be either terminal or disubstituted. The efficiency of the
cyclization reactions shown in Table 2 is noteworthy, gene-
rally corresponding to ca. 90% per ring formed. These
bicyclizations are very easy to perform, as is apparent from
a sample procedure.2
Table 1. In(III)-Catalyzed Polycyclization in CH2Cl2 at 23 °C
Figure 1. Unreactive acetylenic substrate.
Even though seven-membered (Table 1, entries 1 and 3)
or five-membered (entries 2, 4À9) ring formation could, in
principle, have occurred, no such products were observed.
Thus, it appears that coordination of In(III) to a C;CtC
subunit not only induces electrophilicity in the triple bond
but also bends the C;CtC angle in a way that facilitates
six-membered ring formation. We also have found that
acetylenic substrates that can potentially cyclize to form
seven- or eight-membered rings undergo cyclization very
slowly or not at all, as observed for instance with substrate
3 (Figure 1).
We have tested for the possibility that the reactions
summarized in Tables 1 and 2 may involve In(III) activa-
tion by traces of H2O present in the reaction mixture with
the complex H2OÀInI3 essentially behaving as a protic
activation (i.e, Brønsted) catalyst. This was done by study-
ing the cyclization in the presence of 2,6-di-tert-butylpyr-
idine which would innhibit a proton donor but not InI3
(which does not complex with this sterically encumbered
base). It was determined that the cyclizations shown in
Table 2, entries 2 and 3, proceed in the same way in the
presence or absence of di-tert-butylpyridine to give the
same product in >90% yield.
Although six-membered rings are formed preferentially
in the cyclization reactions shown in Tables 1 and 2, it is
possible to generate structures containing five-membered
rings from the products shown in the tables by ring
contraction. For instance, the product in Table 2, entry 5
(4) was readily transformed into the 5À6À6 fused ring
structure 6 via the epoxide 5, as shown in Scheme 2. The
structures of 5 and 6 were established by spectroscopic
measurements, including 1H NMR and NOE measurements.
The details of the preparation of the acetylenic sub-
strates shown in Table 2 are given in the Supporting
Information. In brief, the various starting materials 9
a Isolated yields of products fully characterized by NMR and MS.
b The ratio of cyclization products was a:b = 93:6. c Reaction was
carried out at 55°C. d Reaction was carried out at À20 °C.
In the examples outlined in entries 1 and 3 of Table 1,
cyclization is followed by a prototropic rearrangement to a
ketone. These reactionsillustratea newand useful one-step
route to β-tetralones. The transformation shown in the
example in entry 2 of Table 1 is the result of dehydration of
the initial bicyclic allylic alcohol. The substrates used for
the reactions summarized in Table 1 are readily available
as described in the Supporting Information.
The preference for six- over five-membered ring forma-
tion has also been observed for In(III)-activated triple
bonds proximate to an ethylenic linkage. Table 2 sum-
marizes six examples of such bicyclization processes (with
InI3 in dry CH2Cl2) leading to tri- and tetracyclic products
(racemic) with the exclusive formation of six-membered
rings and with complete diastereoselectivity. As with the
cases disclosed in Table 1, the initiating triple bond may
(2) Procedure for the cyclization shown in Table 2, entry 5: To a
mixture of InI3 (100 mg, 0.2 mmol) and CH2Cl2 (8.0 mL) was added
substrate (286 mg, 1.0 mmol) in CH2Cl2 (2.0 mL) via cannula at À20 °C.
After stirring at À20 °C for 12 h, the reaction mixture was treated with
saturated aqueous NaHCO3 (5 mL) and extracted with CH2Cl2 (10 mL).
The organic layer was washed with brine, dried over Na2SO4, and
concentrated in vacuo. The residue was purified by silica gel chromato-
graphy to afford the tricyclic product in 83% yield (Table 2, entry 5).
(3) Liang, H.; Hu, L.; Corey, E. J. Org. Lett. 2011, 13, 4120–4123.
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Org. Lett., Vol. 13, No. 21, 2011