2. Mitteilung

On Rearrangements by Cyclialkylations of Arylpentanols to 2,3‐Dihydro‐1 H ‐indene Derivatives. Part 2. An Unexpected Rearrangement by the Acid‐Catalyzed Cyclialkylation of 2,4‐Dimethyl‐2‐phenylpentan‐3‐ol under Formation of trans ‐2,3‐Dihydro‐1,1,2,3‐tetramethyl‐1 H ‐indene The acid catalyzed‐cyclialkylation of 4‐(2‐chloro‐phenyl)‐2,4‐dimethylpentan‐2‐ol ( 1 ) gave two products: 4‐chloro‐2,3‐dihydro‐1,1,3,3‐tetramethyl‐1H‐indene ( 2 ) and also trans‐4‐chloro‐2,3‐dihydro‐1,1,2,3‐tetramethyl‐1H‐indene ( 3 ). A mechanism was proposed in Part 1 (cf. Scheme 1) for this unexpected rearrangement. This mechanism would mainly be supported by the result of the cyclialkylation of 2,4‐dimethyl‐2‐phenylpentan‐3‐ol ( 4 ), which, with respect to the similarity of ion II in Scheme 1 and ion V in Scheme 2, should give only product 5 . This was indeed the experimental result of this cyclialkylation. But the result of the cyclialkylation of 1,1,1,2′,2′,2′‐hexadeuterated isomer [²H₆]‐ 4 of 4 (cf. Scheme 3) requires a different mechanism as for the cyclialkylation of 1 . Such a mechanism is proposed in Schemes 5 and 6. It gives a satisfactory explanation of the experimental results and is supported by the result of the cyclialkylation of 2,4‐dimethyl‐3‐phenylpentan‐3‐ol ( 9 ; Scheme 7). The alternative migration of a Ph or of an i‐Pr group (cf. Scheme 6) is under further investigation.     

Bildung von 5,6-Dihydro-1,3(4H)-thiazin-4-carbonsäure-estern aus 4-Allyl-1,3-thiazol-5(4H)-onen

Formation of Methyl 5,6-Dihydro-l, 3(4H)-thiazine-4-carboxyiates from 4-Allyl-l, 3-thiazol-5(4H)-ones . The reaction of N-[1-(N, N-dimethylthiocarbamoyl)-1-methyl-3-butenyl]benzamid ( 1 ) with HCl or TsOH in MeCN or toluene yields a mixture of 4-allyl-4-methyl-2-phenyl-1,3-thiazol-5(4H)-one ( 5a ) and allyl 4-methyl-2-phenyl-1,3-thiazol-2-yl sulfide ( 11 ; Scheme 3). Most probably, the corresponding 1,3-oxazol-5(4H)-thiones B are intermediates in this reaction. With HCl in MeOH, 1 is transformed into methyl 5,6-dihydro-4,6-dimethyl-2-phenyl-1,3(4H)-thiazine-4-carboxylate ( 12a ). The same product 12a is formed on treatment of the 1,3-thiazol-5(4H)-one 5a with HCl in MeOH (Scheme 4). It is shown that the latter reaction type is common for 4-allyl-substituted 1,3-thiazol-5(4H)-ones.     

New Results in the Synthesis of Styrylazulene Derivatives: Application of the ‘Anil synthesis’ to the preparation of azulenes substituted with styryl groups at the seven-membered ring

