The rapid photomediated alkenylation of 2-alkyl-1,3-dioxolanes with alkynes: A stereoelectronically assisted chain reaction

Article abstract of DOI:10.1039/b608979h

The photomediated reaction of alkynes such as DMAD with 1,3-dioxolanes leads to remarkably rapid alkenylation; evidence is presented that these reactions occur via a chain mechanism. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b608979h

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COMMUNICATION
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The rapid photomediated alkenylation of 2-alkyl-1,3-dioxolanes with
alkynes: a stereoelectronically assisted chain reaction
Niall W. A. Geraghty* and Andrea Lally
Received (in Cambridge, UK) 26th June 2006, Accepted 2nd August 2006
First published as an Advance Article on the web 29th August 2006
DOI: 10.1039/b608979h
The photomediated reaction of alkynes such as DMAD with
1,3-dioxolanes leads to remarkably rapid alkenylation; evidence
is presented that these reactions occur via a chain mechanism.
Involving unactivated systems such as cycloalkanes and ethers,
and moderately activated systems such as 1,3-dioxolanes, in
carbon–carbon bond formation is synthetically challenging.
Although the problem is often addressed through the use of
reactions based on carbon radicals, many of these suffer from the
disadvantage that they involve undesirable reagents such as
peroxides, tin hydrides, etc., and/or in many cases require the
synthesis of an appropriate radical precursor. It has been
demonstrated however that the most direct route for the creation
of the key carbon radicals, C–H bond cleavage, is accessible by
exploiting the well-established ability of triplet state ketones to
participate in hydrogen abstraction.1,2 This photochemical pro-
duction of carbon radicals can also be achieved using supported
Scheme 1
photomediators and solar radiation, features that enhance its
attractiveness from the clean/green chemistry perspective.3
Although there is the expectation that pinacol formation should
be the inevitable outcome in such reaction systems, this process is
not competitive in many cases and the available evidence indicates
that this photochemical route to carbon radicals can be
synthetically useful for simple molecules in which the options for
hydrogen abstraction are limited for reasons of symmetry or
substitution. Thus the reaction of cycloalkanes with alkenes and
alkynes carrying electron withdrawing groups (EWGs) produces
alkylated4 and alkenylated2 products, respectively.
resulting radicals adding to a,b-unsaturated aldehydes,5 ketones6,7
and esters8 in a synthetically useful way. The corresponding
thermal process, based on radical initiators such as AIBN or
benzoyl peroxide, is much less efficient with, in some cases,
rearrangement of the dioxanyl radical being competitive with its
addition to the unsaturated system.6 The present communication
reports on the remarkably rapid photomediated reaction between
2-alkyl-1,3-dioxolanes and electron deficient alkynes (Scheme 2),
and presents quantum yield data which suggest that the efficiency
of these reactions is at least in part due to the operation of a chain
mechanism.
There is little uncertainty about most of the mechanistic steps
involved in these reactions: initial formation of the triplet state of
the ketone (the photomediator); hydrogen abstraction from the
substrate generating a carbon radical; and addition of this
nucleophilic radical to an alkene or alkyne carrying an EWG
(Scheme 1). The final step in the process, product formation
through hydrogen abstraction by an alkyl or alkenyl radical, could
however involve two possible hydrogen donors. If the ketyl radical
formed in the first step of the process provides the hydrogen atom
then this completes the cycle and the absorption of a further
photon of UV light is required for further reaction. On the other
hand, if it is provided by a molecule of substrate then this opens up
the intriguing possibility that the reaction could proceed via a chain
mechanism.
The reactions were carried out by irradiating a solution of the
alkyne (1 mmol), the 1,3-dioxolane (20 mmol) and the photo-
mediator benzophenone (0.4 mmol), in acetonitrile (20 cm3), using
a Rayonet reactor equipped with 350 nm lamps. The reactions
were monitored by GC. The reactivity of 1,3-dioxolane 1 itself is
unremarkable and it affords modest yields of addition products
with a range of electron-deficient alkynes (Table 1). Reaction
generally occurs regiospecifically at the 2-position, although
propiolate esters give small amounts of products resulting from
reaction at the 4-position.
