Diastereoselective radical mediated alkylation of a chiral glycolic acid derivative

Article abstract of DOI:10.1039/c1ob05230f

Radical alkylation of 2-(tert-butyl)-2-methyldioxolan-4-one, a chiral equivalent of glycolic acid, occurs with good to high diastereoselectivity that compares favorably with the corresponding enolate alkylation. The importance of the position of the trans

Full text of DOI:10.1039/c1ob05230f

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PAPER
Diastereoselective radical mediated alkylation of a chiral glycolic acid
derivative†‡
Sokol Abazi,a,b Liliana Parra Rapadoa and Philippe Renaud*a
Received 14th February 2011, Accepted 24th May 2011
DOI: 10.1039/c1ob05230f
Radical alkylation of 2-(tert-butyl)-2-methyldioxolan-4-one, a chiral equivalent of glycolic acid, occurs
with good to high diastereoselectivity that compares favorably with the corresponding enolate
alkylation. The importance of the position of the transition state position, early or late, is highlighted.
In order to compare radical and enolate mediated reactions,
it was necessary to find a system that allows to perform both
reaction types. As demonstrated by Beckwith,10 the 2-(tert-butyl)-
1,3-dioxolan-4-one system is suitable for radical processes but pre-
liminary studies with 2-(tert-butyl)-1,3-dioxolan-4-one revealed
Introduction
The stereochemical control of radical reactions has been a field of
intense investigation in the past 20 years. Rules have been proposed
to rationalize the results. Interestingly, these rules parallel the
ones formerly developed for ionic and concerted reactions.1 The
that the corresponding enolate is difficult to alkylate due to
enolate mediated alkylation of chiral equivalents of glycolic acid
competing decomposition. We have shown that the closely related
opens a direct access to optically active a-hydroxy acids and
has attracted the interest of many synthetic chemists over the
years.2,3 The use of chiral 1,3-dioxolanone for the alkylation
of a-hydroxyacids, has been pioneered by Seebach and Frater4
and extended to glycolic acid derivatives.5,6 In this last case,
however, the diastereoselectivities were not as high as expected7,8
except when N,N-diisopropyl-10-camphorsulfonamide was used
as a chiral auxiliary for the ketal formation.9 The corresponding
radical process is less documented but interestingly, Beckwith has
reported a highly stereoselective radical bromination of racemic
2-(tert-butyl)-1,3-dioxolan-4-one.10 Surprisingly, closely related
radical reactions with tin deuteride and allylstannane gave low
stereoselectivities.10,11 We report here a study of the stereochemical
outcome of reactions involving 4-oxo-1,3-dioxolan-5-yl radical A
derived from a chiral derivative of glycolic acid. The results are
compared with the one obtained for the corresponding enolate
B and a model is proposed to explain the important variation of
stereoselectivities.
2-(tert-butyl)-2-methyl-1,3-dioxolan-4-one 1 leads to enolates that
are sufficiently stable for efficient alkylation.6,7a Therefore, we
decided to focus our attention on this substrate.
Results and Discussion
Radical reactions
Dioxolanone 1 was prepared by condensation of trimethylsilyl
trimethylsilyloxyacetate with pinacolone in 92% yield by analogy
to Pearson’s procedure.7a,12 The radical precursor 2 was prepared
in 91% yield by selanylation of 1 with LDA/PhSeCl.7a The
selenoacetal 2 is stable and can be stored at 4 ◦C for several weeks.
A first series of experiments was conducted with tin reagents
at different temperatures (eqn (1)) and results are summarized in
Table 1.13 Deuteration experiments using tributyltindeuteride gave
the mono deuterated compound 3 in good yields and moderate
stereoselectivity (Table 1, entries 1–2). Increasing the temperature
from 0 ◦C to 40 ◦C led, as anticipated, to a slight decrease of the
stereoselectivity. Allylation using allyltributyltin was attempted
next. The reaction at 40 ◦C (Table 1, entry 3) gave the desired
product 4 with low diastereoselectivity and low yield due to
dimerization of the intermediate captodative radical A. A higher
yield of 4 was obtained at 80 ◦C together with an unexpected
increase of diastereoselectivity (Table 1, entry 4). The temperature
effect was further confirmed by running the reaction in toluene
(or 1,2-dichlorobenzene) at temperatures ranging from -80 to
180 ◦C (Table 1, entries 5–11). Diastereoselectivties between 1 : 1
aUniversita¨t Bern, Departement fu¨r Chemie und Biochemie, Freiestrasse
3, CH-3012, Bern, Switzerland. E-mail: philippe.renaud@ioc.unibe.ch;
Fax: +41 (0)31 631 34 26
bUniversiteti i Tirane¨s, Departmenti Kimise¨, Blv. Zogu i Pare¨, Tirana,
Albania
† This paper is dedicated to the memory of Professor Athel L. J. Beckwith,
a genuine pioneer in organic free radical chemistry. His immense contri-
bution to the development of radical reactions and the understanding of
their stereochemical outcome is a constant source of inspiration.
