Radical dearomatization of benzene leading to phenanthridine and phenanthridinone derivatives related to (±)-pancratistatin

Article abstract of DOI:10.1016/j.tet.2006.04.096

The synthesis of the phenanthridinone nucleus common to the Amaryllidaceae series of natural products is achieved by a sequence involving tributylstannane-mediated, benzeneselenol-catalyzed addition of ortho-nitrogen functionalized aryl radicals to benzen

Full text of DOI:10.1016/j.tet.2006.04.096

Tetrahedron 62 (2006) 6830–6840
Radical dearomatization of benzene leading to phenanthridine
and phenanthridinone derivatives related to ( )-pancratistatin
*
David Crich and Venkataramanan Krishnamurthy
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA
Received 18 February 2006; revised 28 April 2006; accepted 28 April 2006
Available online 30 May 2006
Abstract—The synthesis of the phenanthridinone nucleus common to the Amaryllidaceae series of natural products is achieved by a sequence
involving tributylstannane-mediated, benzeneselenol-catalyzed addition of ortho-nitrogen functionalized aryl radicals to benzene, yielding
aryl-substituted cyclohexadienes. These cyclohexadienes may be manipulated by oxidative ring closure sequences to generate functionalized
phenanthridines. Beginning from 2-hydroxy-6-iodopiperonic acid a key intermediate in the Danishefsky synthesis of (ꢀ)-pancratistatin is
achieved in two steps.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
The four-propagation step chain sequence is completed by
regeneration of the selenol by reaction of the selenyl radical
with the stannane (Scheme 1).9
Aryl radicals add rapidly to arenes to give cyclohexadienyl
radicals substituted with aryl groups at the 6-position
(Scheme 1).1 Under typical preparative radical chain condi-
tions the cyclohexadienyl radical is insufficiently reactive to
propagate the radical chain by hydrogen atom abstraction
from stannane or silane hydrogen atom donors and the even-
tual outcome is the formation of rearomatized biaryls.2
Similarly the intramolecular version of this reaction, cycli-
zation of an aryl radical onto an arene, is marked by the
formation of fully re-oxidized products.3 This breakdown
in propagation typically results in poor conversion of the
substrate and/or the need for excessive quantities of radical
‘initiator’. Indeed, the azo-type initiators are now seen to
serve the important function of oxidant for the cyclohexa-
dienyl radical in addition to their more obvious planned
function.4 On the other hand, we have shown how the inclu-
sion of a catalytic quantity of benzeneselenol in the stan-
nane-mediated radical addition of aryl iodides to benzene,
and other heterocycles, enables smooth trapping of the
cyclohexadienyl radical by the selenol, leading to the iso-
lation of aryl-substituted cyclohexadienes.5 Although the
Sn–H and Se–H bond dissociation energies are very similar,6
the selenol traps alkyl radicals some 500 times faster than
the stannane,7 because of the operation of a polarity effect.8
Bu3SnI
Ar
+
Ar
(1)
(2)
Bu3Sn
Ar
+
Ar-I
+
Ar
Ar
+
PhSe-H
Bu3SnH
+
PhSe
(3)
(4)
PhSe
+
PhSeH
+
Bu3Sn
Scheme 1. Mechanism of dearomatizing aryl radical addition to arenes.
The chemistry is rendered practical by the rapid in situ
reduction of diphenyl diselenide to benzeneselenol by the
stannane, which enables the direct handling of the air sensi-
tive selenol to be avoided (Scheme 2).9
Bu3SnH + PhSeSePh
Bu3SnSePh + PhSeH
Scheme 2. In situ selenol generation.
The chemistry is particularly attractive when the aryl iodide
is functionalized with a nucleophile at the ortho-position,
thereby permitting the ring closing desymmetrization of
the product cyclohexadiene.10,11 We have employed this
chemistry in syntheses of carbazomycin B (Scheme 3),12
and of Kelly’s b-sheet initiator (Scheme 4).13
Keywords: Radical; Arylation; Cyclohexadienyl; Dearomatization;
Phenanthridinone.
* Corresponding author. Tel.: +1 312 996 5189; fax +1 312 996 0431;
e-mail: dcrich@uic.edu
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.096

D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
6831
MeO
OAc
the dearomatization step. Thus, reduction of commercial
o-iodobenzonitrile 1 with aluminum hydride,20 followed
by protection of the resulting amine with methyl chlorofor-
mate gave the iodo carbamate 2 (Scheme 5).21
AcO
MeO
H
N
PhSeBr
NHCO2Me
H
SePh
CO2Me
HO
I
I
i) AlH3
MeO
NHCO2Me
ii) MeOCOCl, 74%
CN
N
H
1
2
Carbazomycin B
Scheme 5. Preparation of iodide 2.
Scheme 3. Synthesis of carbazomycin B.
Iodide 3, obtained from piperonyl alcohol with iodine and
silver trifluoroacetate according to a literature procedure,22
was converted to iodopiperonal 4 with PCC, and to the cor-
responding nitrile 6 by dehydration of oxime 5 (Scheme 6).
H
i) DMDO,
ii) SiO2
OH
O
H
OH
I
I
O
O
O
O
PCC, CH2Cl2,
rt, 82%
EtO2C
EtO2C
OH
CHO
3
4
O
I
I
O
O
O
O
i) Ac2O, py
NH2OH.HCl
py/EtOH
rt, 94%
ii) DBU, CH2Cl2,
95%
NHBoc
EtO2C
CN
NOH
Scheme 4. Synthesis of a b-sheet initiator.
5
6
Scheme 6. Preparation of iodide 6.
With a view to probing further the scope of the reductive
radical arylation reaction and to exploiting more fully the
potential of the aryl cyclohexadiene products we turned
our attention to the preparation of phenanthridinone deriva-
tives as found in the antineoplastic Amaryllidaceae natural
products pancratistatin and lycoricidine and their analogs.
The biological activity and densely arrayed functionality
of these molecules have combined to make them the targets
of numerous, successful synthetic endeavors since their
discovery.14–18 Moreover, it is especially noteworthy in the
context of the present work that cyclohexadienes featured
prominently in the original synthesis of (ꢀ)-pancratistatin
by Danishefsky15a and in the very extensive work by
Hudlicky group when they were generated, moreover, by
dearomatization of arenes.19 We report here on our work
in this area, including an improved preparation of an inter-
mediate in the Danishefsky synthesis of (ꢀ)-pancratistatin.
Finally, ortho-metallation of amide 7, prepared by the
Danishefsky route from resorcinol,15a and quenching with
iodine gave the o-iodobenzamide 8,23 which could be hydro-
lyzed to the corresponding des-silyl acid 9 following con-
version to the intermediate ester with trimethyloxonium
tetrafluoroborate, and, then, heating with methanolic sodium
hydroxide (Scheme 7).24
1. t-BuLi, TMEDA
I
O
O
O
O
°
THF, -78 C, 1h
N
2. I2, THF, -78 °C, rt
N
78%
TBSO
O
TBSO
O
8
7
1. Me3O+BF4-, CH3CN
rt, 5h
2. 4N NaOH, MeOH/THF
reflux, 15h
I
O
O
OH
OH
OH
HO
OH
OH
OH
OH
HO
O
86% overall
9
O
O
O
O
NH
NH
Scheme 7. Preparation of iodides 8 and 9.
R
O
R
O
R = OH Pancratistatin
With these iodides in hand, the dearomatizing radical addi-
tion to benzene was investigated. These reactions were
carried out according to a standard protocol involving the
dropwise addition of tributyltin hydride and the initiator
AIBN to a mixture of diphenyl diselenide and the substrate
in benzene at reflux under argon, leading to the results
outlined in Table 1, entries 1–5. As is typical for this type
of addition5a,10,12,13 the products were obtained as mixtures
of 1,3- and 1,4-dienes in which the latter predominated,
reflecting the known propensity of cyclohexadienyl radicals
for kinetic trapping at the internal position.25 The most
R = OH Narciclasine
R = H 7-deoxypancratistatin
R = H Lycoricidine
2. Results and discussion
We began our investigation by accessing the suitability of
a series of ortho-functionalized aryl iodides for the key rad-
ical step, whose ortho-substituent should be convertible
under mild conditions to a nucleophilic nitrogen species
suitable for cyclization onto the cyclohexadiene formed in

6832
D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
surprising, with carbamates having been previously shown
Table 1. Aryl radical addition to benzene
to be compatible with the method (Table 1, entry 6)10 Two
major products 19 and 20 were isolated from this reaction
in 30 and 32% yield, respectively, in addition to 35% of
the recovered substrate. The formation of the des-iodo prod-
uct 19 by intramolecular hydrogen atom transfer from the
NH group to the aryl radical was excluded as a major path-
way through an experiment employing N-deuterio 2 as sub-
strate, when only 5% incorporation of deuterium into the
ortho-position of 19 was observed. It is clear that most of
the benzeneselenol is removed from this reaction mixture
through the formation of selenide 20. This results in a break-
down of the propagation cycle (Scheme 1), allowing an
increase in stannane concentration as the addition proceeds,
and ultimately results in the formation of the reduction prod-
uct 19. It is not clear why selenide 20 is formed in such high
yield from substrate 2, but it may be the result of hydrogen
bonding of benzeneselenol to the carbamate, which facili-
tates a nucleophilic aromatic substitution reaction. Under-
standably in view of the obvious steric hindrance and the
potential for intramolecular 1,5-hydrogen atom transfer
from the amide group, only trace amounts of the adduct
from the reaction between iodide 8 and benzene were ob-
tained (Table 1, entry 4), with the major product 7 (64%)
being that of simple reduction. This problem was remedied
by use of the corresponding acid 9, which reproducibly
gave yields of 30% of the adduct 14 (Table 1, entry 5).
