A 11‐Steps Total Synthesis of Magellanine through a Gold(I)‐Catalyzed Dehydro Diels–Alder Reaction

Abstract

We have developed an innovative strategy for the formation of angular carbocycles via ag old(I)-catalyzed dehydro Diels-Alder reaction. This transformation provides rapid access to avariety of complex angular cores in excellent diastereoselectivities and high yields.T he usefulness of this Au I -catalyzed cycloaddition was further demonstrated by accomplishing a1 1-steps total synthesis of (AE)-magellanine. Scheme 3. Total synthesis of magellanine 7.Reagents and conditions: a) TMAD, TBP, 19, o-xylene, 0 8 8C; then BHT 150 8 8C. b) OsO 4 ,NMO, NaIO 4 , THF:H 2 O, 20 8 8C. c) Piperidine, AcOH, PhMe, 20 8 8C. d) TIPSOTf, DMS, LiHMDS, THF, À78 8 8C. e) [L6AuNCMe][SbF 6 ](1mol %) PhMe, 20 8 8C; then CSA (1 equiv). f) TBAF, 60 8 8C; then LiOH, H 2 O/THF, 140 8 8C. g) DMP, DCM, 20 8 8C. h) PtO 2 ,H 2 ,E tOAc, 20 8 8C. i) i-PrCO 2 Cl, NMM, Et 3 N, 25,P hMe, 0 8 8C; then 365 nm LED, O 2 , tert-dodecylmercaptan, 0 8 8C; then PPh 3 .j )DIAD, HCO 2 HPPh 3 ,THF;then LiOH. k) Na, naphthalene, THF, À78 8 8C; then AcOH, formaldehyde, NaBH 3 CN, 20 8 8C. l) LDA (2 equiv),T MSCl (1 equiv), 30,THF, 0 8 8C; then HCl, 20 8 8C. TMAD = tetramethyl azodicarboxamide, TBP = tributylphosphine, BHT = butylated hydroxytoluene, NMO = N-methylmorpholine N-oxyde, THF = tetrahydrofuran, TIP-S = triisopropylsilyl, DMS = dimethyl sulfide, CSA = camphorsulfonic acid, TBAF = tetrabutylammonium fluoride, DMP = Dess-Martin periodinane, DCM = dichloromethane, NMM = N-methylmorpholine, DIAD = diisopropyl azodicarboxylate, LDA = lithium diisopropylamide, TMS = trimethylsilyl.

Empowering Synthesis of Complex Natural Products

“…This is epitomized by the recent developments in gold-catalyzed carbocyclizations, particularly Barriault'sd ehydro-Diels-Alder reaction, which can set quaternary stereocenters. [30] With few methods for the generation of quaternary stereocenters, they often becomet he greatesth urdles in the synthesis of naturalp roducts.T he generation of these carbocycles from arylenyne/dienyne substrates throughg old catalysis was first popularized by Echavarren to form complex tricycles in as ingle operation. [31] Although unable to form qua-ternary centers, this work set the stage for Barriault's contribution, which eventually led to the total synthesis of magellanine (58)( Scheme 6).…”