‡ Electronic supplementary information (ESI) available. See DOI:
10.1039/c1ob05230f
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Table 1 Radical reactions of 2 with Bu3SnY according to eqn (2)a
Table 2 Phenylselanyl group transfer reactions of 2 with different alkenes
according to eqn (3)
Entry
Y
T
Product Yield trans/cis
Entry CHR1 CHR2
Product Yield
trans/cis
1
2
3
4
5
6
7
8
D
D
0 ◦
C
3
3
4
4
4
4
4
4
4
4
4
5
5
6
6
87%
87%
30%
78%
5%
50%
55%
70%
65%
80%
30%
27%
85%
43%
87%
6 : 1
40 ◦
40 ◦
80 ◦
C
C
C
4.5 : 1
1.8 : 1
3.5 : 1
1 : 1
1.4 : 1
1.6 : 1
2.5 : 1
3.3 : 1
4.5 : 1
7 : 1
6.8 : 1
9.2 : 1
16 : 1
11.5 : 1
1
2
3
4
CH2 CHC6H13
CH2 CHC6H13
CH2 CHC6H13
CH2 CHCO2Me
CH2 CHSO2C6H5
7
7
7
8
9
65%a
70%a,b
25%a,c
67%
83%
79%
10 : 1
7.5 : 1
12 : 1
15 : 1
16 : 1
23 : 1d
22 : 1e
10 : 1
10 : 1
10 : 1
8.8 : 1
CH2 CHCH2
CH2 CHCH2
CH2 CHCH2
CH2 CHCH2
CH2 CHCH2
CH2 CHCH2
CH2 CHCH2
CH2 CHCH2
CH2 CHCH2
CH2 C(SiMe3)CH2
CH2 C(SiMe3)CH2
-80 ◦Cb
-10 ◦Cb
30 ◦Cb
5
6
7
8
(E)-MeO2CCH CHCO2Me 10
50 ◦Cb
N-Phenylmaleimide
11
12
13
14
15
79%
37%
40%
40%
9
80 ◦Cb
CH2 CHC6H5
10
11
12
13
14
15
110 ◦Cb
180 ◦Cc
9
10
11
CH2 CH(p-CF3–C6H4)
CH2 CH(p-AcO–C6H4)
CH2 CH(p-MeO–C6H4)
40 ◦
80 ◦
C
C
C
C
50%
a Reaction performed in toluene. b Reaction performed at 110 ◦C.
c Reaction performed at 25 ◦C. d Mixture of isomers (1.5 : 1) relative to
the second stereogenic center. e Mixture of isomers (1.9 : 1) relative to the
second stereogenic center.
CH2 C(CO2Me)CH2 40 ◦
CH2 C(CO2Me)CH2 80 ◦
a A solution of 2 (1.0 mmol) and Bu3SnY (4.0 mmol) in benzene (4 mL) was
irradiated with a 300 W sun lamp at the indicated temperature. b Reaction
performed in toluene. c Reaction performed in 1,2-dichlorobenzene.
(-80 ◦C) and 7 : 1 (180 ◦C) were recorded. The allylation with
tributyl-(2-trimethylsilylallyl)tin gave 5 with higher diastereose-
lectivities and a similar temperature dependence (Table 1, entries
12 and 13). Finally, reaction with 2-(methoxycarbonyl)allyltri-
butyltin at 40 ◦C afforded 6 (Table 1, entries 14) with a much higher
trans selectivity compared to the less activated allylstannanes
(Table 1, entries 3 and 12). In this case, however, increasing the
temperature led to a decrease of diastereoselectivity (Table 1, entry
15). The trans relative configuration of the major isomer of 6 was
established by difference n.O.e measurements (see ESI‡).
