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4M lithium perchlorate-nitromethane: An efficient solvent in Diels-Alder reactions using nitroalkenes as dienophiles
Tetrahedron Letters, Vol. 36, No. 25, pp. 4447-4450, 1995
Pergamon
Elsevier Science Ltd Printed in Great Britain 0040-4039/95 $9.50+0.00
0040-4039(95)00678-8
4M L i t h i u m Perchlorate-Nitromethane: An Efficient Solvent in Diels-Alder Reactions Using Nitroalkenes as Dienophiles Mirari Ayerbe and Fernando P. Cossio* gimika Fakultatea. Euskal Herriko Unibertsitatea.P.K. 1072, 20080 San Sebastifm-Donostia.Spain.
Abstract. Diels-Alder reactions in which nitroalkenesact as dienophilesare substantiallyaccelerated
in 4M lithium perchlorate-nitromethanesolutions.This accelerationis higher than that observed when the known 5M lithium perchlorate-diethylether system is used.
Nitroalkenes are extremely versatile reagents which have found extensive applications in organic synthesis, since the nitro group can be transformed into a wide range of functionalities1. In particular, these compounds have proved to be useful in Diels-Alder (DA) reactions. Under thermal conditions, they behave as electron-deficient alkenes and react with dienes to yield 3-nitrocyclohexenes2. This reaction is usually carried out at relatively high temperatures (sealed tubes, benzene or toluene as solvents). On the other hand, nitroalkenes can also act as dienes and react with olefins, usually in the presence of Lewis acids to yield cyclic alkyl nitronates3.
,,,,~0.~ .0"
L.A.
alkene
~N 02
A
diene
~ 0%2
Scheme 1. L.A.: Lewis acid. The possible substituentsat the different positions are not specified. An outstanding discovery in thermal cycloadditions was produced in 1990, when Grieco 4 et al. reported high rate accelerations of Diels-Alder reactions in 5M lithium perchlorate-diethyl ether (5M LPDE) solutions. Since then, the scope of this method has been extended to diverse reactions 5. In addition, some deal of controversy exists on the reasons underlying this dramatic rate acceleration. Some authors 6 (including Grieco himself4) have attributed this effect to the high internal pressure generated by the solvent, as well as to other non-specific solvent effects, whereas others 7 explain the acceleration in terms of Lewis acid catalysis by the lithium cation. Within the above context, we decided to investigate the behaviour of nitroalkenes in Diels-Alder (DA) reactions carried out in highly polar media. First, we have studied the DA reaction between 2,3dimethylbutadiene I with nitrostirenes 2a (R=OMe, see Scheme 2) and 2b (R=C1). When toluene under reflux conditions was used as solvent, the observed conversions for the cycloadducts 3a and 3b were 15% and 46%, respectively after 24 h. These conversions increased slowly with time. For example, the conversion for 3b after 48 h was of 54%. (See Table 1). As expected, the more activated methoxyphenyl ring induces lower reactivity 4447
in the niu'oalkene 2a. When we repeated the reaction of 2a and 2 b with I in 5M LPDE at room temperature under the conditions reported by Grieco, the DA reactions resulted to be slower than in the preceding case (see
R 1
R
2e,b
(+)-3a,b a: R=OMe
b: RfCI
Scheme 2. See Table 1 for reaction conditions. T a b l e 1. Diels-Alder reactions between diene I and nitroalkenes 2a~b
Entry
Solventa
Temp.(°C)
Time (h)
Conversionb(%) 3a
3b
1 Toluene 115 24 15 46 2 Toluene 115 48 22 54 3 5M LPDE r.t. 24 7 13 4 4M LPNM r.t. 16 35 40 5 4M LPNM r.t. 24 42 50 6 4M LPNM r.t. 67 83/60) 86 ~70) aLl'DE: LiOfiumperchlorate-diethylether. LPNM: Lithium perchlorate-niavmethane.All reactions were conducted in a 2:1 ratio of 1:2 and 0.5 M in 2. bDetermined by IH-NMR. Numbers in parentheses correspond~ isolated yields after flash chromatography. (Sifiea gel 230-400 mesh, ethyl acetate-hexane(1:20) as eluent). Table 1, entry 3). In view of this result, we decided to use ni~omethane instead of diethyl ether as solvent of lithium perchlorate, hoping that the higher dipole moment of nitmmethane (3.40 D) with respect to diethyl ether (1.33 D) could favour the acceleration of our reactions at room temperature. This was found to be the case, and we observed that DA reactions of I with either 2a or 2b in 4M lithium perchiorate in nitromethane (4M LPNM) take place much more efficiently than in 5M LPDE. For example, the conversion of 3a and 3b after 24 h at room temperature in 4M LPNM are 42% and 50% respectively (see Table l, entry 5). After 67 h of reaction, these conversions were 83% and 86%, respectively. The isolated yields 8 after purification by column chromatography were reasonable given the low reactivity of these nitroalkenes (see Table 1, entry 6). It is important to note that (i) the cycloadducts obtained under thermal conditions and in these highly polar media are identical, and (ii) no reaction was observed when either diethyl ether or nitromethane were used as solvents, in the absence of lithium perchlorate.
