Novel intramolecular cyclisations involving ketene radical intermediates as an approach to the synthesis of polyquinanes

Article abstract of DOI:10.1055/s-1999-2980

Treatment of the polyene selenyl ester 1 with Bu₃SnH-AIBN leads to a concise synthesis of the diquinane 6 via a novel cyclisation involving a ketenyl radical intermediate. By contrast under the same radical initiating conditions the selenyl est

Full text of DOI:10.1055/s-1999-2980

LETTER
1917
Novel Intramolecular Cyclisations Involving Ketene Radical Intermediates as
an Approach to the Synthesis of Polyquinanes
Nicole M. Harrington-Frost, Gerald Pattenden*
School of Chemistry, Nottingham University, Nottingham NG7 2RD, England
Fax +44 115 9513535; E-mail: gp@nottingham.ac.uk
Received 23 September 1999
Abstract: Treatment of the polyene selenyl ester 1 with Bu3SnH-
AIBN leads to a concise synthesis of the diquinane 6 via a novel cy-
clisation involving a ketenyl radical intermediate. By contrast under
the same radical initiating conditions the selenyl esters 2 and 10 pro-
duced cyclopentenone products, viz 9 and 11, and the allene substi-
tuted selenyl ester 16 led to the unusual cyclooctadienone 18.
i
COR
O
ii
iii
vi
R=OEt
R=OH
R=OH
1, R=SePh
iv
CO2Et
Key words: cyclisations, tandem radical reactions
COR
OHC
v
R=OEt
2, R=SePh
A wide range of ingenious methods based on tandem rad-
ical-mediated cyclisation processes are now available for
the synthesis of ring-fused cyclopentanes, including natu-
rally occurring linear, angular and propellane
triquinanoids.1 In recent studies we have identified the
scope for a,b-unsaturated acyl radical intermediates, re-
acting as their a-ketenyl radical counterparts, viz R-
CH=CH-•CO´R-•CH-CH=C=O, in the synthesis of ring
fused cyclopentanones;2 we have also applied this chem-
istry in a formal synthesis of the natural 3,3,3-propellane,
(±)-modhephene.3 In pursuance of further novel chemis-
try associated with acyl radical intermediates4 we have
now synthesised a range of new a,b-unsaturated selenyl
esters containing additional alkene bonds and examined
their modes of radical cyclisation.
Reagents and conditions: i, (EtO)2P(O)CH2CO2Et, NaH, THF, 0°-
r.t., 82%; ii, KOH, MeOH/H2O (1.2:1), D, 99%; iii, N-(phenylsele-
no)phthalimide (NPSP), Bu3P, CH2Cl2, -30°, 74%; iv, geranyltriphe-
nylphosphonium bromide, n-BuLi, THF, r.t., 90%; v, KOH, MeOH/
H2O (1.2:1), D, 73%; vi, NPSP, Bu3P, CH2Cl2, -30°, 97%.
Scheme 1
it underwent tandem cyclisation to produce a 1:1 mixture
of diastereomers of the bicyclo[3.3.0]octenone 6 in 69%
yield.6 The bicyclooctenone 6 is produced from the sele-
nyl ester 1 by way of a 5-exo-dig cyclisation of the unsat-
urated a-ketenyl radical counterpart 4 of the diene acyl
radical intermediate 3, leading to the dienolate radical 5,
followed by a 5-exo-trig cyclisation onto the adjacent
butenyl double bond. The diastereomers of 6 could be sep-
arated by chromatography and their structures followed
conclusively from examination of their n.m.r. spectro-
scopic properties and comparison with corresponding
data for similar compounds in the literature.7 By contrast
when a solution of the conjugated triene selenyl ester 2
was treated with Bu3SnH-AIBN the only product pro-
duced was a mixture of E and Z isomers of the simple cy-
clopentanone 9 (75%) resulting from mono-cyclisation of
the radical intermediate 7 via 8. In a similar manner the
radical cyclisation of the a,b,g,δ-unsaturated selenyl ester
O
C
Bu3SnH
1
O
AIBN
3
4
O
O
1
7
3
5
H
9
6
5
Bu3SnH
Thus, we first examined the radical cyclisation chemistry
associated with the polyene acyl radical intermediates
produced from the polyunsaturated selenyl esters 1 and 2.
The phenyl selenyl esters 1 and 2 were smoothly synthe-
sised from citral and geranyltriphenylphosphonium bro-
mide respectively as highlighted in Scheme 1.5 When a
solution of the a,b,g,δ-unsaturated selenyl ester 1 in ben-
zene was treated with Bu3SnH-AIBN at reflux over 4.5h,
2
AIBN
O
7
O
O
C
9
8
Synlett 1999, No. 12, 1917–1918 ISSN 0936-5214 © Thieme Stuttgart · New York

