Photocyclization Reactions of Pyridinium Salts
N1,C6,C5- versus C1′,N1,C2,C3-dihedral angles in the
calculated structure of 19 (Table 2). Importantly, this
distortion is not present in the cyclohexa-fused tricyclic
allylic cation 12. It is difficult to assess the importance
of the nitrogen lone pair orientation in governing the
regiochemical course of hydroxide addition to 19. It is
interesting and perhaps relevant that the calculated
natural charges (Table 2) at the C-3 allylic carbon and
attached hydrogen H-3 in 19 are higher than those at
C-5 and H-5, a difference not seen in the homologous
cyclohexa-fused allylic cation 12. Although the differences
in the positive charge densities are small, they might be
sufficiently large to drive counter-steric nucleophilic
addition to C-3 in 19.
8.6 mmol UV: γmax 266 nm) and HClO
4
(5 mL, 70%) in water
(
500 mL) was irradiated (RPR-2537Å reactor lamps, Rayonet
company) at 25 °C for 28 h (76% conversion) and concentrated
in vacuo, giving a residue. A solution of the residue, DMAP
(
0.1 g), pyridine (10 mL), and Ac
was stirred at 25 °C for 12 h, diluted with saturated NaHCO
and extracted with CHCl . The CHCl extracts were dried and
2 2 2
O (5 mL) in CH Cl (30 mL)
3
,
3
3
concentrated in a vacuum to give a residue that was subjected
to column chromatography (2:3 acetone/hexane) to yield the
spirocyclic amido diester 15 (58 mg, 3%) as a colorless oil and
fused hydroazepine 16 (0.38 g, 20%) also as a colorless oil.
1
15: H NMR 1.69-1.71 (m, 6H), 2.08 (s, 6H), 2.09 (s, 3H),
1
3
3.38 (d, J ) 5.7 Hz, 2H), 5.87 (s, 2H), 6.36 (s, 2H); C NMR
16.7, 21.0(2), 22.4, 22.9, 24.1, 42.9, 71.0, 82.0(2), 132.0(2),
1
70.2, 171.2 (2); HRMS (ES) m/z 318.1303 (M + Na), calcd for
15
C
H
21NO
1
5
Na 318.1312.
1
6: H NMR mixture of two rotamers (1:1) 5.91 (d, J ) 6.5
Summary
Hz, 1H), 5.75 (d, J ) 16.5 Hz, 2H), 5,62-5.64 (m, 2H), 5.05 (t,
J ) 6.0 Hz, 2H), 4.9 (t, J ) 5.5 Hz, 1H), 4.21 (d, J ) 134.0 Hz,
The results described in the previous section demon-
strate that the photocyclization reaction of cyclopenta-
fused pyridinium perchlorate 18 is remarkably regiose-
lective, forming the tricyclic allylic alcohol 20 exclusively.
Moreover, the transformation of 20 to the spirocyclic
amido diester 21, followed by enzymatic desymmetriza-
tion, produces enantiomerically pure monoalcohol 22.
This chemistry comprises a highly concise sequence for
the preparation of what should become a useful synthon
in synthetic organic chemistry.
1
1
2
3
1
2
H), 3.63 (d, J ) 12.5 Hz, 1H), 2.80 (dd, J ) 12.0, 15.3 Hz,
H), 2.61 (∼t, J ) 14.0 Hz, 2H), 2.36 (∼t, J ) 13.0 Hz, 1H),
.22 (s, 3H), 2.17 (s, 3H), 2.15 (s, 3H), 2.08 (s, 3H), 2.06 (s,
H), 2.04 (s, 3H), 1.81-1.95 (m, 7H), 1.42-1.53 (m, 2H), 1.22-
13
.27 (m, 1H); C NMR 20.4, 20.7, 20.7, 20.8, 21.5, 21.7, 28.7,
9.4, 29.5, 29.8, 30.1, 30.8, 41.6, 44.3, 61.8, 66.2, 73.0, 73.4,
73.6, 74.6, 123.8, 124.0, 152.1, 152.7, 169.8, 170.1, 170.4, 170.6,
170.7, 171.2; HRMS (FAB) m/z 318.1325 (M + Na), calcd for
C H21NO Na 318.1312.