¢x2
,
02NA~, "X:
0
OH
4a,b
5a,b OBn a: X c* = . . ~ M e
6a,b
b: X c* =
Scheme 3. Reagents and conditions: i. MeNO2. NEt3 (cat.), r.t, lh. ii. MeSO2CI (1.2 eq.), NEtipr2 (2.5 eq.), CH2CI2, -78°C-)r.t., 2h.
In order to extend our study to more valuable substrates, we decided to prepare the homochiral nitroalkenes 6a and 6b, via Henry reaction between nitromethane and aldehydes 4a,b, followed by elimination
4449
of the intermediate nitroaldols 5a,b under McMurry conditions9,10 (Scheme 3). The reason for selecting these nitroalkenes is that in both of them the nitro group and the chiral auxiliaries can be subsequently elaborated and transformed into synthetically useful intermediates11. Nitroalkenes 6a,b (particularly the latter) resulted to be more reactive than their analogues 3a,b in presence of 2,3-dimethylbutadiene 1 (Scheme 4). Inspection of the data collected in Table 2 indicates that, as in the preceding case, 4M LPNM is substantially more efficient OBn
OBn
6a,.
+
7a
(80 : 20~
ea
7b
180 : 20~
8b
1
Scheme 4. aDiastereoselectivityobservedunderconditionsdescribedin Table2, entry 8.
bDiastereoselectivityobservedunderconditionsdescribedin Table2, entry6. T a b l e 2.Diels-Alder reactions between diene I and nitroalkenes 6arb
Entry
Solventa
Ternp.(°C)
Time(h) 7a + 8 a 54 (35) 20 40 60 (48) 71
Conversionb(%) 7b + 8 b 65 (43) 66 77 88 (70) 96 100 (85)
1 Toluene 115 24 2 5M LPDE r.t. 24 3 5M LPDE r.t. 48 4 5M LPDE r.t. 72 5 4M LPNM r.t. 24 6 4M LPNM r.t. 38 7 4M LPNM r.t. 48 78 8 4M LPNM r.t. 96 >98c (90) aThereactionconcentrationsare the sameas indicatedin Table 1. bDetenninedby 1H-NMR.Numbersin parenthesescorrespondto the isolatedyieldafter flash chromatographyunderthe sameconditionsreportedin Table l.cCompleteconversionwas observedby 1H-NMR,but tracesof 6a wererecoveredby flashchromatography. than refluxing toluene, and achieves this efficiency at room temperature, thus allowing to perform DA reactions with thermolabile substrates. Furthermore, the isolated .yields are satisfactory 12 (see Table 2, entries 6 and 8). Again, the cycloadducts obtained under thermal conditions and in polar media are identical. It is also noteworthy that the 5M LPDE system is clearly less efficient that 4M LPNM. The diastereomeric excesses 13 are acceptable and do not change significantly from one solvent to another, thus suggesting that the homochiral nitroalkenes 6a,b are promising substrates in asymmetric synthesis involving DA reactions. In summary, we have shown that 4M LPNM provides an efficient entry for the synthesis of 3nitrocyclohexenes via Diels-Alder reactions, and that the asymmetric version of this reaction is also feasible. Work is in progress in our laboratories on the scope and the applications of the methodology reported here, and the results will be published in due course.
