Total syntheses of angelicoin A, hericenone J, and hericenol A via migratory prenyl- and geranylation-aromatization sequences

Article abstract of DOI:10.1021/jo202354j

A five-step synthesis of the natural product angelicoin A using a late stage highly regioselective palladium(0)-catalyzed decarboxylative prenyl migration and aromatization sequence as the key step is reported. The method was extended with geranyl migrati

Full text of DOI:10.1021/jo202354j

Supporting Information
Total Syntheses of Angelicoin A, Hericenone J and
Hericenol A via Migratory Prenyl- and Geranylation-
Aromatization Sequences
Jens Cordes, Frederick Calo, Katie Anderson, Toni Pfaffeneder,
Sylvain Laclef, Andrew J. P. White, and Anthony G. M. Barrett*
Department of Chemistry, Imperial College, London, SW7 2AZ, England.
agm.barrett@imperial.ac.uk
S1

Contents
1
1. H and 13C spectra (CDCl
3
, respectively 400 MHz and 100 MHz)
Hericenone J
((E)-6-(3,7-dimethylocta-2,6-dienyl)-7-hydroxy-5-methoxyisobenzo-
furan-1(3H)-one, 2)………………………………………………………………………… S3
Hericenol A ((E)-(4-(3,7-dimethylocta-2,6-dienyl)-3-hydroxy-5-methoxy-1,2-phenyl-
ene)-dimethanol, 3)……...………..……………………………………………..………… S5
(S)-Pent-4-en-2-yl 3-allyl-6-((E)-4-((4S,5S)-2,2-dimethyl-5-((Z)-prop-1-enyl)-1,3-diox-
olan-4-yl)but-1-enyl)-2,4-dihydroxybenzoate (10)……………………………………... S7
(2R)-7-(2,2-Dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-8,8-dimethyl-2-(tri-isopropylsilyloxy)-
dec-9-ene-4,6-dione (16)……………………………...…………………………………… S9
(R)-7-Hydroxy-2,2-dimethyl-8-(3-methylbut-2-enyl)-5-(2-(triisopropylsilyloxy)-
propyl)-4H-benzo[d][1,3]dioxin-4-one (17)……………………………….…………… S11
(E)-3-(3,7-Dimethyl-2,6-octadienyl-1-oxy)-3-oxopropanoic acid (20)...…..……..… S13
(E)-3,7-Dimethyl-2,6-octadien-1-yl 4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-oxo-
butanoate (21)…………………………………………………………………………..… S15
(E)-7-Chloro-3,7-dimethyloct-2-enyl 4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-oxo-
butanoate (22).………………………………………………………………………….… S17
(E)-3,7-Dimethylocta-2,6-dienyl 4-acetoxy-2-(2-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-
yl)acetyl)-3-oxobutanoate (24).………………………………………………………….. S19
(E)-(8-(3,7-Dimethylocta-2,6-dienyl)-7-hydroxy-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]-
dioxin-5-yl)methyl acetate (26).………………………………………………………..... S21
(E)-(8-(3,7-Dimethylocta-2,6-dienyl)-7-methoxy-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]-
dioxin-5-yl)methyl acetate (27).………………………………………………………..... S23
2. Crystallographic data
X-ray crystal structure of 2………………………………………..................................... S25
M
S2

Hericenone J ((E)-6-(3,7-dimethylocta-2,6-dienyl)-7-hydroxy-5-methoxyisobenzofuran-1(3H)-one, 2)
10.0
ppm(t1)
5.0
0.0
S3

Hericenone J ((E)-6-(3,7-dimethylocta-2,6-dienyl)-7-hydroxy-5-methoxyisobenzofuran-1(3H)-one, 2)
200
150
100
50
0
ppm(t1)
S4

Hericenol A ((E)-(4-(3,7-dimethylocta-2,6-dienyl)-3-hydroxy-5-methoxy-1,2-phenylene)-dimethanol, 3)
10.0
ppm(t1)
5.0
0.0
S5

Hericenol A ((E)-(4-(3,7-dimethylocta-2,6-dienyl)-3-hydroxy-5-methoxy-1,2-phenylene)-dimethanol, 3)
200
150
100
50
0
S6
ppm (t1)

(S)-Pent-4-en-2-yl 3-allyl-6-((E)-4-((4S,5S)-2,2-dimethyl-5-((Z)-prop-1-enyl)-1,3-diox-olan-4-yl)but-1-enyl)-2,4-dihydroxybenzoate (10)
10.0
5.0
0.0
ppm(t1)
S7

(S)-Pent-4-en-2-yl 3-allyl-6-((E)-4-((4S,5S)-2,2-dimethyl-5-((Z)-prop-1-enyl)-1,3-diox-olan-4-yl)but-1-enyl)-2,4-dihydroxybenzoate (10)
200
150
100
50
0
S8
ppm(t1)

