Article pubs.acs.org/joc
Nonconcerted Cycloaddition of 2H-Azirines to Acylketenes: A Route to N-Bridgehead Heterocycles Alexander F. Khlebnikov,*,† Mikhail S. Novikov,† Viktoriia V. Pakalnis,† and Dmitry S. Yufit‡ †
Department of Chemistry, Saint-Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, Russia Department of Chemistry, University of Durham, Durham, South Rd., DH1 3LE, U.K.
‡
S Supporting Information *
ABSTRACT: Reactions of acylketenes, generated from diazo diketones, with 2-unsubstituted and 2-monosubstituted 3-aryl-2H-azirines lead to 1:1 or 2:1 adducts, which are derivatives of 5-oxa-1-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-1azabicyclo[4.4.1]undeca-3,8-diene. According to DFT B3LYP/6-31G(d) computations, the formation of (4+2)-monoadducts proceeds via a stepwise non-pericyclic mechanism. Reaction with methanol transforms quantitatively both 1:1 and 2:1 adducts into 1,4-oxazepine derivatives.
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Scheme 1
INTRODUCTION Ketenes have found wide application in organic synthesis because of their high reactivity and availability via Wolff rearrangement.1 They react even with such weak nucleophiles as 2H-azirines. 2 Hassner has shown that reactions of 3-arylazirines with diphenyl- and tert-butylcyanoketenes lead to the formation of 1:1 adducts, 3,3-diphenyl-1,3-dihydropyrrol-2-ones, or 1:2 adducts, 6-phenyl-2,4-bis(diphenylmethylen)1-azabicyclo[4.1.0]heptane-3,5-diones, depending on the substitution in position 2 of the azirine.3 Derivatives of pyrrolin-2ones are the products of reaction of 2-(2-formylvinyl)-3-phenyl2-methyl-2H-azirines with diphenylketene. 4 Reactions of ketenes with 2-(dimethylamino)-2H-azirines can lead to the formation of 5-(dimethylamino)pyrrolin-2-ones, 1,3-oxazolines, benzazepines, and ketene imines.5 Acylketenes are highly reactive intermediates that can be trapped by different nucleophiles and dienophiles.1,6 Their reactions give rise to products of formal [4+2]-cycloaddition. In particular, reactions of acylketenes with the CN double bond of imines and heterocycles lead to derivatives of 1,3-oxazines. 7 Reactions of acylketenes with azirines that can serve as both a nucleophile and dipolarophile are, to the best of our knowledge, still unknown. Because of our research interest concerning the chemistry of azirines8 and the synthesis of nitrogenated heterocycles via reactions of diazo compounds with imines, 8c,d,f,g,9 we envisioned the possibility of assembling a new heterocyclic system, 5-oxa-1-azabicyclo[4.1.0]hept-3-ene 1, by the reaction of azirines 2 with acylketenes 3, according to the retrosynthetic sequence described in Scheme 1.
Scheme 2
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RESULTS AND DISCUSSION Heating a toluene solution of azirines 2a−c and diazo diketone 4a (in 1:1.1 ratio), as precursor of acylketene 3a via Wolff rearrangement,1b led unexpectedly to the formation of unusual bridged heterocycles 5a−c, which are formed from one azirine and two acylketene units (Scheme 2). © 2011 American Chemical Society
The structures of compounds 5 were verified by 1H and 13C NMR, IR spectroscopy, and elemental analysis and the Received: August 1, 2011 Published: October 10, 2011 9344
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structure of 5c was confirmed by X-ray analysis (Figure 1, the nitro group is disordered over two positions).
mechanism, the calculations were performed at the DFT B3LYP/6-31G(d) level of the energy profiles of the interaction of acylketene 3a with azirine 2a and monoadduct 1a, as well as the two model reactions of azirine 2a with acrolein 8 and buta2,3-dienal 9 (Scheme 3). Scheme 3
According to the calculations, the transition states for the reactions of heterodienes 8, 9 with azirine 2a are typical for asynchronous hetero-Diels−Alder cycloaddition11 (Figure 2)
Figure 1. X-ray crystal structure of 5c.
A change in the 2a−c/4a ratio from 1:1.1 to 1:2.2 led to improved yields of compounds 5, whereas using microwave irradiation as a heat source led to a decrease in yields, although the reaction occurred much faster (Table 1).
Figure 2. Structures of transition states for the reactions of heterodienes 8, 9 with azirine 2a computed at the DFT B3LYP/631G(d) level. Hydrogen atoms on the Ph-ring are omitted for clarity.
with the activation barriers (ΔG #) of 30.8 and 27.4 kcal·mol−1, respectively. In contrast to these model reactions, no similar four-center transition state was found for the formation of the monoadduct 1a from azirine 2a and acylketene 3a. Instead of this, the intermediate 6a (Scheme 2) was located, which then cyclizes via transition state TS2 to the monoadduct 1a (Figures 3 and 4). That the reaction proceeds via route b rather than routes
Table 1. Reaction of Azirines 2a−c with Diazo Diketone 4a Ar
ratio 2:4a
solvent/temperature (°C)/time (h)
yield of 5 (%)a
Ph Ph Ph Ph 4-MeOC6H4 4-MeOC6H4 4-O2NC6H4 4-O2NC6H4
1:1.1 1:2.2 1:2.2 1:2.2 1:1.1 1:2.2 1:1.1 1:2.2
toluene/90/2 toluene/90/2 toluene/mwb/0.17 neat/mwb/0.17 toluene/90/2 toluene/90/2 toluene/90/2 toluene/90/2
55 70 25 6 48 69 49 55
a
Isolated yield based on starting azirine. bMicrowave irradiation at 160 W.
The formation of bisadducts 5 proceeds obviously via monoadduct 1. The latter may be the product of the heteroDiels−Alder cycloaddition of acylketene 3a to the CN double bond of azirine 2 (Scheme 2, route a). The alternative route (Scheme 2, route b) to monoadduct 1 could involve the formation of zwitterionic intermediate 6 by nucleophilic attack of the azirine nitrogen lone pair on the ketene, which then cyclizes to monoadduct 1. Earlier, Regits and Michels10 proposed a nonconcerted mechanism for the formation of 5-oxa-2-azatricyclo[5.2.0.02,4]nona-6,8-diens by the reaction of tert-butyl 2,3,4-tri-tert-butylcyclobutadienecarboxylate with 2H-azirines, which involved the nucleophilic addition of the carbonyl oxygen atom across the azirine CN bond to form a stabilized zwitterion and subsequent ring closure in the latter. However, in our case the analogous route c (Scheme 2) is the least probable in the absence of the specific stabilization of zwitterions 6′, which is characteristic of the zwitterion described in the work.10 The formation of bisadducts 5 proceeds most probably via the formation of zwitterionic intermediate 7 by nucleophilic attack of the aziridine nitrogen lone pair on the ketene CO group (Scheme 2). To verify the reaction
Figure 3. Energy profiles for the reactions of azirine 2a and acylketene 3a (route b), as well as acylketene 3a with monoadduct 1a. Relative free energies (kcal·mol−1, 298 K, toluene) computed at the DFT B3LYP/6-31G(d) level.