Higher yields had been previously obtained with o-iodoben-
zoic acid (Table 1, entry 7),10 but we were unable to improve
on this yield despite repeated attempts. Nevertheless, it is in-
teresting to note that the formation of 14 (Table 1, entry 5)
took place with high regioselectivity in the hydrogen atom
transfer step and afforded a product almost free of the minor,
conjugated, isomeric diene. This unusually high regioselec-
tivity in the quenching step was previously seen in the for-
mation of 18 from o-iodobenzoic acid (Table 1, entry 7).10
Bu3SnH, AIBN,
R
R
(PhSe)2, C6H6, ∆
I
Substrate
Product
% Yield ratio
(1,4-/1,3)
I
1
44% (6/1)
CN
CN
1
10
I
2b
0%
NHCO2Me
NHCO2Me
2
11
I
O
O
O
CN
3
44% (3/1)
O
CN
12
6
I
O
O
O
NEt2
N
O
4
5
Traces
TBSO
13
O
TBSO
O
8
I
O
O
O
OH
OH
30% (>10/1)
O
HO
14
O
HO
O
9
SePh
I
6
7
41% (3/2)a
NHCO2Me
NHCO2Me
NHCO2Me
NHCO2Me
19
20
16
15
Turning to the desymmetrization step adduct 10 was
converted to carbamate 11 by reduction with aluminum
hydride,20 and subsequent reaction with methyl chlorofor-
mate (Scheme 8).26 Treatment with a controlled amount of
m-CPBA subsequently afforded the mono epoxide 21 in
71%, which underwent the desired cyclization on exposure
to boron trifluoride etherate27 giving the phenanthridine
derivative 22 in 79% yield (Scheme 8). The relative stereo-
chemistry of 22, with its cis-fused ring junction, was con-
firmed by X-ray crystallographic analysis.y An analogous
series of experiments was also conducted on the correspond-
ing t-butyl carbamates, and in the methylenedioxy series
beginning from adduct 12, with parallel results (Scheme 8).
I
54% (10/1)a
OH
O
OH
O
18
17
a
Reproduced from Ref. 10.
Compounds 19 and 20 were also isolated from this reaction in 30 and
32% yield, respectively.
b
satisfactory results were obtained with the two nitriles 1 and
6 both of which gave 44% yields of the benzene adducts
(Table 1, entries 1 and 3). These yields while only moderate
are typical for additions of this kind5a,10,12,13 and, given the
significant increase in complexity obtained and the simplic-
ity of the starting materials, are acceptable for our purposes.
The mass balance is typically made up of the deiodinated
substrate and of the biaryl formally derived by oxidation
of the cyclohexadiene: despite our best efforts over a number
of years we have been unable to suppress formation of by-
products of this type.5a,10,12,13 The failure of the radical de-
rived from the iodobenzyl carbamate 2 (Table 1, entry 2) was
The asymmetric epoxidation of cyclohexadiene 11 with
Jacobsen’s catalyst28 was attempted, but the only product
y
CCDC 298768 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
6833
°
i) AlH3, THF, 0
C
R
R
R
R
ii) MeOCOCl or Boc2O
NHCO2R'
CN
11: R = H, R' = Me, 60%
23: R = H, R' = t-Bu, 76%
24: R,R = methylenedioxy,
R' = t-Bu, 71%
10: R = H
12: R,R = methylenedioxy
O
m-CPBA,
H
BF3.Et2O,
R
R
°
CH2Cl2,
0
C
OH
H
CO2R'
°
0
C
N
NHCO2R'
R
R
21: R = H, R' = Me, 71%
25: R = H, R' = t-Bu, 67%
26: R,R = methylenedioxy,
R' = t-Bu, 60%
22: R = H, R' = Me, 79%
27: R = H, R = t-Bu, 86%
28: R,R = methylenedioxy,
R' = t-Bu, 68%
Scheme 8. Cyclization by epoxidation.
obtained was the biaryl system 29.29 A range of stoichio-
metric oxidants and additives was assayed in this catalytic
protocol, including N-methyl morpholine N-oxide, sodium
hypochlorite, iodosobenzene, and 4-phenylpyridine N-ox-
ide, but we were unable to suppress the aromatization, which
is, perhaps, not too surprising in view of the presence of
the doubly allylic benzylic C–H bond in the substrate.
Epoxidation of 11 with Shi catalyst 30 and dimethyl dioxir-
ane did afford 21 in 48% yield, but in racemic form, consis-
tent with the known substrate range of this system.30 On the
other hand, the more recent catalyst 31 developed by Shi
group for cis-olefins gave 21 in 40% yield and 30% ee as
determined by chiral HPLC methods.31 In view of the poor
enantioselectivity obtained with this system, no further
investigations into enantioselective epoxidations were con-
ducted although it is possible that other systems reported
to bring about the enantioselective epoxidation of cis-
alkenes, and which have appeared in the literature since
this work was completed, may achieve the desired result.32
co-workers who achieved the analogous oxidation of a series
of cyclic and acyclic alkylarenes, including the transfor-
mation of ethylbenzene to acetophenone, with m-CPBA,
for which they postulated a mechanism involving hydrogen
atom abstraction and trapping of the benzylic radical by
air.33 Dess Martin oxidation34 of 32 gave the corresponding
ketone, which on passage over silica gel, afforded the antic-
ipated hydroxyenone 33 in 68% yield, in which the enone
ring derives its carbon skeleton from a benzene ring, of
which every carbon has been modified.
Iodolactonization35 of adduct 14 provided lactone 34, a key
intermediate in Danishefsky’s synthesis of (ꢀ)-pancratis-
tatin,15a in 71% yield (Scheme 10). In his synthesis
Danishefsky constructed cyclohexadiene 13 from amide 7,
I2, NaHCO3
71%
O
O
This work
3 steps
OH
O
O
O
OH
14
O
O
O
O
O
O
H
N-Boc
O
O
O
O
I
H
O
O
O
NHCO2Me
O
N
O
O
O
ref 15a
pancratistatin
OH
TBSO
O
29
30
31
34
7
In exploring the further functionalization of the phenanthri-
dine derivative 22, an unexpected benzylic oxidation was
encountered. Thus, treatment of 22 with excess m-CPBA
in dichloromethane at room temperature gave not the
expected simple epoxidation product but that of concomitant
benzylic oxidation, the amide 32, in 80% yield (Scheme 9).
This interesting reaction has precedent in the work of Ma and
O
O
ref 15a
5 steps
ref 15a
2 steps
NEt2
TBSO
O
13
Scheme 10. Improved synthesis of a key intermediate in the Danishefsky
(ꢀ)-pancratistatin synthesis.
O
HO
H
i) Dess Martin
ii) SiO2, 68%
H
m-CPBA,
H
OH
O
OH
rt, 80%
H
H
H
N
N
N
CO2Me
CO2Me
CO2Me
O
O
22
Scheme 9. Functionalization of the ‘benzene’ ring.
32
33

6834
D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
and following removal of the silyl ether subjected it to iodo-
lactonization to arrive at 34. In that pioneering synthesis a se-
quence of five steps, including a tributyltin hydride mediated
radical elimination reaction, were required to obtain 13 from
7, and the complete sequence from 7 to iodolactone 34 was
achieved in seven steps and 12.7% overall yield. The
sequence of reactions that we describe here (Scheme 7,
Table 1, and Scheme 10) proceeds from 7 to 34 in four steps
and 14.3% overall yield, provides a convenient short cut in
the original synthesis, and serves to highlight the advantages
of the dearomatizing aryl radical addition to benzene as
a means of aryl cyclohexadiene formation.
nitrogen or argon. Extracts were dried over sodium sulfate
and concentrated under reduced pressure at room tem-
1
perature. Unless otherwise stated H and 13C NMR spectra
were carried out at 400 and 100 MHz, respectively, in
CDCl3 solution. Chemical shifts are given in parts per mil-
lion downfield from tetramethylsilane. Microanalyses were
carried out by Midwest Microlabs, Indianapolis, IN. Mass
spectra were recorded in the Research Resources
Laboratory at UIC.
4.1.1. Methyl (2-iodobenzyl)carbamate (2). LiAlH4
(173 mg, 4.6 mmol) was suspended in THF (8 mL), cooled
to 0 ꢁC, stirred vigorously, and treated with concentrated
sulfuric acid (127 mL, 2.3 mmol). This mixture was stirred
for 1 h at 0 ꢁC, before a solution of 2-iodobenzonitrile
(500 mg, 2.2 mmol) in THF (8 mL) was added dropwise.
Stirring was continued for 1 h before the reaction was
stopped by the addition of ethanol (10 mL) at 0 ꢁC, followed
by few drops of 2 N NaOH. The suspension was diluted with
EtOAc (50 mL), filtered, and concentrated to provide
a brown residue, which was taken directly to the next step.
