Stereoselective preparation and reactions of configurationally-defined mixed acyclic dialkylzincs

Article abstract of DOI:10.1039/a707570g

Mixed acyclic dialkylzincs are stereoselectively prepared from E- and Z-trisubstituted alkenes.

Full text of DOI:10.1039/a707570g

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Stereoselective preparation and reactions of configurationally-defined mixed
acyclic dialkylzincs
Christophe Darcel, Felix Flachsmann and Paul Knochel*
Fachbereich Chemie der Philipps-Universit a¨ t Marburg, Hans-Meerwein-Strasse, D-35032 Marburg, Germany
Mixed acyclic dialkylzincs are stereoselectively prepared
leading after treatment with allyl bromide to the desired
allylated products 12 with a syn:anti ratio of 24:76 starting
from the zinc intermediate 9 and 81:19 starting from the zinc
reagent 10. The lower stereoselectivity of the allylation of 9
compared to the deuterolysis may be due to a slow isomeriza-
tion of 9 during the allylation reaction.†
Whilst the presence of the o-methoxy group of 8 facilitates
the subsequent boron–zinc exchange, it is possible to extend the
reaction to (E)- and (Z)-styrenes 13 with similar selectivities.
This proves that the configurational stability of the organozinc
intermediates does not depend on the presence of a heteroatom
in close proximity. In this case, the deuterium signals after
quenching of the intermediate zinc reagent 14 were not
separated, so that the selectivity could not be determined.
However, after transmetalation with CuCN·2LiCl and allylation
the desired allylated product 15 was obtained stereoselectively.
The Z-olefin 13 gave allylation product 15 with a syn:anti ratio
of 19:81, whereas the E-olefin 13 gave a syn:anti ratio of
78:22 for 15 (Scheme 3).
from E- and Z-trisubstituted alkenes.
The preparation of configurationally defined reactive organo-
1
metallics is of great interest, since it offers the potential of
transferring the stereochemical information at the a-carbon of
the metal to a variety of organic compounds via reaction with
2
various electrophiles. Recently, we have shown that organo-
3
boranes 1 can be converted by an exchange reaction with
i
Zn to configurationally stable4 mixed diorganozincs 2.
Pr
2
2
These zinc reagents can be reacted with electrophiles like D O
or allylic halides, providing products of type 3 (Scheme 1).
i
Et2B
i
PrZn
H
E
2
1
Pr2Zn
2
1
E–X
2
1
R
R
R
R
R
R
H
H
1
2
3
E–X = D2O, allyl bromides
Scheme 1
The relative stereochemistry of the product 15 (syn:anti ratio
of 78:22) was determined by converting it to 3,4-dimethyl-
In all these experiments, trans-cycloalkylborane derivatives
were used and converted to trans-cycloalkylzinc compounds
. To demonstrate the stereoselectivity of the boron–zinc
4
5
1
-tetralone 18 by ozonolysis followed by oxidation of the
exchange, the use of cis-cycloalkylboranes 6 would have been
necessary. Since these molecules are not available by hydrobor-
Me
Me
ation with Et
2
BH, we examined the hydroboration of open-
Me
i, ii
chain trisubstituted E- and Z-olefins 7. Herein, we report the
stereoselective preparation of open-chain secondary dialkyl-
zincs and their stereoselective deuterolysis and allylation.
ZnPri
Me
OMe
O
(
Z)-7
Me
Me
iii
9 (74% conversion)
R
R
R
Me
iv, v
R
ZnPri
Me
Me
BEt2
BEt2
H
D
4
5
6
(E)- and (Z)-7
Me
OMe
Me
OMe
Thus, the hydroboration of E- and Z-styrene derivatives 8
with Et BH was complete after 14 h at 25 °C; the intermediate
diethylorganoboranes were treated with Pr
mixed diorganozincs 9 and 10, which were quenched with D
resulting in the formation of the deuterated product 11 (Scheme
). The presence of the o-methoxy group was found to
1
1 (60%)
12 (47%)
2
syn : anti <1 : 99
syn : anti 24 : 76
i
2
Zn, furnishing the
Me
Me
Me
Me
2
O
i, ii
2
ZnPri
O
accelerate significantly the rate of the boron–zinc exchange
reaction, allowing the completion of this exchange starting from
OMe
(
E)-8
(
Z)- or (E)-8 within 3 h at 0 °C. Under these conditions, the
deuterolysis of 9 provides mainly the anti-deuterated product 11
syn:anti < 1:99) whereas the deuterolysis of 10 furnishes the
Me
10 (51% conversion)
iv, v
iii
(
product 11 as a syn:anti mixture of 77:23. The syn:anti ratio
of the deuterated products was determined by 2H NMR
spectroscopy. These experiments demonstrate for the first time
the stereoselectivity of the boron–zinc exchange reaction for
open-chain systems. It is interesting to note that performing the
boron–zinc exchange at 25 °C instead of 0 °C leads to lower
stereoselectivities, i.e. a syn:anti ratio of 22:78 starting from
Me
Me
D
Me
OMe
Me
OMe
11(44%)
syn : anti 77 : 23
12 (40%)
syn : anti 81 : 19
(
Z)-8 and 73:27 starting from (E)-8.
The mixed dialkylzincs 9 and 10 could also be transmetalated
Scheme 2 Reagents and conditions: i, HBEt
2
(3 equiv.), 25 °C, 14.5 h; ii,
i
Pr Zn (2 equiv.), 0 °C, 3 h; iii, D O, THF, 278 °C; iv, CuCN·2LiCl; v, allyl
2
2
to copper–zinc compounds via reaction with CuCN·2LiCl,
bromide, 278 to 25 °C
Chem. Commun., 1998
205