a and c is most probably because of the extremely high electrophilicity of the ketene carbonyl group. Formally, the nitrogen atom in the monoadducts 1 is amidic and consequently should have low nucleophilicity. But because of the specific geometry of the amidic fragment of the monoadducts 1, in which the nitrogen atom is included into a three-membered ring, conjugation between the carbonyl group 9345
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Figure 4. Structures of intermediates 6a, 7a and transition states TS2 and TS4 computed at the DFT B3LYP/6-31G(d) level. Hydrogen atoms are omitted for clarity.
and the nitrogen lone pair is ineffective. Thus, according to the DFT B3LYP/6-31G(d) computations, the amidic C−N bond in 1a is much longer than that in the related molecule, 3-methyl-2,5,6-triphenyl-2H-1,3-oxazin-4(3H)-one, which contains no three-membered ring: 1.421 and 1.385 Å, respectively. The nitrogen atom in monoadducts 1 has then sufficiently high nucleophilicity that it can attack the ketene CO group of 3a. According to the calculations, the interaction of 1a with 3a leads to the formation of an unstable zwitterionic intermediate 7a with an activation barrier similar to the barrier for formation of the intermediate 6a (Figure 3). The intermediate 7a further cyclizes to bisadduct 5a through a low energy barrier (TS4) due to opening of the strained aziridine ring (Figures 3 and 4), which undergoes the bridge C−N bond cleavage in the transition state (Figure 4). Further evidence for the proposed reaction route was found by studying the reactions of acylketene 3a with 2-methyl3-phenyl-2H-azirine 12 and 2,3-diphenyl-2H-azirine 13 (Scheme 4).
Figure 5. X-ray crystal structure of exo-14.
methyl-substituted azirine 12 with acylketene 3a leads to the formation of both exo-monoadduct exo-14 and endo-monoadduct endo-14, but, because of steric reasons, only the endomonoadduct endo-14 reacts further with the second molecule 3a, giving bisadduct 15. (2) The reaction of phenyl-substituted azirine 13 with acylketene 3a leads, because of steric reasons, to the formation of only the exo-monoadduct exo-16, which is unreactive toward acylketene 3a (Scheme 5). To verify this hypothesis, the DFT B3LYP/6-31G(d) computations of the interaction of acylketene 3a with 3-aryl-2H-azirines 12, 13 were performed (Figure 6). The calculations support the above hypothesis. Thus, in the case of the reaction of the methyl-substituted azirine 12, both the free energy of the transition states TS5 and TS6 leading to the intermediates syn-17, anti-17 and the free energy of the transition states TS7 and TS8 leading to endo-monoadduct endo-14 and exo-monoadduct exo-14 are close to one another. This means that both monoadducts (exo- and endo-14) have to be formed in the reaction of azirine 12 with acylketene 3a. Further reaction of isomers 14 with a second molecule of 3a is possible only for the endo-monoadduct endo-14. This is because the formation of an intermediate of type 7 from the exomonoadduct exo-14 is hindered by the exo-methyl group. This is evident from the fact that even the distance between the exohydrogen of the aziridine ring and the enolate oxygen in the intermediate 7a is only 2.22 Å. Unlike in the case of azirine 12, with azirine 13 the free energy of the transition states TS11 leading to endo-monoadduct endo-16 is much higher (by 3.5 kcal·mol−1) than the free energy of the transition state TS12 leading to exo-monoadduct exo-16. This makes the first route noncompetitive. The exo-monoadduct exo-16 is unreactive toward acylketene 3a for the reasons mentioned above for the exo-monoadduct exo-14. The 13C NMR spectrum of bisadduct 5a shows only one signal for the imidic carbonyl groups at 169.3 ppm, and the IR spectrum in KBr pellet shows a single CO vibration band υ = 1717 cm−1. This is due to actual equivalence of the carbonyl groups both in solution and in solid. Thus according to X-ray analysis, the lengths of the NCO/CO bonds in compound 5c are in fact equal (1.401(2)/1.212(2) and 1.393(2)/1.206(2) Å), and, according to the calculations, the conformations of
Scheme 4
Heating a toluene solution of azirine 12 and diazo diketone 4a (in 1:1.1 ratio), as precursor of acylketene 3a, for 2 h gave rise to the exo-monoadduct exo-14 and bisadduct 15 in 7 and 40% yield, respectively. exo-Monoadduct exo-16 was obtained as a sole product in 47% yield from azirine 13 and diazo diketone 4a under the same reaction conditions. The structures of compounds exo-14, 15, and exo-16 were verified by 1H and 13 C NMR, IR spectroscopy, and elemental analysis and the structure of exo-14 was confirmed by X-ray analysis (Figure 5). The stereochemistry of exo-monoadduct exo-16 was confirmed by X-ray analysis of the product of methanolysis of compound exo-16 (vide infra). Heating the monoadducts exo-14, exo-16 with excess of diazo diketone 4a gave no bisadducts. We believe that the substituent at position 2 of the 3-aryl-2H-azirine determines the pathway (Scheme 5) of the reaction: (1) The reaction of the 9346
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Scheme 5
Scheme 6
116.1 ppm corresponding to 25 C3 and 26 C3,9 and one quartet signal at 159.0 ppm corresponding to 25 C8 in the 13C NMR spectrum indicate the formation of isomer 26 rather than 24. This result implies that both acylketenes 20 and 21 were formed (Scheme 6) and that they further reacted with azirine 2a to give monoadducts 22 and 23. Bisadduct 26 can be formed only by reaction of monoadduct 23 with acylketene 21, whereas bisadduct 25 could be a product of the interaction of monoadduct 22 with acylketene 21 and of monoadducts 23 with acylketene 20. The absence of the bisadduct 24 in the reaction mixture indicates that acetylphenylketene 20 is less reactive toward monoadducts. Xu and Chen found that N-benzylidenanilines are much more reactive to ketene 20 than to ketene 21.7e We can suppose, therefore, that the formation of monoadduct 22 prevails over the formation of monoadduct 23. All this allows us to conclude that the formation of bisadducts proceeds mostly by reaction of both monoadducts with acylketene 21. The reaction of acylketene 3a with azirine 27, containing the fluorene moiety, proves to be more complicated because the primary intermediate 28 is more crowded and especially because of the specific stabilization by the aromatic fluorenyl anion fragment of the products of the transformations of the primary intermediate 28. Heating of a toluene solution of azirine 27 and diazo diketone 4a (in 1:1.1 ratio) gave compounds 29 (7%), 30 (31%), and 31 (6%) (Scheme 7). The structures of compounds 29−31 were verified by 1H and 13C NMR, IR spectroscopy, and elemental analysis and the structures of 29 and 30 were confirmed by X-ray analysis (Figure 7). An attack of azirine 27 on the ketene carbonyl group of acylketene 3a leads to intermediate 28, which, unlike intermediate 6, cannot cyclize with the formation of an oxazine ring as the fluorene fragment shields the aziridine carbon atom. Intermediate 28 in fact undergoes aziridine ring-opening to the zwitterion 32, which further cyclizes to monoadduct 29. Though the compound 30 can be considered as the product of (2+4)-cycloaddition of acylketene 3a to pyrrolinone 29, these
Figure 6. Energy profiles for the reaction of azirines 12 and 13 with acylketene 3a. Relative free energies (kcal·mol−1, 298 K, toluene) computed at the DFT B3LYP/6-31G(d) level.
