Communications
Table 1: Yields of the isolated products, reaction conditions, chemoselectivity and
absorption with a maximum at 340–350 nm. Irradi-
stereoselectivity of cycloadditions.[a]
ations were carried out with a Rayonet broadband
300–400 nm UV source or Nichia 365 nm UV LEDs
and gave stable polyheterocycles 2, 3, and 5. The [4 +
2] photoadducts 3 and 5 possess unprecedented
doubly fused furo[2,3-b]quinoline and pyrrolo[1,2-
a]quinoline motifs and the [4 + 4] photoadducts 2
possess an O-bridged pyrrolo[1,2-a]benzazocine core
(Scheme 2, for experimental details see the Support-
ing Information).
With regard to the chemoselectivity, the furan-
based precursors (1a–1e) yielded both [4 + 4] and
[4 + 2] cycloadducts 2 and 3 (Scheme 2). The ratio of
the [4 + 4] to the [4 + 2] cycloadducts generally
ranged from 1:1 to 2:3 (Table 1). In contrast, the
thiophene derivatives 4a and 4b undergo mostly [4 +
2] cycloaddition forming dihydrothiophenes 5a and
5b (major products) and 5’a (a minor hydroxy
epimer observed for R = H). Cycloadditions of
thiophenes, especially in the acetophenone series
(b; R = Me), most efficiently occur upon heating the
reaction mixture during irradiation.
The diastereoselectivity, that is the syn/anti con-
figuration of the hydroxy group relative to the
heteroatom in the annelated ring or the bridge, was
high in this series, with predominant formation of the
anti diastereomer of the [4 + 2] adducts and the
syn diastereomer of the [4 + 4] adducts (Table 1). In
some cases, the benzaldehyde derivatives produced a
small amount of the minor hydroxy epimer (denoted
with a prime). Ketones always reacted to yield
exclusively the anti isomer of the [4 + 2] adducts and
the syn isomer of the [4 + 4] adducts.
Precursor
Solvent
T [8C] Yield [%][b]
[4+4]/
[4+2][c]
d.r.[c,d]
[4+2] [4+4]
>30:1 >30:1
1a
1b
1c
1d
1e
C6H6
20
20
20
20
20
20
2a, 25
3a, 55
2b, 30
3b, 53
2c, 53
3c, 23
2d, 43
3d, 46
2e, 38
3e, 44
5a, 64
1:1
0.7:1
2.1:1
1:1
C6H6
>30:1 >30:1
>30:1 >30:1
>30:1 >30:1
>30:1 >30:1
>30:1 >30:1
CH3CN
CH3CN
CH3CN
CH3CN
1.2:1
1:9
–
4a
4b
CH3C6H5 reflux 5b, 60
2:1
–
10a
CH3CN
20
16a, 47
16’a, 33
19a, 9
12:1
1.5:1 >30:1
11a
12a
13a
CH3CN
CH3CN[e]
CH3CN
reflux 17a/17’a 26
0
>30:1
>30:1
1.1:1
–
–
0.55:1
>30:1
4.3:1
18a[f]
20
21a, 32
21’a, 8
23a 33
21b, 59
23b[g]
22b, 57
24b, 28
25a, 46
25’a, 7
26a, 29
25b, 45
26b, 36
>30:1
13b
14b
15a
CH3CN
CH3CN
CH3CN
20
20
20
4.6:1
2.6:1
1.9:1
>30:1 >30:1
>30:1 >30:1
>30:1
1:1.3
15b
CH3CN
20
1.4:1
>30:1 >30:1
32C (X=CH2) CH3CN[h]
32S (X=S)
0
0
33 (X=CH2), 53 >30:1
–
–
9:1
8:1
CH3CN[h]
33 (X=S), 61
33’ (X=S), 11
35a, 30
>30:1
Mechanistically, the reaction with tetralone 1d, 34a
C6H6
20
20
–
–
1:1
3:1
–
–
35’a, 26[i]
35b, 38
which lacks a rotatable carbonyl group, pointed to
the endo transition state (or intermediate) in both
the [4 + 2] and [4 + 4] cycloadditions (Scheme 3).
Our hypothesis is that benzaldehyde- or acetophe-
34b
C6H6
35’b, 13[j]
38a, 87
36a
36b
36 f
37a
C6H6
C6H6
C6H6
C6H6
20
20
20
20
–
–
–
–
>30:1
>30:1
>30:1
>30:1
–
–
–
–
38b, 85
38 f, 47[k]
39a, 70
none-derived azaxylylenes also react with the furan
or thiophene pendant groups via a similar endo tran-
sition state (or intermediate). In these cases, where
the carbonyl group is rotatable, the minor hydroxy
epimers potentially result from the out-hydroxy
conformer of azaxylylene; at this point, however,
we do not know whether the mechanism is concerted
or stepwise.
While a detailed photophysical mechanistic study
of these cycloadditions is ongoing, we suggest that
these are excited-state reactions and not ground-
state additions of the photogenerated azaxylylenes.
All photoactive precursors possess two characteristic
[a] Reaction carried out with 100–300 mg loading of the precursor. [b] Yields of the
isolated products after column chromatography. [c] Determined by 1H NMR
spectroscopy. [d] anti:syn for [4+2] and syn:anti for [4+4]. [e] Two equivalents of
HMPA. [f] Quantitative yield as determined by 1H NMR spectroscopy (see the
Supporting Information). 18a decomposes during chromatography. [g] The [4+4]
and [4+2] cycloadducts are not separable. [h] 5 vol% HMPA. [i] At 208C aminal 42a
(17%) was also formed. [j] At 208C aminal 42b (30%) was also formed. [k] At 208C
aminal 43 f (30%) was also formed.
emission bands in their fluorescence spectra: the 400 nm
fluorescence from the initial amide form, and the 540–550 nm
band with a remarkably large Stokes shift. This second band is
attributable to an excited-state intramolecular proton transfer
(ESIPT), which in this particular case is due to the emission
from the S1 state of azaxylylene. Conceivably this band can be
used in a fluorescence-quenching assay for high-throughput
screening and optimization of the reaction conditions, an
assay similar to that reported by Porco, Jones, and co-
workers[8] for 3-hydroxyquinolines.
At this point, it was clear that we had uncovered a
powerful photoassisted reaction that offers expeditious access
to topologically unique N,O,S-polyheterocycles. The prepa-
rative potential of similar all-carbon [4 + 4] photoinduced
cycloadditions of pyran-2-ones and pyridones to tethered
furans, to access cyclooctane cores, is exemplified in the
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 9423 –9428