This residue was dissolved in CH2Cl2 (8 mL) and cooled
to 0 ꢁC, then treated with Et3N (750 mL, 5 mmol) and methyl
chloroformate (394 mL, 5 mmol). The resultant solution was
stirred for 6 h, diluted with CH2Cl2 (50 mL), and washed
with saturated aqueous NaHCO3 (25 mL), and brine
(25 mL). The dichloromethane layer was dried, concen-
trated, and purified by chromatography over silica gel
(eluent: 20% EtOAc in hexanes) to afford carbamate 2
(456 mg, 74%) as a white solid. Mp 77 ꢁC (lit.21 mp
Finally, we note an interesting cyclization giving rise to the
7-oxa-g-lycorane skeleton. Thus, catalytic hydrogenation of
both 27 and 28 provided the dihydro analogs 35 and 36,
respectively, in excellent yield. The desmethylenedioxy
system 35 was converted to the corresponding mesylate 37
by standard methods (Scheme 11). Interestingly enough
this compound resisted all our attempts to bring about elim-
ination of the mesyl group, with the major product being the
oxazolidinone 38 resulting from displacement of the mesy-
late with inversion by the carbamate group. An analogous
result was obtained on attempted elimination of water from
36 with the Burgess reagent,36 when 39 was formed in
56% yield (Scheme 11).
R = H
H
MsCl, Et2Ni-Pr
t-BuOK
OMs
H
N
63%
1
74 ꢁC); H NMR: d 3.68 (s, 3H), 4.37 (d, J¼6.2 Hz, 2H),
45%
Boc
37
5.25 (br s, 1H), 6.97 (t, J¼8.0 Hz, 1H), 7.30–7.39 (m, 2H),
7.81 (d, J¼7.7 Hz, 1H); 13C NMR: d 49.7, 52.3, 98.8,
128.5, 129.3, 129.5, 139.4, 140.5, 156.9.
H
H
H
H
O
R
R
R
R
R,R = methylenedioxy
O
OH
H
N
N
Boc
Et3N
S
N CO2Me 56%
O
4.1.2. 6-Iodo-1,3-benzodioxole-5-methanol (3). To a solu-
tion of piperonyl alcohol (5.15 g, 34 mmol), CF3CO2Ag
(9.7 g, 44 mmol), and dry CHCl3 (90 mL) at ꢂ5 ꢁC was
added I2 (11.1 g, 44 mmol) in one portion. The resulting
yellow mixture was maintained at ꢂ5 ꢁC for 10 min, where-
upon it was filtered. The filtrate was washed with 20%
aqueous sodium thiosulfate (3x50 mL), dried, and concen-
trated. Recrystallization from chloroform afforded iodide 3
(6.1 g, 66%) as white needles. Mp 110–111 ꢁC (lit.22a mp
38: R = H
O
35: R = H
39: R,R = methylenedioxy
36: R,R = methylenedioxy
Scheme 11. Formation of the 7-oxa-g-lycorane skeleton.
3. Conclusion
The efficiency of the benzeneselenol-catalyzed, tributylstan-
nane-mediated addition of aryl iodides to benzene depends
strongly on the nature of the ortho-substituent. For reasons
that are not yet clear, little or no addition takes place with
an o-(methoxycarbonylaminomethyl) substituent, as in 2,
whereas the closely analogous o-(methoxycarbonylamino)
group, as in 15, is satisfactory. An o-cyano group functions
well (1 and 6) and may be subsequently converted to the
desired o-(methoxycarbonylaminomethyl) substituent by
reduction with aluminum hydride followed by methyl
chloroformate, without detriment to the 1,4-cyclohexadiene
functionality. Further manipulations then lead rapidly to a
variety of phenanthridine and phenanthridinone derivatives.
1
106–107 ꢁC); H NMR (500 MHz): d 2.06 (t, J¼6.0 Hz,
1H), 4.57 (d, J¼6.0 Hz, 2H), 6.0 (s, 2H), 6.98 (s, 1H), 7.26
(s, 1H); 13C NMR (125 MHz): d 69.2, 85.4, 101.7, 109.0,
118.5, 136.2, 147.9, 148.6.
4.1.3. 6-Iodo-1,3-benzodioxole-5-carbaldehyde (4). To a
solution containing iodide 3 (6.1 g, 22.2 mmol) and dry
CH2Cl2 (300 mL) at 0 ꢁC was added PCC (9.6 g,
44 mmol). The mixture was allowed to warm to room
temperature and was stirred for 5 h at 25 ꢁC. The reaction
mixture was concentrated to one third of its original volume
and filtered through silica gel column (eluent: 30% EtOAc
in hexanes) to give 4 as a pale yellow solid (5.7 g, 94%).
Mp 110–112 ꢁC; 1H NMR (500 MHz): d 6.08 (s, 2H), 7.32
(s, 1H), 7.35 (s, 1H), 9.86 (s, 1H); 13C NMR (125 MHz):
d 93.3, 102.7, 108.8, 119.4, 129.5, 149.2, 153.5, 194.5.
Anal. Calcd for C8H5O3I: C, 34.81; H, 1.83. Found: C,
34.56; H, 1.70.
4. Experimental
4.1. General
All solvents were dried and distilled by standard techniques.
All experiments were carried out in an atmosphere of dry

D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
6835
4.1.4. 6-Iodo-1,3-benzodioxole-5-carbaldoxime (5). A
solution of aldehyde 4 (5.7 g, 20.7 mmol) in 1:1 pyridine
(20 mL) and ethanol (20 mL) was treated with hydroxyl-
amine hydrochloride (2.2 g, 31.1 mmol) and stirred at
room temperature. After 8 h, the resulting solution was
diluted with EtOAc (80 mL) and washed with saturated
aqueous NH4Cl solution (50 mL), followed by brine
(50 mL). The organic layer was dried, concentrated, and
purified by chromatography over silica gel (eluent: 30%
EtOAc in hexanes) to afford oxime 5 (5.9 g, 94%) as a white
tetrafluoroborate (205 mg, 1.4 mmol). The reaction was
stirred at room temperature for 5 h after which the reaction
was quenched by slow addition of saturated aqueous sodium
bicarbonate solution (5 mL). The resulting mixture was
stirred for 7 h at room temperature, and then diluted with
EtOAc (25 mL), followed by water (10 mL). The organic
layer was separated and the aqueous layer was extracted
with EtOAc (2ꢃ15 mL). The combined organic layer was
dried and concentrated. The residue was dissolved in
MeOH/THF (5 mL, 1/1) mixture, treated with 4 N NaOH
(3 mL) and heated to reflux for 15 h. The reaction mixture
was neutralized with 6 N HCl followed by removal of the
methanol in vacuo. The resulting residue was dissolved in
EtOAc (25 mL) and water (15 mL), and the aqueous layer
was extracted with EtOAc (3ꢃ20 mL). The combined
organic layer was dried, concentrated, and purified by chro-
matography over silica gel (eluent: 70% EtOAc in hexanes)
to afford 9 (122 mg, 86%) as white solid. Mp 147–148 ꢁC;
1H NMR: d 6.0 (s, 2H), 7.14 (s, 1H); 13C NMR: d 85.4,
102.8, 112.8, 115.2, 136.4, 146.5, 152.3, 170.1; ESIHRMS
Calcd for C8H5IO5 [MꢂH]ꢂ: 306.9103, found: 306.9105.
1
solid. Mp 148 ꢁC; H NMR (500 MHz, CD3OD): d 6.0 (s,
2H), 7.24 (s, 1H), 7.26 (s, 1H), 8.20 (s, 1H); 13C NMR
(125 MHz, CD3OD): d 87.2, 102.2, 105.6, 118.08, 128.0,
148.7, 149.7, 151.8. Anal. Calcd for C8H6NO3I: C, 33.01;
H, 2.08. Found: C, 33.12; H, 2.15.
4.1.5. 6-Iodo-1,3-benzodioxole-5-carbonitrile (6). A solu-
tion of oxime 5 (5.9 g, 19.4 mmol) and DMAP (236 mg,
1.9 mmol) in pyridine (50 mL) was treated with Ac2O
(2.7 mL, 29 mmol), and stirred at room temperature for
10 h. After complete consumption of 5, DBU (3.5 mL,
23 mmol) was added to the reaction mixture, and stirring
continued for 6 h during the course of which further DBU
(2ꢃ1.7 mL) was added. The mixture was diluted with
dichloromethane (70 mL), and washed with saturated
NH4Cl (2ꢃ40 mL) and brine. The dichloromethane layer
was dried, concentrated, and purified by chromatography
over silica gel (eluent: 20% EtOAc in hexanes) to afford
nitrile 6 (5.03 g, 95%) as pale yellow solid. Mp 127–
4.2. General procedure for radical addition to benzene
A dry flask was charged with aryl iodide (6.1 mmol) and
diphenyl diselenide (380 mg, 1.22 mmol), fitted with a reflux
condenser, and flushed with argon. Dry, degassed benzene
(122 mL, 0.05 M) was added; the resulting solution was
heated to reflux. A solution of AIBN (100 mg, 0.61 mmol)
and tributyltin hydride (7.3 mmol, 1.96 mL) in dry degassed
benzene (18 mL) was added via syringe pump at rate of
1.5 mL hꢂ1. On completion of the addition, the reaction mix-
ture was refluxed for 1 h, then cooled to room temperature
and the solvent removed in vacuo. The residue was taken
up in acetonitrile (200 mL) and washed with (4ꢃ25 mL)
hexane. The acetonitrile phase was concentrated and purified
by silica gel chromatrography (eluent: EtOAc in hexanes) to
yield the adducts.
1
29 ꢁC; H NMR (500 MHz): d 6.09 (s, 2H), 7.01 (s, 1H),
7.28 (s, 1H); 13C NMR (125 MHz): d 89.8, 102.9, 113.0,
113.1, 119.2, 119.5, 148.3, 152.0. Anal. Calcd for
C8H4NO2I: C, 35.19; H, 1.48; N, 5.13; I, 46.48. Found: C,
35.10; H, 1.46; N, 4.96; I, 46.19.