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Me
Me
Me
The authors thank the Deutsche Forschungsgemeinschaft
(SFB 260 and Leibniz program) and the Fonds der Chemischen
Industrie for generous support of this research. We thank the A.
von Humboldt-Stiftung for a fellowship to C. D., and BASF
(Ludwigshafen), Witco (Bergkamen), Chemetall (Frankfurt)
and Sipsy (Avrill e´ ) for generous gifts of chemicals.
ZnPri
iii, iv
i, ii
Ph
Ph
Ph
Me
Me
anti-14
67% conversion)
Me
15 : 65%
syn : anti = 19 : 81
(
Z)-13
(
Me
Me
Me
Footnotes and References
ZnPri
iii, iv
i, v
Me
Ph
* E-mail: knochel@ps151S.chemie.uni-marburg.de
Ph
Ph
†
We have observed in separate experiments that secondary copper–zinc
Me
Me
(
E)-13
reagents are more prone to epimerization than the organozinc precursors.
Treatment of trans-1-methylindanyl)(isopropyl)zinc 19 (see ref. 2) with
D
syn-14
40% conversion)
15 (36%)
syn : anti = 78 : 22
(
2
O affords the corresponding trans-deuterated indane 20 with a cis:trans
Scheme 3 Reagents and conditions: i, BHEt
2
(3 equiv.), 25 °C, 13 h; ii,
Zn (2 equiv.), 25 °C, 3 h; iii, CuCN·2LiCl, 278 °C; iv, allyl bromide,
i
Me Me
Pr
2
78 to 25 °C; v, Pr Zn (2 equiv.), 25 °C, 4 h
2
i
2
ZnPri
ZnPri
resulting aldehyde 16 to the acid 17. Friedel–Crafts cyclization
of the corresponding acid chloride furnishes the cis- and trans-
ketones 18 (cis:trans = 22:78). Both the major trans isomer
and the minor cis isomer could be unequivocally identified by
NMR spectroscopy (Scheme 4).
1
9
20
ratio of 1:99. Treatment of this zinc reagent with stoichiometric amounts of
CuCN·2LiCl provides a copper–zinc reagent which was slowly warmed to
0 °C. After deuterolysis a cis:trans ratio of 11:89 was obtained. However,
keeping this copper–zinc reagent at 278 °C and treating it with another
Me
2
equivalent of ZnBr provides a cis:trans ratio of 1:99, showing that the
zinc–copper reagent has good configurational stability at 278 °C and that,
at this temperature, the zinc salts produced during the allylation reaction are
not responsible for the epimerization reaction.
Y
Me
X
‡
The relative configuration between the methyl group and the deuterium
1
1
1
5 X = H, Y = CH2, syn:anti = 78 : 22
atom in 20 was proven to be trans by comparison of NOE measurements for
dihydro-1-methylindane and 20.
i
6 X = H, Y = O, syn:anti = 77 : 23 (95%)
7 X = OH, Y = O, syn:anti = 78 : 22 (77%)
ii
1
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Me
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HA
HB
Me
HA
HB
Me
+
5
9%
78 : 22
J (HA,B) = 5.5 Hz
O
trans-18
cis-18
J (HA,B) = 3.8 Hz
Scheme 4 Reagents and conditions: i, O
3
, then Me
, Bu OH, 25 °C, 1 h; iii, SOCl
(1.25 equiv.), ClCH CH Cl, 25 °C, 4 h
2
S; ii, NaClO
2
,
t
Me
AlCl
2
CNCHMe, NaH
2
PO
4
2
, 60 °C, 1 h; iv,
3
2
2
3
In conclusion, we have shown that the boron–zinc exchange
performed with Pr Zn on open-chain secondary zinc reagents
2
i
2
449.
proceeds stereoselectively. Although the relative stereoche-
mistry of the zinc reagents could not be directly determined, we
assume that this exchange reaction proceeds with retention of
configuration as well as the allylation (and deuterolysis),‡ since
an overall retention of configuration is observed. Current work
in order to improve the level of stereoselectivity and to extend
the number of electrophiles that can quench stereoselectively
the intermediate organozinc reagents is underway.
4
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Lett., 1996, 37, 1045.
Received in Liverpool, UK, 20th October 1997; 7/07570G
206
Chem. Commun., 1998