Specific o-alkylation of aromatic amines

Abstract

588first step, giving 12. Rearrangement of this highly strained peroxide to 13 is a reaction similar to one which proceeds readily at higher temperatures in lessstrained systems.Addition of a second singlet oxygen molecule to the resulting product would be rapid, to give 10. Because of the mode of formation, V 12 X 13 the epoxide groups are assigned to be cis; models show the top face is the less hindered, so that the peroxide bridge is suggested to be trans to the epoxides.The intermediacy of 12 provides a rationale for the formation of compounds 6-8 as well. Rearrangement of 12 to the 2,3-dioxetane followed by cleavage has analogy,20b and would account for the formation of homophthalaldehyde and 8; 6 and 7 could derive either from the dioxetane or from 12 directly by nucleophilic attack followed by allylic shift.The behavior of compound 10d on heating provides further evidence for the assigned structure. Warming gives rapid rearrangement to a mixture of two compounds of which the major (>70% by nmr) product, an isomer by analysis and mass spectrum, had mp 184.5-186'; the compound has neither C=O nor OH bands in the ir; nmr shows no peaks (except phenyl) below 3.8 ppm. The spectrum and its analysis are summarized in Tables I and 11. On the basis of its spectra and analogy, the compound was assigned the tetraepoxide (benzene trioxide!) structure 14. The 13C spectra agree with the assignment.l9 An exactly analogous rearrangement in a simpler system has been found by Foster and Berchtold. 2 1 Nmr chemical shifts of 14 agree well with the values of these authors. 14 Compounds loa-c undergo similar rearrangements in good yield. The stereochemistry is assigned as shown consistent with that of 10d; only in this stereochemistry do protons A and C but not B and D have the W arrangement required for long-range coupling. 2 2 These novel compounds are all produced in synthetically useful yields. The above experiments make it less (20) (a) J. Boche and 0. A. Rundquist, J. Org. Chem., 33, 4285 (1968); (b) J.-P. LeRoux and J.-J. Basselier, C. R. Acad. Sci. Paris, 271, 461 (1970). (21) C. H. Foster and G. A . Berchtold, J . Amer. Chem. Soc., 94, 7939 (1972). We thank Professor Berchtold for a prepublication copy of his manuscript.(22) Other formulations in which some of the oxygen bridges are not epoxides are less likely because they would be expected to have nmr absorption at lower field for the a protons. likely that 6 and 7 are derived from any intermediate related to the ene reaction.sc The greater rate of photooxidation of indene at low temperature suggests that the formation of 12 may be reversible at higher temperatures; attempts to trap 12 are in progress.

Enantioselective Total Synthesis of (−)‐Deoxoapodine

“…Exposure of indoline (−)- 7 to N - tert -butylbenzenesulfinimidoyl chloride [20] in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene efficiently provided the corresponding C2-imine in 85% yield, offering a new and efficient method for C2-oxidation of the aspidosperma core. [3k,21] This new oxidation of the indoline substructure of aspidosperma avoids an undesired (methylthio)methylation side-product [22, 23] that is commonly formed using Swern conditions. The resulting imine was deprotonated by treatment with n -butyllithium, and the corresponding metaloenamine was captured with methyl cyanoformate [24, 3h, 3k] to provide (−)-deoxoapodine ( 1 ) in 61% yield.…”

Synthesis of heterocycles: Indolo (2,1-a) isoquinolines, renewables, and aptamer ligands for cellular imaging

“…24 The resulting aniline was subjected to standard Kraus indole conditions to generate 2,3-disubstitued indoles 8 and 9 in modest to good yields. In agreement with the phenylsulfide results, we saw loss of one methylsulfide group in aromatization of the indole unit.…”

Dimethyl Sulfide

“…2-(Methylthiomethyl)aniline is obtained in 90% yield; its desulfurization by Raney Nickel gives o-toluidine (eq 4). 4 2-Amino-3-methylpyridine is obtained in 50% overall yield by a similar sequence of reactions starting from 2-aminopyridine (eq 5). 5 The above o-methylation can be successfully extended to o-alkylation 4 and also to the synthesis of indoles and hetero analogs.…”