Stereoselection at the Steady State in Radical Cyclizations of Acyclic Systems Containing One Radical Acceptor and Two Precursors in a 1,5- Relationship under Pseudo-First-Order Conditions

Article abstract of DOI:10.1021/jo035310p

The first example of a successive kinetic resolution of acyclic diastereomeric radical intermediates in a 1,5-relationship under pseudo-first-order conditions is reported. A mechanistic model involves nonselective generation of the radical intermediates followed by different partitioning of these between two different chemical pathways. The "2,5-cis" selectivity in the radical cyclization step arises from transition geometries with the substituents aligned in pseudoequatorial positions.

Full text of DOI:10.1021/jo035310p

Ster eoselection a t th e Stea d y Sta te in Ra d ica l Cycliza tion s of
Acyclic System s Con ta in in g On e Ra d ica l Accep tor a n d Tw o
P r ecu r sor s in a 1,5- Rela tion sh ip u n d er P seu d o-F ir st-Or d er
Con d ition s†
Robert Andrukiewicz, Piotr Cmoch, Anna Gaweł, and Krzysztof Stalin´ski*
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/ 52, 01-224 Warsaw, Poland
stalinsk@icho.edu.pl
Received September 5, 2003
The first example of a successive kinetic resolution of acyclic diastereomeric radical intermediates
in a 1,5-relationship under pseudo-first-order conditions is reported. A mechanistic model involves
nonselective generation of the radical intermediates followed by different partitioning of these
between two different chemical pathways. The “2,5-cis” selectivity in the radical cyclization step
arises from transition geometries with the substituents aligned in pseudoequatorial positions.
SCHEME 1. Acyclic Mod el Con ta in in g P r ecu r sor s
in a 1,3-Rela tion sh ip
In tr od u ction
The substituted tetrahydrofurans are of interest as
building blocks in organic synthesis, chiral auxiliaries,
and the structural units of many natural products.1,2 The
stereoselective approach to this class of compounds is still
problematic because of flexible transition states leading
to the tetrahydrofuran system.3 Among the different
strategies available, free carbon radical cyclizations are
of particular interest as an alternative to ionic ones.4
Especially, â-alkoxyacrylates are excellent precursors for
stereoselective preparation of cis-2,5-substituted tetrahy-
drofurans via radical cyclizations.5 Another radical ap-
proach to tetrahydrofurans relies on the addition of
electrophilic alkoxy radicals to multiple bonds.6
Recently, Curran proposed a new type of stereoselec-
tive process founded on the transiency of radicals and
called it “stereoselection at the steady state”.7 The most
important difference between traditional multistep
stereoselective processes and the proposed one seems to
be selective partitioning of stereomeric intermediates at
the steady state between two different chemical (not
stereochemical) pathways to the same stereomeric prod-
uct.8 Most of the existing examples of stereoselection at
the steady state are diastereoselective and involve bi- and
tricyclic systems.8,9 Due to lack of rigidity, acyclic systems
seem to be more difficult in predicting a stereochemical
outcome of the radical cyclizations. However, in most
cases the major product(s) can be successfully predicted
using the Beckwith-Houk model.10 So far only one acyclic
system containing radical precursors in a 1,3-relationship
has been subjected to stereoselection at the steady state
(Scheme 1).11
There are relatively few examples of desymmetriza-
tions of pseudo-C2-symmetric acyclic systems.12 All of
them are outside radicals. Desymmetrization in such
systems requires diastereotopic group selection. However,
in light of the stereoselection at the steady state, group
selection processes (obviously involved) do not directly
control the level of stereoselection as they do in all known
processes. The stereocontrol rather results from a com-
plex interplay of reaction paths that diverge and recon-
verge at various points.
† Dedicated to Prof. Dennis P. Curran for his fundamental contribu-
tion to stereoselection at the steady state.
* Corresponding author.
(1) Lord, M. D.; Negri, J . T.; Paquette, L. A. J . Org. Chem. 1995,
60, 191-195.
