R. N. Ram, R. K. Tittal / Tetrahedron Letters 55 (2014) 4448–4451
4449
contra-thermodynamic direction to radical and afforded rear-
ranged product 1-chloroethyl carboxylate. A concerted mechanism
involving copper-complexed three- or six-member cyclic
transition states were proposed for this CuCl/bpy-promoted
dechlorinative 1,2-acyloxy migration.9 No sign of the formation
of diffusively free alkene radical cation was discerned when the
reaction was conducted by us during the reaction of 2,2,2-trichlo-
roethyl benzoate in more polar 1:1 v/v mixture of DCE and MeOH.
In view of overwhelming evidence for the formation of alkene
radical cation in the rearrangement and fragmentation reaction
of b-phosphatoxyalkyl radical and the uncertainty about the mech-
anism of b-acyloxyalkyl radical rearrangement, it was considered
worthwhile to investigate the effect of the substituent that favours
the formation of the alkene radical cation on the reaction of b-
acyloxyalkyl radical in order to gain further insight into the mech-
anism of the reaction under these conditions. This would enable
the synthesis of variously substituted, synthetically important
trisubstituted alkenes, having all three heteroatom substituents,
which are otherwise very difficult to synthesize.
The trisubstituted alkenes are an important part of many
natural products (such as hennoxazole A,10 discodermolide11 and
ratjadone12) and have also been used as precursors for the synthe-
sis of other type of organic molecules and materials. Most of the
methods relied on synthesis of the thermodynamically more stable
E-alkenes with very good selectivity.13 In a majority of cases either
a mixture of alkenes favouring E-isomer was obtained as the final
reaction product14 or the Z-isomer formed at the initial stage
which quickly gets transformed to the more stable E-isomer.15
Only a few methods provided direct synthesis of thermodynami-
cally less stable Z-alkenes, though Z-alkenes are commonly found
in natural products16 and have great scope in synthesis. In order
to overcome the thermodynamically dominated selectivity, a
directing group strategy has been used to access less stable
Z-isomer.17 Advances in catalyst design have put forward some
of the Z-selective olefin metathesis with Mo and W catalysts,18
Ru-phosphine catalysts,19 and Ru containing NHC ligand.19–22
Other methods include the reduction of alkynes over a poisoned
catalyst,23 Wittig olefination,24 cross-coupling of Z-vinyl halides
or Z-vinyl organometallic reagents,25 Still–Gennari modification
to the Horner Wadsworth–Emmons olefination,26 and some other
Z-selective olefin metathesis.18a,20a Very recently Weix and co-
workers have reported the selective isomerization of terminal
alkene to Z-stereoselective internal alkenes by the action of steri-
cally demanding cobalt(II) catalyst.27 Zhu and co-workers contrib-
uted much28 and recently reported the regio- and stereoselective
synthesis of (Z)-1-thio- and (Z)-2-thio-1-alkenyl boronates by Cu-
oxygen and chlorine heteroatom containing trisubstituted alkenes
by the ring opening reaction of trans-2,3-dichlorooxirane with
dimethyl sulfide via the formation of sulfonium salt. Barluenga
et al.37 and Jiang and co-workers38 have reported the preparation
of haloenol acetates from terminal alkynes by stereoselective
difunctionalization in the presence of tetrafloroborate. Kowalski
and Haque39 prepared bromoenol acetates from respective esters
with dibromomethyllithium at À90 °C followed by reaction with
n-butyl lithium and acetic anhydride. These bromoenol acetates
are good precursors for the formation of
and co-workers40 introduced CrCl2-promoted Z-stereoselective
transformation of trihalomethylcarbinol to (Z)- -haloenol ester
a-keto dianions. Falck
a
and (Z)-b-haloenol ether, a kind of trisubstituted alkene with O
and Cl as two hetero atoms by intramolecular 1,2-shift of acyloxy
and hydrogen atom, respectively.
