Organic Letters
Letter
a
all suitable nucleophiles to form the benzene-fused 2,3-
dehydrobenzofuran products 5 with good efficiency (Scheme
Scheme 5. Product Derivatizations
4
). Phenols can also react in a similar manner, but their
a
Scheme 4. Synthesis of 2,3-Dihydrobenzofurans
a
Reaction conditions: (a) Tf O, Et N, DCM, 0 °C to rt, 50%. (b) Mg,
2
3
Pd/C, NH OAc, MeOH, rt, 48%. (c) DMP, DCM, rt, 31%. (d)
4
TEMPO, Fe(NO ) ·9H O, DCE, rt, 91%. (e) PhI(OAc) , MeOH, rt,
3
3
2
2
a
80%.
Reaction scale: 1a (0.3 mmol), 4 (0.3 mmol), In(OTf)3 (0.03
mmol), CH CN (1.5 mL). Isolated yield.
3
believed that the free phenol hydroxyl group initially
reactivity is generally lower than β-naphthols. A diverse set of
functional groups could be tolerated in these reactions,
including aryl halide, alkyne, ether, acetal, amine, and alcohol.
Interestingly, 3-aminophenol 4m reacted with excellent
chemoselectivity. 2,3-Dihydrobenzofuran 5m was obtained as
the only isomer, and its indoline isomer 5m′ was not observed
at all. This observation is consistent with the relatively lower
reactivity of such oxetane substrates in the synthesis of
indolines with this protocol. Finally, a gram-scale synthesis of
participates in ligand exchange with PhI(OAc) to form IM3,
2
which then triggers oxidative dearomatization of the phenol
1
3
ring to form cyclohexadienone IM4. With the cyclo-
hexadienone unit as a good leaving group, the lone pair on
the oxygen then pushes the electron density via the arene to
trigger C−C bond cleavage. Next, a similar deprotonation/
rearomatization step as in the case of 8 delivers the final
observed product 10.
In summary, we have developed a new intermolecular [3 +
] annulation for the synthesis of 2,3-dihydro-1H-benzo[e]-
5
a was also demonstrated to be comparably efficient.
The 2,3-dihydro-1H-benzo[e]indole and 2,3-dihydro-benzo-
2
indoles, an important family of heterocycles whose efficient
synthesis remains in high demand. The proper combination of
the two versatile structural units, oxetane and para-quinone
methide, in the key intermediate has enabled the successful
design of the highly expedient approach for the synthesis of the
benzoindoline core structure from readily available starting
materials. This is also a rare example of using β-naphthyl-
amines for direct intermolecular [3 + 2] annulation. The
furan products generated in our process are precursors to other
useful molecules. First of all, product 3a was synthesized in
gram scale from 1a and 2a in 81% yield (Scheme 5). The para-
hydroxyl group in 3a, which was needed to form the p-QM
intermediate, could be easily removed to form 7 by Pd-
catalyzed reduction of its triflate derivative 6. Furthermore, in
the presence of the Dess−Martin periodinane (DMP), the
hydroxymethyl group in triflate 6 could be eliminated to form
benzoindole 8. This reaction might proceed via initial ligand
exchange of the hypervalent iodine with the hydroxyl group to
form IM1, which then undergoes elimination to form iminium
IM2. Subsequent deprotonation led to rearomatization to form
the observed benzoindole product. Furthermore, the electron-
rich phenol ring in product 5a could undergo selective
nitration to form 9, whose structure was confirmed by X-ray
crystallography. More interestingly, when 5a was treated with
PhI(OAc)2 in MeOH, the whole phenol ring unit was
eliminated to form naphthofuran 10 in high yield. It is
choice of In(OTf) as the optimized Lewis catalyst, together
3
with other reaction parameters (such as solvent MeCN),
proved critical in achieving high efficiency and selectivity. This
protocol was also successfully extended to the synthesis of a
range of 2,3-dihydrobenzofurans without modification. Control
experiments indicated that the free para-hydroxyl group in the
phenol unit is important to the reactivity of this type of
substrates, thus providing support to the possible involvement
of the p-QM intermediate. Finally, these heterocyclic products
have also been demonstrated as useful precursors to other
related heterocycles.
C
Org. Lett. XXXX, XXX, XXX−XXX