(2) (a) Shaw, D. E.; Fenton, G.; Knight, D. W. J . Chem. Soc., Chem.
Commun. 1994, 2447-2448. (b) Paolucci, C.; Mazzini, C.; Fava, A. J .
Org. Chem. 1995, 60, 169-175.
(3) Trost, B. M.; Li, C.-J . J . Am. Chem. Soc. 1994, 116, 10819-10822.
(4) Bartlett, P. A. In Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: New York, 1984; Vol. 3, pp 411-453.
(5) (a) Lee, E.; Choi, S. J . Org. Lett. 1999, 7, 1127-1128. (b) Lee,
E.; Song, H. Y.; Kim, H. J . J . Chem. Soc., Perkin Trans. 1 1999, 3395-
3396. (c) Lee, E.; J eong, E. J .; Kang, E. J .; Sung, L. T.; Hong, S. K. J .
Am. Chem. Soc. 2001, 123, 10131-10132.
(9) (a) Curran, D. P.; Qi, H. Helv. Chim. Acta 1996, 79, 21-30. (b)
Curran, D. P.; Qi, H.; DeMello, N. C.; Lin, C.-H. J . Am. Chem. Soc.
1994, 116, 8430-8431. (c) Villar, F.; Equey, O.; Renaud, P. Org. Lett.
2000, 2, 1061-1064.
(10) (a) Spellmeyer, D. C.; Houk, K. N. J . Org. Chem. 1987, 52, 959-
974. (b) Beckwith, A. L. J .; Lawrence, T.; Serelis, A. K. J . Chem. Soc.,
Chem. Commun. 1980, 482-483. (c) Beckwith, A. L. J .; Easton, C. J .;
Serelis, A. K. J . Chem. Soc., Chem. Commun. 1980, 484-485.
(11) Curran, D. P.; Stalin´ski, K. J . Org. Chem. 2002, 67, 2982-2988.
(12) Magnuson, S. R. Tetrahedron 1995, 51, 2167-2213 and refer-
ences therein.
(6) Hartung, J .; Gallou, F. J . Org. Chem. 1995, 60, 6706-6716.
(7) (a) Curran, D. P.; DeMello, N. C. J . Am. Chem. Soc. 1998, 120,
329-341. (b) Curran, D. P.; DeMello, N. C.; J unggebauer, J .; Lin, C.-
H. J . Am. Chem. Soc. 1998, 120, 342-351.
(8) Kagan, H. Tetrahedron 2001, 47, 2449-2468.
10.1021/jo035310p CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/20/2004
1844
J . Org. Chem. 2004, 69, 1844-1848

Radical Cyclizations of Acyclic Systems
SCHEME 2. Mod els Ha vin g Tw o Ra d ica l
P r ecu r sor s in a 1,5-Rela tion sh ip
SCHEME 3. Syn th esis of th e Ra d ica l P r ecu r sor s
1, 2, a n d 9a
a
Reagents and conditions: (i) TBAF, THF, rt, 3 h, 100%; 2,2-
dimethoxypropane, DMF, p-TSOH, rt, 24 h, 90%; (ii) O3, MeOH/
CH2Cl2, -78 °C, 1.5 h, NaBH4, rt, 16 h, 67%; (iii) I2, Im, Ph3P,
THF, 3 h, 0 °C, 82%; (iv) p-TSOH, MeOH, 24 h, rt, 92%; I2, Im,
Ph3P, THF, 3 h, 0 °C, 82%; (v) 1,1-dimethoxy-2-methylpropane,
PPTS, PhH, reflux, 18 h, 78% or diphenylacetaldehyde dimethyl-
acetal, p-TSOH, reflux 24 h, 70%; (vi) NaH, BnBr, DMF, 0 °C, 24
h, 86%; p-TSOH, MeOH, 24 h, rt, 96%; (vii) p-TsCl, Py, CH2Cl2, 0
°C, 24 h, 81%; NaI, acetone, 65 °C, 24 h, 69%; 1,1-dimethoxy-2-
methylpropane, PPTS, PhH, reflux, 18 h, 55%.