However, these methods have one or more drawbacks like use
of strong basic conditions (t-C4H9OK, KOH, etc.), non friendly sol-
vents (DMSO, DMF, etc.), costly reagents (Au, Pd-complexes, etc.),
or modification of pre-existing alkenes and alkynes. Therefore,
the selective formation of less stable Z-alkene having all the het-
eroatom substitutions under mild reaction condition, easy route
and cheaply available reagents remains an unsolved problem. We
report herewith the synthesis of Z-stereoselective trisubstituted
alkene of the type a-haloenol ester having all the three heteroatom
substituents under non-reducing and milder reaction condition
wherein a range of functional groups have been survived.
Our results with Cu(I)/bpy promoted dechlorinative Surzur–
Tanner rearrangement of 2,2,2-trichloroethyl carboxylates have
motivated us to check the effect of various alkoxy substituted car-
boxylates under similar reaction condition. Some attempts have
been made in this direction and the results are being presented
here with, which indicate the formation of the alkene radical cat-
ion. Thus, the readily available 2,2,2-trichloro-1-benzyloxyethyl
acetates 1 (Scheme 1) were treated with CuCl/bpy (1:1 molar ratio)
in 1,2-dichloroethene (DCE) at reflux under a nitrogen atmosphere
to meet the above expectations. Reaction smoothly completed
with 2 equiv of Cu(I)-complex to give fragmentation products 2
(Table 1; see SI, p S-2) as well as rearranged products Z-3 and E-
3. Formation of these products together in the same reaction vessel
strongly supports the dissociative mechanism involving heteroly-
sis to contact alkene radical cation/anion pair (CIP). This CIP col-
lapses to major rearranged products at one side and little
solvation of CIP resulting in minor fragmentation product at other
side.
The crude reaction mixture was purified by silica gel (60–120
mesh) column chromatography using n-hexane and ethyl acetate
mixture in different proportions as the solvent for elution. The
fragmentation products 2 were eluted first with n-hexane only in
3–15% chemical yield. The rearranged products Z-3 were then
eluted with 2–3% ethyl acetate in n-hexane followed by the other
rearranged product E-3 with 3–4% ethyl acetate in n-hexane in
40–62% and 20–36% yield, respectively. The rearrangement was
found to be stereoselective with Z-3 enol acetates.
catalyzed selective
a- and b-borylation of thioacetylenes. This
method represents the first method of its kind for generating all
possible regio- and stereoisomers of trisubstituted alkene.29
It has been observed that the stereoselective synthesis of the
trisubstituted alkene of the type
cult. Ferreira described the selective and efficient Hiyama coupling
of -silylenoate and -silylenamides obtained from platinum-
a-haloenol acetates is very diffi-
a
a
catalyzed hydrosilylation for selective and efficient synthesis of
stereodefined trisubstituted alkenes.30 Kim and Lee proposed
gold(I)-catalyzed regio- and stereodefined synthesis of trisubsti-
tuted alkenes via hydrophosphoryloxylation of haloalkynes
followed by transition-metal-catalyzed cross coupling reaction.31
McElvain and Stammer,32 O’Connor33 and Pericas and Serratosa34
reported use of strong bases like t-C4H9OK or KOH for the dehydro-
halogenation of trans-substituted hydrogen and halogen from 1,
2-dihalo-1,2-dialkoxyethane. Mueller and Seyferth35 showed the
formation of cis and trans isomers of 1-chloro-1,2-diethoxyethyl-
ene during thermolysis of organomercurials in a total 49% yield
along with other thermolysis products ethyl chloroacetate and
ethyl ethoxychloroacetate. Griesbaum et al.36 reported sulfur,
Assignment of stereochemistry
The NOE experiments with Z-3a,b,g and E-3a,b,g were inconclu-
sive for the determination of the configuration of the enol acetates.
However, it was observed that the major enol acetates moved
faster than the minor enol acetate on column chromatography in
all the cases. It could be explained by assuming that the major enol
acetates 3 had Z configuration and the minor had E configuration.
Based on this crude method for the determination of configuration,
presumably Z-3 and E-3 isomers were arranged along with the 1H
and 13C NMR chemical shift values of some relevant signals as
Ram, Ram N.