compound 5a (see the Supporting Information) have close energies and a low barrier to interconversion, resulting in a Cs average molecular symmetry (on the NMR time scale at rt). Unlike bisadducts 5, bisadduct 15, because of the steric influence of the 11-Me-group, has a conformation in which the carbonyl groups have rather different structural characteristics. As follows from the calculations, one carbonyl group in compound 15 is conjugated with the nitrogen lone pair (N CO/CO bond lengths 1.389/1.223 Å), whereas the second is not (NCO/CO bond lengths 1.462/1.206 Å). In accordance with this, the 13C NMR spectrum of bisadduct 15 shows two imidic carbonyl signals at 166.6 and 169.0 ppm, and the IR spectrum shows two vibration bands υ = 1716 and 1718 cm−1. It is known that thermal decomposition of 2-diazo-1phenylbutane-1,3-dione 19 leads to two acylketenes 20 and 21.7d,12 In particular, when a xylene solution of diazo diketone 19 was heated at 100 °C for 0.25 h and methanol was used as a trap for the ketenes, compounds 20 and 21 were formed in the ratio of 1.3:1.7d We could therefore expect the formation of the three isomeric bisadducts 24−26 in the reaction of azirine 2a with diazo diketone 19. Heating a toluene solution of azirine 2a and diazo diketone 19 (in 1:1.1 ratio) led, however, to a mixture of only compounds 25 and 26 in a 2:1 ratio (Scheme 6). The structure of bisadducts 25 and 26 was elucidated by 1H and 13C NMR spectroscopy. The proton AB system of C11H2 proves the presence of isomer 25 of C1-symmetry, whereas the singlet of C11H2 corresponds to one of isomers 24 or 26 of Cs-symmetry. The 13C NMR spectrum (without proton decoupling) allows us to distinguish between 24 and 26. The two quartet signals at 115.6 and 9347
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Scheme 7
Figure 7. X-ray crystal structures of 29, 30.
compounds were not found to react with each other under the reaction conditions. We suppose, therefore, that zwitterion 32 interacts with a second molecule of 3a to give finally bisadduct 30. The formation of product 31 most probably proceeds via a quite different pathway. Earlier, we found that 1,4-oxazine derivatives can be prepared by the reaction of azirines with Rhcarbenoids generated from diazo keto esters. This reaction proceeds via formation of azirinium ylide, which undergoes ring-opening to oxazatriene, followed by 6π-cyclization of the latter.8f According to this, the carbene, derived from diazo compound 4a, would be expected to react with azirine 27 to give ylide 34, which is then further transformed to compound 31 via 6π-cyclization of oxazatriene 35. To prove the role of the aromatic fluorenyl anion fragment in the aforementioned transformations, the reaction between diazo compound 4a with 2,2,3-triphenyl-2H-azirine 36, containing a crowded CN bond like in 27, was investigated. In accordance with the discussed hypotheses, the only product of this reaction was oxazine 37, which was obviously formed analogously to oxazine 31 via carbene 33 and ylide 38 (Scheme 8). The low yields of oxazines 31, 37 is due to easiness of the Wolff rearrangement of diazo compound 4a.1 Compounds 5 isolated as solids are fairly stable and can be stored indefinitely at rt. However, when solutions of compounds 5a,c in a mixture of CH2Cl2/MeOH (1:2) were kept at room temperature, they were quantitatively transformed into
Scheme 8
Scheme 9
oxazepines 40a,b (Scheme 9). Analogously, when a solution of compound exo-16 in a mixture of CH2Cl2/MeOH was boiled for 2 h, it was transformed stereoselectively into oxazepine 41 (Scheme 9). The structures of compounds 40a,b and 41 were verified by 1H and 13C NMR, IR spectroscopy, and elemental analysis and the structures of 40a and 41 were confirmed by X-ray analysis (see the Supporting Information). 9348
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128.7 (2CH), 129.1 (2CH), 129.9 (4CH), 130.1 (CH), 131.1 (4CH), 135.1 (2C), 135.4 (2C), 137.2 (C), 157.4 (2C), 166.3 (2C); IR (KBr, cm−1) ν 3060, 1717, 1637, 1616, 1445, 1391, 1357, 1223, 1096, 1040, 974, 754, 694, 614, 486, 474. Anal. Calcd for C38H27NO4: C 81.27, H 4.85, N 2.49. Found: C 81.43, H 4.87, N 2.70. 6-(4-Methoxyphenyl)-3,4,8,9-tetraphenyl-5,7-dioxa-1azabicylo[4.4.1]undeca-3,8-diene-2,10-dione, 5b. White solid: mp 193−195 °C (hexane−CH2Cl2); yield, 69%; 1H NMR (CDCl3) δ 3.81 s (3H, OCH3), 5.03 s (2H, CH2), 6.81− 6.85 m (2H, arom), 6.94−6.97 m (4H, arom), 7.01−7.06 m (4H, arom), 7.11−7.16 m (2H, arom), 7.21−7.24 m (6H, arom), 7.32−7.35 m (4H, arom), 7.51−7.54 m (2H, arom); 13 C NMR (CDCl3) δ 47.6 (CH2), 55.3 (OCH3), 113.9 (2CH), 114.0 (C, C), 121.6 (C), 126.9 (2CH), 127.5 (2CH), 127.6 (4CH), 128.1 (4CH), 129.1 (2CH), 129.5 (C), 129.9 (4CH), 131.2 (4CH), 135.2 (2C), 135.5 (2C), 157.5 (2C), 160.6 (C), 166.4 (2C); IR (KBr, cm−1) ν 3062, 1718, 1637, 1616, 1351, 618, 475. Anal. Calcd for C39H29NO5: C 79.17, H 4.94, N 2.37. Found: C 79.19, H 4.92, N 2.14. 