The present study was initiated by our interest in
discovering examples of radical-based processes of acyclic
pseudo-C2-symmetric precursors at the steady state
leading to substituted tetrahydrofurans. The possibility
of manipulation of stereocontrol by reaction topography
prompted us to investigate whether radical cyclizations
of acyclic vinyl ethers having two radical precursors in a
1,5-relationship will meet the requirements of the
stereoselective process. Herein, we describe the results
of our efforts along these lines.
2-methylpropane in boiling benzene in the presence of
an acid catalyst to give the radical precursors 1, 2, and
9.
Compound 9 was prepared to measure the rate con-
stant of the slower cyclization. Radical cyclizations of 9
with tris(trimethylsilyl)silane (TTMSH) in the presence
of Et3B/O2 at ∼20 °C gave four different products (eq 1).14
The calculated rate constant was estimated as 1 × 105
s-1 M-1. The value is in agreement with the rate constant
of the rearrangement of 6,6-dimethyl-5-hexenyl radical
to the isopropylcyclopentyl radical (5 × 105 s-1 M-1).15
Resu lts a n d Discu ssion
Diiodides 1 and 2 were designed as models represent-
ing the pseudo-C2-symmetric family of compounds having
two radical precursors in a 1,5-relationship and one
radical acceptor. We assumed that transition states of
the radical pair of monoiodides obtained after nonselec-
tive abstraction of the first iodine atom from any of the
diiodides would adopt the chairlike geometry (Scheme 2).
The chairlike transition state should favor products
derived from intermediates having substituents in pseu-
doequatorial positions. On the other hand substituents
which are aligned pseudoaxially should slow the cycliza-
tions. In both the radicals derived from 1 or 2 the methyl
group adopts either the pseudoaxial or the pseudoequa-
torial position. Therefore, one of them was expected to
close faster than the other one. We expected that, at
suitable trapping agent concentrations, the process would
converge on the formation of one major product.
Both model compounds were obtained in a multistep
synthesis starting from commercially available (S)-(+)-
3-hydroxy-2-methylpropionate (Scheme 3). Compound 3
was prepared in four synthetic steps via chiral crotyl-
boronate chemistry.13 The alcohol thus obtained was
converted into acetonide 4 via TBS deprotection and
acetal protection with 2,2-dimethoxypropane. Ozonolysis
of 4, a reductive workup with Me2S, and treatment of
the resulting aldehyde with sodium borohydride gave the
corresponding alcohol 5 in 67% yield. Compound 5 was
then either reacted with iodine to give iodide 6 or
benzylated. Both the acetonides were then hydrolyzed to
the corresponding diols, which after conversion to the
primary iodides were treated with an excess of either
diphenylacetaldehyde dimethylacetal or 1,1-dimethoxy-
We next studied radical cyclizations of diiodide 1. A
preparative cyclization of 1 was conducted under stan-
dard conditions at a 0.05 M TTMSH concentration (2.2
equiv) in benzene at rt. GC/MS analysis of the reaction
mixture revealed formation of two major products, pre-
sumably the isomeric tetrahydrofurans as concluded from
the MS spectra. Due to technical difficulties we had to
abandon the radical cyclizations of 1 and move to 2.16
A
preparative cyclization of 2 was conducted under the
same standard conditions. The reaction provided two
major products in a ratio of ∼1:1 in 90% yield and
benzophenone (7%). The products were separated by
preparative HPLC, and individual pure samples of each
were obtained (eq 2).
(14) Compounds 10a ,b are formed via a chairlike transition state.
Compound 11 is presumably formed via a boatlike transition state.