The synthesis of 4,6,8-trimethyl-1-[(E)-4-R-styryl]azulenes 5 (R=H, MeO, Cl) has been performed by Wittig reaction of 4,6,8-trimethylazulene-1-carbaldehyde ( 1 ) and the corresponding 4-(R-benzyl)(triphenyl)phosphonium chlorides 4 in the presence of EtONa/EtOH in boiling toluene (see Table 1). In the same way, guaiazulene-3-carbaldehyde ( 2 ) as well as dihydrolactaroviolin ( 3 ) yielded with 4a the corresponding styrylazulenes 6 and 7 , respectively (see Table 1). It has been found that 1 and 4b yield, in competition to the Wittig reaction, alkylation products, namely 8 and 9 , respectively (cf. Scheme 1). The reaction of 4,6,8-trimethylazulene ( 10 ) with 4b in toluene showed that azulenes can, indeed, be easily alkylated with the phosphonium salt 4b . 4,6,8-Trimethylazulene-2-carbaldehyde ( 12 ) has been synthesized from the corresponding carboxylate 15 by a reduction (LiAlH₄) and dehydrogenation (MnO₂) sequence (see Scheme 2). The Swern oxidation of the intermediate 2-(hydroxymethyl)azulene 16 yielded only 1,3-dichloroazulene derivatives (cf. Scheme 2). The Wittig reaction of 12 with 4a and 4b in the presence of EtONa/EtOH in toluene yielded the expected 2-styryl derivatives 19a and 19b , respectively (see Scheme 3). Again, the yield of 19b was reduced by a competing alkylation reaction of 19b with 4b which led to the formation of the 1-benzylated product 20 (see Scheme 3). The ‘anil synthesis’ of guaiazulene ( 21 ) and the 4-R-benzanils 22 (R=H, MeO, Cl, Me₂N) proceeded smoothyl under standard conditions (powered KOH in DMF) to yield the corresponding 4-[(E)-styryl]azulene derivatives 23 (see Table 4). In minor amounts, bis(azulen-4-yl) compounds of type 24 and 25 were also formed (see Table 4). The ‘anil reaction’ of 21 and 4-NO₂C₆H₄CH=NC₆H₅ ( 22e ) in DMF yielded no corresponding styrylazulene derivative 23e . Instead, (E)-1,2-bis(7-isopropyl-1-methylazulen-4-yl)ethene ( 27 ) was formed (see Scheme 4). The reaction of 4,6,8-trimethylazulene ( 10 ) and benzanil ( 22a ) in the presence of KOH in DMF yielded the benzanil adducts 28 to 31 (cf. Scheme 5). Their direct base-catalyzed transformation into the corresponding styryl-substituted azulenes could not be realized (cf. Scheme 6). However, the transformation succeeded smoothly with KOH in boiling EtOH after N-methylation (cf. Scheme 6).     

Zinkchloridkatalysierte,thermische Umlagerungen von N-Allyl in C-Allyl-aniline; ladungsinduzierte,aromatische Amino-Claisen-Umlagerungen

N-Allyl-2-methylaniline ( 12 ) forms on heating at 140° in xylene in the presence of zinc chloride 2-allyl-6-methylanline ( 19 ) as major compound and 4-allyl-2-methylaniline ( 20 ) as well as 2,7-dimethyl-indoline ( 21 ) as minor products. Compound 21 is also formed when 19 is heated in the presence of zinc chloride (scheme 2). That 19 arises from a charge-induced [3s, 3s] sigmatropic rearrangement of 12 – and 20 from two consecutive [3s, 3s]-sigmatropic transformations – follows from the reaction of N-crotyl-2-methylaniline ( 13 ) in the presence of zinc chloride at 140°. 2-(1′-Methylallyl)-6-methylaniline ( 22 ) and 4-crotyl-2-methylaniline ( 23 ) are formed exclusively. Small amounts of 2,3,7-trimethyl-indoline ( 24 ) and 2-(cis- and trans-1′-methyl-propenyl)-6-methylaniline (cis- and trans- 25 ) are observed as by-products. Compound 24 arises from 22 in the presence of zinc chloride (scheme 3). Similar results are obtained when N-allyl and N-(2′-methylallyl)-N-methyl-aniline ( 14 and 15 , respectively) are heated in the presence of zinc chloride. Whereas 14 gives nearly exclusively 2-allyl-N-methyl-aniline ( 28 ) and only small amounts of the corresponding 1, 2-dimethyl-indoline ( 29 ) and of 2-(cis- and trans-propenyl)-N-methyl-aniline (cis- and trans- 27 ), 15 forms comparable amounts of 2-(2′-methylallyl)-N-methyl-aniline ( 30 ), 1,2,2-trimethyl-indoline ( 31 ), and 2-isobutenyl-N-methyl-aniline ( 32 ) (scheme 4). Compound 30 , and also 32 , are transformed into 31 on heating in the presence of zinc chloride. Charge-induced aromatic amino-Claisen rearrangements are also observed when N-allylated anilinium tetraphenylborates are heated at 100–105° in hexamethyl phosphoric acid triamide. Thus, N-allyl- and N-crotyl-N, N-dimethyl-anilinium tetraphenylborate ( 16 and 17 , respectively) yield 2-allyl- and 2-(1′-methylallyl)-N,N-dimethyl-aniline ( 33 and 34 , respectively) besides small amounts of N, N-dimethyl-aniline. N-Cinnamyl-N, N-dimethyl-anilinium tetraphenylborate ( 18 ) gives, besides appreciable amounts of N,N-dimethyl-aniline, a mixture of 2-(1′-phenylallyl)-,2-cinnamyl-, and 4-cinnamyl-N, N-dimethyl-aniline ( 35 , 36 , and 37 , respectively) in which the first two compounds predominate.     