(2)
Finally, the radical bromination of 1 with N-bromosuccinimide
(NBS) in refluxing CCl4 was investigated (eqn (3)). In analogy to
Beckwith’s work,10 a high stereoselectivity (trans/cis 21 : 1) and a
good yield were obtained.
(1)
(3)
Due to the high stability of the intermediate radical, it is
possible to run addition of 2 to alkenes under phenylseleno
group transfer conditions (eqn (2)).14,15 A series of alkenes were
investigated and results are summarized in Table 2. A good trans
selectivity (trans/cis 10 : 1) was observed with 1-octene (Table 2,
entry 1). In contrast to the allylation reactions, the stereoselectivity
increases slightly when decreasing the temperature (compare
entries 1–3 in Table 2). Methyl acrylate and phenyl vinyl sulfone
gave higher stereoselectivities (Table 2, entries 4 and 5). The
highest trans selectivity was obtained with alkenes activated by
two electron withdrawing groups such as dimethyl fumarate
(trans/cis 23 : 1) and N-phenylmaleimide (trans/cis 22 : 1) (Table
2, entries 6 and 7). As anticipated for these two last examples,
low diastereoselectivities (1.5 : 1 and 1.9 : 1) were observed relative
to the formation of the side chain stereogenic center. In order to
test the influence of electronic factors, we examined the addition to
different para-substituted styrenes (Table 2, entries 8–11). Electron
withdrawing groups such as CF3 and OAc have no effect on the
stereoselectivity relative to unsubstituted styrene (trans/cis 10 : 1).
The methoxy group induces only a slight decrease of selectivity
(trans/cis 8.8 : 1).
Enolate reactions
The alkylation of 1 via its enolate was investigated next (eqn (4)).
Results are presented in Table 3. A standard procedure (LDA in
THF) was used for the deprotonation, the electrophile was added
at -78 ◦C and allowed to warm up to room temperature overnight
(except for entry 5 where the reaction mixture was neutralized at
◦
-78 C). Even in cases where the reaction was allowed to warm
up to room temperature, it is◦believed that the reaction takes place
at a temperature below -30 C since rapid decomposition of the
enolate is observed at higher temperature.
(4)
Reactions with alkyl halides (Table 3, entries 1–4), acetone
(Table 3, entry 5) and with 2-methoxycarbonylpropenyl phenyl
sulfone (Table 3, entry 6) gave stereoselectivities between 1.7 : 1
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Table 3 Enolate alkylation of 1 according to eqn (4)
Entry Electrophile E+
major trans product is produced by the reaction of the radical
from the less hindered face anti to the tert-butyl group. Factors
which favor early (= reactant-like) transition states as well as
steric effects are expected to favour the formation of the trans
compounds. According to the Hammond postulate,19 an increase
of the exothermicity of the reaction by introducing a radical
stabilizing substituent on the olefin should lead to a more early
transition state and therefore to higher selectivity. This is the
case for the reaction of 2 with the ester substituted allylstannane
(Table 1, entries 14–15), which is more selective than the simple
allyltributylstannane (Table 1, entries 3–4). The same trend is also
present in the results collected in Table 2 (compare entries 1, 4,
and 6 for instance). The high stereoselectivity of the bromination
reaction (eqn (3)) can also be rationalized by this model since this
process is expected to proceed via early transition state due to its
high exothermicity.20 Stereoelectronic effects may also influence
the stereoselectivity as suggested by the lower selectivity observed
for the addition to p-methoxy styrene (Table 2, entry 11) relative
to less electron rich systems (Table 2, entries 8–10) and by the high
selectivities observed with highly electrophilic radical traps such as
NBS (eqn (3)), dimethyl fumarate and N-phenylmaleimide (Table
2, entries 6 and 7).
The stability of the intermediate captodative radical A con-
tributes to this unexpected effect since it leads to less exothermic
radical processes (less early transition states) than usual. There-
fore, small changes of the relative stability of the products influence
effectively the energy of the transition states. The highly stere-
oselective C–C bond formations involving 5-substituted 2-tert-
butyl-4-oxo-1,3-oxazolidin-5-yl radicals reported by Beckwith10
and Mattay11d can also be explained by this model. In their study,
the products are disubstituted at C(5) and therefore the cis and the
trans isomers possess similar energies and have no influence on the
relative energies of the transition states.