(15) Rate constants for 5-exo cyclizations of alkenyl radicals at 25
°C are in the range of (1-5) × 105 s-1 M-1; see: (a) Lusztyk, J .;
Maillard, B.; Deycard, S.; Lindsay, D. A.; Ingold, K. U. J . Org. Chem.
1987, 52, 3509-3514. (b) Beckwith, A. L. J .; Easton, C. J .; Lawrence,
T.; Serelis, A. K. Aust. J . Chem. 1983, 36, 545-556. (c) Chatgilialoglu,
C.; Ferreri, C.; Lucarni, M. J . Org. Chem. 1991, 56, 6399-6403.
(13) (a) Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.;
Halterman, R. L. J . Am. Chem. Soc. 1990, 112, 6339-6348. (b) Roush,
W. R.; Ando, K.; Palkowitz, A. D. J . Am. Chem. Soc. 1990, 112, 6348-
6359.
J . Org. Chem, Vol. 69, No. 6, 2004 1845

Andrukiewicz et al.
at 3.55 (H5), 3.39 (H2), 2.00 (H3), 1.71 (H4R), and 1.47
(H4â). A careful analysis of the NOE effects for 11, where
weak but measurable NOE effects (Figure 1) for pairs
H3-H4R, H2-H3, and H4â-H5 were observed, indicates
that this time protons H2, H3, and H4R share a cis
relationship.
The stereochemistry of isomeric tetrahydrofurans 13a,b
1
was also determined on the basis of the H NMR NOE
measurements. In the case of 13a ,b almost all signals of
the aliphatic protons, including H2 and H5, were well
separated (in different solvents); thus, the interpretation
F IGURE 1. 1H NMR NOE results of compounds 10a and 11.
1
of the H NMR NOE experiments was rather straight-
forward. The most significant NOEs observed for 13a and
13b are presented in Figure 2. At first we decided to
determine the structure of the compound obtained with
44% yield (eq 2). Irradiation of the H2 signal (δ ) 4.46
ppm) leads to observation of an NOE (4.8%) at H5 (3.20
ppm), and two indistinguishable effects at H3R (1.98
ppm) and H4 (1.96 ppm). When H5 was irradiated, one
measurable effect (4.8%) was observed at H2 (δ ) 4.46
ppm) and an additional enhancement at δ ) ∼1.97 ppm
(H3R and H4) was also detected. Irradiation of the signal
at δ ) 1.26 ppm (H3â) caused another effect (1.9%) at
0.74 ppm (methyl group at C4). Furthermore, two other
enhancements were observed. A proton (CH) of the
isopropyl group at 1.77 ppm interacts with the methyl
group at C4, and H3â interacts strongly with a proton
from the benzhydryl group at δ ) 4.07 ppm. The above-
mentioned effects suggest that the H2, H3R, H4, and H5
protons are in a cis position to each other and the
structure of this compound is 13b.
In the case of 13a (46% yield) a relatively strong effect
(3.0%) between the H2 and H5 protons was observed.
Irradiation of the H2 proton at 4.61 ppm provided an
additional effect at 1.34 ppm (3.6%, H3â), whereas
irradiation of the H3â proton gives an answer at 4.61
ppm (5.1%, H2). Medium effects were obtained for the
methyl group (C4) at 0.86 ppm, when the H2 (1.8%) and
H5 (3.5%) protons were respectively irradiated. Similarly
to 13b, two other effects were observed. A proton (CH)
of the isopropyl group at 1.69 ppm interacts only with
the H5 proton, whereas a proton from the benzhydryl
group (δ ) 4.00 ppm) interacts strongly with that at 1.34
ppm. All the NOE enhancements obtained for 13a
suggest that the H2, H3â, H5, and protons of the methyl
group (C4) share a cis relationship.
