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Scheme 2. Reagents and conditions: a) 30% H2O2, NaOH (aq),
MeOH, 08C; b) H2SO4, THF/H2O (5:1), reflux; c) NaIO4, iPrOH/H2O
(1:1), 08C to RT; d) I2, KI, NaHCO3, CH2Cl2/H2O (1:3), 08C, 51% for 4
steps; e) NaBH4, MeOH, 08C, 85%; f) AIBN, Bu3SnH, toluene, 1008C,
90%; g) PPh3, I2, imidazole, 08C to RT, THF, 84%. AIBN=
2,2’-azobis(2-methylpropionitrile), THF=tetrahydrofuran.
ing aldehyde 13 in a four-step sequence involving epoxidation,
epoxide hydrolysis, oxidative cleavage of diols, and iodolac-
tonization in 51% overall yield (4 steps). The aldehyde 13 was
selectively reduced with NaBH4 to provide the alcohol 14 in
85% yield. The deiodination of 14 with AIBN and Bu3SnH
afforded the compound 15, which was converted into the
corresponding 7 with I2 in the presence of Ph3P and imidazole
in 84% yield.[8]
Scheme 4. Reagents and conditions: a) TPP, O2, hu, CCl4, À108C then
thiourea, MeOH; b) BzCl, Et3N, DMAP, CH2Cl2, RT, 73% for 2 steps;
c) [{Pd(allyl)Cl}2] (3 mol%), ligand A, 22, K2CO3, MeOH, THF, 08C;
then DIPEA, 558C; 70%; d) NaH, CH3I, DMF, 08C, 90%, d.r. (at
C13)=4:1; e) NaBr, DMF, 1808C, 88%, d.r. (at C13)=1:1; f) LDA,
BrCH2CO2tBu, THF, À788C; g) TFA, CH2Cl2, 08C to RT, 93% for 2
steps; h) EtMgBr, THF/Et2O (1:1), À788C to RT, 80%; i) O3, CH2Cl2/
MeOH (1:1), À788C, then Me2S, À788C to RT; j) (Bn2NH2)(OCOCF3),
toluene, 638C, 80% for 2 steps. Bz=benzoyl, DIPEA=diisopropyl-
ethylamine, DMAP=4-(N,N-dimethylamino)pyridine, LDA=lithium-
diisopropyl amide, TPP=5,10,15,20-tetraphenyl-21H,23H-porphine.
Thermal ellipsoids are shown at 50% probability.[21]
Depicted in Scheme 3 is the construction of the vinyl
stannane compound 4. The vinyl bromide 18 was prepared
Trost and co-workers,[11] the lactone 23 was obtained in
a reported three-step process from the commercially available
1,3-cyclohexadiene (19). The steps included asymmetric
palladium-catalyzed allylic alkylation. Methylation of 23
with NaH and CH3I provided the compound 24 in 90%
yield with 4:1 diastereoselectivity at C13, and was then
subjected to decarboxylation mediated by NaBr to produce
a 1:1 mixture of the lactone 25 in 88% yield. Alkylation of 25
with tert-butyl bromoacetate gave the single diastereomer 26.
Deprotection of 26 was achieved using trifluoroacetic acid
and gave the acid 27 in 93% yield (two steps). Addition of
ethyl magnesium bromide followed by acidic workup gave
rise to the tricycle 28, having an ethyl group installed
stereoselectively onto the tricyclic framework.[12] The abso-
lute configuration of 28 was determined by X-ray crystallo-
graphic analysis. The cyclohexene ring in 28 was oxidatively
cleaved by ozonolysis and the resulting dialdehyde 29 was
directly subjected to intramolecular aldol condensation, thus
yielding the ring-closed unsaturated aldehyde 8 (80% yield
for two steps).[13]
Scheme 3. Reagents and conditions: a) PPh3CHCO2tBu, toluene, RT,
54%; b) TFA, CH2Cl2, 08C; c) Br2, TFA, CDCl3/CCl4 (1:1), RT; (d) Et3N,
DMF, 08C to RT, 76% for 3 steps; (e) [{Pd(allyl)Cl}2] (5 mol%),
(Bu3Sn)2, LiCl, 1,4-dioxane, RT, 49%. DMF=N,N-dimethylformamide,
TFA=trifluoromethanesulfonyl.
from the commercially available compound citraconic anhy-
dride (16) in a reported four-step process in a 41% overall
yield.[9] Stannylation of 18 was achieved and afforded 4 with
[{Pd(allyl)Cl}2] and (Bu3Sn)2 in 49% yield.[10] It is noteworthy
that 4 is not stable during purification, thus resulting in a low
yield.
We then moved on to construct the aldehyde compound 8
(Scheme 4). By using the reaction conditions developed by
2
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Angew. Chem. Int. Ed. 2015, 54, 1 – 5
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