bornylmagnesium chloride (1a) and isobornylmagnesium chloride
(1b) with an endo-to-exo ratio of 67 : 33 (Scheme 2).
reactions at these rather hard electrophiles. Preliminary experi-
ments revealed that the substitution reactions of the bornyl and
fenchyl Grignard reagents with Ph2PCl are independent of the di-
astereomeric composition of the Grignard reagents (e.g. the endo-
to-exo ratio) and presumably proceed with an SET transfer prior to
combination of the radical pair formed (‘electron motion precedes
nuclear motion’).2 The Deutsche Forschungsgemeinschaft (DFG)
is gratefully acknowledged for financial support.
The fenchyl Grignard reagent prepared under identical con-
ditions comprises a configurationally stable mixture of a-
fenchylmagnesium chloride (2a) and b-fenchylmagnesium chlo-
ride (2b) with an endo-to-exo ratio of 20 : 80, regardless of
whether a- or b-fenchyl chloride was used as starting material
(Scheme 3). The fact that the formation of both Grignard reagents
is independent of the initial configuration of the a-carbon atom
is consistent with the SET mechanism.1 This implies that the
stereogenic information of the a-carbon atom is lost at the stage
of the intermediately formed bornyl and fenchyl radicals, however,
their rigid bicyclic structures seem to bias the diastereomeric ratios
of the Grignard reagents formed. It is worth emphasizing that in
the case of the fenchyl Grignard reagent, the thermodynamically
less favoured exo-diastereomer is formed in large excess, which
points to a kinetically controlled reaction pathway.
Notes and references
1 Handbook of Grignard Reagents, ed. G. S. Silverman and P. E. Rakita,
Marcel Dekker, New York, 1996.
2 R. W. Hoffmann, Chem. Soc. Rev., 2003, 32, 225 and references cited
therein.
3 J. Beckmann, D. Dakternieks, M. Dra¨ger and A. Duthie, Angew. Chem.,
Int. Ed., 2006, 45, 6509.
4 A. Hill, J. Org. Chem, 1966, 31, 20 and references cited
therein.
5 Synthesis of the bornyl and fenchyl Grignard reagent. A solution of
isobornyl chloride or b-fenchyl chloride (17.2 g, 100 mmol) in THF
(180 mL) was slowly added to a suspension of activated Mg turnings
(2.7 g, 110 mmol) in THF (20 mL). After the addition was completed, the
mixture was heated under reflux for 12 h. Prior to use, the clear solution
was separated from the excess of Mg via cannula. The yield determined
by titration was about 80%. Synthesis of the epimerized bornyl and fenchyl
Grignard reagent. A solution of the bornyl or fenchyl Grignard reagent
was slowly distilled while toluene (220 mL) was constantly added to
replace the original solvent THF. The temperature was slowly raised to
111 ◦C and kept there for 12 h. The yield determined by titration was
between 65 and 75%.
Interestingly, the initial endo-to-exo ratio of both Grignard
reagents can be changed dramatically by thermal epimerization
◦
at temperatures above 100 C (Schemes 2 and 3). Therefore, the
original solvent (THF) was replaced with toluene by distillation
at normal pressure.5 Thermal equilibrium was reached when the
Grignard reagents were heated under reflux in toluene for 12 h.
Upon cooling to room temperature, the epimerized Grignard
reagents are configurationally stable again and then contain the
thermodynamically favoured endo-diastereomers in large excess.
In this manner, the diastereomeric purity of the bornyl Grignard
reagent can be significantly improved from an endo-to-exo ratio
of 67 : 33 to 96 : 4. Similarly, the composition of the fenchyl
Grignard reagent can be entirely inverted from an endo-to-exo
ratio of 20 : 80 to 80 : 20. While the yield of bornyl and fenchyl
Grignard reagents as determined by titration8 is about 80%, the
yield of the epimerized Grignard reagents is only slightly decreased
and still ranges between 65–75%. Attempts were made to change
the diastereomeric composition of the Grignard reagents to even
more favourable endo-to-exo ratios using higher boiling xylene
isomers for the thermal epimerization. However, in this case rapid
metalation of the solvent occurred and the yield of the bornyl and
fenchyl Grignard reagents diminished below 10%.9
To the best of our knowledge, the epimerized bornyl Grignard
reagent is the first chiral Grignard reagent of high diastereomeric
purity (92% d.e.) that can be prepared easily from readily
available starting materials. The fenchyl Grignard reagent can
be prepared easily with moderate diastereomeric purity (60%
d.e.) but with either of the two diastereomers being in excess.
Chiral Grignard reagents hold great potential in mechanistic
studies of substitution reactions,2 which, however, has not yet been
exploited in organometallic chemistry. We are currently investi-
gating the reaction of the bornyl and fenchyl Grignard reagents
with chlorosilanes and chlorophosphanes, respectively, to examine
the possibility if SET processes are involved in substitution
6 Results of the 119Sn NMR analysis. In case of the bornyl Grignard
reagent regardless whether it was prepared from bornyl chloride or
isobornyl chloride, the 119Sn NMR spectrum revealed signals at d
-49.0 (integral 16%), -85.5 (integral 3%), -101.4 (integral 54%) and
-108.1 (integral 27%), which were assigned to unreacted triphenyltin
chloride, triphenyltin hydroxide (formed by hydrolysis during the work
up), bornyltriphenyltin (3a) and isobornyltriphenyltin (3b), respectively.
In the case of the epimerized bornyl Grignard reagent, the 119Sn NMR
spectrum revealed signals at d -49.0 (integral 24%), -85.5 (integral
9%), -101.4 (integral 64.5%) and -108.1 (integral 2.5%), which were
assigned to unreacted triphenyltin chloride, triphenyltin hydroxide,
bornyltriphenyltin (3a,) and isobornyltriphenyltin (3b), respectively. In
the case of the fenchyl Grignard reagent regardless whether it was
prepared from a- or b-fenchyl chloride, the 119Sn NMR spectrum
revealed signals at d -49.0 (integral 15%), -85.5 (integral 6%), -123.5
(integral 16%) and -126.4 (integral 63%), which were assigned to unre-
acted triphenyltin chloride, triphenyltin hydroxide, a-fenchyltriphenyltin
(4a) and b-fenchyltriphenyltin (4b), respectively. In the case of the
epimerized fenchyl Grignard reagent, the 119Sn NMR spectrum revealed
signals at d -49.0 (integral 13%), -85.5 (integral 5%), -123.5 (integral
57.5%) and -126.4 (integral 14.5%), which were assigned to unreacted
triphenyltin chloride, triphenyltin hydroxide, a-fenchyltriphenyltin (4a)
and b-fenchyltriphenyltin (4b), respectively.
7 D. Doddrell, I. Burfitt, W. Kitching, M. Bullpitt, C.-H. Lee, R. J. Mynott,
J. L. Considine, H. G. Kuivila and R. H. Sarma, J. Am. Chem. Soc., 1974,
96, 1640.
8 A. Krasovskiy and P. Knochel, Synthesis, 2006, 890.
9 The two main signals in the 119Sn NMR spectrum were detected at d
118.9 and 122.3, which compare well with the chemical shift reported
for PhCH2SnPh3 (d 117.1). D. Marton, U. Russo, D. Stivanello and G.
Tagliavini, Organometallics, 1996, 15, 1645.
42 | Org. Biomol. Chem., 2009, 7, 41–42
This journal is
The Royal Society of Chemistry 2009
©
Beckmann, Jens