The two diastereomeric radicals shown in Scheme 2
were expected to cyclize at different rates. The assump-
tion was made on the basis of analysis of the correspond-
ing Beckwith-Houk models. For such a purpose the rate
constants of the competing process (reduction of the first
and second pairs of radicals) must be between the rate
constants of both cyclizations. This was clearly not the
case when typical hydrides were used. None of the tested
hydrides (TTMSH, n-Bu3SnH, Ph3SnH) were fast enough
to compete with the cyclizations. Even experiments with
5 equiv of Ph3SnH at lower temperatures did not alter
the ratio of the products. The rate constant of the
rearrangement of the 6,6-diphenyl-5-hexenyl radical to
the cyclopentyldiphenylmethyl radical has been reported
as 4 × 107 s-1 M-1 at 20 °C.18 We roughly estimated that
F IGURE 2. 1H NMR NOE results of compounds 13a ,b.
The structures of the cyclic products were derived from
the (H, H) and (C, H) correlation experiments, and the
NOE differential measurements.17 To properly describe
the structures of the products of the radical cyclizations
of 9 and 2 with TTMSH, we decided to assign the 1H
NMR signals in the spectra of compounds 10a , 11, and
13a ,b. For this purpose two different NMR techniques,
including 1H-13C gradient-selected HSQC and HMBC
methods, were used. Next we employed the results of
1
NOE differential experiments. The results of the H and
13C NMR signal assignments for compounds 10a , 11, and
13a ,b are collected in the Supporting Information, but
the chosen NOE results are presented in Figures 1 and
2. At first we decided to determine the structure of the
main product obtained after radical cyclization of 9 with
TTMSH. In C6D6, CDCl3, acetonitrile-d3, acetone-d6, and
methanol-d4 signals of the H2 and H5 protons as well as
H3 and one of the H4 protons of 10a are very close to
each other; thus, observation of the NOEs is rather
complicated. However, on the basis of the results of the
H2-H3, H4-H5, and H4-H2 NOEs for 10a (Figure 1),
the stereochemistry of this compound could be deter-
mined with a relatively good probability. Additionally,
in the NOESY experiment taken from 10a we found that
dipolar interactions exist between the H2 and H5 pro-
tons. On the basis of the NOE and NOESY experiments,
we concluded that the H2, H3, and H5 protons share a
cis relationship.
Contrary to the structure of 10a , where the H2, H3,
and H5 protons are in a cis position to each other, the
analysis of NOE differential measurements for 11 sug-
gests that protons H2 and H5 are in a trans relationship.
This suggestion is supported by the NOE effects observed
after irradiation of all well-separated 1H NMR signals
(16) The products could not be separated by chromatography to give
the individual pure isomers. Moreover, they appeared to be quite
volatile, and we were not able to purify them from impurities. The
phenyl groups in 2 allowed us to separate the reaction mixture by
means of HPLC (UV detection) and added molecular weight so that
the products were not volatile.
(17) The 1H NMR NOE enhancements in tetrahydrofurans are
usually smaller than in other systems; see: Kadota, T.; Oguro, N.;
Yamamoto, Y. Tetrahedron Lett. 2001, 42, 3645-3648.
(18) Newcomb, M.; Horner, J . H.; Filipowski, M. A.; Ha, C.; Park,
S.-U. J . Am. Chem. Soc. 1995, 117, 3674-3684.
1846 J . Org. Chem., Vol. 69, No. 6, 2004

Radical Cyclizations of Acyclic Systems
TABLE 1. Ra d ica l Cycliza tion s of 2 w ith n -Bu 3Sn H/
P h SeH a t 70 °C
amount of the hydride and mixed until the yellow color
was discharged. Then the diiodide 2 was added and
heated for 2 h, during which time a solution of the
hydride and AIBN in benzene was added dropwise. After
the reaction was completed the solvent was removed and
the reaction mixture passed through a pad of silica gel.
The ratio of 13a to 13b was determined using GC/MS
with 9-fluorenone as an internal standard.24 Each of the
products was calibrated against the standard. The ratio
of 13a to 13b appeared to depend on the concentration
of PhSeH. Starting from relatively low PhSeH concentra-
tions, the process converged on the formation of 13a .
