New preparation of stereodefined α,α-unsaturated ketones by carbomagnesiation of α-allenyl ketones

Article abstract of DOI:10.1016/S0040-4039(02)01211-X

The addition of several alkylmagnesium halides to an α-allenyl ketone leads to the corresponding α,β-unsaturated ketones as single geometrical isomers. A π-chelation between the metal and the unsaturation is proposed to explain the steric outcome of this reaction.

Full text of DOI:10.1016/S0040-4039(02)01211-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6009–6010
New preparation of stereodefined a,a-unsaturated ketones by
carbomagnesiation of a-allenyl ketones
Nicka Chinkov, Natalia Morlender-Vais and Ilan Marek*
Department of Chemistry and Institute of Catalysis Science and Technology, Technion-Israel Institute of Technology,
Technion City, Haifa 32 000 Israel
Received 7 May 2002; revised 11 June 2002; accepted 24 June 2002
Abstract—The addition of several alkylmagnesium halides to an a-allenyl ketone leads to the corresponding a,b-unsaturated
ketones as single geometrical isomers. A p-chelation between the metal and the unsaturation is proposed to explain the steric
outcome of this reaction. © 2002 Published by Elsevier Science Ltd.
In the course of our study on the preparation of
polysubstituted olefins as single isomers via a car-
bometalation reaction, we became interested in the
tions), which were rationalized by the presence of two
possible copper complexed intermediates in equilibrium
(C-metallated and O-metallated). In a similar manner,
1
3
reaction of a-allenyl ketones with organomagnesium
derivatives. The addition of alkyl magnesium bromide
to a-allenyl ketones 1 was originally reported by
the addition of lithium dimethyl cuprate to an uniso-
lated steroidal a-allenyl ketone gave the unconjugated
4
ene-ketone. In this Letter, we would like to report that
2
Bertrand et al. at the beginning of the 1960s and was
a-allenyl ketone 1a reacts smoothly under mild condi-
described to proceed the 1,4-addition of the
organometallic to the activated carbonꢀcarbon double
bond (namely at the central carbon of the allenyl
system). After hydrolysis, the b,g- and a,b-unsaturated
isomers 2 and 3, respectively, were formed in variable
ratios as shown in Scheme 1.
tions with organomagnesium compounds in Et O to
2
give, after hydrolysis, only the a,b-unsaturated ketone
derivative 3 as single stereoisomer, in contrast to the
previous reports. Allenyl ketone 1a (R=Bu) was easily
5
prepared by a Dess–Martin oxidation (DMP) of
homopropargylic alcohol 4a followed by purification of
the crude reaction mixture by column chromatography
on silica gel. Under these conditions, terminal propar-
gyl ketones are isomerized into the corresponding a-
The presence of the a,b-unsaturated ketone 3 was ratio-
nalized by the isomerization of the double bond of the
non-conjugated isomer 2 into the most stable isomer 3
during the aqueous work-up and the purification step.
Moreover, no information on the stereochemistry of the2
double bond of 3 was described in the original work.
When the a-allenyl ketone 1 was treated with lithium
dialkylcuprate, variable proportions of unconjugated 2
and conjugated 3 adducts were also formed (in a 30:70
to 90:10 ratio according to the experimental condi-
6
allenyl ketones in quantitative yields. When 1a was
treated with Grignard reagents at −78°C, followed by
hydrolysis at low temperature, the corresponding a,b–
unsaturated ketones 5–9 were obtained in good yields
as described in Scheme 2. The scope of the reaction is
broad since primary, secondary and even tertiary alkyl
magnesium bromide derivatives react cleanly with the
allenyl ketone 1a. Only phenylmagnesium bromide gave
a low yield since a small amount of the 1,2-adduct was
formed (direct addition to the ketone) to give the
phenyl allenyl carbinols. In all cases, only the E-isomer
was formed. We believe that this unique stereoselectiv-
ity in the formation of the a,b-unsaturated enones 5–9
cannot be the result of the isomerization of the non-
conjugated enones into the conjugated enones (i.e. the
difference between the two geometrical isomers of 5 is
too small to explain the formation of a unique product)
but must be due to the stereochemical outcome of the
O
O
O
EtMgBr
•
1
R
+
R
R
2
3
Scheme 1.
*
Corresponding author. Fax: (972)-4 829 37 09; e-mail: chilanm@
tx.technion.ac.il
7
hydrolysis of the dienolate anion.
0
040-4039/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(02)01211-X

6
010
N. Chinko6 et al. / Tetrahedron Letters 43 (2002) 6009–6010
OH
O
O
the double bond. We thus compared the reactions in
Et O and THF. In ether, a single isomer was formed
DMP
Bu
Silica gel
Bu
2
(
Scheme 2) whereas in THF the ratio of 2:3 was now
3:66. This result can be interpreted as a result of the
4a
3
1
a
•
weakening p-chelation favoring solvation of the metal
by a more electron donating solvent. Similarly, when an
aldehyde is added as the electrophile, the chelation
between the magnesium enolate and the carbonyl moi-
ety of the electrophile is stronger than the chelation
between the magnesium and the double bond. In this
case, the aldolization reaction occurs via a chair-like
transition state to give exclusively the homoallylic aldol
product 13 in good yield but in a modest diastereomeric
ratio. In conclusion, the reaction between the organo-
magnesium halide and the allenyl ketone has been
reinvestigated and was found to give only the a,b-
unsaturated ketone as single geometrical isomer.
Bu
O
MeMgBr
EtMgBr
5
Bu 82%
O
O
6
Bu 72%
7
iPrMgBr
1a
Bu 89%
O
O
tBuMgBr
8
Bu 95%
PhMgBr
9
Acknowledgements
Bu 60%
Ph
Scheme 2.
This research was supported by the Israel Science
Foundation administrated by the Israel Academy of
Sciences and Humanities (79/01-1) and by the Fund for
the Promotion of Research at the Technion.
In order to gain more insight into the mechanism, we
trapped the intermediate 10 at low temperature by the
addition of MeOD and iodine to give 11 and 12 as
single geometrical isomers (Scheme 3). This unique
stereoselectivity result is most probably due to the
p-chelation of the magnesium enolate with the terminal
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8
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O
Scheme 3.