An Alternative Access to (±)-α-Irones and (±)-β-Irone via Acid-Mediated Cyclisation

Acid-mediated cyclisation of trienone 8 , readily available from 2,3-dimethylbutanal ( 1 ; five steps: 47% yield), using fluorosulfonic acid (6.8 mol-equiv.) in 2-nitropropane at ?70°, afforded a 14:9:1 mixture (70% yield) of (±)-cis-α-irone ( 9 ), (±)-trans-α-irone ( 10 ), and (±)-β-irone ( 11 ). Other acidic conditions examined, using 95% aq. H₂SO₄ solution, 85% aq. H₃PO₄ solution, or SnCl₄, gave inferior results.     

Asymmetric oxidative coupling polymerization affording polynaphthylene with 1,1′-bi-2-naphthol units

The oxidative coupling polymerizations of racemic-, (R)-, and (S)-2,2′-dimethoxymethoxy-1,1′-binaphthalene-3,3′-diols were carried out with a copper catalyst with various ligands, such as N,N,N′,N′-tetramethylethylenediamine (TMEDA), (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine, (−)-sparteine, and (S)-(−)-2,2′-isopropylidenebis(4-phenyl-2-oxazoline) [(−)-Phbox], under an O₂ atmosphere. For example, a 10/1 (v/v) MeOH · H₂O-insoluble polymer with a number-average molecular weight of 3.8 × 10³, from a polymerization with CuCl–TMEDA followed by acetylation of the hydroxyl groups, was obtained in a 71% yield. Polymerization with (−)-Phbox proceeded in an S-selective manner to give a polymer with the highest negative specific rotation from the (S)-monomer. The obtained polymer was successfully converted into a polymer with the optically pure 1,1′-bi-2-naphthol unit based on the original monomer structure, which could be used as a polymeric chiral auxiliary and showed catalytic activity for the asymmetric diethylzinc addition reaction to aldehydes. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4528–4534, 2004     

New Optically Active 2H‐Azirin‐3‐amines as Synthons for Enantiomerically Pure 2,2‐Disubstituted Glycines: Synthesis of Synthons for Tyr(2Me) and Dopa(2Me), and Their Incorporation into Dipeptides

The synthesis of novel unsymmetrically 2,2‐disubstituted 2H‐azirin‐3‐amines with chiral auxiliary amino groups is described. Chromatographic separation of the mixture of diastereoisomers yielded (1′R,2S)‐ 2a , b and (1′R,2R)‐ 2a , b (c.f. Scheme 1 and Table 1), which are synthons for (S)‐ and (R)‐2‐methyltyrosine and 2‐methyl‐3′,4′‐dihydroxyphenylalanine. Another new synthon 2c , i.e., a synthon for 2‐(azidomethyl)alanine, was prepared but could not be separated into its pure diastereoisomers. The reaction of 2 with thiobenzoic acid, benzoic acid, and the amino acid Fmoc‐Val‐OH yielded the monothiodiamides 11 , the diamides 12 (cf. Scheme 3 and Table 3), and the dipeptides 13 (cf. Scheme 4 and Table 4), respectively. From 13 , each protecting group was removed selectively under standard conditions (cf. Schemes 5–7 and Tables 5–6). The configuration at C(2) of the amino acid derivatives (1R,1′R)‐ 11a , (1R,1′R)‐ 11b , (1S,1′R)‐ 12b , and (1R,1′R)‐ 12b was determined by X‐ray crystallography relative to the known configuration of the chiral auxiliary group.