1918
N. M. Harrington-Frost, G. Pattenden
LETTER
10 gave rise to only the cyclopentenone 11 (56%); neither
of the anticipated bicyclooctenones 12 and 13 were de-
tected amongst the products.
.
.
8-exo dig
COSePh
O
O
In earlier studies we have shown that the 2,7-diene selenyl
ester 14 undergoes bi-cyclisation leading to a concise syn-
thesis of the diquinane 15.2 Interestingly, when the non-
conjugated double bond in the selenyl ester 14 was re-
placed by an allene electrophore, as in the allene ester 16,
treatment with Bu3SnH-AIBN led to the novel cycloocta-
dienone 18 in an unoptimised 25% yield. We surmise that
the cyclooctadienone 18 is produced from the selenyl es-
ter 16 by way of ring opening of the bicyclooctene radical
intermediate 19 rather than by a direct acyl radical 8-endo/
exo dig cyclisation involving the intermediate 17.
16
17
18
H
O
O
C
19
The studies described here considerably extend our
knowledge base for the use of acyl radical-mediated cycli-
sations in the synthesis of polyquinanes. Extensions to
these fundamental studies and their applications in target
synthesis, particularly within the pentalenene family of
triquinanoids, are in progress in our laboratories.
(2) C. J. Hayes and G. Pattenden, Tetrahedron Lett. 1996, 37, 271.
(3) B. De Boeck and G. Pattenden, Tetrahedron Lett. 1998, 39,
6975.
(4) N. Herbert and G. Pattenden, Synlett 1997, 69; B. De Boeck,
N. Herbert and G. Pattenden, Tetrahedron Lett. 1998, 39,
6971.
(5) Satisfactory spectroscopic data were obtained for all new
compounds. Experimental procedures for the preparation of
the precursors to 1 were based on those of W. Boland, A.
Gaebler, U. Preiss and H. Simon, Helv. Chim. Acta 1991, 74,
1773, and for the conversion of the acids into the selenyl esters
on that of K. C. Nicolaou, N. A. Petasis and D. A. Claremon,
Tetrahedron 1985, 41, 4835.
Bu3SnH
SePh
O
O
AIBN
C
(6) Typical procedure: A solution of tributyltin hydride (245mL,
0.91mmol) and AIBN (6mg, 37mmol) in dry benzene (5mL),
was added dropwise over 4.5h (via syringe pump) to a stirred,
refluxing solution of 1 (253mg, 0.76mmol) and AIBN (6mg,
37mmol) in dry, degassed benzene (210mL), under an
atmosphere of argon. The resulting mixture was heated for a
further 6h, then allowed to cool to room temperature. The
solvent was evaporated under reduced pressure to leave an oil,
which was purified by column chromatography on silica gel
(eluent:0-5% diethyl ether - 40-60 petroleum ether) to give a
1:1 mixture of the diastereomeric bicycles 6 (93mg,
0.52mmol, 69%), as a pale yellow oil. Repeated
10
O
O
11
O
O
chromatography afforded clean samples of each compound:
l
max/nm (EtOH) 224 (6825) and 290 (603); nmax/cm-1 (film)
1710, 1586; dH (diastereomer 1) 0.90 (d, J 6.5, CH3-C9), 0.90-
0.96 (m, Ha-C7), 1.08 (d, J 6.5, CH3-C9), 1.17 (s, CH3-C1), 1.32
(dd, J 6.0 and 13.0, Ha-C8), 1.35-1.45 (m, H-C9), 1.60-1.70 (m,
H-C6 and Hb-C7), 1.92 (dd, J 6.4 and 13.0, Hb-C8), 2.93 (dm, J
6.7, H-C5), 6.22 (dd, J 1.7 and 5.8, H-C3) and 7.61 (dd, J 2.6
and 5.8, H-C4); dH (diastereomer 2) 0.92 (d, J 6.6, CH3-C9),
1.02 (d, J 6.6, CH3-C9), 1.19 (s, CH3-C1), 1.35-1.45 (m, H-
C6,), 1.5-1.8 (m, 2H-C7, 2H-C8 and H-C9), 2.65 (dm, J 5.7, H-
C5), 5.96 (dd, J 1.7 and 5.7, H-C3) and 7.52 (dd, J 2.8 and 5.7,
H-C4); dC (diastereomer 1) 22.0, 22.2 and 22.5 (CH3 x 3), 28.8
(CH2), 30.2 (CH), 37.0 (CH2), 50.5 (CH), 54.1 (quat. C), 56.4
(CH), 134.9 and 163.9 ( = CHx2), and 215.7 (C = O); dC
(diastereomer 2) 21.3, 21.6 and 22.6 (CH3 x 3), 31.3 (CH2),
32.4 (CH), 34.9 (CH2), 51.6 (CH), 54.6 (quat. C), 60.0 (CH),
130.5 and 166.4 ( = CHx2), and 215.1 (C = O); m/z 178.1360
(M+. C12H18O requires M+, 178.1358).
12
13
MOMO
MOMO
H
SePh
O
Bu3SnH
AIBN
O
14
15
Acknowledgement
We thank the Commonwealth Scholarship Commission for a scho-
larship (to N.H-F.).
(7) M. Karpf and A. Dreiding, Helv. Chim. Acta 1977, 60, 3045;
M. Koller, A. Drieding and M. Karpf, Helv. Chim. Acta 1983,
66, 2760; A. Balog, S. J. Geib and D. P. Curran, J. Org. Chem.
1995, 60, 345.
References and Notes
(1) See for example: C. P. Jasperse, D. P. Curran and T. L. Fevig,
Chem. Rev. 1991, 91, 1237; S. Kim, J. H. Cheong and J. Yoo,
Synlett 1998, 981; P. Devin, L. Fensterbank and M. Malacria,
J. Org. Chem. 1998, 63, 6764 and references cited therein.
Article Identifier:
1437-2096,E;1999,0,12,1917,1918,ftx,en;L15599ST.pdf
Synlett 1999, No. 12, 1917–1918 ISSN 0936-5214 © Thieme Stuttgart · New York