Product Yield trans/cis
1
2
3
4
5
6
MeI
17
4
18
7
19
6
87%
81%
70%
20%
85%
80%
1.7 : 1a
3.0 : 1b
3.6 : 1
3.0 : 1
3.0 : 1c
5.0 : 1
CH2 CHCH2Br
C6H5CH2Br
CH3(CH2)7I
(CH3)2C
CH2 CH(CO2Me)CH2SO2C6H5
O
a Taken from reference 6 b Taken from reference 7b. c Reaction entirely
performed at -78 ◦C.
to 5 : 1. Efforts to increase the stereoselectivity by changing
the base (NaHMDS, KHMDS) or adding cosolvents (HMPA,
DMPU) were not successful. Exposing a sample of pure trans-
18 to the work-up conditions left it unchanged demonstrating
that no epimerization of the acetal center occurred during the
work-up procedure. The low diastereoselectivities are surprising
relative to the excellent stereocontrol observed by Seebach and
Frater during the alkylation of the dioxolane derived from lactic
acid and pivalaldehyde.4 The low diastereocontrol could not be
attributed to the presence of the methyl substituent at position
2. Indeed, in a control experiment, we observed that the second
alkylation proceeds with excellent stereoselectivities. For instance,
the benzylation of 17 furnished 20 as a trans/cis 16 : 1 mixture of
isomers (eqn (5)).
(5)
It can be concluded that the reactivity-selectivity principle21 does
not apply for the dioxolanyl radicals A at the temperature used
to run our radical reactions (below 100 ◦C). Such behaviour is
well documented in the literature and is related to the isoselective
relationship.22,23 The increase of selectivity when increasing the
temperature observed for the allylation of 2 with allyltributyltin
and (2-trimethylsilylallyl)tributyltin (Table 1, entries 5–13) is
unexpected but not exceptional.23 The more product-like character
of the transition state of this reaction reinforces the influence
of entropy factors that favor the formation of trans-4 at higher
temperature. Similar effects have been reported by Metzger et al.
for hydrogen atom transfer involving late transition states.24
The low stereoselectivity of enolate reactions can be rationalized
by similar arguments. The hypothesis that the transition states
of enolate reactions are not very early is reasonable. Therefore
product stability influences the stereochemical outcome of the
reactions and favors the formation of the more stable cis products.
This explains also why the second alkylation is more stereoselective
(eqn (5)). Indeed, the thermodynamic stability of the cis and trans
isomers of 5,5-disubstituted dioxolanones are similar and their
influence on the stereochemical outcome vanishes.
Discussion
Greiner has shown that cis-2,5-disubstituted dioxolan-4-ones are
more stable than the corresponding trans isomers due to their
existence in a half-chair or envelope conformations.16 The two
substituents of the cis isomer occupy pseudo-equatorial positions
(Fig. 1). For example the 5-methylated dioxolanone 17 exists under
equilibrium in refluxing cyclohexane as a cis/trans 95 : 5 mixture
of diastereoisomers. This corresponds to a 8.8 kJ mol-1 difference
in free energy.
Fig. 1 Relative stability of cis- and trans-17.
The preferential formation of trans compounds in radical reac-
tions (contrathermodynamic stereoselectivity) is best explained
by the occurrence of early transition states for reactions with
olefins and other radical traps.17 This point was already pointed
out by Beckwith and Zavitsas using AM1 calculations for the
hydrogen atom transfer process with tributyltin hydride.18 The
Conclusions
In conclusion, we have presented here radical processes
where increasing the exothermicity results in a stereoselectivity
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enhancement. Such effects are limited to particular cases but they
are probably more frequent than expected as demonstrated by
the work of Beckwith,21 Giese22 and Metzger.22b,24 Moreover, in
the perspective of using a chiral dioxolanone derived from glycolic
acid for asymmetric synthesis of a-monoalkylated a-hydroxyacids,
the radical mediated alkylation compares favourably to the enolate
alkylation. This point is best illustrated by the preparation of the
n-octylated derivative 7 that provides a trans/cis 10 : 1 ratio (65%
yield) via radical pathway versus a 3 : 1 ratio (20%) via enolate
alkylation.
Acknowledgements
We thank the Swiss National Science Foundation (grant 20-
135087) for financial support.
Notes and references
1 (a) B. Giese, Angew. Chem., Int. Ed. Engl., 1989, 28, 969; (b) N. A.