It has already been shown that 1,3-dioxolanes and 2-substituted-
1,3-dioxolanes can participate in this photomediated process, the
Chemistry Department, National University of Ireland, Galway, Ireland.
E-mail: niall.geraghty@nuigalway.ie; Fax: +353 91 525700;
Tel: +353 91 492474
Scheme 2
4300 | Chem. Commun., 2006, 4300–4302
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Table 1 The photomediated reaction of alkynes with dioxolanes
1
2
3
4
Alkyne
Timea
Yieldb
E : Zc
Timea
Yieldb
E : Zc
Timea
Yieldb
E : Zc
Timea
Yieldb
E : Zc
R1 = H, R2 = CO2Me
R1 = H, R2 = SO2Tol
R1 = H, R2 = Ph
R1 = R2 = CO2Me
R1 = R2 = CO2But
a
60
22
32
39
3
42
—
1.3 : 1
10 : 1
1 : 2
1 : 3.1
—
15d
15
52
60
19
89
64
1 : 7.7
E only
1 : 1.7
5.1 : 1
4.0 : 1
30
15
—
15
15
50
46
—
74
79
1 : 7.3
E only
—
6.2 : 1
4.4 : 1
15
25
—
25
30
75
27
—
70
53
1 : 12.2
E only
—
10.4 : 1
5.5 : 1
c
3960e
25
570f
15
—
15
b
Time in minutes for complete reaction of alkyne, unless otherwise indicated. Combined isolated yield of E and Z isomers (%). GC.
d
e
Reaction time determined by monitoring product formation as alkyne co-eluted with solvent. 88% conversion. 75% conversion.
f
A remarkable enhancement in reactivity is observed however
reaction with alkynes reported here. The C2 hydrogens in the other
2-alkyl-1,3-dioxolanes considered in this study also enjoy favour-
able stereoelectronic relationships with both oxygen atoms. The
importance of this type of stereoelectronic effect in these systems is
underlined by the fact that, whereas small amounts of a C4
alkenylated product are obtained in the reaction of 1 with
propiolate esters, no such products are obtained in the reactions of
2–4 with any of the alkynes used. This effect has also been
observed in the reactions of these dioxolanes with alkenes.8 This
can be rationalised on the basis that two of the C4/C5 hydrogens in
1 have, uniquely, almost coplanar relationships with p-type lone-
pairs on the oxygen atoms.
when an alkyl group is introduced at the 2-position of the
dioxolane (Table 1). Thus the reaction of 2-methyl-1,3-dioxolane 2
with dimethyl acetylenedicarboxylate (DMAD) is complete in
15 min and gives the alkenylated products in a combined isolated
yield of 89%. A GC determination of the yield suggests that this
reaction is essentially quantitative. Although the effect of
dioxolane substitution is less pronounced in reactions involving
monosubstituted alkynes, it can even be observed in the reactions
of styrene (Table 1). 2-Ethyl- and 2-isopropyl-1,3-dioxolane, 3 and
4, respectively, behave in a parallel fashion, although the reactivity
of the latter is lower, presumably because of the steric bulk of the
isopropyl group.
The enhanced stereoelectronic effect operating in 2-alkyl-1,3-
dioxolanes influences their reactivity in another way. As indicated
above, the suggested mechanism (Scheme 1) allows for the
operation of a chain process involving hydrogen transfer from a
second molecule of dioxolane to the initially formed alkenyl
radical, a process which in the case of the 2-alkyl-1,3-dioxolanes is
now seen to be stereoelectronically facilitated. Quantum yield
measurements using a valerophenone actinometer12,13 provide
evidence for the availability of such a route to product formation
and indicate that the reactivity of dioxolane–alkyne combinations
depends on the extent to which product formation involves this
chain process. Thus, whereas the most reactive combination,
2-methyl-1,3-dioxolane–DMAD, occurs with a quantum yield
which is much greater than unity (W = 4.8), the reaction of 1,3-
dioxolane with methyl propiolate involves a quantum yield which
is less than one (W = 0.5), with that for 2-methyl-1,3-dioxolane–
methyl propiolate being intermediate between the two (W = 1.4).
