Denksport

A scalable total synthesis of (-)-nakadomarin A R. K. Boeckman, Jr. et al., Org. Lett. 2016, 18, 6136-6139
08.03.2017
Dima 1) (R)-CBS (20mol%)
BH3*SMe2, DCM
O 3) NaH, toluene,
20 h, 98%, 95% ee reflux, 12 h, 3:1 dr
TBSO CO2iPr
2) I, DMAP, py, 4) LiAl(tBu)2(OtBu)H, THF
SO2Ph DCM, 273K, 3 h 273K to rt, 12 h
95%
50% (2 steps)

5) TMSN3, PPh3 8) LDA, ClCO2Me, THF

toluene, rt, 2 h 6) TBAF, THF, 273K, 1 h, 90% 195K, 4 h, 90%

then 14, rt, 10 h 7) TPAP, NMO, DCM

9) hept-5-yn-1-amine, MeOH
then reflux, 48 h MS, 3 h, rt, 85%
323K, 12 h, 95%
90%

a) NaH, nBuLi, THF

c) 1M HCl, H2O/EtOH e) II, LDA, THF
273K, 30 min
O O then 1-bromo-2-butyne, 2h 338K, 24 h, 80% rt, 12 h
P(OMe)2 then aq. 1N HCl
Me b) NaH, 1,3-diacetoxy- d) (COCl)2, DMSO
acetone, THF, 273K to rt PE, 86%
Et3N, 195K to rt, 85%
76%

10) III, PhCO2H (10mol%) 11) BF3*OEt2, Et3SiH

MS, DCM, rt, 18 h DCM, rt, 12 h, 76%
73% brsm yield
85% conversion
H 13) IV (5mol%)
15) TFA ZnCl2 (5mol%) 12) LiEt3BH
N 16) Li/NH3 toluene, MS
O Et3SiH, DCM DCM
(NH4)2SO4 253K, 2 h 18 h, rt 303K, 2 h
H H
N 17) tBuOH then DIBAL-H 14) H2, quinoline then acetone
THF, 195K DCM Lindlar's cat. Tf2O, rt
1h, 75% 253K, 60% EtOAc, 1h, rt 2h, 76%
OMe
82% (2 steps)

(-)-nakadomarin A

OSiPh3
Ph3SiO Mo OSiPh3
O O Me Ph
N N
Ph
Cl O (EtO)2P N N
N Me OTMS
H
I II III IV