4.1.6. N,N-Diethyl-4-(tert-butyldimethylsiloxy)-6-iodo-
1,3-benzodioxole-5-carboxamide (8). In a dry flask, amide
7
15a (3.0 g, 8.54 mmol) was dissolved in THF (80 mL), and
cooled to ꢂ78 ꢁC. To this solution was added TMEDA
(1.94 mL, 12.8 mmol), and n-BuLi (6.82 mL, 17.1 mmol,
2.0 M in hexanes). The resulting deep brown mixture was
stirred at ꢂ78 ꢁC for 1 h before I2 (4.34 g, 17.1 mmol) in
THF (20 mL) was added, and the reaction mixture allowed
warm to room temperature overnight with stirring. The reac-
tion mixture was quenched with saturated NH4Cl, and the
THF was removed in vacuo. The resulting residue was dis-
solved in EtOAc (50 mL) and H2O (50 mL), and the aqueous
layer was extracted with EtOAc (30 mL). The combined
organic layers were washed with brine (30 mL) and dried.
Purification by chromatography over silica gel (eluent:
12% EtOAc in hexanes) afforded 8 as yellow oil (3.2 g,
4.2.1. 2-(2,5-Cyclohexadienyl)benzonitrile (10). Yield
44%; yellow oil; IR (neat): 2221, 2360, 2817, 2867,
1
3029 cmꢂ1; H NMR (500 MHz): d 2.78 (m, 2H), 4.43 (br
t, J¼7.5 Hz, 1H), 5.69–5.72 (br d, J¼9.0 Hz, 2H), 5.89–
5.92 (br d, J¼10.5 Hz, 2H), 7.30 (t, J¼7.3 Hz, 1H), 7.38
(d, J¼7.9 Hz, 1H), 7.53 (t, J¼7.9 Hz, 1H), 7.62 (d,
J¼7.7 Hz, 1H); 13C NMR (125 MHz): d 25.7, 40.2, 125.1,
125.3, 126.2, 126.8, 126.9, 129.4, 132.9, 132.91, 133.0,
133.1, 148.6; EIHRMS Calcd for C13H11N [MꢂH]+:
180.0813, found: 180.0747. The product was contaminated
with an inseparable minor isomer (1,3-cyclohexadien-5-yl)-
benzonitrile, which accounted for 14% of the mass as deter-
mined by NMR. This isomer was characterized by 1H NMR
1
78%). H NMR: d 0.17 (s, 3H), 0.22 (s, 3H), 0.92 (s, 9H),
1.1 (t, J¼7.2 Hz, 3H), 1.25 (t, J¼7.2 Hz, 3H), 3.1–3.21
(m, 3H), 3.79–3.88 (m, 1H), 5.91 (s, 1H), 5.94 (s, 1H), 6.9
(s, 1H); 13C NMR: d ꢂ4.6, ꢂ4.1, 12.6, 13.8, 18.3, 25.7
(3C), 39.3, 43.1, 82.3, 101.4, 112.7, 130.5, 136.9, 137.6,
149.3, 167.5; ESIHRMS Calcd for C18H28INO4Si [M+H]+:
478.0911, found: 478.0917.
(500 MHz):
d
2.34 (dddd, J¼17.6 Hz, J¼11.8 Hz,
J¼4.1 Hz, J¼2.2 Hz, 1H), 2.67 (dddd, J¼17.6 Hz, J¼
9.5 Hz, J¼4.8 Hz, J¼1.8 Hz, 1H), 4.05–4.10 (br t, J¼
10.0 Hz, 1H), 5.76–5.79 (m, 2H), 5.9–6.1 (m, 1H), 6.13–
6.17 (m, 1H), 7.30 (t, J¼7.3 Hz, 1H), 7.38 (d, J¼7.9 Hz,
1H), 7.53 (t, J¼7.9 Hz, 1H), 7.62 (d, J¼7.7 Hz, 1H); 13C
NMR (125 MHz): d 30.8, 37.7, 111.6, 117.9, 123.9, 125.1,
125.9, 126.8, 127.5, 128.4, 128.7, 133.0, 148.9.
4.1.7. 4-Hydroxy-6-iodo-1,3-benzodioxole-5-carboxylic
acid (9). To a stirred solution of benzamide 8 (220 mg,
0.46 mmol) in CH3CN (5 mL) was added Na2HPO4
(98 mg, 0.69 mmol), followed by trimethyloxonium
4.2.2. 6-(2,5-Cyclohexadienyl)-1,3-benzodioxole-5-
1
carbonitrile (12). Yield 44%; white solid; mp 101 ꢁC; H

6836
D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
NMR (500 MHz): d 2.73–2.76 (m, 2H), 4.36–4.40 (m, 1H),
5.66 (ddt, J¼10.0 Hz, J¼5.5 Hz, J¼1.5 Hz, 2H), 5.89 (ddt,
J¼10.5 Hz, J¼5.5 Hz, J¼1.5 Hz, 2H), 6.02 (s, 2H), 6.79
(s, 1H), 6.97 (s, 1H); 13C NMR (125 MHz): d 25.7, 39.8,
102.2, 109.5, 111.0, 118.1, 123.8, 125.2, 125.7, 126.5,
127.4, 145.5, 146.3, 152.0. Anal. Calcd for C14H11NO2: C,
74.65; H, 4.92. Found: C, 74.46; H, 4.99. The product was
contaminated with an inseparable minor isomer, 6-(1,3-
cyclohexadien-1-yl)-1,3-benzodioxole-5-carbonitrile, which
accounted for 25% of the mass as determined by NMR
and which was characterized by the following resonances:
1H NMR (500 MHz): d 2.29 (dddd, J¼17.6 Hz, J¼
11.1 Hz, J¼4.4 Hz, J¼2.3 Hz, 1H), 2.65 (dddd, J¼
17.6 Hz, J¼9.5 Hz, J¼4.7 Hz, J¼1.8 Hz, 1H), 4.01 (br t,
J¼9.5 Hz, 1H), 5.71 (dd, J¼9.0 Hz, J¼4.0 Hz, 1H), 5.76
(dt, J¼9.5 Hz, J¼4.5 Hz, 1H), 5.96–5.99 (m, 1H), 6.03 (s,
2H), 6.06–6.14 (m, 1H), 6.98 (s, 1H), 6.99 (s, 1H); 13C
NMR (125 MHz): d 30.8, 37.3, 103.3, 108.8, 113.3, 118.1,
125.0, 125.1, 126.3, 128.6, 128.7, 145.6, 145.3, 151.7.
over silica gel (eluent: 20% EtOAc in hexanes) to afford car-
bamate 11 (459 mg, 60%) as a white solid. Mp 81–83 ꢁC; 1H
NMR (500 MHz): d 2.75–2.79 (m, 2H), 3.68 (s, 3H), 4.21
(m, 1H), 4.47 (d, J¼5.5 Hz, 2H), 4.92 (br s, 1H), 5.69
(ddt, J¼10.0 Hz, J¼5.0 Hz, J¼1.0 Hz, 2H), 5.83–5.85 (m,
2H), 7.19–7.29 (m, 4H); 13C NMR (125 MHz): d 25.7,
38.1, 42.5, 52.2, 123.8, 124.8, 127.7, 127.9, 128.2, 128.8,
129.1, 129.8, 135.3, 143.0, 156.7; ESIHRMS Calcd for
C15H17NO2 [M+Na]+: 266.1157, found: 266.1161.
4.2.7. tert-Butyl 2-(2,5-cyclohexadien-1-yl)benzylcarba-
mate (23). This carbamate was prepared from 10 analo-
gously to 11, except that the methyl chloroformate was
replaced by Boc2O. It was obtained as a colorless oil in
76% yield. IR (neat): 1168, 1511, 1694, 2976, 3340 cmꢂ1
;
1H NMR: d 1.46 (s, 9H), 2.74–2.78 (m, 2H), 4.23 (br t,
J¼8.5 Hz, 1H), 4.42 (d, J¼5.3 Hz, 2H), 4.72 (br s, 1H),
5.68 (br d, J¼10.0 Hz, 2H), 5.82–5.85 (m, 2H), 7.17–7.27
(m, 4H); 13C NMR: d 25.7, 28.4 (3C), 37.8, 42.1, 79.5,
123.9, 126.6, 127.9, 128.1, 128.5, 128.9, 129.6, 130.0,
135.6, 143.1, 155.5; ESIHRMS Calcd for C18H23NO2
[M+Na]+: 308.1627, found: 308.1625.
4.2.3. 4-Hydroxy-6-(2,5-cyclohexadien-1-yl)-1,3-benzo-
dioxole-5-carboxylic acid (14). Yield 30%; white solid;
1
mp 152 ꢁC; H NMR: d 2.71–2.76 (m, 2H), 4.96–5.0 (m,
1H), 5.69–5.74 (m, 2H), 5.82–5.87 (m, 2H), 6.05 (s, 2H),
6.61 (s, 1H); 13C NMR: d 25.7, 36.7, 102.5, 103.8, 106.9,
124.2, 128.3, 128.5, 130.3, 133.1, 145.8, 146.8, 153.4,
173.6; ESIHRMS Calcd for C14H12O5 [MꢂH]ꢂ: 259.0606,
found: 259.0599.
