Allyl- and propargylchromium reagents generated by a chromium(III) ate-type reagent as a reductant and their reactions with electrophiles

Article abstract of DOI:10.1039/b009351n

A chromium ate-type reagent 'Bu₅CrLi₂' reacts with allylic and propargylic phosphates to generate the corresponding allyl- and propargylchromium (propargyl = prop-2-ynyl) reagents which further react with a variety of electrophiles such as aldehydes, ketones, imines, and isocyanates to afford the corresponding adducts in high yields.

Full text of DOI:10.1039/b009351n

Allyl- and propargylchromium reagents generated by a chromium(III) ate-type
reagent as a reductant and their reactions with electrophiles†
Makoto Hojo, Rie Sakuragi, Satoru Okabe and Akira Hosomi*
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki
305-8571, Japan. E-mail: hosomi@chem.tsukuba.ac.jp
Received (in Cambridge, UK) 21st November 2000, Accepted 16th January 2001
First published as an Advance Article on the web 8th February 2001
Table 1 Reaction with allyl phosphate 1aa
A chromium ate-type reagent ‘Bu5CrLi2’ reacts with allylic
and propargylic phosphates to generate the corresponding
Entry
Chromium reagent
Conditions
Alkene (%)b
allyl- and propargylchromium (propargyl = prop-2-ynyl)
reagents which further react with a variety of electrophiles
such as aldehydes, ketones, imines, and isocyanates to afford
the corresponding adducts in high yields.
1
2
3
4
‘Bu5CrLi2’
‘Bu4CrLi’
‘Bu4CrLi’
‘Bu3Cr’
278 °C, 5 min
278 °C, 1 h
278 °C, 3 h
278 °C, 24 h
96 (83+17)
77 (82+18)c
91 (83+17)
61 (80+20)d
Organochromium(III) reagents are well-known to be nucleo-
philic, and have been used for the selective transformation of
organic molecules. These reagents are usually generated from
organic halides or their equivalents by reduction with chro-
mium(II) as a ‘one-electron’ reductant.1 We found that a
chromium ate-type reagent, ‘Bu5CrLi2’‡ easily prepared from
chromium(III) chloride and butyllithium reacted with an equi-
molar amount of allylic phosphates to produce a nucleophilic
allylation agent2 where the butylchromium ate reagent served
not as an alkylation agent, but formally as a ‘two-electron’
reductant [eqn. (1)].
a The reduction was conducted at 278 °C for 5 min using 1.2 equiv. of
‘Bu5CrLi2’. Reactions were quenched with saturated NH4Cl solution.
b Isolated yield and isomeric ratio are shown in parentheses. c 20% of
starting material 1a was recovered. d 31% of starting material 1a was
recovered.
4), ketones also reacted with the present allylchromium reagent
(entries 5 and 6). To cyclohex-2-enone, 1,2-addition took place
to give the corresponding homoallyl alcohol 2g (entry 7). Imine
and isocyanate gave homoallylamine 2h and but-3-enoyl amide
2i, respectively, in high yields (entries 8 and 9). The generation
and reactions of other substituted allylchromium reagents were
also successful. A b-methallyl-type reagent reacted efficiently
with an aldehyde [(eqn. (2)]. Unsymmetrical reagents were also
(2)
(1)
At the outset, we had found that ‘Bu4CrLi’ reacted with an
allylic phosphate, which can be easily prepared from the
corresponding allyl alcohol, to produce reduction products,
after aqueous workup. Therefore, we examined the reactivity of
some butylchromium(III) reagents to 5-phenylpent-1-en-3-yl
diethyl phosphate (1a) in a simple reduction to yield a mixture
of terminal and internal alkenes. As can be seen in Table 1,
‘Bu5CrLi2’ was the most reactive toward the allyl phosphate 1a.
With ‘Bu4CrLi’ it took 3 h to consume the starting material, and
in a reaction of ‘Bu3Cr’, 31% of 1a was recovered even after 24
h.§ Next, we tested reactions of allyl bromide,3 phosphate,4 and
acetate with ‘Bu5CrLi2’. Allyl phosphate, diethyl 5-phenylpent-
2-enyl phosphate (1b) was the best choice as precursor of the
postulated allylchromium reagent, compared to 5-phenylpent-
2-enyl bromide and acetate (Table 2). With an allylic bromide,
butylation and dimerization competed with the desired reduc-
tion, and the acetate gave the starting allyl alcohol, suggesting
a nucleophilic reaction of the ‘Bu5CrLi2’ reagent to the carbonyl
of an acetoxy moiety.
generated from 1d and 1f under the same conditions, 278 °C, 5
min, and these isomeric reagents both reacted with heptanal to
give the same mixture of a- and g-allylation products,
suggesting that these reactions proceeded through a common
intermediate [eqn. (3)].∑ Interestingly, the same reagent derived
(3)
from 1d afforded only g-allylation product 2l, when reacted
with pivalaldehyde [eqn. (4)]. These results imply that the
By virtue of the reducing ability of the chromium ate-type
reagent ‘Bu5CrLi2’, an allylchromium reagent was prepared
from allyl phosphate 1c under mild conditions, and the thus-
generated reagent reacted with many types of electrophiles
(Table 3).¶ Throughout this conversion, an allylic moiety of
phosphate 1c changes from electrophilic to nucleophilic.5
Besides aliphatic (entries 1–3) and aromatic aldehydes (entry
(4)
common intermediate would possibly be labile or not responsi-
ble for the regiochemical outcome, and the regioselectivity
would be affected by the steric requirements of both a bulky
allylchromium reagent and an aldehyde in the transition state
for the allylation. The reagent was chemoselective for ketones
in the presence of esters. The chemoselective allylation with the
present allylchromium reagent is exemplified by eqn. (5).
† Electronic supplementary information (ESI) available: experimental
details. See http://www.rsc.org/suppdata/cc/b0/b009351n/
DOI: 10.1039/b009351n
Chem. Commun., 2001, 357–358
This journal is © The Royal Society of Chemistry 2001
357