4450
Acknowledgement. The present work has been supported by the Euskal Herriko Unibertsitateat (project UPV 170.215-EA156/94), and by Eusko Jaurlaritza (project GV 170.215-0119/94). References and Notes I.2.3.4.5.6.7.8.-
9.10.-
11.12.-
13.-
(a) Barrett, A.G.M.; Grabosky, G.G. Chem.Rev. 1956, 86, 751. (b) Barrett, A.G.M. Chem.Soc.Rev. 1991, 20, 95. (a) Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon: Oxford, 1990. (b) Oppolzer, W. In Comprehensive Organic Synthesis; Trost, B.M.; Fleming, I.; Paquette, L.A., Eds; Pergamon: Oxford, 1991; Vol. 5, p.315. See for example; (a) Denmark, S.E.; Stolle, A.; Dixon, J.A.; Guagnano, V. J.Am.Chem.Soc. 1995, 117, 2100. (b) Denmark, S.E.; Schnule, M.E.J.Org.Chem. 1994, 59, 4576. Grieco, P.A.; Nunes, J.J.; Gaul, M.D.J.Am.Chem.Soc. 1990, 112, 4595. Waldmann, H. Angew.Chem.lnt.Ed.Engl. 1991, 30, 1306. Kumar, A. J.Org.Chem. 1994, 59, 4612. Forman, M.A.; Dailey, W.P.J.Am.Chem.Soc. 1991, 113, 2761. Selected data for 3a: white crystalline solid, m.p. 99-101°C(EtOH/H20). IR(KBr, ~ cm-1) 1543, 1362 (NO2). 1HNMR(CDCI 3, 8 ppm): 7.15-7.10(d, 2H, J=8.8Hz, atom); 6.85-6.80(d, 2H, J=8.8Hz, atom); 4.96-4.82(td, 1H, J=10.2Hz, J'=5.7Hz, CH-NO2); 3.76(s, 3H, OCH3); 3.36-3.26(m, 1H, CH-Ph); 2.85-2.72(mb, 1H, HCH); 2,61-2.50(mb, 1H, HCH); 2.32-2.28(db, 2H, J=8.2Hz, CH2); 1.68(Sb, 3H, CH3); 1.64(Sb, 3H, CH3). 13C-NMR(CDC13, 8 ppm): 158.8, 132.0, 128.2, 125.7, 121.9, 114.1, 88.2, 55.2, 44.1, 39.4, 37.0, 18.5, 18.4. 3b: white crystalline solid, m.p. 75-76°C(Et20/hx). IR(KBr, ~ cm -1) 1546, 1364 (NO2). 1H-NMR(CDCI3, 8 ppm): 7.30-7.24(d, 2H, J=8.6Hz, arom.); 7.17-7.13(d, 2H, J=8.5Hz, atom.); 4.97-4.83 (td, 1H, J=10.2Hz, J'= 4.4Hz, CH-NO2); 3.50-3.31(m,lH, CH-Ph); 2.85-2.70(m, 1H, HCH); 2.63-2.53(m, 1H, HCH); 2.32-2.25(db, 2H, J=8.7H7, CH2); 1.70(Sb, 3H, CH3); 1.65(Sb, 3H, CH3). 13C-NMR(CDCI3, 8 ppm): 138.6, 133.2, 128.9, 128.6, 125.4, 122.1, 87.6, 44.2, 39.2, 36.9, 18.5, 18.3. Melton, J.; McMurry, J.E.J.Org.Chem. 1975, 40, 2138. Selected data for 6a : pale yellow oil. lOt]D/25=-39.1°. b.p.(0.04 mmHg)= 92-94°C. IR(film, ~ cm-1): 1523, 1351 (NO2). 1H-NMR(CDCI3, 8 ppm): 7.36-7.30(m, 5H, arom.); 7.19-7.17(m, 2H, =CH); 4.61(s, 2H, CH2-Ph); 4.42-4.21(qd, 1H, J=6.6Hz, J'=3.3Hz, CH-O); 1.41-1.38(d, 3H, J=6.6Hz, CH3). I3C-NMR(CDCI3, 6 ppm): 142.8, 139.3, 137.3, 128.4, 127.8, 127.4, 70.9, 19.9. 