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2,3,3a,6,7,7a-hexahydroindole core could be prepared by the
reliable approach, which should provide a solid basis for the
synthesis of other natural products featuring the hydroindole
structure. Monomer 7 represents a key intermediate in the
divergent synthetic strategy for natural products of the ETP
family; further progress towards divergent total synthesis of
ETPs and related natural products will be reported in the future.
Notes and references
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Scheme 3 Conditions: (a) EDCl, DMAP, Spy-OH, DCM/toluene, rt; (b) O2,
60%, 25 : 26 = 1 : 3; (c) p-NO2PhCOOH, Ph3P, DIAD, THF, 0 1C to rt,
(d) K2CO3, MeOH, rt, 66% over 2 steps; (e) TBSOTf, 2,6-lutidine, DCM,
ꢁ40 1C, 85%; (f) K2OsO4ꢀ2H2O, NMO, t-BuOH/H2O, 50 1C; (g) TPAP, NMO,
DCM, silica gel, rt; (h) SmI2, THF, rt, 35% over 3 steps; (i) NaOH, THF/H2O,
60 1C, 42% (51% b.r.s.m); (j) LiOH (1 M aq.)/THF, EtOH, rt, 95%; (k) TBAF,
THF, rt. 92%; (l) Pd(OH)2/C, H2, EtOAc, rt, 98%.
alcohol or aldehyde, a variety of reducing reagents were investigated.
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quantitative yield via an SN20 (conjugate reduction/elimination pro-
cess) process (22) upon treatment with NaBH4. Under the optimized
conditions, the first three steps could be carried out in a sequence
without purification. And twenty grams of carboxylic acid 23 could be
prepared, which demonstrated the efficiency of the approach.
With the abundant intermediate 23, containing the
2,3,3a,6,7,7a-hexahydroindole core, we proceeded with its conversion
to the key monomer 7 (Scheme 3). First, the carboxyl group was
converted to the hydroxyl group by a Barton decarboxylative oxygena-
tion.11 Alcohols 26 and 25 were isolated as diastereoisomers (dr =
3 : 1). Furthermore, the minor product 25 with an opposite configu-
ration of the hydroxyl group in position 7, characterized by X-ray
crystallography, could be transformed to 26 with the desired
configuration by the Mitsunobu process. After t-butyldimethylsilyl
protection of the hydroxyl group, the dihydroxylation/Ley oxida-
tion12/dehydroxylation13 sequence was performed, furnishing the
b-methoxycarbonyl ketone 28. After demethoxycarbonylation by
sodium hydroxide, the N,O-protected monomer 29 was obtained,
whose t-butyldimethylsilyl group could be easily removed in excellent
yield (92%), followed by the removal of the benzyl protection (98%)
affording key monomer 7. Meanwhile, carboxylic acid 30 could be
obtained by saponification of 29 in excellent yield (95%) as well.
In conclusion, a stereoselective synthesis of the key monomer
of ETP natural products which involves a diastereoselective
IEDDA reaction and the firstly reported NaBH4 promoted
bridged-lactone ring opening reaction has been successfully
accomplished. The abundant intermediate 23 containing the
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9692 | Chem. Commun., 2014, 50, 9690--9692
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