Synthesis of crinane utilizing an allylic sulfoxide for the construction of a hydroindole ring via vinylogous C–N bond formation

Abstract

The synthesis of crinane is disclosed via intramolecular C-N bond formation by the displacement of an allylic sulfoxonium salt. The allylic sulfide precursor was synthesized by a ring-closing metathesis reaction. The quaternary carbon stereocenter was created by alkylation of a benzylic cyanide. The allyl sulfide 14 was prepared by adding vinylmagnesium bromide to an α-chlorosulfide.

Application of Electrocyclic Ring-Opening and Desymmetrizing Nucleophilic Trappings of meso-6,6-Dibromobicyclo[3.1.0]hexanes to Total Syntheses of Crinine and Haemanthamine Alkaloids

“…The combined organic phases were dried (Na 2 SO 4 ), filtered, and then concentrated under reduced pressure. The resulting yellow oil was subjected to flash chromatography (1:10 v/v ammonia-saturated methanol/chloroform) to afford, after concentration of the appropriate fractions ( R f = 0.4), compound 1 (R,R = CH 2 ) (57 mg, 78%) as a clear, colorless oil. 1 H NMR (400 MHz, CDCl 3 ) δ 6.65 (s, 1H), 6.41 (s, 1H), 5.83 (s, 2H), 4.34 (d, J = 16.6 Hz, 1H), 3.73 (d, J = 16.6 Hz, 1H), 3.36 (m, 1H), 2.86–2.75 (complex m, 2H), 2.29 (m, 1H), 2.19 (m, 1H), 1.80–1.72 (complex m, 4H), 1.57 (m, 1H), 1.47 (m, 1H), 1.27–1.13 (complex m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 146.2, 145.5, 141.6, 125.1, 106.1, 103.1, 100.6, 67.3, 61.6, 51.7, 42.7, 37.4, 28.7, 27.1, 24.1, 21.5; IR (KBr): ν max 2931, 2855, 1503, 1481, 1310, 1232, 1094, 1039 cm –1 ; MS (EI, 70 eV): m / z 257 (M +· , 100%); HRMS M +· Calcd for C 16 H 19 NO 2 : 257.1416, Found: 257.1417; [α] D 20 = −11.6 ( c = 1, CHCl 3 ).…”

A Review on Recent Syntheses of Amaryllidaceae Alkaloids and Isocarbostyrils (Time period mid-2016 to 2017)

“…In their new approach to the crinane alkaloids, Raghavan and Ravi made use of a vinylogous Pummerer reaction to form the octahydroindole central core [21]. Their synthesis commenced by treating the monoprotected 1,3-propanediol 69 with diphenyl disulfide under conditions developed by Hata [22] to afford sulfide Scheme 10: Synthesis of vinyl iodide 72.…”

“…Finally treatment of ketoaldehyde 66 with ammonium acetate under the standard reductive amination conditions afforded an 85% yield of 68 followed by a rather ingenious usage of Eschenmoser's salt (N,N-dimethylmethylene ammonium iodide) to complete the synthesis of crinane 44 (Scheme 9). ii) Synthesis of crinane utilizing an allylic sulfoxide for the construction of a hydroindole ring, by Raghavan and Ravi: In their new approach to the crinane alkaloids, Raghavan and Ravi made use of a vinylogous Pummerer reaction to form the octahydroindole central core [21]. Their synthesis commenced by treating the monoprotected 1,3-propanediol 69 with diphenyl disulfide under conditions developed by Hata [22] to afford sulfide Scheme 10: Synthesis of vinyl iodide 72.…”

Total Synthesis of (±)-Crinane from 6,6-Dibromobicyclo[3.1.0]hexane Using a 5-exo-trig Radical Cyclization Reaction to Assemble the C3a-Arylated Perhydroindole Substructure

“…A range of significant biological effects has been attributed to such compounds, including, for example, antiviral and antitumor properties . Given this and the often-limited availability of certain of these alkaloids from their natural sources, significant attention has been directed toward their synthesis. ,,− Some of these efforts have been focused on the synthesis of compound 1 , a.k.a. crinane (which is not itself a natural product). , Wildman reported the first synthesis of (±)-crinane in 1956, the final step of which involved forming the D-ring by subjecting a C3a-arylated perhydroindole (embodying the ACD-ring system) to a Pictet–Spengler cyclization reaction.…”