Table 4 Reaction of propargylchromium reagenta
(5)
The present protocol can be applied even to the generation of
a propargylic reagent6 from the corresponding phosphate 3
[eqn. (6)]. With aromatic aldehydes, only homopropargyl
(6)
alcohols 4 were obtained, while with an aliphatic aldehyde,
allenylmethyl alcohol 4A was also co-produced as well as
homopropargyl alcohol 4 (Table 4).
In conclusion, a chromium ate-type reagent ‘Bu5CrLi2’
reduces allyl and propargyl phosphates to generate allyl- and
propargylchromium reagents, respectively, where no alkylation
takes place, while these thus-generated reagents act as nucleo-
philic reagents toward a variety of electrophiles. From a
synthetic point of view, many types of allyl- and proparg-
ylchromium reagents can be generated by the present protocol,
starting from allyl and propargyl alcohols. Further study on the
generation and reaction of these reagents is now in progress.
The present work was partly supported by Grants-in-Aid for
Scientific Research, Grants-in-Aid for Scientific Research on
Priority Areas (No. 706: Dynamic Control of Stereochemistry)
from the Ministry of Education, Science, Sports and Culture,
Japan.
Table 2 Reactions of allylic bromide, phosphate and acetate with
‘Bu5CrLi2’a
Notes and references
‡ Formulae ‘BunCrLin23’ are tentatively used, since the precise structures
of the species are not clear at present.
§ These ‘BunCrLin 2 3
disproportionation.
’ species are possibly in equilibrium through
Table 3 Reaction of allyl phosphate 1c with electrophilea
¶ A solution of ‘Bu5CrLi2’ in THF was prepared from BuLi in hexane (1.62
mL, 2.6 mmol) and a suspension of chromium(III) chloride in THF (0.52
mmol in 5 mL) with stirring at 278 °C for 30 min. Allyl phosphate (0.43
mmol) was added at 278 °C, and the mixture was stirred for 5 min. To the
flask, an electrophile (1.72 mmol) was added and the resulting mixture was
further stirred for 30 min. After quenching with saturated NH4Cl and
conventional workup, the crude mixture was subjected to chromatography
to give a pure product.
∑ The stereoselectivity in the reactions of a crotyl-type reagent to aldehydes
was not so high compared to that of the reported crotylchromium reagent
generated by the reduction with a chromium(II) reagent. At the moment,
reaction conditions for the selectivity were not optimized, and more likely,
this lower selectivity may possibly be due to the crowded chromium-metal
center to which remaining butyls would coordinate.
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