15 5
Bis-p-Nitrobenzoate Diester 17. A solution of hydroazepine
diester 16 (0.2 g, 0.68 mmol) and NaOMe (36.6 mg, 0.68 mmol)
in MeOH (10 mL) was stirred at 25 °C for 12 h, diluted with
water, and concentrated in vacuo to yield the crude diol. A
Experimental Section
solution of the diol, Et
(0.5 g, 2.7 mmol) in CH
12 h, diluted with saturated NaHCO
CHCl . The CHCl
3
N (0.5 mL), and p-nitrobenzoyl chloride
Cl (10 mL) was stirred at 25 °C for
, and extracted with
3
extracts were dried and concentrated in
1
,2-Cyclohexa-Fused Pyridinium Perchlorate 9. A
solution of 4-(2-pyridyl) butanol (13 g, 86 mmol) and thionyl
2
2
chloride (31 g, 0.26 mol) in CHCl
3
(100 mL) was stirred at 25
3
°
C for 12 h and diluted with 10% aq. NaOH to adjust the pH
3
to 13-14. Extraction with CHCl
3
gave extracts that were dried
vacuo, giving a residue that was subjected to column chroma-
and concentrated in vacuo to yield the crude chloride as an
oil that was heated at 80 °C for 3 h, then recooled to 25 °C
tography (1:2 acetone/hexane) to give bis-ester 17 (0.30 g, 85%)
1
as a white solid. mp 211-213 °C (CH
2
Cl
2
/hexane); H NMR
and mixed with CH
3
CN (100 mL) and AgClO
4
(12 g, 58 mmol).
(major rotamer) 8.18-8.27 (m, 4H), 8.10-8.13 (m, 4H), 6.25-
6.26 (m, 1H), 6.05-6.07 (m, 1H), 5.96 (m, 1H), 5.31-5.36 (m,
1H), 3.73 (d, J ) 15.4 Hz, 1H), 2.91 (dd, J ) 11.8, 15.4 Hz,
1H), 2.70-2.72 (m, 1H), 2.17 (s, 3H), 1.97-2.06 (m, 3H), 1.54-
The resulting mixture was stirred at 25 °C for 12 h and
filtered. The filtrate was concentrated in vacuo to yield the
1
pyridinium salt 9 (15 g, 100%) as a solid. mp 105-107 °C. H
1
3
NMR 1.91-1.97 (m, 2H), 2.07-2.12 (m, 2H), 3.20 (t, J ) 6.7
Hz, 2H), 4.50 (t, J ) 6.2 Hz, 2H), 7.73-7.80 (m, 2H), 8.27-
1.56 (m, 1H), 1.30-1.38 (m, 1H); C NMR 21.6, 29.5, 29.8,
30.2, 44.6, 62.0, 75.1, 75.6, 123.6, 123.7, 123.8, 130.5, 130.7,
8
2
1
.30 (m, 1H), 8.47 (d, J ) 6.2 Hz, 1H); 13C NMR 18.9, 22.4,
1
30.8, 134.7, 134.9, 150.6, 153.8, 164.2, 164.4, 171.3. HRMS
9.9, 57.6, 126.7, 130.7, 146.1, 146.3, 158.8. HRMS (ES) m/z
(
ES) m/z 510.1522 (M + 1), calcd for C25
24 3 9
H N O 510.1513
+
34.0968 (M ), calcd for C
9
H
12N 134.0964.
