Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

Abstract

8-Allylcoumarins are conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination/cyclization sequence. They serve as a versatile platform for the annellation of five- to seven-membered rings using ring-closing olefin metathesis (RCM). Furano-, pyrano-, oxepino- and azepinocoumarins were synthesized from the same set of precursors using Ru-catalyzed double bond isomerizations and RCM in a defined order. One class of products, pyrano[2,3-f]chromene-2,8-diones, were inaccessible through direct RCM of an acrylate, but became available from the analogous allyl ether via an assisted tandem catalytic RCM/allylic oxidation sequence.

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

“…An exceptionally stereoselective synthesis of erogorgiaene (12) (95% E-selectivity) was reported by Hoveyda et al [80]. They combined an enyne ring-closing metathesis and an alkene crossmetathesis reaction in a sequential mode, using the appropriate enantiopure enynes and the Hoveyda-Grubbs catalyst in both transformations (Scheme 15).…”

“…Alkene and alkyne metathesis [1][2][3][4], constituting highly versatile and powerful catalytic processes for constructing complex organic molecules [5][6][7][8][9][10][11][12], have found broad application in the fields of pharmaceutical synthesis [13][14][15], materials science [16][17][18][19][20], or in advanced techniques and technologies [21][22][23][24][25][26][27][28][29][30]. Thus, numerous multistep total syntheses of organic compounds, including bioactive molecules [31][32][33][34][35] and natural products [36,37], have been performed in a highly chemo-and stereoselective manner through metathesis routes [38][39][40][41][42][43].…”

A Coumarin−Donepezil Hybrid as a Blood−Brain Barrier Permeable Dual Cholinesterase Inhibitor: Isolation, Synthetic Modifications, and Biological Evaluation of Natural Coumarins

“…Yield: 81 %; white powder; HPLC purity: 99 %; m.p. 190–192 °C; IR (CHCl 3 ) (cm −1 ): 3549, 3429, 3120, 17106, 1655, 1674, 1380, 1205 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.71 (d, J =12.6 Hz, 1H), 7.54 (d, J =12.9 Hz, 1H), 7.47 (d, J =8.3 Hz, 1H), 7.16 (s, 1H), 6.29 (s, 1H), 2.53 (s, 3H); 13 C NMR (101 MHz, CDCl 3 ): δ (ppm) 161.21, 158.07, 154.50, 148.76, 145.62, 121.35, 118.81, 116.61, 113.66, 109.26, 105.19, 19.43; ESIMS: m/z 201.1 [M+H] + [25] …”

“…190-192 °C (Lit. [25] 191-193 °C); IR (CHCl 3 ) v max (cm À 1 ): 3550, 3424, 3110, 1736, 1688, 1674, 1380, 1205; 1 H NMR (400 MHz, CDCl 3 ): δ (ppm) 7.72 (d, J = 1.5 Hz, 1H), 7.54 (d, J = 10.4 Hz, 1H), 7.47 (d, J = 8.7 Hz, 1H), 7.17 (d, J = 8.8 Hz, 1H), 6.30 (s, 1H), 2.53 (s, 3H); 13…”

Functionalized Benzofurans via Microwave‐Promoted Tandem Claisen‐Rearrangement/5‐endo‐dig Cyclization

“…Along these lines, straightforward syntheses of pyranocoumarins , prenylcoumarins , furanocoumarins , chroman‐4‐ones , and chromene‐4‐ones were developed and implemented in the total synthesis of several natural products. In the above‐mentioned examples, the cyclization step proceeds through a nucleophilic acyl substitution (for the synthesis of coumarins) or through an addition across an electronically biased C─C‐multiple bond (for the synthesis of chroman‐4‐ones and chromene‐4‐ones).…”