4.2.8. tert-Butyl 6-(2,5-cyclohexadien-1-yl)-1,3-benzo-
dioxole-5-ylmethylcarbamate (24). This carbamate was
prepared from 12 in the same manner as 23 was obtained
from 10. It was obtained in 71% yield as a white solid. Mp
1
106 ꢁC; H NMR: d 1.44 (s, 9H), 2.71–2.73 (m, 2H), 4.13
(m, 1H), 4.23 (d, J¼5.1 Hz, 2H), 4.74 (br s, 1H), 5.59 (br
d, J¼10.1 Hz, 2H), 5.79 (br d, J¼10.1 Hz, 2H), 5.89 (s,
2H), 6.72 (s, 1H), 6.73 (s, 1H); 13C NMR: d 25.7, 28.4
(3C), 37.4, 41.9, 79.4, 100.9, 108.6, 109.6, 123.7, 125.2,
128.2, 128.7, 129.9, 136.9, 146.0, 147.3, 155.5. Anal.
Calcd for C19H23NO4: C, 69.28; H, 7.04. Found: C, 69.35;
H, 6.99.
4.2.4. Methyl benzylcarbamate (19). This compound was
isolated in 30% yield from the attempted addition of 2 to
benzene. White solid; mp 57–58 ꢁC (lit.37 mp 59–61 ꢁC);
1H NMR: d 3.70 (s, 3H), 4.38 (d, J¼5.9 Hz, 2H), 5.03
(br s, 1H), 7.26–7.35 (m, 5H); 13C NMR: d 45.0, 52.2,
127.2, 127.4, 127.5, 128.4, 128.6, 138.6, 157.2.
4.2.5. Methyl 2-phenylselenobenzylcarbamate (20). This
compound was isolated in 32% yield from the attempted
addition of 2 to benzene. Colorless oil; H NMR: d 3.65
(s, 3H), 4.46 (d, J¼6.1 Hz, 2H), 5.05 (br s, 1H), 7.18 (t,
J¼7.5 Hz, 1H), 7.23–7.51 (m, 8H); 13C NMR: d 45.4,
52.2, 127.2, 127.8, 128.4, 128.5, 128.6, 128.9, 129.5 (2C),
130.3, 132.0, 135.6, 140.5, 156.9; EIHRMS Calcd for
C15H15NO2Se [M]+: 321.0268, found: 321.0257.
4.3. General procedure for the epoxidation of dienes
1
3-Chloroperoxybenzoic acid (230 mg, 1.03 mmol) was
added portionwise to a stirred solution of the diene
(0.94 mmol) in dry CH2Cl2 (10 mL) at 0 ꢁC. After 2 h, the
reaction mixture was diluted with dichloromethane
(40 mL) and washed with saturated aqueous sodium bicar-
bonate (3ꢃ25 mL). The dichloromethane layer was dried,
concentrated, and purified by chromatography on silica gel
(eluent: EtOAC in hexanes) to afford the epoxide.
4.2.6. Methyl 2-(2,5-cyclohexadien-1-yl)benzylcarba-
mate (11). LiAlH4 (250 mg, 6.6 mmol) was suspended in
THF (8 mL), cooled to 0 ꢁC, stirred vigorously, and treated
with concentrated sulfuric acid (182 mL, 3.3 mmol). This
mixture was stirred for 1 h at 0 ꢁC, before a solution of diene
10 (570 mg, 3.14 mmol) in THF (7 mL) was added drop-
wise. Stirring was continued for 1 h before the reaction
was stopped by the addition of ethanol (10 mL) at 0 ꢁC, fol-
lowed by few drops of 2 N NaOH. The suspension was
diluted with EtOAc (50 mL), filtered, and concentrated to
provide a brown residue, which was taken directly to the
next step. This residue was dissolved in CH2Cl2 (8 mL)
and cooled to 0 ꢁC, and then treated with Et3N (750 mL,
5 mmol) and methyl chloroformate (386 mL, 5 mmol). The
resultant solution was stirred for 6 h, diluted with CH2Cl2
(50 mL), and washed with saturated aqueous NaHCO3
(25 mL) and brine (25 mL). The dichloromethane layer
was dried, concentrated, and purified by chromatography
4.3.1. Methyl 2-(2-cyclohexen-5,6-epoxy-1-yl)benzylcar-
1
bamate (21). Yield 71%; white solid; mp 87–88 ꢁC; H
NMR (500 MHz): d 2.61–2.70 (m, 2H), 3.15 (m, 1H), 3.36
(m, 1H), 3.70 (s, 3H), 4.09 (m, 1H), 4.48 (d, J¼6.5 Hz,
2H), 4.96 (br s, 1H), 5.53–5.60 (m, 2H), 7.22–7.35 (m,
4H); 13C NMR (125 MHz): d 24.9, 37.5, 42.7, 51.1, 52.3,
54.8, 121.5, 125.6, 127.2, 128.2, 128.8, 129.2, 136.0,
138.8, 156.7; ESIHRMS Calcd for C15H17NO3 [M+H]+:
260.1287, found: 260.1288.
4.3.2. tert-Butyl 2-(2-cyclohexen-5,6-epoxy-1-yl)benzyl-
carbamate (25). Yield 67%; white solid; mp 88 ꢁC; IR
(neat): 1167, 1248, 1519, 1699, 2359, 2977, 3354 cmꢂ1
;
1H NMR: d 1.45 (s, 9H), 2.60–2.69 (m, 2H), 3.15 (d, J¼
4 Hz, 1H), 3.35 (m, 1H), 4.10 (m, 1H), 4.44 (d, J¼5 Hz,
2H), 4.79 (br s, 1H), 5.54–5.58 (m, 2H), 7.21–7.22

D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
6837
(m, 4H); 13C NMR: d 25.1, 28.4 (3C), 37.5, 42.3, 51.9, 54.9,
79.7, 121.5, 125.7, 127.4, 128.1, 128.8, 129.2, 136.4, 138.8,
155.6; ESIHRMS Calcd for C18H23NO3 [M+Na]+:
324.1576, found: 324.1574.
chloride (7 mg, 0.01 mmol) in CH2Cl2 (0.6 mL) was added
NaOCl (1 mL) buffered to pH 11.3. The reaction mixture
was stirred at room temperature for 4 h, then was diluted
with CH2Cl2 (20 mL) and washed with H2O (2ꢃ20 mL).
The aqueous layer was back extracted with CH2Cl2
(10 mL). The combined organic layer was dried, concen-
trated, and purified by chromatography over silica gel (elu-
ent: 25% EtOAc in hexanes) to yield 29 (40 mg, 58%) as
a colorless oil. IR (neat): 1251, 1527, 1708, 3023,
4.3.3. tert-Butyl 6-(2-cyclohexen-5,6-epoxy)-[1,3]benzo-
dioxole-5-ylmethyl)carbamate (26). Yield 60%; white
1
solid; mp 143 ꢁC; H NMR: d 1.44 (s, 9H), 2.60–2.69 (m,
2H), 3.08 (m, 1H), 3.31 (m, 1H), 4.01 (m, 1H), 4.30 (d,
J¼5.2 Hz, 2H), 4.80 (br s, 1H), 5.46–5.50 (m, 2H), 5.90
(s, 2H), 6.66 (s, 1H), 6.83 (s, 1H); 13C NMR: d 25.0, 28.3
(3C), 37.2, 42.4, 51.8, 54.9, 79.7, 101.2, 108.7, 109.3,
121.5, 125.9, 130.0, 132.1, 146.7, 147.3, 155.5. Anal.
Calcd for C19H23NO5: C, 66.07; H, 6.71. Found: C, 66.24;
H, 6.70.
1
3332 cmꢂ1; H NMR: d 3.6 (s, 3H), 4.33 (d, J¼6.0 Hz,
2H), 4.76 (br s, 1H), 7.23–7.46 (m, 9H); 13C NMR: d 42.9,
52.1, 127.3, 127.4, 127.7, 128.4, 128.9, 129.0, 130.2,
135.7, 140.7, 141.6, 156.9; ESIHRMS Calcd for
C15H15NO2 [M+H]+: 242.1175, found: 242.1170.
4.4.5. [( )-1R,2S,4S,4aS,10bR] Methyl 1,2-epoxy-4-hy-
droxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-one-5-
carboxylate (32). A solution of 3-chloroperoxybenzoic acid
(255 mg, 1.2 mmol) and alcohol 22 (100 mg, 0.38 mmol) in
dry CH2Cl2 (5 mL), was stirred at room temperature for
24 h, then diluted with dichloromethane (30 mL), washed
with saturated aqueous sodium bicarbonate (3ꢃ25 mL),
and brine (25 mL). The dichloromethane layer was dried,
concentrated, and purified by chromatography over silica
gel (eluent: 70% EtOAc in hexanes) to afford epoxide 32
as a white foam (89 mg, 80%). 1H NMR: d 2.09 (dd,
J¼15.6 Hz, J¼9.3 Hz, 1H), 2.37–2.44 (m, 1H), 3.25 (br s,
1H), 3.29 (t, J¼4.2 Hz, 1H), 3.63–3.68 (m, 1H), 3.91 (s,
3H), 3.91 (m, 1H), 4.10–4.14 (m, 1H), 4.70 (dd, J¼
10.8 Hz, 5.1 Hz, 1H), 7.40 (t, J¼7.5 Hz, 1H), 7.51 (d,
J¼7.8 Hz, 1H), 7.59 (t, J¼6.5 Hz, 1H), 8.1 (d, J¼8.6 Hz,
1H); 13C NMR: d 33.1, 36.2, 51.4, 54.5, 54.6, 56.8, 64.2,
124.3, 127.4, 128.6, 130.4, 133.8, 136.8, 156.3, 162.5;
ESIHRMS Calcd for C15H15NO5 [M+Na]+: 312.0842,
found: 312.0847.