Porter, B. Giese and D. P. Curran, Acc. Chem. Res., 1991, 24, 296;
(c) W. Smadja, Synlett, 1994, 1; (d) D. P. Curran, N. A. Porter and
B. Giese, Stereochemistry of Radical Reactions, VCH, Weinheim,
1996.
2 For a review on chiral glycolate equivalents, see: S. V. Ley, T. D.
Sheppard, R. M. Myers and M. S. Chorghade, Bull. Chem. Soc. Jpn.,
2007, 80, 1451.
Experimental
General procedure 1. Radical reaction of 2 with Bu3SnY
3 For selected references on chiral glycolic acid equivalents, see: A. I.
Meyers, G. Knaus and P. M. Kendall, Tetrahedron Lett., 1974, 15, 3495;
D. Seebach and R. Naef, Helv. Chim. Acta, 1981, 64, 2704; J. D’Angelo,
O. Pages, J. Maddaluno, F. Dumas and G. Revial, Tetrahedron Lett.,
1983, 24, 5869; G. Helmchen and R. Wierzchowski, Angew. Chem., Int.
Ed. Engl., 1984, 23, 60; S. V. Ley, E. Diez, D. J. Dixon, R. T. Guy,
P. Michel, G. L. Nattrass and T. D. Sheppard, Org. Biomol. Chem.,
2004, 2, 3608; S. V. Ley, D. J. Dixon, R. T. Guy, M. A. Palomero, A.
Polara, F. Rodriguez and T. D. Sheppard, Org. Biomol. Chem., 2004, 2,
3618.
A soln. of 2 (1.0 mmol) and Bu3SnY (4.0 mmol) in benzene (4 ml)
was irradiated with a 300 W sun lamp. The reaction was monitored
by TLC. After solvent evaporation, the crude product was purified
by flash column chromatography (FC).
General procedure 2. Radical addition of 2 to olefins
4 Enolate reactions of 5-substituted 1,3-dioxolan-4-one are reported D.
Seebach and R. Naef, Helv. Chim. Acta, 1981, 64, 2704; D. Seebach,
R. Naef and G. Calderari, Tetrahedron, 1984, 40, 1313–1324; G. Frater,
U. Mu¨ller and W. Gu¨nther, Tetrahedron Lett., 1981, 22, 4221; For
a review, see:D. Seebach and E. Hungerbu¨hler, in Modern Synthetic
Methods, R. Scheffold, Ed.; Springer-Verlag: Berlin, 1986, Vol. 2, p. 91;
G. M. Coppola and H. F. Schuster, a-Hydroxy Acids in Enantioselective
Synthesis, VCH: Weinheim, 1997.
A soln. of 2 (1.5 mmol) and the olefin (1.0 mmol) in benzene
(4.5 ml) was irradiated with a 300 W sun lamp at 80 ◦C. The
reaction was monitored by TLC. After solvent evaporation, the
crude product was purified by FC.
General procedure 3. Radical addition of 2 to 4-substituted styrenes
5 M. Gander-Coquoz, Dissertation ETH No. 8381, Zu¨rich,
1987.
A soln. of 2 (1.5 mmol) and 4-substituted styrene (1.0 mmol)
in benzene (4 ml) was irradiated with a 300 W sun lamp under
reflux. The reaction was monitored by TLC. After complete
disapearance of the styrene derivative, the reaction was cooled
down to rt. Bu3SnH (3 mmol) and AIBN (10 mg) were added
and the irradiation was continued for 2 h at rt. After solvent
evaporation, the crude product was purified by FC.
6 P. Renaud and S. Abazi, Helv. Chim. Acta, 1996, 79, 1696.
7 (a) S. Abazi, L. Parra Rapado, K. Schenk and P. Renaud, Eur. J.
Org. Chem., 1999, 477; (b) L. Parra Rapado, V. Bulugahapitiya and
P. Renaud, Helv. Chim. Acta, 2000, 83, 1625.
8 W. H. Pearson and M.-C. Chen, J. Org. Chem., 1986, 51, 3746.
9 J. W. Chang, D. P. Jang, B. J. Uang, F. L. Liao and S. L. Wang, Org.
Lett., 1999, 1, 2061.
10 A. L. J. Beckwith and C. L. L. Chai, Tetrahedron, 1993, 49,
7871.
11 For radical reactions of 5-substituted 4-oxo-1,3-dioxolan-5-yl radicals,
see: (a) A. L. J. Beckwith and C. L. L. Chai, J. Chem. Soc., Chem.