However, in all the radical experiments the doubly
reduced product 19 was not isolated. The absence of 19
is incompatible with the proposed kinetic Scheme 4.
When an authentic sample of 1925 was treated with the
tin hydride and AIBN in benzene at 70 °C for 48 h,
benzophenone was formed (84%). We have also observed
some unidentified minor products. Thus, the consumption
of 19 could be explained in terms of hydrostannylation
of the double bond and further radical rearrangements
leading mainly to benzophenone. Further investigations
concerning the formation of benzophenone are in progress.
yield (%)
entry [PhSeH] 13a :13b 13a 13b 13a + 13b Ph2CO
1
2
3
4
0.05
0.10
0.13
0.20
1.06
1.84
2.33
2.95
1.32a
1.84b
4.33
5.90
7.66
48
59
63
69
53a
59b
65
59
46
45
32
27
23
40a
32b
15
10
6
93
91
90
92
93a
91b
80
69
52
2
4
6
3
3
5
5
6
7
0.29
0.51
1.00
14
24
41
a
b
50 mol % PhSeH. 100 mol % PhSeH.
the rate constant of diiodide 2 could be in the range of 5
× 107 to 5 × 109 s-1 M-1 19
.
Recently, Newcomb introduced the use of hydrogen
atom abstraction from PhSeH.20 The rate constant for
trapping of radicals at 25 °C was determined as 2.1 ×
109 M-1s-1. However, PhSeH is a very unpleasant
substance. It is noxious and must be handled with care.21
Fortunately, it can be introduced in the form of Ph-
SeSePh and generated by the addition of n-Bu3SnH as
reported by Crich (eq 3).22
Scheme 4 summarizes all the possible reaction path-
ways which can be envisioned during the radical cycliza-
tion at the steady state of diiodide 2. The first pair of
isomeric radicals 14a ,b is formed in a nonselective way.26
Both the radicals can either cyclize in the 5-exo fashion,
giving 15a ,b, or be reduced to monoiodides 16a ,b.
However, the cyclizations occur at different rates due to
the pseudoequatorial or pseudoaxial position of the
methyl group in 14a ,b. We propose that at suitable
trapping agent concentrations the slower cyclizing 14b
is mostly reduced to 16b while the faster cyclizing 14a
closes to 15a . Cyclic monoiodides 15a ,b are reduced via
radicals 17a ,b to the tetrahydrofurans 13a ,b. The process
repeats again in the second stage, where the roles of the
radicals 18a ,b are now reversed. Now radical 18a is
preferably reduced to the doubly reduced 19 while 18b
closes to 13a . The difference in the rates of reduction and
cyclization of the first (14a ,b) and the second (18a ,b)
pairs of radicals is crucial, as suggested by Curran for
the overall outcome of the radical process at the steady
state. Such a difference sets up a concentration gradient
that allows the slower cyclizing radicals 14b and 18a to
be mostly reduced while the faster cyclizing radicals 14a
and 18b cyclize to 13a . Taking into account that the
former pair leads to 13b and the latter to 13a , further
increase of the PhSeH concentration results in the
preferable formation of 13a . Therefore, the yield of 13a
can exceed the level of stereoselection in the lowest
stereoselective step, i.e., nonselective formation of the
first pair of radicals (14a ,b).
n-Bu3SnH + (PhSe)2 f n-Bu3SnSePh + PhSeH
n-Bu3Sn• + RI f n-Bu3SnI + R•
(3)
R• + PhSeH f RH + PhSe•
PhSe• + n-Bu3SnH f PhSeH + n-Bu3Sn•
Taking into account that PhSeH reacts with primary
alkyl radicals ∼20 times faster than PhSH23 and ∼1000
times faster than n-Bu3SnH and its recycling is immedi-
ate, PhSeH seems to be the fastest pseudo-first-order
radical trapping agent. The most striking advantage in
comparison with other trapping agents is that only a
small or even catalytic amount of PhSeH is necessary to
establish the conditions for pseudo-first-order kinetics.