6-(4-Nitrophenyl)-3,4,8,9-tetraphenyl-5,7-dioxa-1azabicylo[4.4.1]undeca-3,8-diene-2,10-dione, 5c. White solid: mp 220−222 °C (toluene); yield, 55%; 1H NMR (CDCl3) δ 5.11 s (2H, CH2), 6.95−6.99 m (4H, arom), 7.02− 7.07 m (4H, arom), 7.12−7.17 m (2H, arom), 7.22−7.30 m (10H, arom), 7.66−7.70 m (2H, arom), 8.04−8.08 m (2H, arom); 13C NMR (CDCl3) δ 47.1 (CH2), 112.5 (C, C), 122.9 (C), 123.6 (2CH), 126.7 (2CH), 127.8 (4CH), 127.9 (2CH), 128.2 (2CH), 128.3 (4CH), 129.5 (4CH), 131.0 (4CH), 134.8 (2C), 134.9 (2C), 143.5 (C), 148.3 (C), 156.7 (2C), 166.0 (2C); IR (KBr, cm−1) ν 3057, 1730, 1609, 1527, 1445, 1349, 1222, 1041, 963, 697. Anal. Calcd for C38H26N2O6: C 75.24, H 4.32, N 4.62. Found: C 75.43, H 4.26, N 4.71. Crystal data: C38H26N2O6, M = 606.61, monoclinic, space group P21/n (No. 14), a = 9.5212(3), b = 10.8122(4), c = 28.4537(11) Å, β = 94.39(1)°, U = 2920.56(18) Å3, Z = 4; F(000) = 1264, Dc = 1.380 mg/m3, μ = 0.094 mm−3. 39887 reflections were measured yielding 7747 unique data (Rint = 0.0325). The final wR(F 2) was 0.1482 (all data), conventional R1(F) = 0.0530 for 6152 reflections with I ≥ 2σ, GOF = 1.062. Reaction of 2-Methyl-3-phenyl-2H-azirine 12 and 2Diazo-1,3-diphenylpropane-1,3-dione 4a. A mixture of azirine 12 (65.5 mg, 0.5 mmol) and diazo diketone 4a (137.5 mg, 0.55 mmol) in dry toluene (4 mL) was heated with stirring at 90 °C for 2 h. The reaction was monitored by TLC (eluent hexane/ethyl acetate, 5:1). The crystalline compound 15 (115 mg, 40%) obtained on cooling the reaction mixture was filtered off and washed with diethyl ether. The solvent was removed in vacuum, and the residue was purified by recrystallization from hexane/CH2Cl2 mixture (3:1) to give compound exo-14 (12.4 mg, 7%). (6RS,7RS)-7-Methyl-3,4,6-triphenyl-5-oxa-1azabicyclo[4.1.0]hept-3-en-2-one, exo-14. Colorless crystals: mp 59−60 °C (hexane−CH2Cl2); 1H NMR (CDCl3) δ 1.21 d (3H, J = 5.5 Hz, CH3), 3.31 q (1H, J = 5.8 Hz, CH), 7.18−7.27 m (8H, arom), 7.49−7.53 m (5H, arom), 7.72−7.75 m (2H, arom); 13C NMR (CDCl3) δ 13.7 (CH3), 42.8 (CH), 78.5 (C), 110.2 (C), 127.28 (2CH), 127.32 (CH), 127.8 (2CH), 128.1 (2CH), 128.2 (2CH), 129.1 (CH), 129.4 (2CH), 130.2 (CH), 131.0 (2CH), 132.6 (2C), 134.0 (C), 162.2 (C), 173.5 (C); IR (KBr, cm−1) ν 3060, 1619, 1612, 1597, 1446, 982, 996, 716, 697. Anal. Calcd for C 24H19NO2: C 81.56, H 5.42, N 3.96. Found: C 81.46, H 5.48, N 3.84. Crystal
CONCLUSION Acylketenes, generated from diazo diketones, react with 2unsubstituted and 2-monosubstituted 2H-azirines with formation of 2:1 or 1:1 adducts, derivatives of 5,7-dioxa-1azabicyclo[4.4.1]undeca-3,8-diene or 5-oxa-1-azabicyclo[4.1.0]hept-3-ene. The composition and the stereochemistry of the products, as well as the DFT B3LYP/6-31G(d) calculations, prove a stepwise non-pericyclic mechanism for the formation of 5-oxa-1-azabicyclo[4.1.0]hept-3-ene derivatives. This is due, on the one hand, to the extremely high electrophilicity of the ketene carbonyl group and, on the other hand, due to the sufficiently high nucleophilicity of the nitrogen atom in the monoadducts 1 because of the specific geometry of the amidic fragment in the bicycle 1. The reaction of 2-diazo-1,3diphenylpropane-1,3-dione with the 2,2-disubstituted azirine, 3-phenylspiro[2H-azirine-2,9′-fluorene], proceeds via quite different routes for steric reasons and because of the stabilization of the intermediates by the aromatic fluorenyl anion fragment. Both the 1:1 and 2:1 adducts are quantitatively transformed under mild conditions with methanol into 1,4oxazepine derivatives.
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EXPERIMENTAL SECTION General Methods. Melting points were determined on a hot stage microscope and are uncorrected. 1H (300 MHz) and 13 C (75 or 150 MHz) NMR spectra were determined in CDCl3. Chemical shifts (δ) are reported in ppm downfield from tetramethylsilane. Single crystal X-ray data for all compounds were collected at 120 K on a SMART-6000 diffractometer (graphite-monochromated Mo−Kα radiation, λ = 0.71073 Å) equipped with open-flow nitrogen cryostat. All structures were solved by direct method and refined by fullmatrix least-squares on F 2 for all data using OLEX213 and SHELXTL14 software. All non-disordered non-hydrogen atoms were refined with anisotropic displacement parameters; Hatoms were located on the difference map and refined isotropically in all structures except 30, where they were placed into calculated positions and refined in the riding mode. The reactions under microwave irradiation at 160 W were carried out in a sealed flask in Minotavr-2 microwave oven for laboratory experiments. Compounds 2a,b,15 2c,16 4a, 19,17 12,18 13,19 and 2720 were prepared by the reported procedures. General Procedures for Reactions of Azirines 2a−c and 2-Diazo-1,3-diphenylpropane-1,3-dione 4a. A mixture of compound 2a−c (0.5 mmol) and 4a (275 mg, 1.1 mmol) in dry toluene (4 mL) was heated at the reaction temperature and reaction time indicated in Table 1. The reaction was monitored by TLC (eluent hexane/ethyl acetate, 5:1). The crystalline substance obtained after cooling the reaction mixture to rt was filtered off and washed with diethyl ether. An additional amount of the product was isolated from the filtrate by removing the solvent in vacuum, followed by recrystallization of the residue from hexane/CH2Cl2 mixture (5:1). 3,4,6,8,9-Pentaphenyl-5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene-2,10-dione, 5a. White solid: mp 221− 223 °C (hexane−CH2Cl2); yield, 70%; 1H NMR (CDCl3) δ 5.07 s (2H, CH2), 6.93−6.99 m (4H, arom), 7.00−7.04 m (4H, arom), 7.10−7.15 m (2H, arom), 7.19−7.23 m (6H, arom), 7.30−7.38 m (7H, arom), 7.60 dd (2H, J = 7.8 Hz, J = 1.4 Hz, arom); 13C NMR (CDCl3) δ 47.4 (CH2), 113.9 (C, C), 121.8 (C), 125.3 (2CH), 127.5 (4CH), 127.6 (2CH), 128.1 (4CH), 9349