6b: pale yellow oil. [~]D/25= +35.6°C. b.p.(0.2 mmHg)=72-74°C. IR(film, ~ cm-1): 1527, 1353 (NO2). IH-NMR(CDCI3, 8 ppm): 7.26-7.21(m, 2H, =CH); 4.84-4.76(tt, IH. J=6.7Hz, J'=l.4Hz, CH-O); 4.324.24(dd, IH, J=8.5Hz, J'=8.4Hz, HCH-O); 3.81-3.74(dd, IH, J=8.5Hz, J'--8.4Hz, HCH-O); 1.48(s, 3H, CH3); 1.42(s, 3H, CH3). I3C-NMR(CDCI3, 8 ppm): 140.0, 139.0, 110.5, 71.8, 68.1, 26.0, 25.1. Jurczak, J.; Pikul, S.; Bauer, T. Tetrahedron 1986, 42,447. Selected data for 7a + 8a:IR(film, u cm-1): 1545, 1371 (NO2). 1H-NMR (CDCI3, 8 ppm): 7.36-7.29(m, 5H, atom.); 5.01-4.88(m, 1H, CH-NO 2 minor is.); 4.71-4.59(m, 1H, CH-NO2major is.); 4.56-4.51(d, 1H, J=ll.5Hz, HCH-Ph major is.); 4.54-4.48(d, IH, J=l 1.0Hz, HCH-Ph, minor is.); 4.41-4.36(d, 1H, J=l 1.51-1z, HCH-Ph, major is.); 4.32-4.26(d, 1H, J=l 1.0Hz, HCH-Ph minor is.); 3.59-3.39(m, IH, CH-O both is.); 2.75-1.84(m, 5H, CH2, CH2, CH, both is.); 1.61(s, 6H, CH 3, CH3); 1.23-1.20(d, 3H, J=6.4Hz, CH3, minor is.): 1.22-1.19(d, 3H, J=6.2Hz, CH3 major is.). 13CNMR(CDCI3, 8ppm): 138.2, 138.1, 128.3, 128.2, 127.7, 127.6, 127.5, 125.2, 124.3, 121.5, 121.3, 85.1, 84.5, 74.6, 72.5, 71.2, 70.7, 43.3, 41.8, 37.0, 35.3, 30.5, 29.6, 29.3, 18.6, 18.5, 18.4, 18.1, 16.4, 15.7. 7b + 8b:IR(film, ~ cm-1); 1545, 1369 (NO2). 1H-NMR(CDCI3, 8ppm): 4.76-4.63(m, 1H, CH-NO2); 4.11-3.93(m, 2H, CH2-O); 2.82-2.10(m, 5H, CH2, CH2, CH); 1.65, 1.60(Sb, 6H, CH3-C=); 1.41(s, 3H, CH3-CO); 1.32(s, 3H, CH3-CO, major.is.); 1.31(s, 3H, CH3-CO, minor.is). 13C-NMR(CDCI3, 8ppm): 128.3, 123.1, 121.9, 121.4, 109.6, 109.2, 85.1, 83.5, 76.4, 74.1, 67.8, 66.2, 40.3, 40.2, 39.7, 36.8, 33.3, 33,1, 30.5, 30.0, 26.5, 25.4, 24.7, 18.8, 18.6. Although the structural assignment of diastereomers 7 and 8 is not univocally stablished at this stage of our research, we tentatively propose that the cycloadducts 7 are the major diastereomers, on the basis of previous studies for related chiral dienophiles. See (a) Kant, T.; Oikawa, M.; Hosokawa, S.; Yanagiya, M.; Matsuda, F.; Shirahama, H. Synlett 1994, 801. (b) Trost, B.H.; Lynch, J.; Renaut, P.; Steinman, D.H.J.Am.Chem.Soc. 1986, 108, 284. (e) Trost, B.M.; Mignani, S.M. Tetrahedron Lett. 1986, 27, 4137.