(2R)-7-(2,2-Dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-8,8-dimethyl-2-(tri-isopropylsilyloxy)-dec-9-ene-4,6-dione (16)
15.50 15.00
ppm (t1)
10.0
ppm(t1)
5.0
0.0
S9

(2R)-7-(2,2-Dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-8,8-dimethyl-2-(tri-isopropylsilyloxy)-dec-9-ene-4,6-dione (16)
200
150
100
50
0
ppm(t1)
S10

(R)-7-Hydroxy-2,2-dimethyl-8-(3-methylbut-2-enyl)-5-(2-(triisopropylsilyloxy)-propyl)-4H-benzo[d][1,3]dioxin-4-one (17)
10.0
ppm(t1)
5.0
0.0
S11

(R)-7-Hydroxy-2,2-dimethyl-8-(3-methylbut-2-enyl)-5-(2-(triisopropylsilyloxy)-propyl)-4H-benzo[d][1,3]dioxin-4-one (17)
200
150
100
50
0
S12
ppm(t1)

(E)-3-(3,7-Dimethyl-2,6-octadienyl-1-oxy)-3-oxopropanoic acid (20)
10.0
5.0
0.0
S13
ppm(t1)

(E)-3-(3,7-Dimethyl-2,6-octadienyl-1-oxy)-3-oxopropanoic acid (20)
200
150
100
50
0
S14
ppm(t1)

(E)-3,7-Dimethyl-2,6-octadien-1-yl 4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-oxobutanoate (21)
10.0
ppm(t1)
5.0
0.0
S15

(E)-3,7-Dimethyl-2,6-octadien-1-yl 4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-oxobutanoate (21)
200
150
100
50
0
S16
ppm(t1)

(E)-7-Chloro-3,7-dimethyloct-2-enyl 4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-oxobutanoate (22)
10.0
ppm(t1)
5.0
0.0
S17

(E)-7-Chloro-3,7-dimethyloct-2-enyl 4-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)-3-oxobutanoate (22)
200
150
100
50
0
S18
ppm(t1)

(E)-3,7-Dimethylocta-2,6-dienyl 4-acetoxy-2-(2-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)acetyl)-3-oxobutanoate (24)
10.0
ppm(t1)
5.0
0.0
S19

(E)-3,7-Dimethylocta-2,6-dienyl 4-acetoxy-2-(2-(2,2-dimethyl-4-oxo-4H-1,3-dioxin-6-yl)acetyl)-3-oxobutanoate (24)
200
150
100
50
0
S20
ppm(t1)

(E)-(8-(3,7-Dimethylocta-2,6-dienyl)-7-hydroxy-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]dioxin-5-yl)methyl acetate (26)
10.0
ppm(t1)
5.0
0.0
S21

(E)-(8-(3,7-Dimethylocta-2,6-dienyl)-7-hydroxy-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]dioxin-5-yl)methyl acetate (26)
200
150
100
50
0
S22
ppm(t1)

(E)-(8-(3,7-Dimethylocta-2,6-dienyl)-7-methoxy-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]dioxin-5-yl)methyl acetate (27)
10.0
ppm(t1)
5.0
0.0
S23

(E)-(8-(3,7-Dimethylocta-2,6-dienyl)-7-methoxy-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]dioxin-5-yl)methyl acetate (27)
200
150
100
50
0
S24
ppm(t1)

X-ray crystal structure of 2
Crystal data for 2: C19
H
24O
4
, M = 316.38, monoclinic, P2 /c (no. 14), a = 7.8863(2),
1
3
–3
b = 23.7456(5), c = 9.0571(2) Å, β = 97.213(3)°, V = 1682.66(7) Å , Z = 4, D
c
= 1.249 g cm ,
–1
μ(Mo-Kα) = 0.086 mm , T = 173 K, colorless tablets, Oxford Diffraction Xcalibur 3
2
diffractometer; 5677 independent measured reflections (Rint = 0.0202), F refinement,
R
1
(obs) = 0.0502, wR
2
(all) = 0.1367, 4342 independent observed absorption-corrected
|), 2θmax = 65°], 256 parameters. CCDC 850168.
reflections [|F | > 4σ(|F
o
o
The C(12) to C(20) portion of the structure of 2 was found to be disordered. Two
orientations were identified of ca. 75 and 25% occupancy, their geometries optimized, the
thermal parameters of adjacent atoms restrained to be similar, and only the major occupancy
non-hydrogen atoms were refined anisotropically.
The O–H proton on O(10) was located from a ΔF map and refined freely subject to an O–H
distance constraint of 0.90 Å, and is involved in an intramolecular O–H···O hydrogen bond
with O(2), the O···O and H···O separations being 3.0824(12) and ca. 2.38 Å respectively, with
an O–H···O angle of ca. 135°.
Figure S1. The molecular structure of 2 (50% probability ellipsoids).
S25