Thus, we decided to take advantage of a polarity-matched
reaction in radical cyclizations of diiodide 2.
The appropriate amount of PhSeH was estimated by
performing three radical experiments with 50, 200, and
500 mol % PhSeH generated in situ from PhSeSePh and
n-Bu3SnH. A 500 mol % excess of PhSeH appeared to give
the highest 13a :13b ratio, and it was used for further
radical cyclizations of diiodide 2 at different PhSeH
concentrations (Table 1).
In each experiment a strictly degassed solution of
PhSeSePh in benzene was treated with an equimolar
(19) One might hope that the relatively slow delivery of hydrogen
to the first pair of radicals could be compensated by a huge excess of
Ph3SnH. But the analysis of small quantities of the products in the
presence of a large excess of the hydride could be very difficult and
give rather inconsistent results. Therefore, we then turned our
attention to the use of much faster trapping agents.
(20) Newcomb, M.; Varick, T. R.; Ha, Ch.; Manek, M. B.; Yue, X. J .
Am. Chem. Soc. 1992, 114, 8158-8163.
(24) 13a ,b after being resubjected to the reaction conditions ap-
peared to be stable and were recovered almost quantitatively (>96%).
(25) For comparison purposes 19 was prepared independently.
Commercially available diisopropyl ketone was reduced with lithium
aluminum hydride, and the resulting alcohol was reacted with an
excess of 1,1-dimethoxy-2,2-diphenylacetaldehyde acetal in the pres-
ence of p-toluenesulfonic acid.
(26) A reversible iodine transfer does not seem to play a role; see:
(a) Newcomb, M.; Sanchez, R. M.; Kaplan, J . J . Am. Chem. Soc. 1987,
109, 1195-1199. (b) Newcomb, M.; Curran, D. P. Acc. Chem. Res. 1988,
21, 206-214. (c) Drury, R. F.; Kaplan, L. J . Am. Chem. Soc. 1972, 94,
3982-3986.
(21) Paulmier, C. Selenium Reagents and Intermediates in Organic
Synthesis; Pergamon Press: Oxford, 1986; p 26.
(22) Crich, D.; J iao, X.-Y.; Yao, Q.; Harwood, J . S. J . Org. Chem.
1996, 61, 2368-2373.
(23) Franz, J . A.; Bushaw, B. A.; Alnajjar, M. S. J . Am. Chem. Soc.
1989, 111, 268-275.
J . Org. Chem, Vol. 69, No. 6, 2004 1847

Andrukiewicz et al.
SCHEME 4. Over a ll Kin etic F r a m ew or k for Ster eoselection a t th e Stea d y Sta te in th e Ra d ica l Cycliza tion s
of Diiod id e 2a
a
Bold arrows represent faster reactions. Dashed arrows represent slower reactions. Standard arrows represent nonselective reactions.
Con clu sion s
of stereoselection at the steady state will be reported in
due course.
The radical cyclizations of diiodide 2 provide another
efficacious example of manipulation of stereocontrol by
reaction topography. At a suitable PhSeH concentration,
high 13a :13b ratios can be achieved. The yields of the
major product are higher than the level of selectivity in
the group-selective step. The results clearly support
Curran’s kinetic model. The 2,5-cis selectivity of the
products arises from chairlike transition states with the
pseudoequatorial substituents. This approach might be
of further use wherever functionalized alkyl tetra-
hydrofurans are needed in organic chemistry. Further
efforts toward diastereo- and enantioselective variants
Ack n ow led gm en t. Financial support by the Insti-
tute of Organic Chemistry, Polish Academy of Sciences,
and the State Committee for Scientific Research (Grant
No. 4 T09A 063 25) is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Complete experi-
mental details and copies of the 1H and 13C spectra for all new
compounds (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
J O035310P
1848 J . Org. Chem., Vol. 69, No. 6, 2004