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Cis-fused pyrrolizidines are normally more stable than the corresponding trans-fused compounds (see ref 13a). 3,5-Dimethylpyrrolizidines having the cis relative configuration for the two methyl groups are instead reported to have a trans-fused stereochemistry for the ring junction. Antipova, I. V.; Negrebetskii, V. V.; Skvortsov, I. M. Khim. Geterotsikl. Soed. 1982, 39-46.
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17
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0344869615
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note
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We also tried to generate the 4-amino group by hydrogenation (over Raney Nickel in MeOH) of the 4-nitro-1,7-dimesylate derivatives obtained by reaction of 3a,b with MsCl in dichloromethane (route not shown in Scheme 1). However, this procedure was ineffective in yielding cyclization products, since solvolysis of the O-mesyl groups (to give mixtures of 1,7-dimethoxy-substituted products) was much faster than the reduction of the nitro to amino group.
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22
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84986437005
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The MacroModel (v4.5) molecular modeling software was used for molecular mechanics calculations and Monte Carlo conformational searchs (MM2* force field). Mohamadi, F.; Richards, N. G.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J. Comput. Chem. 1990, 11, 440-467.
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Caufield, C.6
Chang, G.7
Hendrickson, T.8
Still, W.C.9
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23
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0001694460
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In cyclic systems, the protons adjacent to the nitrogen atom and on the same side of the N lone pair undergo a strong deshielding effect, whereas the protons on the opposite side are strongly shielded: (a) Crabb, T. A.; Newton, R. F.; Jackson, D. Chem. Rev. 1971, 71, 109-126.
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0344869612
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Manske, R. H. F., Ed.; Academic Press: New York, Chapter 5
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(e) Bohlmann, F.; Shumann, D. In The Alkaloids; Manske, R. H. F., Ed.; Academic Press: New York, 1967; Vol IX, Chapter 5.
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