AuI-Catalyzed Regiodivergent Rearrangements
FULL PAPER
Conclusion
Although there have been numerous reports of reactions
that incorporate a 1,2-alkyl migration step, only a few proc-
esses had been described that employ the same substrates to
provide different products along different rearrangement
pathways. In this report, we have shown that a range of cy-
clopentene-based 2-alkynyl carbonyl compounds can be
transformed into various dihydrobenzofurans by following a
1,2-alkyl migration sequence catalyzed by a gold(I) complex.
Furthermore, treatment of 4-styrylcyclopent-1-ene-carboxy-
lates 2 with gold(I) catalyst that possesses non-nucleophilic
À
SbF6 counterion affords a range of highly functionalized di-
Scheme 3. Proposed mechanism.
hydroisobenzofurans 7; and with the OMsÀ counterion,
highly substituted dihydrobenzofurans 8 can be obtained.
Thus, a clear-cut divergence in rearrangement directions was
observed, which indicates that the regioselectivity of Au-cat-
alyzed 1,2- versus 1,2’-alkyl migration is counterion-depend-
ent. In addition, it was found that the 2-alkynyl carbonyl
heterocyclic compounds that contain pyrrolidine rings un-
derwent a 1,2-alkyl migration step, and in the case of tetra-
hydroquinoline, the substrate-assisted 1,2’-alkyl migration is
the major process. The present study might provide a better
understanding of the reaction of 1,2-alkyl migration by a
concerted mechanism and the reaction of 1,2’-alkyl migra-
which might in turn undergo a 1,2-alkyl migration through
pathway a, or a 1,2’-alkyl migration through pathway b.
Through path a, intermediate A forms the allylic cation-con-
taining vinyl–gold intermediate B by the selective 1,2-alkyl
migration from the 3- to the 2-position by means of a three-
membered cyclic transition state. Upon subsequent deproto-
nation and protodeauration, intermediate B would give the
[2,3-c]furan 18. Through path b, oxonium-containing vinyl–
gold intermediate A would undergo 1,2’-alkyl migration
À
from the 3- to the 4-position by means of a C C bond cleav-
age and subsequently ring closing[29] to produce [3,4-c]furan
19. The rearrangement that possesses a more stable cation
intermediate D favors undergoing a 1,2’-alkyl migration re-
action.
tion by means of a key C C bond cleavage and C Au bond-
substitution pathway. Nevertheless, in light of the fact that
various effects on the rearrangement reactions have not
been studied systematically, the migratory aptitude remains
to be fully elucidated. This method allows for efficient syn-
thesis of multisubstituted and fused furans, and we antici-
pate that an array of other processes might benefit from this
approach.
À
À
The generally observed divergence in product selectivity
can be thoroughly explained by the nature of the counteran-
ion and the stability of intermediates. In general, if the
effect favors the formation a more stable carbocation D, the
1,2’-migration pathway will be the predominant one. 1) For
4-styrylcyclopentene derivatives 2, counteranion factors
govern the regioselectivity of the reaction. The 4-styrylcyclo-
pentene derivatives can participate in either a 1,2- or 1,2’-
alkyl migration pathway. When a more nucleophilic anion
(OMsÀ) is used, 1,2’-alkyl migration pathway is disfavored
due to the fact that free carbocation D might react with the
nucleophilic anion and hinder the subsequent cyclization.
2) The heteroatom effect was crucial for the regioselectivity
of the rearrangement. Indeed, tetrahydrofuran-based 2-al-
kynyl carbonyl compound 16 favors the formation of the
carbocation D stabilized by the oxygen (also called oxonium
intermediate), thus leading to a 1,2’-alkyl migration product.
3) A substituent with a different electronic nature at the N
position did alter the reactivity: substrates 4 with the elec-
tron-withdrawing Ts group reacted smoothly to afford 1,2-
alkyl migration products, and those compounds 5 with an
electron-donating alkyl group afforded 1,2’-alkyl migration
products under the reaction conditions, which probably orig-
inates from stabilization of the iminum ion intermediate.
Experimental Section
General procedure for the preparation of compounds 7: IPrAuCl
(0.0125 mmol), AgSbF6 (0.0125 mmol), and dry toluene (2.5 mL) were
added to a dry Schlenk tube, and the mixture was stirred at room temper-
ature for 0.5 h in the dark. Compound 2 (0.25 mmol) was added, and the
resulting mixture was stirred at 808C for 2–6 h. After the reaction was
complete, which was determined by TLC analysis, the reaction mixture
was concentrated under reduced pressure. The crude product was puri-
fied by flash column chromatography on silica gel (hexanes/acetate=5:1)
to give 7 as a yellow solid.
General procedure for the preparation of compounds 8: IPrAuCl
(0.0125 mmol), AgOMs (0.0125 mmol), and dry toluene (2.5 mL) were
added to a dry Schlenk tube, and the mixture was stirred at room temper-
ature for 0.5 h in the dark. Compound 2 (0.25 mmol) was added, and the
resulting mixture was stirred at 808C for 2–5 h. After the reaction was
complete, which was determined by TLC analysis, the reaction mixture
was concentrated under reduced pressure. The crude product was puri-
fied by flash column chromatography on silica gel (hexanes/acetate=5:1)
to give 8 as a red solid or oil.
Chem. Eur. J. 2012, 18, 15113 – 15121
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
15119