4.4. General procedure for cyclization to the tricyclic
skeleton
A solution of epoxide (1.0 mmol) in CH2Cl2 (4 mL)
was treated with BF3$Et2O (0.4 mmol, 118 mL) at ꢂ10 ꢁC
and stirred for 20 min, before the addition of saturated
aqueous sodium bicarbonate (10 mL) and dichloromethane
(40 mL). The dichloromethane layer was dried, concen-
trated, and purified by chromatography over silica gel
(eluent: EtOAc in hexanes).
4.4.1. [( )-4S,4aS,10bR] Methyl 4-hydroxy-4,4a,6,10b-
tetrahydro-3H-phenanthridine-5-carboxylate (22).
Yield 79%; colorless oil; IR (neat): 1242, 1456, 1698,
1
2360, 3479 cmꢂ1; H NMR: d 1.95 (br s, 1H), 2.17–2.23
(m, 1H), 2.52–2.58 (m, 1H), 3.63 (m, 1H), 3.78 (s, 3H),
4.31–4.50 (m, 3H), 4.75–5.08 (m, 1H), 5.74 (m, 1H), 6.14
(m, 1H), 7.09–7.32 (m, 4H); 13C NMR: d 35.7, 38.2, 43.5,
53.1, 56.1, 66.5, 125.3, 126.2, 126.3, 127.1, 127.3, 127.6,
131.4, 136.8, 158.4; EIHRMS Calcd for C15H17NO3 [M]+:
259.1208, found: 259.1204.
4.4.6. [( )-1R,4S,4aS,10bR] Methyl 1-hydroxy-4,6-dioxo-
4,4a,6,10b-tetrahydro-1H-phenanthridine-5-carboxylate
(33). Dess–Martin periodinane (88 mg, 0.21 mmol) was
added to a solution of epoxide 32 (50 mg, 0.17 mmol) in
dry CH2Cl2 (3 mL) and stirred for 4 h. When the reaction
was complete, saturated aqueous sodium thiosulfate
(15 mL) was added, and the reaction mixture stirred for
0.5 h, before it was poured into saturated aqueous sodium
bicarbonate. The dichloromethane layer was dried, concen-
trated, and purified by chromatography over silica gel (elu-
ent: 3% MeOH in CH2Cl2) to afford hydroxyenone 33
(33 mg, 68%) as a white solid. Mp 98 ꢁC; IR (neat): 1376,
4.4.2. [( )-4S,4aS,10bR] tert-Butyl 4-hydroxy-4,4a,6,10b-
tetrahydro-3H-phenanthridine-5-carboxylate (27).
Yield 86%; colorless oil; IR (neat): 1419, 1683, 2977,
1
3426 cmꢂ1; H NMR: d 1.45 (s, 9H), 2.15–2.21 (m, 1H),
2.52–2.58 (m, 1H), 3.55 (m, 1H), 3.74 (m, 1H), 4.43–4.98
(m, 3H), 5.76 (m, 1H), 6.14 (m, 1H), 7.11–7.26 (m, 4H);
13C NMR: d 28.4 (3C), 36.3, 38.5, 44.0, 55.7, 66.9, 80.7,
125.5, 126.1, 126.3, 127.0, 127.1, 127.7, 131.7, 137.0,
157.6; ESIHRMS Calcd for C18H23NO3 [M+Na]+:
324.1576, found: 324.1566.
1
1598, 1689, 1762, 3413 cmꢂ1; H NMR (CD3OD): d 4.02
4.4.3. [( )-4S,4aS,10bR] tert-Butyl 4-hydroxy-4,4a,6,10b-
tetrahydro-3H-[1,3]dioxolo[4,5-j]phenanthridine-5-car-
boxylate (28). Yield 68%; colorless oil; 1H NMR: d 1.45 (s,
9H), 2.03 (m, 1H), 2.50–2.55 (m, 1H), 2.67 (br s, 1H), 3.56
(m, 1H), 3.61 (m, 1H), 4.25–4.84 (m, 3H), 5.73 (m, 1H), 5.90
(s, 1H), 5.93 (s, 1H), 6.02 (m, 1H), 6.56 (s, 1H), 6.69 (s, 1H);
13C NMR: d 28.4 (3C), 34.5, 36.2, 42.3, 55.7, 66.7, 80.7,
100.9, 106.3, 107.3, 124.2, 126.5, 126.8, 130.3, 145.9,
146.7, 157.4; ESIHRMS Calcd for C19H23NO5 [M+Na]+:
368.1468, found: 368.1475.
(s, 3H), 4.1 (m, 1H), 5.28 (dd, J¼5.5, J¼2.6 Hz, 1H), 5.82
(d, J¼4.9 Hz, 1H), 5.92 (d, J¼9.9 Hz, 1H), 7.01 (dd,
J¼10.0 Hz, 5.3 Hz, 1H), 7.41 (t, J¼7.6 Hz, 1H), 7.44 (d,
J¼8.0 Hz, 1H), 7.55 (t, J¼7.5 Hz, 1H), 8.06 (d, J¼7.9 Hz,
1H); 13C NMR (CD3OD): d 44.8, 53.3, 59.1, 63.3, 124.4,
127.6, 128.8, 128.9, 129.6, 133.7, 136.8, 146.3, 154.1,
163.1, 193.4; ESIHRMS Calcd for C15H13NO5 [M+Na]+:
310.0686, found: 310.0690.
4.4.7. [( )-(4S,4aS,10bR)] 3,4,4a,10b-Tetrahydro-4-iodo-
7-hydroxy-6H-[1,3]benzodioxolo[5,6-c]benzopyran-6-
one (34). A solution of 14 (20 mg, 0.076 mmol) in THF
(3 mL) was treated with NaHCO3 (13 mg, 0.15 mmol),
then I2 (23 mg, 0.09 mmol), and stirred at room temperature
4.4.4. Methyl 2-phenylbenzylcarbamate (29). To a solution
of diene 11 (70 mg, 0.27 mmol) and (R,R)-(ꢂ)-N,N-bis(3,5-di-
tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III)

6838
D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
for 15 h. Saturated Na2S2O3 solution (10 mL) was then
added and the mixture was extracted with EtOAc
(3ꢃ10 mL). The aqueous layer was washed with EtOAc
(15 mL), and the combined organic layer was dried, concen-
trated, and purified by chromatography over silica gel (elu-
ent: 30% EtOAc in hexanes) to provide iodolactone 34
(30 mg, 71%) as a white solid. Mp 179 ꢁC (lit.26 mp
4.4.11. [( )-3aS,11bR,11cR] 4-Oxa-1,2,3,3a,4,5,11b,11c-
octahydro-7H-pyrrolo[3,2,1-de]phenanthridin-5-one
(38). Mesylate 37 (19 mg, 0.05 mmol) dissolved in DMF
(0.5 mL) was treated with potassium tert-butoxide (6 mg,
0.055 mmol) and heated to 65 ꢁC for 6 h. The reaction mix-
ture was diluted with EtOAc (30 mL), washed with saturated
aqueous NH4Cl (20 mL) and brine (20 mL). The organic
layer was dried, concentrated, and purified by chromato-
graphy over silica gel (20% EtOAc in hexanes) to provide
38 (7 mg, 63%) as a colorless oil. IR (neat): 1308, 1751,
1
177 ꢁC); H NMR: d 2.63–2.72 (m, 1H), 3.30–3.37 (m,
1H), 4.06–4.10 (m, 1H), 4.57–4.60 (m, 1H), 4.90–4.92 (m,
1H), 5.46–5.50 (m, 1H), 5.69–5.73 (m, 1H), 6.09 (s, 2H),
6.46 (s, 1H), 10.86 (s, 1H); 13C NMR: d 19.6, 30.8, 35.6,
77.7, 100.4, 102.7, 103.0, 124.2, 124.3, 133.5, 137.9,
145.8, 154.5, 168.0; EIHRMS Calcd for C14H11IO5 [M]+:
385.9651, found: 385.9663.
1
1800, 2940 cmꢂ1; H NMR: d 1.37–1.43 (m, 1H), 1.44–
1.50 (m, 1H), 1.60–1.72 (m, 1H), 1.78–1.86 (m, 2H),
2.10–2.13 (m, 1H), 2.90 (dt, J¼12.4 Hz, J¼4.8 Hz, 1H),
3.98 (dd, J¼7.6 Hz, 4.0 Hz, 1H), 4.35 (d, J¼13.2 Hz, 1H),
4.75 (d, J¼13.3 Hz, 1H), 4.80 (q, J¼7.6 Hz, 1H), 7.15–
7.26 (m, 4H); 13C NMR: d 15.3, 26.5, 28.5, 37.7, 43.1,
53.3, 74.1, 126.8, 127.0, 127.1, 129.3, 130.3, 136.6, 158.4;
ESIHRMS Calcd for C14H15NO2 [M+H]+: 230.1181, found:
230.1173.