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data: C24H19NO2, M = 353.40, monoclinic, space group C2/c (No. 15), a = 9.6834(2), b = 19.3806(4), c = 19.9584(4) Å, β = 98.46(1)°, U = 3704.80(13) Å3, Z = 8; F(000) = 1488, Dc = 1.267 mg/mm3, μ = 0.080 mm−1. 30608 reflections were measured yielding 4933 unique data (Rint = 0.0430). The final wR(F 2) was 0.1176 (all data), conventional R1(F) = 0.0431 for 3619 reflections with I ≥ 2σ, GOF = 1.030. 11-Methyl-3,4,6,8,9-pentaphenyl-5,7-dioxa-1azabicyclo[4.4.1]undeca-3,8-diene-2,10-dione, 15. White solid: mp 190−192 °C (toluene); 1H NMR (CDCl3) δ 1.81 d (3H, J = 7.3 Hz, CH3), 5.16 q (1H, J = 7.3 Hz, C11H), 6.68−6.70 m (2H, arom), 6.88−6.93 m (2H, arom), 7.04−7.09 m (1H, arom), 7.15−7.19 m (3H, arom), 7.22−7.27 m (8H, arom), 7.31−7.34 (2H, arom), 7.38−7.41 m (2H, arom), 7.50− 7.52 m (3H, arom), 7.82−7.85 m (2H, arom); 13C NMR (CDCl3) δ 13.4 (CH3), 54.8 (CH), 111.2 (C), 117.1 (C), 122.0 (C), 125.2 (2CH), 126.9 (CH), 127.4 (2CH), 127.7 (2CH, CH), 127.8 (2CH), 128.2 (2CH), 128.9 (CH), 129.2 (2CH), 129.5 (2CH), 129.6 (CH), 130.3 (CH), 130.8 (2CH), 131.3 (2CH), 131.7 (2CH), 135.0 (C), 135.4 (C), 136.3 (C), 137.0 (2C), 155.0 (2C), 166.6 (C), 169.0 (C); IR (KBr, cm −1) ν 3058, 1717, 1716, 1600, 1445, 1331, 1322, 1235, 1144, 987, 742, 696. Anal. Calcd for C39H29NO4: C 81.37, H 5.08, N 2.43. Found: C 81.30, H 4.96, N 2.17. (6RS,7RS)-3,4,6,7-Tetraphenyl-5-oxa-1-azabicyclo[4.1.0]hept-3-en-2-one, exo-16. A mixture of azirine 13 (96.5 mg, 0.5 mmol) and diazo diketone 4a (137.5 mg, 0.55 mmol) in dry toluene (7 mL) was heated with stirring at 90 °C for 2 h. The reaction was monitored by TLC (eluent hexane/ ethyl acetate, 5:1). The solvent was removed in vacuum, and the residue was crystallized from petroleum ether/ethyl acetate mixture (4:1) to give compound exo-16 (97.5 mg, 47%). Yellowish solid: mp 149−150 °C (petroleum ether−ethyl acetate, 4:1); 1H NMR (CDCl3) δ 4.36 s (1H, CH), 7.16−7.39 m (18H, arom), 7.59−7.62 m (2H, arom); 13C NMR (CDCl3) δ 48.2 (CH), 79.5 (C), 110.4 (C), 127.4 (CH), 127.47 (2CH), 127.49 (2CH), 127.8 (CH), 127.9 (2CH), 128.0 (2CH), 128.17 (2CH), 128.23 (2CH), 129.0 (CH), 129.5 (2CH), 130.3 (CH), 131.0 (2CH), 132.4 (2C), 132.5 (C), 133.0 (C), 162.5 (C), 172.7 (C); IR (KBr, cm−1) ν 3061, 1690, 1681, 1608, 1595, 1571, 1497, 1448, 1356, 1231, 1223, 1014, 767, 751, 695. Anal. Calcd for C29H21NO2: C 83.83, H 5.09, N 3.37. Found: C 83.76, H 5.10, N 3.28. 3,8-Dimethyl-4,6,9-triphenyl-5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene-2,10-dione, 25, 3,9-Dimethyl4,6,8-triphenyl-5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8diene-2,10-dione, 26. A mixture of 3-phenyl-2H-azirine 2a (117 mg, 1 mmol) and 2-diazo-1-phenyl-butane-1,3-dione 19 (207 mg, 1.1 mmol) in dry toluene (4 mL) was heated with stirring at 90 °C for 2 h. The reaction was monitored by TLC (eluent hexane/ethyl acetate, 4:1). A solid mixture of compounds 25 and 26 was obtained on cooling the reaction mixture, and this was filtered off and washed with diethyl ether. An additional amount of compounds 25 and 26 was isolated from the filtrate by removing the solvent in vacuum, followed by recrystallization of the residue from hexane/CH 2Cl2 mixture to give the 2:1 mixture of compounds 25 and 26 (131 mg, 30% overall yield). White solid: mp 168−173 °C (petroleum ether−CH2Cl2, 4:1); 1H NMR (CDCl3) δ 1.78 s (3H, CH3, major), 2.04 s (3H, CH3), 2.05 s (3H, CH3), 4.73 d (1H, JAB = 16.3 Hz, CHAHB, major), 4.74 s (2H, CH2, minor), 4.78 d (1H, JAB = 16.3 Hz, CHAHB, major), 7.13−7.19 m (4H, arom), 7.22−7.27 m (3H,
arom), 7.29−7.41 m (13H, arom), 7.51−7.53 m (2H, arom); 13 C NMR (CDCl3) δ 16.36, 16.42 (2CH3 minor, CH3 major), 22.1 (CH3 major), 47.3 (CH2 minor), 47.5 (CH2 major), 112.7 (C), 113.7 (C), 115.6, 116.1 (2C minor, C major), 120.2 (C), 125.0 (CH), 125.2 (CH), 127.7 (CH), 127.89 (CH), 127.94 (CH), 128.2 (CH), 128.3 (CH), 128.6 (CH), 128.67 (CH), 128.70 (CH), 129.1 (CH), 129.2 (CH), 129.6 (CH), 129.9 (CH), 130.3 (CH), 135.69 (C), 135.71 (C), 137.5 (C), 137.9 (C), 156.16 (C), 156.24 (C), 159.0 (C major), 165.3 (C major), 167.65 (C), 167.69 (C); IR (KBr, cm −1) ν 3056, 1725, 1620, 1450, 1443, 1381, 1358, 1230, 1152, 1053, 1030, 779, 775, 760, 697. Anal. Calcd for C28H23NO4: C 76.87, H 5.30, N 3.20. Found: C 76.63, H 5.14, N 3.37. Reaction of 3-Phenylspiro[2H-azirine-2,9′-fluorene] 27 and 2-Diazo-1,3-diphenyl-propane-1,3-dione 4a. A mixture of azirine 27 (267 mg, 1 mmol) and diazo diketone 4a (275 mg, 1.1 mmol) in dry toluene (5.5 mL) was heated with stirring at 90 °C for 2 h. The reaction was monitored by TLC (eluent hexane/ethyl acetate, 4:1). The solvent was removed in vacuum, the residue was purified by flash chromatography on silica (hexane/ethyl acetate, 10:1) to give compounds 29 (34 mg, 7%), 30 (123 mg, 17%), and 31 (30 mg, 6%). 