Microwave-Assisted Rearrangement of Vinylaziridines to 3-Pyrrolines: Formal Synthesis of (-)-Anisomycin

Abstract

An efficient microwave-assisted rearrangement of activated vinylaziridines to 3-pyrrolines is described. The rearrangement proceeds in good to excellent yields and is mediated by NaI or LiI in MeCN at elevated temperatures. The synthetic utility of this reaction is shown in an efficient formal total synthesis of the antibiotic (-)-anisomycin.

Key words

vinylaziridines - pyrrolines - rearrangement - ring expansion - total synthesis

References

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5

Vinylaziridines 1a,b were synthesized from the corresponding vinylepoxides. [10b]

6

The cis- and trans-vinylaziridines can be distinguished by the ³ J _HH coupling constant of the ring protons (cis ca. 6.8-8.4 Hz; trans ca. 4.1-4.4 Hz).

17

For ee determination, the chlorohydrine was converted to the corresponding vinylepoxide by treatment with 5 equiv DBU in CH₂Cl₂ (r.t., 12 h, 96%). [16b] The ee was shown to be >95% by chiral HPLC analysis (Chiracel OD, hexane-i-PrOH, 99.5:0.5, 0.5 mL/min).

18

[α]_D ²⁵ -99.9 (c 1.20, THF) {lit: [α]_D ²⁵ -93.8 (c 0.485, THF); [15c] [α]_D ²⁵ -101.2 (c 1.44, THF); [15d] [α]_D ²⁵ -89.3 (c 1.26, THF) [15e] }.

19

[α]_D ²⁵ -48.4 (c 0.37, CH₂Cl₂).