4.4.8. [( )-4R,4aR,10bR] tert-Butyl 4-hydroxy-
2,3,4,4a,6,10b-hexahydro-1H-phenanthridine-5-carboxy-
late (35). A solution of alcohol 27 (237 mg, 0.78 mmol) in
methanol (4 mL) was stirred with 10% Pd–C (80 mg) under
1 atm of H2 for 3 h, then was filtered through CeliteÒ and pu-
rified by chromatography over silica gel (eluent: 30% EtOAc
4.4.12. [( )-3aS,11bR,11cR] 4-Oxa-1,2,3,3a,4,5,11b,11c-
octahydro-7H-[1,3]dioxolo[4,5-j]pyrrolo[3,2,1-de]phe-
nanthridin-5-one (39). A solution of alcohol 36 (40 mg,
0.12 mmol) in benzene (3 mL) was treated with methyl
N-(triethylammoniosulfonyl)carbamate38 (30 mg, 0.17 mmol)
and heated to reflux. After 12 h, the reaction was diluted
with EtOAc (25 mL) and washed with saturated aqueous
NH4Cl solution, followed by brine. The organic layer was
dried, concentrated, and purified by chromatography over
silica gel (eluent: 40% EtOAc in hexanes) to provide the
oxazolidinone 39 as a colorless oil (18 mg, 56%). IR
1
in hexanes) to yield 35 (77 mg, 95%) as a colorless oil. H
NMR: d 1.25–1.27 (m, 2H), 1.45 (s, 9H), 1.56–1.59 (m,
1H), 1.67–1.76 (m, 1H), 1.96–1.99 (m, 1H), 2.30 (br s,
1H), 2.47 (dd, J¼13.5 Hz, J¼2.8 Hz, 1H), 3.30 (m, 2H),
4.25 (m, 1H), 4.45 (d, J¼16.8 Hz, 1H), 4.70 (d,
J¼16.9 Hz, 1H), 7.11–7.29 (m, 4H); 13C NMR: d 19.6,
26.7, 28.4 (3C), 35.4, 37.4, 44.3, 58.3, 69.3, 80.5, 125.4,
126.1, 126.5, 126.8, 133.2, 135.2, 157.2; EIHRMS Calcd
for C18H25NO3 [M]+: 303.1834, found: 303.1848.
1
4.4.9. [( )-4R,4aR,10bR] tert-Butyl 4-hydroxy-2,3,4,4a,
6,10b-hexahydro-1H-[1,3]dioxolo[4,5-j]phenanthridine-
5-carboxylate (36). Analogous to the conversion of 27 to 35,
hydrogenation of alcohol 28 gave 36 in 95% yield as color-
less oil. IR (neat): 1251, 1689, 2933, 3428 cmꢂ1; 1H NMR:
d 1.22–1.30 (m, 2H), 1.44 (s, 9H), 1.49–1.56 (m, 2H), 1.96–
1.98 (m, 1H), 2.31–2.34 (d, J¼11.2 Hz, 1H), 2.60 (br s,
–OH, 1H), 3.18 (m, 1H), 3.30 (m, 1H), 4.19 (m, 1H), 4.32
(d, J¼13.2 Hz, 1H), 4.59 (d, J¼13.0 Hz, 1H), 5.90 (s, 1H),
5.91 (s, 1H), 6.57 (s, 1H), 6.74 (s, 1H); 13C NMR: d 19.5,
27.2, 28.5 (3C), 35.3, 37.2, 44.3, 58.2, 69.1, 80.5, 100.9,
105.6, 106.5, 126.3, 128.6, 145.9, 146.8, 157.1; EIHRMS
Calcd for C19H25NO5 [M]+: 347.1733, found: 347.1723.
(neat): 1201, 1484, 1751, 2936 cmꢂ1; H NMR: d 1.35–
1.45 (m, 2H), 1.61–1.81 (m, 3H), 2.05–2.08 (m, 1H), 2.77
(dt, J¼12.4 Hz, J¼4.8 Hz, 1H), 3.93 (dd, J¼7.5 Hz,
J¼4.3 Hz, 1H), 4.23 (d, J¼16.2 Hz, 1H), 4.62 (d,
J¼16.3 Hz, 1H), 4.77 (q, J¼7.6 Hz, 1H), 5.93 (s, 2H),
6.58 (s, 1H), 6.59 (s, 1H); 13C NMR: d 19.2, 26.4, 28.9,
37.7, 43.2, 53.3, 74.1, 101.2, 106.3, 108.7, 123.3, 129.8,
146.8, 146.9, 158.2; ESIHRMS Calcd for C15H15NO4
[M+H]+: 274.1079, found: 274.1077.
Acknowledgements
We thank the NSF (CHE 9986200) for partial support of this
work, Bhushan Surve for the X-ray structure, and Professor
Yian Shi for a sample of oxazolidinone 31.
4.4.10. [( )-4R,4aR,10bR] tert-Butyl 4-methanesulfonyl-
oxy-2,3,4,4a,6,10b-hexahydro-1H-phenanthridine-5-
carboxylate (37). Alcohol 35 (92 mg, 0.3 mmol) was dis-
solved in dry CH2Cl2 (3 mL) and cooled to 0 ꢁC. To this so-
lution was added Hunig’s base (79 mL, 0.45 mmol) and
methanesulfonyl chloride (37 mL, 0.45 mmol). The reaction
mixture was slowly warmed to room temperature and stirred
overnight. The mixture was diluted with dichloromethane
(30 mL) and washed with saturated NH4Cl (20 mL) and
brine (20 mL). The dichloromethane layer was extracted,
dried, and purified by chromatography over silica gel
(20% EtOAc in hexanes) to provide mesylate 37 (52 mg,
45%) as a colorless oil, which was used immediately in
References and notes
1. The rate constant for the addition of the phenyl radical to benz-
ene is 4.5ꢃ105 Mꢂ1 sꢂ1 at 25 ꢁC. Scaiano, J. C.; Stewart, L. C.
J. Am. Chem. Soc. 1983, 105, 3609–3614.
´
2. Martınez-Barrasa, V.; Garcia de Viedma, A.; Burgos, C.;
Alvarez-Builla, J. Org. Lett. 2000, 2, 3933–3935.
3. Studer, A.; Bossart, M. Homolytic Aromatic Substitutions.
Radicals in Organic Synthesis; Renaud, P., Sibi, M., Eds.;
Wiley-VCH: Weinheim, 2001; Vol. 2, pp 62–80.
4. (a) Beckwith, A. L. J.; Bowry, V. W.; Bowman, W. R.; Mann,
E.; Parr, J.; Storey, J. M. D. Angew. Chem., Int. Ed. 2004, 43,
95–98; (b) Curran, D. P.; Yu, H.; Liu, H. Tetrahedron 1994,
1
the next step. H NMR (500 MHz): d 1.24–1.27 (m, 1H),
1.50 (s, 9H), 1.60–1.73 (m, 3H), 2.03–2.2 (m, 1H), 2.47–
2.50 (m, 1H), 2.97 (s, 3H), 3.41 (m, 1H), 4.38–4.41 (m,
1H), 4.51–4.59 (m, 2H), 4.82–4.86 (m, 1H), 7.15–7.28
(m, 4H).

D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
6839
50, 7343–7366; (c) Curran, D. P.; Liu, H. J. Chem. Soc., Perkin
Trans. 1 1994, 1377–1393; (d) Engel, P. S.; Wu, W.-X. J. Am.
Chem. Soc. 1989, 111, 1830–1835.
McHardy, S. F.; Murray, J. A. J. Org. Chem. 1999, 64, 4465–
4476; (g) Acena, J. L.; Arjona, O.; Leon, M. L.; Plumet, J.
Org. Lett. 2000, 2, 3683–3686; (h) Rinner, U.; Siengalewicz,
P.; Hudlicky, T. Org Lett. 2002, 4, 115–117.
5. (a) Crich, D.; Hwang, J.-T. J. Org. Chem. 1998, 63, 2765–2770;
(b) Crich, D.; Patel, M. Org. Lett. 2005, 7, 3625–3628.
17. Total synthesis of narciclasine: (a) Rigby, J. H.; Mateo, M. E.
J. Am. Chem. Soc. 1997, 119, 12655–12656; (b) Gonzalez,
D.; Martinot, T.; Hudlicky, T. Tetrahedron Lett. 1999, 40,
3077–3080; (c) Keck, G. E.; Wagger, T. T.; Rodriquez,
J. F. D. J. Am. Chem. Soc. 1999, 121, 5176–5190; (d)
Elango, S.; Yan, T.-H. J. Org. Chem. 2002, 67, 6954–6959;
(e) Hudlicky, T.; Rinner, U.; Gonzalez, D.; Akgun, H.;
Schilling, S.; Siengalewicz, P.; Martinot, T. A.; Pettit, G. R.
J. Org. Chem. 2002, 67, 8726–8743.
18. Total synthesis of lycoricidine: (a) Ohta, S.; Kimoto, S.
Tetrahedron Lett. 1975, 16, 2279–2282; (b) Paulsen, H.;
Stubbe, M. Tetrahedron Lett. 1982, 23, 3171–3174; (c)
Paulsen, H.; Stubbe, M. Liebigs Ann. Chem. 1983, 4, 535–
556; (d) Ugarkar, B. G.; DaRe, J.; Schubert, E. M. Synthesis
1987, 8, 715–716; (e) Chida, N.; Ohtsuka, M.; Ogawa, S.
Tetrahedron Lett. 1991, 32, 4525–4528; (f) Hudlicky, T.;
Olivo, H. F.; McKibben, B. J. Am. Chem. Soc. 1994, 116,
5108–5115; (g) Keck, G. E.; Wager, T. T. J. Org. Chem.