4′-Benzoyl-2′,4′-diphenylspiro[fluorene-9,3′-pyrrol]5′(4′H)-one, 29. Colorless crystals: mp 194−195 °C (Et2O); 1 H NMR (CDCl3) δ 6.76 t (2H, J = 7.6 Hz, arom), 6.89 t (1H, J = 7.3 Hz, arom), 7.08−7.25 m (8H, arom), 7.30−7.35 m (2H, arom), 7.40−7.56 m (6H, arom), 7.62−7.65 m (3H, arom), 7.89 d (1H, J = 8.0 Hz, arom); 13C NMR (CDCl3) δ 75.1 (C), 84.0 (C), 119.99 (CH), 120.05 (CH), 124.4 (CH), 127.0 (2CH), 127.2 (CH), 127.3 (CH), 127.5 (2CH), 127.9 (CH), 128.4 (2CH), 128.5 (2CH), 129.0 (CH), 129.1 (CH), 129.3 (CH), 130.0 (2CH), 130.4 (2CH), 130.8 (C), 132.0 (CH), 133.9 (C), 134.0 (CH), 136.7 (C), 139.6 (C), 142.2 (C), 143.1 (C), 143.2 (C), 185.9 (C), 194.6 (C), 197.8 (C); IR (KBr, cm−1) ν 3062, 1739, 1672, 1670, 1599, 1534, 1532, 1446, 1324, 1229, 1137, 988, 962, 756, 750, 737, 707, 694, 651, 581. Anal. Calcd for C35H23NO2: C 85.87, H 4.74, N 2.86. Found: C 85.80, H 4.80, N 2.99. Crystal data: C35H23NO2, M = 489.54, orthorhombic, space group P212121 (No. 19), a = 10.5934(2), b = 12.6294(3), c = 18.7414(4) Å, U = 2507.38(9) Å3, Z = 4; F(000) = 1024, Dc = 1.297 mg/mm−3, μ = 0.080 mm−1. 44620 reflections were measured yielding 7312 unique data (Rint = 0.0540). The final wR(F 2) was 0.0981 (all data), conventional R1(F) = 0.0391 for 6095 reflections with I ≥ 2σ, GOF = 1.036. (7′RS,8a′SR)-7′-Benzoyl-2′,3′,7′,8a′-tetraphenylspiro[fluorene-9,8′-pyrrolo[2,1-b][1,3]oxazine]4′,6′(7′H,8a′H)-dione, 30. Colorless crystals: mp 147−148 °C (CH2Cl2); 1H NMR (CDCl3) δ 6.24 br d (1H, J = 6.2 Hz, arom), 6.57 d (1H, J = 8.0 Hz, arom), 6.78 br t (1H, J = 7.6 Hz, arom), 6.84−6.87 m (3H, arom), 6.96 br t (1H, J = 7.6 Hz, arom), 7.04−7.27 m (18H, arom), 7.30−7.38 m (5H, arom), 7.50 d (1H, J = 6.9 Hz, arom), 7.55 td (1H, J = 7.6 Hz, J = 0.7 Hz, arom), 7.77 d (1H, J = 7.3 Hz, arom); 13C NMR (CDCl3) δ 65.5 (C), 75.4 (C), 97.3 (C), 115.4 (C), 119.8 (CH), 119.9 (CH), 123.2 (CH), 123.4 (CH), 125.5 (CH), 126.6 (CH), 126.9 (2CH), 127.0 (CH), 127.4 (CH), 127.7 (CH), 127.8 (CH), 127.9 (3CH), 128.0 (2CH), 128.3 (2CH), 128.7 (CH), 129.0 (CH), 129.1 (CH), 129.7 (2CH), 129.8 (2CH), 129.9 (2CH), 130.7 (CH), 130.8 (CH), 131.4 (2CH), 131.5 (CH), 132.26 (C), 132.30 (C), 134.0 (C), 134.5 (C), 137.8 (C), 138.4 (C), 140.7 (C), 144.1 (C), 146.2 (C), 160.2 (C), 163.4 (C), 171.5 (C), 196.4 (C); IR (KBr, cm−1) ν 3061, 1769, 1685, 1560, 1447, 1356, 1297, 1277, 1263, 1231, 1181, 782, 757, 739, 9350
dx.doi.org/10.1021/jo201563b | J. Org. Chem. 2011, 76, 9344−9352
The Journal of Organic Chemistry
Article
697, 624. Anal. Calcd for C50H33NO4: C 84.37, H 4.67, N 1.97. Found: C 84.43, H 4.62, N 2.02. Crystal data: C 50H33NO4 × CH2Cl2, M = 769.70, monoclinic, space group Cc (No. 9), a = 14.3216(5), b = 14.1401(5), c = 20.2005(7) Å, β = 93.068(10)°, U = 4084.9(2) Å3, Z = 4; F(000) = 1656, Dc = 1.295 mg/mm−3, μ = 0.207 mm−1. 38350 reflections were measured yielding 9858 unique data (Rint = 0.0686). The final wR(F 2) was 0.1322 (all data), conventional R1(F) = 0.0529 for 6802 reflections with I ≥ 2σ, GOF = 0.987. (3′,6′-Diphenylspiro[fluorene-9,2′-[1,4]oxazine]-5′-yl)(phenyl)methanone, 31. Yellow solid: mp 249−251 °C (hexane−ethyl acetate); 1H NMR (CDCl3) δ 7.05 t (2H, J = 7.3 Hz, arom), 7.12−7.17 m (1H, arom), 7.22−7.27 m (5H, arom), 7.30−7.36 m (4H, arom), 7.48−7.53 m (4H, arom), 7.56−7.60 m (3H, arom), 7.82 d (2H, J = 7.3 Hz, arom), 8.11− 8.14 m (2H, arom); 13C NMR (CDCl3) δ 98.1 (C), 110.0 (C), 121.0 (2CH), 124.9 (2CH), 126.7 (CH), 128.27 (2CH), 128.35 (2CH), 128.4 (2CH), 128.6 (2CH), 128.7 (2CH), 128.9 (2CH), 129.8 (2CH), 130.7 (2CH), 132.0 (CH), 132.5 (CH), 134.8 (C), 139.8 (C), 140.5 (2C), 142.3 (2C), 164.3 (C), 172.3 (C), 196.4 (C); IR (KBr, cm−1) ν 3057, 1667, 1636, 1536, 1448, 1218, 1002, 757, 733, 686. Anal. Calcd for C35H23NO2: C 85.87, H 4.74, N 2.86. Found: C 85.74, H 4.87, N 2.81. Phenyl(2,5,6,6-tetraphenyl-6H-[1,4]oxazin-3-yl)methanone, 37. A mixture of 2,2,3-triphenyl-2H-azirine 36 (128 mg, 0.475 mmol) and diazo diketone 4a (131 mg, 0.52 mmol) in dry toluene (3 mL) was heated with stirring at 90 °C for 2 h. The reaction was monitored by TLC (eluent petroleum ether/ethyl acetate, 5:1). The solvent was removed in vacuum, and the residue was purified by flash chromatography on silica (petroleum ether/ethyl acetate, 10:1) to give compound 37 (15 mg, 6%). Yellow solid: mp 172−173 °C (Et2O); 1H NMR (CDCl3) δ 7.18−7.23 m (4H, arom), 7.27−7.32 m (3H, arom), 7.40−7.41 m (10H, arom), 7.51−7.63 m (6H, arom), 8.02−8.05 m (2H, arom); 13C NMR (CDCl3) δ 99.1, 109.7, 126.560, 126.564, 126.57, 128.21, 128.24, 128.26, 128.34, 128.456, 128.460, 128.6, 128.9, 129.7, 129.95, 129.96, 130.9, 131.7, 132.3, 134.8, 138.4, 139.7, 163.0, 173.2, 196.4; IR (KBr, cm −1) ν 2961, 2925, 1634, 1617, 1446, 1359, 1262, 1219, 1180, 1100, 986, 760, 693, 615; HRMS-ESI calcd for C35H26NO2+ [M + H]+, 492.1964, found 492.1940. General Procedure for Reactions of 5a,c with Methanol. Solutions of 5a,c (0.036 mmol) in methanol/ CH2Cl2 mixture (2:1) were kept at rt until the reaction was completed (24 h for 5a, 2 weeks for 5c). The reaction was monitored by TLC (eluent hexane/ethyl acetate 2:1). The solvent was removed in vacuum, and the residue was recrystallized from methanol to give compounds 40a (20 mg, 95%) and 40b (21.5 mg, 93%). (Z)-Methyl 3-(5-Oxo-2,6,7-triphenyl-2,3,4,5-tetrahydro-1,4-oxazepin-2-yloxy)-2,3-diphenylacrylate, 40a. Colorless crystals: mp 175−180 °C (methanol); 1H NMR (CDCl3) δ 3.82 s (3H, OCH3), 4.19 dd (1H, JAB = 15.3 Hz, JBX = 6.9 Hz, CHBHA), 4.48 dd (1H, JAB = 15.3 Hz, JAX = 6.9 Hz, CHAHB), 6.02 br (1H, NH), 6.24 d (2H, J = 7.7 Hz, arom), 6.68−6.73 m (2H, arom), 6.74−6.78 m (2H, arom), 6.93−6.98 m (1H, arom), 7.00−7.03 m (3H, arom), 7.11−7.14 m (2H, arom), 7.17−7.24 m (6H, arom), 7.29−7.49 m (5H, arom), 7.49−7.51 m (2H, arom); 13C NMR (CDCl3) δ 50.1 (CH2), 52.0 (OCH3), 111.4 (2C), 121.0 (C), 126.6 (2CH), 126.8 (CH), 127.15 (CH), 127.23 (2CH), 127.7 (2CH), 127.8
