Total Synthesis of (−)-Sinulariadiolide.

A Transannular Approach
Zhanchao Meng and Alois Fürstner; J. Am. Chem. Soc. 2019, 141, 805–809.

1) Name the starting material. How is this commercially

O prepared from isoprenol?
1) Me2SO4, i-Pr2NEt, 0 °C
HO
then O3, −78 °C, then PPh3
2) Z (25 mol%), CuCl2 (12 mol%),
2) Name of the organocatalyst Z? How would you
TEMPO, MS 4 Å, −10 °C (e.r. 83%)
prepare it?
1-6 3) propyn-1-ylmagnesium bromide, pentane
4) TBSCl, imidazole
5) B2(pin)2, t-BuONa (15 mol%), CuCl (6 mol%),
(S,S)-methyl-DUPHOS (6 mol%), MeOH/THF
6) NaBO3·6H2O, aq. THF, 90 °C
Me
O P
N
Me
Me
A N P
Ph H2 BF –
4
Me
Z
(S,S)-methyl-DUPHOS
(R)-(–)-carvone
7) aq. H2O2, NaOH
8) TsNHNH2, HOAc, CH2Cl2 8) Hint: a fragmentation occurs
7-10
9) NaClO2, NaH2PO4, 2-methylbut-2-ene, t-BuOH/H2O
10) Y, DCC, DMAP, Et3N, CH2Cl2, then A, PhMe, 60 °C

O
Me O OH
O pKa? MeOOC
Ph O
O O OH

Y H O H
H
O
B (−)-sinulariadiolide
 11) Ac2O, DMAP (20 mol%), Et3N, CH2Cl2, −40 °C; 11) Hint: 1,3-dicarbonyl compounds are not well-
12) aq. HF, THF tolerated by the molybdenum alkylidynes/silanolate
13) X (30 mol%), PhSi[CH2CH2(Ph)2SiOH]3 (30 mol%) catalyst-ligand systems
11-15
toluene, 120 °C
14) Zn, HOAc, THF/H2O
15) Bu3SnH, [Cp*RuCl]4 (11 mol%) 15) Mechanism?

Mo N
N
N t-Bu

C X

16) CO (1 atm), Pd(OAc)2 (20 mol%), AsPh3 (40 mol%)

1,4-benzoquinone, TFA (40 mol%), MeOH 17) Hint: numerous attempts to induce ring contraction at
16-19 17) triphosgene, CH2Cl2, pyridine, 0 °C this stage failed, hence two hydroxyl groups were
18) Cs2CO3, CH2Cl2, MeOH/H2O functionalized first.
19) BBr3, 2-methyl-2-butene, CH2Cl2

Me O OH
MeOOC
O
OH

H O H
H
O
(−)-sinulariadiolide