1996, 61, 8366–8367; (h) Keck, G. E.; Wager, T. T.;
Rodriquez, J. F. D. J. Am. Chem. Soc. 1999, 121, 5176–5190;
(i) Elango, S.; Yan, T.-H. Tetrahedron 2002, 58, 7335–7338;
(j) Zhang, H.; Padwa, A. Org. Lett. 2006, 8, 247–250.
19. (a) Hudlicky, T.; Thorpe, A. J. J. Chem. Soc., Chem. Commun.
1996, 1993–2000; (b) Hudlicky, T.; Gonzalez, D.; Gibson, D.
Aldrichim. Acta 1999, 32, 35–62.
6. BDE Me3Sn–H, 78 kcal molꢂ1
;
BDE PhSe–H 78ꢀ4
78 kcal molꢂ1: (a) Laarhoven, L. J. J.; Mulder, P.; Wayner,
D. D. M. Acc. Chem. Res. 1999, 32, 342–349; (b) Leeck,
D. T.; Li, D. T.; Chyall, L. J.; Kenttamaa, H. I. J. Phys.
Chem. 1996, 100, 6608–6611.
7. Rate constants for trapping of primary alkyl radicals by
Bu3SnH and PhSeH at 25 ꢁC are, respectively, 2ꢃ106 and
1ꢃ109 Mꢂ1 sꢂ1: (a) Newcomb, M.; Choi, S.-Y.; Horner, J. H.
J. Org. Chem. 1999, 64, 1225–1231; (b) Chatgilialoglu, C.;
Ingold, K. U.; Scaiano, J. C. J. Am. Chem. Soc. 1981, 103,
7739–7742.
8. Roberts, B. P. Chem. Soc. Rev. 1999, 28, 25–35.
9. (a) Crich, D.; Yao, Q. J. Org. Chem. 1995, 60, 84–88; (b) Crich,
D.; Jiao, X.-Y.; Yao, Q.; Harwood, J. S. J. Org. Chem. 1996, 61,
2368–2373; (c) Crich, D.; Hwang, J.-T.; Gastaldi, S.; Recupero,
F.; Wink, D. J. J. Org. Chem. 1999, 64, 2877–2882.
10. Crich, D.; Sannigrahi, M. Tetrahedron 2002, 58, 3319–3322.
11. Reviews on desymmetrization of cyclohexadienes generated
by other means: (a) Rahman, N. A.; Landais, Y. Curr. Org.
Chem. 2002, 6, 1369–1395; (b) Studer, A.; Kim, Y. H.
Synlett 2005, 3033–3041.
12. Crich, D.; Rumthao, S. Tetrahedron 2004, 60, 1513–1516.
13. Crich, D.; Grant, D. J. Org. Chem. 2005, 70, 2384–2386.
14. Reviews: (a) Martin, S. F. The Alkaloids; Brossi, A., Ed.;
Academic: San Diego, CA, 1987; Vol. 30, pp 252–376; (b)
Polt, R. Organic Synthesis: Theory and Applications;
Hudlicky, T., Ed.; JAI: Greenwich, 1996; Vol. 3, pp 109–148;
(c) Hoshino, O. The Alkaloids; Cordell, G. A., Ed.;
Academic: New York, NY, 1998; Vol. 51, pp 323–424; (d)
Jin, Z. Nat. Prod. Rep. 2003, 20, 606–614; (e) Rinner, U.;
Hudlicky, T. Synlett 2005, 365–405.
20. (a) Yoon, N. M.; Brown, H. C. J. Am. Chem. Soc. 1968, 90,
2927–2938; (b) Windhorst, A. D.; Timmerman, H.;
Worthington, E. A.; Bijloo, G. J.; Nederkoorn, P. H. J.;
Menge, W. M. P. B.; Leurs, R.; Herschield, J. D. M. J. Med.
Chem. 2000, 43, 1754–1761.
21. Beugelmans, R.; Chastanet, J.; Roussi, G. Tetrahedron 1984,
40, 311–314.
15. Total synthesis of pancratistatin: (a) Danishefsky, S.; Lee, J. Y.
J. Am. Chem. Soc. 1989, 111, 4829–4837; (b) Tian, X. R.;
Hudlicky, T.; Konigsbeger, K. J. Am. Chem. Soc. 1995, 117,
3643–3644; (c) Trost, B. M.; Pulley, S. R. J. Am. Chem. Soc.
1995, 117, 10143–10144; (d) Keck, G. E.; McHardy, S. F.;
Murry, J. A. J. Am. Chem. Soc. 1995, 117, 7289–7290; (e)
22. (a) Abelman, M. M.; Overman, L. E.; Tran, V. D. J. Am. Chem.
Soc. 1990, 112, 6959–6964; (b) Cossy, J.; Tresnard, L.; Gomez
Pardo, D. Tetrahedron Lett. 1999, 40, 1125–1128; (c) Janssen,
D. E.; Wilson, C. V. Org. Synth. Coll. Vol. 1963, 4, 547–549.
23. The corresponding N,N-dimethylamide was similarly accessed
by: Keck, G. E.; Wager, T. T.; Rodriguez, J. F. D. J. Org. Chem.
Soc. 1999, 121, 5176–5190.
Hudlicky, T.; Tian, X. R.; Konigsberger, K.; Maurya, R.;
¨
Rouden, J.; Fan, B. J. Am. Chem. Soc. 1996, 118, 10752–
10765; (f) Doyle, T. J.; Hendrix, M.; VanDerveer, D.;
Javanmard, S.; Haseltine, J. Tetrahedron 1997, 53, 11153–
11170; (g) Magnus, P.; Sebhat, I. K. J. Am. Chem. Soc. 1998,
120, 5341–5342; (h) Rigby, J. H.; Maharoof, U. S. M.;
Mateo, M. E. J. Am. Chem. Soc. 2000, 122, 6624–6628; (i)
Pettit, G. R.; Melody, N.; Herald, D. L. J. Org. Chem. 2001,
66, 2583–2587; (j) Kim, S.; Ko, H.; Kim, E.; Kim, D. Org
Lett. 2002, 4, 1343–1345; (k) Kim, H.; Kim, E.; Park, J. E.;
Kim, D.; Kim, S. J. Org. Chem. 2004, 69, 112–121; (l)
Moser, M.; Sun, X.; Hudlicky, T. Org. Lett. 2005, 7, 5669–5672.
16. Total synthesis of 7-deoxypancratistatin: (a) Tian, X.; Maurya,
24. This hydrolysis protocol, necessitated because of the extremely
sterically hindered and unreactive nature of the amide, was
based on a conversion of the corresponding N,N-dimethyl-
amide to the methyl ester by Keck.23
25. Beckwith, A. L. J.; O’Shea, D. M.; Roberts, D. H. J. Am. Chem.
Soc. 1986, 108, 6408–6409.
26. A number of other reducing agents were assayed for this trans-
formation but none were as effective as AlH3 in effecting the
reduction while minimizing decomposition of the cyclohexa-
diene functionality.
27. Gorzynski Smith, J. Synthesis 1984, 629–656.
28. Jacobsen, E.; Zhang, W.; Muci, A. R.; Ecker, J. R.; Deng, L.
J. Am. Chem. Soc. 1991, 113, 7063–7064.
R.; Konigsberger, K.; Hudlicky, T. Synlett 1995, 1125–1126;
¨
(b) Keck, G. E.; McHardy, S. F.; Murray, J. A. J. Am. Chem.
Soc. 1995, 117, 7289–7290; (c) Chida, N.; Jitsuoka, M.;
Yamamoto, Y.; Ohtsuka, M.; Ogawa, S. Heterocycles 1996,
29. Jacobsen epoxidation of cyclohexa-1,4-dienes does not appear
to have been described in the literature.
30. Frohn, M.; Shi, Y. Synthesis 2000, 1979–2000.
43, 1385–1390; (d) Hudlicky, T.; Tian, X. R.; Konigsberger,
31. (a) Shu, L.; Shen, Y.-M.; Burke, C.; Goeddel, D.; Shi, Y. J. Org.
Chem. 2003, 68, 4963–4965; (b) Lorenz, J. C.; Frohn, M.;
Zhou, X.; Zhang, J.-R.; Tang, Y.; Burke, C.; Shi, Y. J. Org.
Chem. 2005, 70, 2904–2911.
¨
K.; Maurya, R.; Rouden, J.; Fan, B. J. Am. Chem. Soc. 1996,
118, 10752–10765; (e) Keck, G. E.; Wager, T. T.; McHardy,
S. F. J. Org. Chem. 1998, 63, 9164–9165; (f) Keck, G. E.;

6840
D. Crich, V. Krishnamurthy / Tetrahedron 62 (2006) 6830–6840
32. Bulman Page, P. C.; Buckley, B. R.; Heaney, H.; Blacker, A. J.
Org. Lett. 2005, 7, 375–377.
33. Ma, D.; Xia, C.; Tian, H. Tetrahedron Lett. 1999, 40, 8915–
8917.
34. Dess, P. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155–
4156.
35. Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321–3408.
36. (a) Burgess, E. M.; Penton, H. R.; Taylor, E. A. J. Am. Chem.
Soc. 1970, 92, 5224–5226; (b) Burgess, E. R.; Penton, H. R.;
Taylor, E. A. J. Org. Chem. 1973, 38, 26–31.
37. Selva, M.; Tundo, P.; Perosa, A.; Dall’acqua, F. J. Org. Chem.
2005, 70, 2771–2777.
38. Atkins, G. M.; Burgess, E. M. J. Am. Chem. Soc. 1968, 90,
4744–4745.