(2CH), 127.9 (2CH), 128.0 (2CH), 128.1 (CH), 128.6 (CH), 128.8 (CH), 129.7 (2CH), 129.9 (2CH), 130.4 (2CH), 130.9 (2CH), 133.8 (C), 135.1 (C), 135.8 (C), 136.5 (C), 137.4 (C), 155.6 (C), 156.9 (C), 168.5 (C), 170.2 (C); IR (KBr, cm −1) ν 3410, 3186, 3058, 2948, 1717, 1713, 1662, 1631, 1491, 1446, 1325, 1258, 1220, 1099, 1089, 1068, 1001, 970, 774, 696. Anal. Calcd for C39H31NO5: C 78.90, H 5.26, N 2.36. Found: C 79.03, H 5.21, N 2.29. Crystal data: C39H31NO5 × EtOH, M = 639.72, triclinic, space group P1̅ (No. 2), a = 10.1297(3), b = 12.8314(4), c = 14.6074(4) Å, α = 96.969(10), β = 104.944(10), γ = 106.416(10)°, U = 1720.58(9) Å3, F(000) = 676, Dc = 1.235 mg/mm−3, μ = 0.082 mm−1. 26722 reflections were measured yielding 9595 unique data (Rint = 0.0657). The final wR(F 2) was 0.0996 (all data), conventional R1(F) = 0.0441 for 5796 reflections with I ≥ 2σ, GOF = 0.921. (Z)-Methyl 3-(2-(4-Nitrophenyl)-5-oxo-6,7-diphenyl2,3,4,5-tetrahydro-1,4-oxazepin-2-yloxy)-2,3-diphenylacrylate, 40b. Colorless crystals: mp 204−205 °C (methanol); 1 H NMR (CDCl3) δ 3.81 s (3H, OCH3), 4.19 dd (1H, JAB = 15.4 Hz, JBX = 6.5 Hz, CHBHA), 4.50 dd (1H, JAB = 15.4 Hz, JAX = 6.5 Hz, CHAHB), 6.25 br d (2H, J = 7.6 Hz, arom), 6.35 br (1H, NH), 6.69−6.76 m (4H, arom), 6.97−7.08 m (4H, arom), 7.09−7.13 m (2H, arom), 7.18−7.27 m (3H, arom), 7.32−7.37 m (5H, arom), 7.70−7.74 m (2H, arom), 8.00−8.05 m (2H, arom); 13C NMR (CDCl3) δ 49.7 (CH2), 52.2 (OCH3), 110.5 (2C), 121.8 (C), 122.8 (2CH), 126.9 (2CH), 127.1 (CH), 127.4 (CH), 127.9 (2CH), 128.0 (2CH), 128.1 (2CH), 128.6 (2CH), 128.7 (CH), 129.0 (CH), 129.6 (2CH), 129.7 (2CH), 130.5 (2CH), 130.7 (2CH), 133.1 (C), 134.6 (C), 135.2 (C), 136.0 (C), 144.4 (C), 147.9 (C), 155.2 (C), 155.7 (C), 168.5 (C), 170.1 (C); IR (KBr, cm−1) ν 3417, 3057, 2946, 1722, 1693, 1675, 1614, 1523, 1444, 1404, 1346, 1327, 1212, 1097, 1067, 1038, 1017, 1002, 972, 853, 766, 696. Anal. Calcd for C39H30N2O7: C 73.34, H 4.73, N 4.39. Found: C 73.41, H 4.59, N 4.50. (2RS,3SR)-2-Methoxy-2,3,6,7-tetraphenyl-3,4-dihydro1,4-oxazepin-5(2H)-one, 41. Compound 16 (60 mg, 0.1445 mmol) in dry methanol/CH2Cl2 mixture (2:1, 3 mL) was refluxed with stirring for 2.5 h. The reaction mixture was cooled, and the solid product was filtered and washed with methanol. An additional amount of compound 41 (overall yield 56 mg, 86%) was isolated from the filtrate by removing the solvent in vacuum, followed by recrystallization of the residue from a mixture of hexane−CH2Cl2. Colorless crystals: mp >260 °C (ethanol); 1H NMR (CDCl3) δ 2.79 s (3H, OCH3), 5.27 d (1H, J = 6.2 Hz, C3H), 6.31 br d (1H, J = 5.8 Hz, NH), 6.76 d (2H, J = 7.6 Hz, arom), 7.07 br (2H, arom), 7.17−7.29 m (13H, arom), 7.31−7.37 m (1H, arom), 7.40−7.43 m (2H, arom); 13C NMR (CDCl3) δ 51.4 (OCH3), 64.1 (CH), 115.0 (C), 125.4 (C), 127.3 (2CH), 127.6 (CH), 127.8 (2CH), 127.9 (2CH), 128.2 (CH), 128.3 (4CH), 128.77 (CH), 128.85 (CH), 129.0 (2CH), 129.2 (2CH), 130.7 (2CH), 134.1 (C), 134.7 (C), 135.1 (C), 136.0 (C), 155.1 (C), 170.9 (C); IR (KBr, cm−1) ν 3425, 3199, 3058, 1658, 1446, 1395, 1325, 1223, 1122, 980, 719, 698. Anal. Calcd for C30H25NO3: C 80.51, H 5.63, N 3.13. Found: C 80.53, H 5.54, N 3.09. Crystal data: C30H25NO3, M = 447.51, monoclinic, space group C2/c (No. 15), a = 24.4292(6), b = 10.2810(3), c = 21.1739(5) Å, β = 117.263(10)°, U = 4727.2(2) Å3, Z = 8; F(000) = 1888, Dc = 1.258 mg/mm−3, μ = 0.081 mm−1. 26620 reflections were measured yielding 6588 unique data (Rint = 0.0233). The final wR(F 2) was 0.1217 (all data), conventional R1(F) = 0.0411 for 5481 reflections with I ≥ 2σ, GOF = 1.049. 9351
dx.doi.org/10.1021/jo201563b | J. Org. Chem. 2011, 76, 9344−9352
The Journal of Organic Chemistry
Article
L; Li, Y; Dong, Y.; Gong, M.; Zhao, X.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2011, 133, 4330. (i) Presset, M.; Mohanan, K.; Hamann, M.; Coquerel, Y.; Rodriguez, J. Org. Lett. 2011, 13, 4124. (8) (a) Khlebnikov, A. F.; Novikov, M. S.; Amer, A. A. Tetrahedron Lett. 2002, 43, 8523. (b) Khlebnikov, A. F.; Novikov, M. S.; Amer, A. A. Russ. Chem. Bull. 2004, 1092. (c) Khlebnikov, A. F.; Novikov, M. S.; Amer, A. A. Tetrahedron Lett. 2004, 45, 6003. (d) Khlebnikov, A. F.; Novikov, M. S.; Amer, A. A.; Kostikov, R. R.; Magull, J.; Vidovic, D. Russ. J. Org. Chem. 2006, 42, 515. (e) Novikov, M. S.; Amer, A. A.; Khlebnikov, A. F. Tetrahedron Lett. 2006, 47, 639. (f) Khlebnikov, V. A.; Novikov, M. S.; Khlebnikov, A. F.; Rostovskii, N. V. Tetrahedron Lett. 2009, 50, 6509. (g) Khlebnikov, A. F.; Novikov, M. S. Russ. J. Gen. Chem. 2010, 80, 1652. (h) Khlebnikov, A. F.; Novikov, M. S.; Petrovskii, P. P.; Stoeckli-Evans, H. J. Org. Chem. 2011, 76, 5384. (9) (a) Khlebnikov, A. F.; Novikov, M. S.; Kostikov, R. R. Russ. Chem. Rev. 2005, 74, 171. (b) Khlebnikov, A. F.; Novikov, M. S.; Bespokoev, A. A.; Kostikov, R. R.; Kopf, J.; Starikova, Z. A.; Antipin, M. Yu. Russ. J. Org. Chem. 2005, 41, 922. (c) Khlebnikov, A. F.; Novikov, M. S.; Kostikov, R. R.; Kopf, J. Russ. J. Org. Chem. 2005, 41, 1341. (10) Regitz, M.; Michels, G. Chem. Ber. 1990, 123, 927. (11) Ç elebi-Ö lçüm, N.; Ess, D. H.; Aviyente, V; Houk, K. N. J. Org. Chem. 2008, 73, 7472. (12) Tomioka, H.; Hayashi, N.; Asano, T.; Izawa, Y. Bull. Chem. Soc. Jpn. 1983, 56, 758. (13) Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. J. Appl. Crystallogr. 