1
,2-Cyclopenta-Fused Pyridinium Perchlorate 18. A
Photoreaction of 9 in Aqueous KOH. Formation of 10
and 11. A solution of pyridinium salt 9 (2.0 g, 8.6 mmol, UV:
max 266 nm) and KOH (0.51 g, 9.1 mmol) in water (500 mL)
was irradiated (RPR-2537Å reactor lamps, Rayonet company)
at 25 °C for 36 h (70% conversion) and concentrated in vacuo
to give a residue that was subjected to column chromatography
solution of 3-(2-pyridyl)propanol (6.85 g, 0.05 mol) and thionyl
chloride (9 mL) was stirred at 25 °C for 5 h and then cooled to
γ
0
°C, and aq. NaOH was added to bring the pH to 12-14. The
solution was extracted by CHCl . The CHCl extracts were
3
3
concentrated in vacuo to yield the crude chloride as an oil that
was heated at 80 °C for 2 h, recooled to 25 °C, and mixed with
CH CN (50 mL) and AgClO (9 g, 0.043 mol). The mixture was
3 4
(
1:1 acetone/hexane) to give the tricyclic allylic alcohol 10 as
a colorless oil (0.05 g, 5%) and the known dihydropyridone
9
stirred for 12 h at 25 °C and filtered. The filtrate was
concentrated in a vacuum at room temperature to yield the
1
1 as a red oil (0.2 g, 23%).
1
1
0: H NMR 1.25-1.28 (m, 1H), 1.33-1.38 (m, 2H), 1.58-
1
pyridinium salt 18 (9.2 g, 85%) as a solid. mp 112-113 °C. H
1
1
(
7
.62 (m, 1H), 2.18-2.28 (m, 2H), 2.47 (s, 1H), 2.61-2.64 (m,
H), 3.32-3.35 (m, 1H), 4.26 (s, 1H), 5.75-5.77 (m, 1H), 6.26
3
NMR (CD CN) 2.46 (m, 2H), 3.48 (t, J ) 7.6 Hz, 2H), 4.79 (t,
1
3
J ) 7.6 Hz, 2H), 7.82 (t, J ) 6.6 Hz, 1H), 7.95 (d, J ) 8.0 Hz,
d, J ) 5 Hz, 1H); C NMR 18.5, 19.2, 21.5, 49.6, 51.3, 51.8,
1
3
+
1H), 8.36 (t, J ) 7.8 Hz, 1H), 8.66 (d, J ) 6.1 Hz, 1H);
NMR 22.1, 33.2, 60.2, 125.8, 126.5, 142.0, 146.1, 160.4. HRMS
(ES) m/z 120.0809 (M), calcd for C 10N 120.0808.
C
8.0, 136.0, 136.1. HRMS (ES) m/z 152.1075 (M + 1), calcd
for C 14N 152.1075.
9
H
1
8
H
1
1: H NMR 1.10-1.13 (m, 1H), 1.25 (m, 1H), 1.33-1.36
m, 1H), 1.48-1.55 (m, 1H), 1.68-1.75 (m, 1H), 2.27-2.37 (m,
H), 2.78 (s, 2H), 3.65-3.68 (m, 1H), 4.69 (dd, J ) 1.9, 13.1
(
1
Photoreaction of 18 in Aqueous KOH. Formation of
Tricyclic Allylic Alcohol 20. A solution of 18 (2.14 g, 0.01
Hz, 1H), 5.44 (d, J ) 10.2 Hz, 1H), 5.50 (dd, J ) 1.6, 10.2 Hz,
H), 5.70 (d, J ) 9.8 Hz, 1H); C NMR 24.3, 25.0, 31.4, 33.7,
1.8, 57.9, 120.6, 125.4, 165.4.
Photoreaction of 9 in Aqueous Perchloric Acid. For-
mation of 15 and 16. A solution of pyridinium salt 9 (2.0 g,
2
mol, UV: γmax 266 nm) in H O (500 mL) containing KOH (0.6
1
3
1
4
g, 0.01 mol) was irradiated (RPR-2537Å reactor lamps, Rayo-
net company) for 24 h (70% conversion). Concentration in a
3
vacuum was followed by extraction with CHCl . The extracts
were filtered and concentrated in a vacuum, giving a residue
J. Org. Chem, Vol. 70, No. 21, 2005 8511