:
7a
OBn~HH q~%HM. L NOz NQZH~~ ~
(Received in UK 29 March 1995; accepted 11 April 1995)
r
7b
Pergamon
Elsevier Science Ltd Printed in Great Britain 0040-4039/95 $9.50+0.00
0040-4039(95)00678-8
4M L i t h i u m Perchlorate-Nitromethane: An Efficient Solvent in Diels-Alder Reactions Using Nitroalkenes as Dienophiles Mirari Ayerbe and Fernando P. Cossio* gimika Fakultatea. Euskal Herriko Unibertsitatea.P.K. 1072, 20080 San Sebastifm-Donostia.Spain.
Abstract. Diels-Alder reactions in which nitroalkenesact as dienophilesare substantiallyaccelerated
in 4M lithium perchlorate-nitromethanesolutions.This accelerationis higher than that observed when the known 5M lithium perchlorate-diethylether system is used.
Nitroalkenes are extremely versatile reagents which have found extensive applications in organic synthesis, since the nitro group can be transformed into a wide range of functionalities1. In particular, these compounds have proved to be useful in Diels-Alder (DA) reactions. Under thermal conditions, they behave as electron-deficient alkenes and react with dienes to yield 3-nitrocyclohexenes2. This reaction is usually carried out at relatively high temperatures (sealed tubes, benzene or toluene as solvents). On the other hand, nitroalkenes can also act as dienes and react with olefins, usually in the presence of Lewis acids to yield cyclic alkyl nitronates3.
,,,,~0.~ .0"
L.A.
alkene
~N 02
A
diene
~ 0%2
Scheme 1. L.A.: Lewis acid. The possible substituentsat the different positions are not specified. An outstanding discovery in thermal cycloadditions was produced in 1990, when Grieco 4 et al. reported high rate accelerations of Diels-Alder reactions in 5M lithium perchlorate-diethyl ether (5M LPDE) solutions. Since then, the scope of this method has been extended to diverse reactions 5. In addition, some deal of controversy exists on the reasons underlying this dramatic rate acceleration. Some authors 6 (including Grieco himself4) have attributed this effect to the high internal pressure generated by the solvent, as well as to other non-specific solvent effects, whereas others 7 explain the acceleration in terms of Lewis acid catalysis by the lithium cation. Within the above context, we decided to investigate the behaviour of nitroalkenes in Diels-Alder (DA) reactions carried out in highly polar media. First, we have studied the DA reaction between 2,3dimethylbutadiene I with nitrostirenes 2a (R=OMe, see Scheme 2) and 2b (R=C1). When toluene under reflux conditions was used as solvent, the observed conversions for the cycloadducts 3a and 3b were 15% and 46%, respectively after 24 h. These conversions increased slowly with time. For example, the conversion for 3b after 48 h was of 54%. (See Table 1). As expected, the more activated methoxyphenyl ring induces lower reactivity 4447
in the niu'oalkene 2a. When we repeated the reaction of 2a and 2 b with I in 5M LPDE at room temperature under the conditions reported by Grieco, the DA reactions resulted to be slower than in the preceding case (see
R 1
R
2e,b
(+)-3a,b a: R=OMe
b: RfCI
Scheme 2. See Table 1 for reaction conditions. T a b l e 1. Diels-Alder reactions between diene I and nitroalkenes 2a~b
Entry
Solventa
Temp.(°C)
Time (h)
Conversionb(%) 3a
3b
1 Toluene 115 24 15 46 2 Toluene 115 48 22 54 3 5M LPDE r.t. 24 7 13 4 4M LPNM r.t. 16 35 40 5 4M LPNM r.t. 24 42 50 6 4M LPNM r.t. 67 83/60) 86 ~70) aLl'DE: LiOfiumperchlorate-diethylether. LPNM: Lithium perchlorate-niavmethane.All reactions were conducted in a 2:1 ratio of 1:2 and 0.5 M in 2. bDetermined by IH-NMR. Numbers in parentheses correspond~ isolated yields after flash chromatography. (Sifiea gel 230-400 mesh, ethyl acetate-hexane(1:20) as eluent). Table 1, entry 3). In view of this result, we decided to use ni~omethane instead of diethyl ether as solvent of lithium perchlorate, hoping that the higher dipole moment of nitmmethane (3.40 D) with respect to diethyl ether (1.33 D) could favour the acceleration of our reactions at room temperature. This was found to be the case, and we observed that DA reactions of I with either 2a or 2b in 4M lithium perchiorate in nitromethane (4M LPNM) take place much more efficiently than in 5M LPDE. For example, the conversion of 3a and 3b after 24 h at room temperature in 4M LPNM are 42% and 50% respectively (see Table l, entry 5). After 67 h of reaction, these conversions were 83% and 86%, respectively. The isolated yields 8 after purification by column chromatography were reasonable given the low reactivity of these nitroalkenes (see Table 1, entry 6). It is important to note that (i) the cycloadducts obtained under thermal conditions and in these highly polar media are identical, and (ii) no reaction was observed when either diethyl ether or nitromethane were used as solvents, in the absence of lithium perchlorate.