Commun., 1990, 1087; (b) J. Mattay, J. Mertes and G. Maas, Chem.
Ber., 1989, 122, 327; (c) G. Kneer and J. G. Mattay, Tetrahedron Lett.,
1992, 33, 8051; (d) G. Kneer, J. Mattay, A. Heidbreder, G. Raabe, B.
Krebs and M. Laege, J. Prakt. Chem., 1995, 2, 113.
General procedure 4. Enolate alkylation of 1
Diisopropylamine (10 mmol) and 1.6 M BuLi (10 mmol) were
added at -78 ◦C to THF (20 ml) containing HMPA (2 ml). After
5 min, a soln. of 1 (10 mmol) in THF (5 ml) was added dropwise.
After 15 min at -78 ◦C, the electrophile (30 mmol) in THF (10 ml)
was added. The reaction mixture was allowed to warm up to rt
over 2 h. Sat. aq. NaHCO3 (10 ml) and Et2O (200 ml) were added
and the organic layer was separated, washed with sat. NaHCO3
(5 ¥ 20 ml), dried (Na2SO4). After solvent evaporation, the crude
product was purified by FC.
12 W. H. Pearson and M. C. Cheng, J. Org. Chem., 1987, 52,
1353.
13 For clarity reasons, the cis/trans nomenclature is used. This cis isomer
is the one where the largest residue at the C(5) is on the same side of
the ring plane as the C(2) tert-butyl group.
14 For radical-mediated phenylseleno group transfer reactions involving
1-alkoxy acid derivatives, see: P. Renaud and S. Abazi, Synthesis, 1996,
253.
15 For reviews on radical-mediated phenylseleno group transfer reactions,
see:P. Renaud, in Organoselenium Chemistry: Modern Developments in
Organic Synthesis, ed. T. Wirth, Springer, Heidelberg, 2000, vol. 208,
p. 81J. Byers, in Radicals in Organic Synthesis, ed. P. Renaud and M. P.
Sibi, Wiley-VCH, Weinheim, 2001, Vol. 1, p 72.
Product description
16 A. Greiner and J. Y. Ortholand, Bull. Soc. Chim. Fr., 1993, 130,
5-Allyl-2-(tert-butyl)-2-methyl-1,3-dioxolan-4-one 4
133.
17 B. Giese and G. Kretzschmar, Chem. Ber., 1984, 117, 3175.
18 A. L. J. Beckwith and A. A. Zavitsas, J. Am. Chem. Soc., 1995, 117,
607.
Radical procedure. According to General procedure 1, from 2 (313
mg, 1.0 mmol) and allyltributylstannane (1.32 g, 4.0 mmol). After
evaporation, FC (Et2O/hexane, 1 : 20) gave 4 (155 mg, 78%) as
a 3.5 : 1 trans/cis mixture of diastereoisomers. Spectroscopic data
are in accordance with literature.7b
19 G. S. Hammond, J. Am. Chem. Soc., 1955, 77, 334; D. Farcasiu, J.
Chem. Educ., 1975, 52, 76.
20 The occurrence of later transition for radical allylation relative to
deuteration has already been proposed by Beckwith to rationalize the
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stereochemical outcome of reactions involving substitued cyclohexyl
and tetrahydropyranyl radicals: A. L. J. Beckwith and P. J. Duggan,
Tetrahedron, 1998, 54, 6919.
22 (a) B. Giese and K. Jay, Angew. Chem., 1977, 89, 482; (b) B. Giese,
H. Farshchi, J. Hartmanns and J. O. Metzger, Angew. Chem., Int. Ed.
Engl., 1991, 30, 600.
23 For a discussion of such effects, see: (a) B. Giese, Acc. Chem. Res., 1984,
17, 438; (b) H. Buchmann, H.-D. Scharf, N. Hoffmann and P. Esser,
Angew. Chem., Int. Ed. Engl., 1991, 30, 477.
21 The reactivity-selectivity principle has been shown to be an important
factor in controlling the stereoselectivty of radical reactions. See
ref. 1a and: P. Renaud, in Radicals in Organic Synthesis, ed. P.
Renaud and M. P. Sibi, Wiley-VCH, Weinheim, 2001, Vol. 1, p.
400.
24 J. O. Metzger, K. Schwartzkopf, W. Saak and S. Pohl, Chem. Ber., 1994,
127, 1069.
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