Although the above analysis provides a rationale for the effect
of substitution in the 2-position on the reactivity of 1,3-dioxolanes
in their reactions with alkynes, the reactivity of the system in
general is also dependent on the nature of the unsaturated
It is reasonable to look for an explanation of the relative
reactivities of the substituted and unsubstituted dioxolanes in
terms of the hydrogen abstraction process which generates the key
dioxolanyl radical, as the abstraction of a-hydrogens from ethers
by photochemically generated tert-butoxyl has been shown to be
subject to a stereoelectronic effect which is related to the size of the
torsion angle (h) between the a-C–H bond and the p-type lone-pair
on the oxygen.9,10 Thus a small value for h facilitates interaction
between the developing half-filled orbital and the oxygen’s p-type
lone-pair, resulting in enhanced rates of C–H bond cleavage. High
reactivity was predicted9 for the C2–H bond(s) in 1 and 2 on the
basis of measured values (Drieding models) for h of 30u with both
oxygen atoms. This prediction was confirmed by EPR spectro-
scopy, with 1 actually being found to be the more reactive. The
reactivity of the related 2-methyl-1,3-dioxane in this context was
interpreted in terms of a preferred conformation in which the
methyl group is equatorial.10 Although 5-membered rings would
be expected to be more conformationally mobile, the results
reported here can be rationalised in terms of 2-alkyl-1,3-dioxolanes
also having a more clearly defined conformational preference. A
DFT (B3LYP/6-31G*) optimisation of the minimum energy
geometry derived from an MM based conformational search
procedure11 shows that dioxolane 1 and 2-alkylated-1,3-dioxolanes
2–4 prefer half-twist conformations. This indicates that, although
1,3-dioxolane is presumably conformationally mobile, its C2
hydrogens actually have a favourable stereoelectronic relationship
with one of the oxygens in its minimum energy form (Table 2). The
key point however in terms of the remarkable reactivity reported
here for 2, which as indicated above is assumed to exhibit a
conformational preference, is the fact that abstraction of the C2
hydrogen will be significantly accelerated by both oxygen atoms
(h = 7.1, 9.5u). Although this inverts the relative reactivity of 1 and
2 suggested by the EPR spectral data,7 it is clearly entirely
consistent with their behaviour in terms of the photomediated
Table 2 a-C–H/O(p-type lone pair) torsion angles (u) in optimiseda
1,3-dioxolane structures
Torsion angle
1, R = H
2, R = Me
3, R = Et
4, R = Pri
H2O1
H29O1
H2O3
H29O3
H4O3
H49O3
H5O1
H59O1
a
16.1
43.2
43.2
16.1
61.0
1.2
7.1
—
9.5
—
68.1
7.7
11.5
—
7.5
—
68.9
8.8
15.3
—
5.5
—
68.6
8.5
1.2
61.0
27.4
33.2
22.4
38.0
18.8
41.5
B3LYP/6-31G* optimisation using a starting geometry generated
by an MM based conformational search.11
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their reactions with a,b-unsaturated aldehydes.5 Despite this
complexity the results clearly indicate that the photomediated
generation of carbon radicals by direct hydrogen abstraction can
be remarkably efficient and warrants further investigation.
8 I. Rosenthal and D. Elad, J. Org. Chem., 1968, 33, 805.
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Notes and references
1 D. Dondi, A. M. Cardarelli, M. Fagnoni and A. Albini, Tetrahedron,
2006, 62, 5527.
2 R. A. Doohan, J. J. Hannan and N. W. A. Geraghty, Org. Biomol.
Chem., 2006, 4, 942.
3 R. A. Doohan and N. W. A. Geraghty, Green Chem., 2005, 7, 91.
4302 | Chem. Commun., 2006, 4300–4302
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