¢x2
,
02NA~, "X:
0
OH
4a,b
5a,b OBn a: X c* = . . ~ M e
6a,b
b: X c* =
Scheme 3. Reagents and conditions: i. MeNO2. NEt3 (cat.), r.t, lh. ii. MeSO2CI (1.2 eq.), NEtipr2 (2.5 eq.), CH2CI2, -78°C-)r.t., 2h.
In order to extend our study to more valuable substrates, we decided to prepare the homochiral nitroalkenes 6a and 6b, via Henry reaction between nitromethane and aldehydes 4a,b, followed by elimination
4449
of the intermediate nitroaldols 5a,b under McMurry conditions9,10 (Scheme 3). The reason for selecting these nitroalkenes is that in both of them the nitro group and the chiral auxiliaries can be subsequently elaborated and transformed into synthetically useful intermediates11. Nitroalkenes 6a,b (particularly the latter) resulted to be more reactive than their analogues 3a,b in presence of 2,3-dimethylbutadiene 1 (Scheme 4). Inspection of the data collected in Table 2 indicates that, as in the preceding case, 4M LPNM is substantially more efficient OBn
OBn
6a,.
+
7a
(80 : 20~
ea
7b
180 : 20~
8b
1
Scheme 4. aDiastereoselectivityobservedunderconditionsdescribedin Table2, entry 8.
bDiastereoselectivityobservedunderconditionsdescribedin Table2, entry6. T a b l e 2.Diels-Alder reactions between diene I and nitroalkenes 6arb
Entry
Solventa
Ternp.(°C)
Time(h) 7a + 8 a 54 (35) 20 40 60 (48) 71
Conversionb(%) 7b + 8 b 65 (43) 66 77 88 (70) 96 100 (85)
1 Toluene 115 24 2 5M LPDE r.t. 24 3 5M LPDE r.t. 48 4 5M LPDE r.t. 72 5 4M LPNM r.t. 24 6 4M LPNM r.t. 38 7 4M LPNM r.t. 48 78 8 4M LPNM r.t. 96 >98c (90) aThereactionconcentrationsare the sameas indicatedin Table 1. bDetenninedby 1H-NMR.Numbersin parenthesescorrespondto the isolatedyieldafter flash chromatographyunderthe sameconditionsreportedin Table l.cCompleteconversionwas observedby 1H-NMR,but tracesof 6a wererecoveredby flashchromatography. than refluxing toluene, and achieves this efficiency at room temperature, thus allowing to perform DA reactions with thermolabile substrates. Furthermore, the isolated .yields are satisfactory 12 (see Table 2, entries 6 and 8). Again, the cycloadducts obtained under thermal conditions and in polar media are identical. It is also noteworthy that the 5M LPDE system is clearly less efficient that 4M LPNM. The diastereomeric excesses 13 are acceptable and do not change significantly from one solvent to another, thus suggesting that the homochiral nitroalkenes 6a,b are promising substrates in asymmetric synthesis involving DA reactions. In summary, we have shown that 4M LPNM provides an efficient entry for the synthesis of 3nitrocyclohexenes via Diels-Alder reactions, and that the asymmetric version of this reaction is also feasible. Work is in progress in our laboratories on the scope and the applications of the methodology reported here, and the results will be published in due course.