2009, 42, 339. (14) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112. (15) Hortmann, A.; Robertson, D.; Gillard, B. J. Org. Chem. 1972, 37, 322. (16) Brown, D.; Brown, G. A.; Andrews, M.; Large, J. M.; Urban, D.; Butts, C. P.; Hales, N. J.; Gallagher, T. J. Chem. Soc., Perkin Trans. 1 2002, 2014. (17) Popic, V. V.; Korneev, S. M.; Nikolaev, V. A.; Korobitsyna, I. K. Synthesis 1991, 195. (18) Komatsu, M.; Ichijima, S.; Ohshiro, Y.; Agawa, T. J. Org. Chem. 1973, 38, 4341. (19) Fowler, F.; Hassner, A.; Levy, L. J. Am. Chem. Soc. 1967, 89, 2077. (20) Schulthess, A. H.; Hansen, H.-J. Helv. Chim. Acta 1981, 64, 1322. (21) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Becke, A. D. Phys. Rev. A: At., Mol., Opt. Phys. 1998, 38, 3098. (c) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B: Condens. Matter Mater. Phys. 1998, 37, 785. (22) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A. Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuiji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, Revision B.05; Gaussian, Inc.: Pittsburg, PA, 2003.
Computational Details. All calculations were performed with the B3LYP density functional method21 by using the Gaussian suite of quantum chemical programs. Geometry optimizations of intermediates, transition states, reactants, and products in the gas phase were performed at the DFT B3LYP/ 6-31G(d) level using Gaussian 03.22 Stationary points on the respective potential-energy surfaces were characterized at the same level of theory by evaluating the corresponding Hessian indices. Careful verification of the unique imaginary frequencies for transition states was carried out to check whether the frequency indeed pertains to the desired reaction coordinate. Intrinsic reaction coordinates (IRC) were calculated to authenticate all transition states. The energies of the stationary points were corrected by single-point calculations using polarizable continuum solvent model for toluene.
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ASSOCIATED CONTENT
S Supporting Information * 1
H and 13C NMR spectra for all new compounds and crystallographic data for compounds 5c, exo-14, 29, 30, 40a, and 41 (CIF format). Computational details: energies of the reactants, transition states, their Cartesian coordinates. This material is available free of charge via the Internet at http:// pubs.acs.org.
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AUTHOR INFORMATION Corresponding Author *E-mail:
[email protected]. ACKNOWLEDGMENTS
We gratefully acknowledge the financial support of the Russian Foundation for Basic Research (Project 11-03-00186) and the Federal Grant-in-Aid Program “Human Capital for Science and Education in Innovative Russia” (Governmental Contract No. 16.740.11.0442).
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REFERENCES
(1) (a) Tidwell, T. T. Ketenes, 2nd ed.; John Wiley & Sons: Hoboken, NJ, 2006. (b) Kirmse, W. Eur. J. Org. Chem. 2002, 2193. (c) Paull, D. H.; Weatherwax, A.; Lectka, T. Tetrahedron 2009, 65, 6771. (2) (a) Padwa, A. Adv. Heterocycl. Chem. 2010, 99, 1. (b) Pinho e Melo, T. M. V. D.; d’A Rocha Gonsalves, A. M. Curr. Org. Synth. 2004, ́ 1, 275. (c) Palacios, F.; Ochoa de Retana, A. M.; Martinez de Marigorta, E.; de los Santos, J. M. Org. Prep. Proced. Int. 2002, 34, 219. ́ de Marigorta, E.; (d) Palacios, F.; Ochoa de Retana, A. M.; Marti nez de los Santos, J. M. Eur. J. Org. Chem. 2001, 2401. (3) (a) Hassner, A.; Miller, A. S.; Haddadin, M. J. Tetrahedron Lett. 1972, 13, 1353. (b) Haddadin, M. J.; Hassner, A. J. Org. Chem. 1973, 20, 3466. (4) Kascheres, A.; Nunes, J. Jr.; Brandão, F. Tetrahedron 1997, 53, 7089. (5) Schaumann, E.; Grabley, S.; Henriet, M.; Ghoser, L.; Touillaux, R.; Declercq, J. P.; Germain, G.; Van Meerssche, M. J. Org. Chem. 1980, 45, 2951. (6) (a) Wentrup, C.; Heilmayer, W.; Kollenz, G. Synthesis 1994, 1219. (b) Reber, K. P.; Tilley, S. D.; Sorensen, E. J. Chem. Soc. Rev. 2009, 38, 3022. (7) (a) Sato, M.; Ogasawara, H.; Kato, T. Chem. Pharm. Bull. 1984, 32, 2602. (b) Capuano, L.; Wamprecht, C. Liebigs Ann. Chem. 1986, 938. (c) Xu, J.; Jin, S.; Xing, Q. Phosphorus, Sulfur Silicon Relat. Elem. 1998, 141, 57. (d) Xu, J.; Jin, S. Heteroat. Chem. 1999, 10, 35. (e) Xu, J.; Chen, L. Heteroat. Chem. 2002, 13, 162. (f) Presset, M.; Coquerel, Y.; Rodriguez, J. Org. Lett. 2009, 11, 5706. (g) Presset, M.; Coquerel, Y.; Rodriguez, J. Org. Lett. 2010, 12, 4212. (h) Zhang, Z.; Liu, Y.; Ling, 9352
dx.doi.org/10.1021/jo201563b | J. Org. Chem. 2011, 76, 9344−9352
