112221saxitoxin_dubois_k.pdfverygoodorganicchemistry

Good

1. Divergent Synthesis of Natural Derivatives of (+)-Saxitoxin Including 11-Saxitoxinethanoic Acid
Walker, J. R.; Merit, J. E.; Thomas-Tran, R.; Tang, D. T. Y.; DuBois, J.
Angew. Chem. Int. Ed. 2019, 58, 1689–1693.
1–4
1) DCC, NEt
3
2) TBDPS-Cl, imidazole
3) DIBAL-H, DCM, -90°C
4) allylamine, then BF
3•OEt
2
A
5–9
NCOOH MeO
O
NH
3
OH
Saxitoxin (STX)
N NH
HN
NH
NH
2
NH
2
HO
HO
O
NH
2
O
N NH
NH
O
OTBDPS
5) Pd(PPh
3)
4, 1, then Na
2CO
3, 2,
6) EtOSO
2CF
3, 2,4,6-tri-tert-butylpyrimidine
7) NH
3, NH
4OAc, MeOH
8) TrocNMI
+

-
OTf (1.0 equiv.)
9) Rh
2(esp)
2 (cat.), PIDA, MgO
Step 4: Which named reaction takes
place? - Pictet–Spengler reaction
Cl SMe
N
S
O
OCl
3C
O
21
N N
O O
O
Cl
+
Hint for step 7: Two addition/elimination
reactions occur
Step 9: Please provide a mechanism for
this step.

2. B
10–17
Saxitoxin (STX)
N NH
HN
NH
NH
2
NH
2
HO
HO
O
NH
2
O
N NH
NH
HN
TcesN
AcO
NTroc
OTBDPS
10) PhSH, BF
3 • OEt
2
11) urea • H
2O
2, HFIP
12) NaSPh, Cl
3CCH
2OH, 80°C
13) DMP
14) [Ir(cod)(PCy
3)(py)]PF
6, B(Oi-Pr)
3, H
2
15) TBAF, AcOH
16) CDI, then NH
3 (0.5 M in THF)
17) PdCl
2, H
2, TFA
Step 12: What is the name of this step?
Mislow–Evans rearrangement

3. Mechanism of step 9:
N NH
NH
NTroc
OTBDPS
H
2N
NTces
I
OAc
OAc
N NH
NH
NTroc
OTBDPS
N
NTces
I
Ph
N NH
NH
NTroc
OTBDPS
N
NTces
[Rh]
N NH
NH
NTroc
OTBDPS
N
TcesN
- HOAc
N NH
NH
N
TcesN
NTroc
OTBDPS
Rh
2(esp)
2
N NH
NH
HN
TcesN
AcO
NTroc
OTBDPS
AcO
N NH
NH
NTroc
OTBDPS
N
NTces
[Rh][Rh]
[Rh]
Rh
Rh
O
O
O
O
O
O
O
O
Rh
2(esp)
2 =
open coordination site
MgO to neutralize acid