4450
Acknowledgement. The present work has been supported by the Euskal Herriko Unibertsitateat (project UPV 170.215-EA156/94), and by Eusko Jaurlaritza (project GV 170.215-0119/94). References and Notes I.2.3.4.5.6.7.8.-
9.10.-
11.12.-
13.-
(a) Barrett, A.G.M.; Grabosky, G.G. Chem.Rev. 1956, 86, 751. (b) Barrett, A.G.M. Chem.Soc.Rev. 1991, 20, 95. (a) Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon: Oxford, 1990. (b) Oppolzer, W. In Comprehensive Organic Synthesis; Trost, B.M.; Fleming, I.; Paquette, L.A., Eds; Pergamon: Oxford, 1991; Vol. 5, p.315. See for example; (a) Denmark, S.E.; Stolle, A.; Dixon, J.A.; Guagnano, V. J.Am.Chem.Soc. 1995, 117, 2100. (b) Denmark, S.E.; Schnule, M.E.J.Org.Chem. 1994, 59, 4576. Grieco, P.A.; Nunes, J.J.; Gaul, M.D.J.Am.Chem.Soc. 1990, 112, 4595. Waldmann, H. Angew.Chem.lnt.Ed.Engl. 1991, 30, 1306. Kumar, A. J.Org.Chem. 1994, 59, 4612. Forman, M.A.; Dailey, W.P.J.Am.Chem.Soc. 1991, 113, 2761. Selected data for 3a: white crystalline solid, m.p. 99-101°C(EtOH/H20). IR(KBr, ~ cm-1) 1543, 1362 (NO2). 1HNMR(CDCI 3, 8 ppm): 7.15-7.10(d, 2H, J=8.8Hz, atom); 6.85-6.80(d, 2H, J=8.8Hz, atom); 4.96-4.82(td, 1H, J=10.2Hz, J'=5.7Hz, CH-NO2); 3.76(s, 3H, OCH3); 3.36-3.26(m, 1H, CH-Ph); 2.85-2.72(mb, 1H, HCH); 2,61-2.50(mb, 1H, HCH); 2.32-2.28(db, 2H, J=8.2Hz, CH2); 1.68(Sb, 3H, CH3); 1.64(Sb, 3H, CH3). 13C-NMR(CDC13, 8 ppm): 158.8, 132.0, 128.2, 125.7, 121.9, 114.1, 88.2, 55.2, 44.1, 39.4, 37.0, 18.5, 18.4. 3b: white crystalline solid, m.p. 75-76°C(Et20/hx). IR(KBr, ~ cm -1) 1546, 1364 (NO2). 1H-NMR(CDCI3, 8 ppm): 7.30-7.24(d, 2H, J=8.6Hz, arom.); 7.17-7.13(d, 2H, J=8.5Hz, atom.); 4.97-4.83 (td, 1H, J=10.2Hz, J'= 4.4Hz, CH-NO2); 3.50-3.31(m,lH, CH-Ph); 2.85-2.70(m, 1H, HCH); 2.63-2.53(m, 1H, HCH); 2.32-2.25(db, 2H, J=8.7H7, CH2); 1.70(Sb, 3H, CH3); 1.65(Sb, 3H, CH3). 13C-NMR(CDCI3, 8 ppm): 138.6, 133.2, 128.9, 128.6, 125.4, 122.1, 87.6, 44.2, 39.2, 36.9, 18.5, 18.3. Melton, J.; McMurry, J.E.J.Org.Chem. 1975, 40, 2138. Selected data for 6a : pale yellow oil. lOt]D/25=-39.1°. b.p.(0.04 mmHg)= 92-94°C. IR(film, ~ cm-1): 1523, 1351 (NO2). 1H-NMR(CDCI3, 8 ppm): 7.36-7.30(m, 5H, arom.); 7.19-7.17(m, 2H, =CH); 4.61(s, 2H, CH2-Ph); 4.42-4.21(qd, 1H, J=6.6Hz, J'=3.3Hz, CH-O); 1.41-1.38(d, 3H, J=6.6Hz, CH3). I3C-NMR(CDCI3, 6 ppm): 142.8, 139.3, 137.3, 128.4, 127.8, 127.4, 70.9, 19.9. 6b: pale yellow oil. [~]D/25= +35.6°C. b.p.(0.2 mmHg)=72-74°C. IR(film, ~ cm-1): 1527, 1353 (NO2). IH-NMR(CDCI3, 8 ppm): 7.26-7.21(m, 2H, =CH); 4.84-4.76(tt, IH. J=6.7Hz, J'=l.4Hz, CH-O); 4.324.24(dd, IH, J=8.5Hz, J'=8.4Hz, HCH-O); 3.81-3.74(dd, IH, J=8.5Hz, J'--8.4Hz, HCH-O); 1.48(s, 3H, CH3); 1.42(s, 3H, CH3). I3C-NMR(CDCI3, 8 ppm): 140.0, 139.0, 110.5, 71.8, 68.1, 26.0, 25.1. Jurczak, J.; Pikul, S.; Bauer, T. Tetrahedron 1986, 42,447. Selected data for 7a + 8a:IR(film, u cm-1): 1545, 1371 (NO2). 1H-NMR (CDCI3, 8 ppm): 7.36-7.29(m, 5H, atom.); 5.01-4.88(m, 1H, CH-NO 2 minor is.); 4.71-4.59(m, 1H, CH-NO2major is.); 4.56-4.51(d, 1H, J=ll.5Hz, HCH-Ph major is.); 4.54-4.48(d, IH, J=l 1.0Hz, HCH-Ph, minor is.); 4.41-4.36(d, 1H, J=l 1.51-1z, HCH-Ph, major is.); 4.32-4.26(d, 1H, J=l 1.0Hz, HCH-Ph minor is.); 3.59-3.39(m, IH, CH-O both is.); 2.75-1.84(m, 5H, CH2, CH2, CH, both is.); 1.61(s, 6H, CH 3, CH3); 1.23-1.20(d, 3H, J=6.4Hz, CH3, minor is.): 1.22-1.19(d, 3H, J=6.2Hz, CH3 major is.). 13CNMR(CDCI3, 8ppm): 138.2, 138.1, 128.3, 128.2, 127.7, 127.6, 127.5, 125.2, 124.3, 121.5, 121.3, 85.1, 84.5, 74.6, 72.5, 71.2, 70.7, 43.3, 41.8, 37.0, 35.3, 30.5, 29.6, 29.3, 18.6, 18.5, 18.4, 18.1, 16.4, 15.7. 7b + 8b:IR(film, ~ cm-1); 1545, 1369 (NO2). 1H-NMR(CDCI3, 8ppm): 4.76-4.63(m, 1H, CH-NO2); 4.11-3.93(m, 2H, CH2-O); 2.82-2.10(m, 5H, CH2, CH2, CH); 1.65, 1.60(Sb, 6H, CH3-C=); 1.41(s, 3H, CH3-CO); 1.32(s, 3H, CH3-CO, major.is.); 1.31(s, 3H, CH3-CO, minor.is). 13C-NMR(CDCI3, 8ppm): 128.3, 123.1, 121.9, 121.4, 109.6, 109.2, 85.1, 83.5, 76.4, 74.1, 67.8, 66.2, 40.3, 40.2, 39.7, 36.8, 33.3, 33,1, 30.5, 30.0, 26.5, 25.4, 24.7, 18.8, 18.6. Although the structural assignment of diastereomers 7 and 8 is not univocally stablished at this stage of our research, we tentatively propose that the cycloadducts 7 are the major diastereomers, on the basis of previous studies for related chiral dienophiles. See (a) Kant, T.; Oikawa, M.; Hosokawa, S.; Yanagiya, M.; Matsuda, F.; Shirahama, H. Synlett 1994, 801. (b) Trost, B.H.; Lynch, J.; Renaut, P.; Steinman, D.H.J.Am.Chem.Soc. 1986, 108, 284. (e) Trost, B.M.; Mignani, S.M. Tetrahedron Lett. 1986, 27, 4137.
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(Received in UK 29 March 1995; accepted 11 April 1995)
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