Synthesis of propargylic fluorides from allenylsilanes

Article abstract of DOI:10.1039/b610013a

Allenylsilanes reacted at room temperature in acetonitrile with Selectfluor, an electrophilic fluorinating reagent, to give secondary propargylic fluorides in moderate to good yields; mechanistically, a side-product resulting from a 1,2-silyl shift testifies to the presence of a cationic intermediate. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b610013a

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Synthesis of propargylic fluorides from allenylsilanes{
Laurence Carroll, Ma Carmen Pacheco, Ludivine Garcia and Ve´ronique Gouverneur*
Received (in Cambridge, UK) 13th July 2006, Accepted 27th July 2006
First published as an Advance Article on the web 23rd August 2006
DOI: 10.1039/b610013a
for the conversion of the mesylates into the allenylsilanes are good
Allenylsilanes reacted at room temperature in acetonitrile with
Selectfluor, an electrophilic fluorinating reagent, to give
secondary propargylic fluorides in moderate to good yields;
mechanistically, a side-product resulting from a 1,2-silyl shift
testifies to the presence of a cationic intermediate.
to excellent, ranging from 52% to 97%, except for allenylsilane 1f
due to the propensity of the quaternary mesylate to decompose
rapidly at room temperature. The second procedure, developed by
Myers, is an expedient one-step synthesis converting the silylated
propargylic alcohol into the desired allenylsilanes upon treatment
with diethyl azodicarboxylate (DEAD), triphenylphosphine and
o-nitrobenzenesulfonylhydrazine (NBSH).13 This second strategy
was applied for the preparation of allenylsilanes 1g and 1h which
were obtained in 70% and 41% yield respectively (eqn (2),
Scheme 1).
The remarkable characteristics of the fluorine group make it an
ideal substituent to produce compounds with unique properties.1
Although numerous important fluorinated building blocks are
accessible and used for further functional manipulation,2 little
has been done on the synthesis and reactivity of propargylic
monofluorides, apart from the work of Gre´e.3 The most
common synthetic approach to propargylic fluorides relies on a
dehydroxyfluorination of propargylic alcohols using nucleophilic
sources of fluorine with reagents such as fluoroenamine,4
Yarovenko’s reagent,5 tetrabutylammonium fluoride,6 sulfur
tetrafluoride7 or N,N-(diethylamino)sulfur trifluoride (DAST).3,8
It is noteworthy that piperidinosulfur trifluoride has been used in
the nucleophilic substitution of a protected trimethylsilylated
propargylic alcohol in the synthesis of structurally elaborated
prostacyclin analogues.9
An initial evaluation of the proposed route was performed with
allenylsilane 1a in the presence of Selectfluor [1-chloromethyl-4-
fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)] as
the electrophilic fluorinating reagent. The desired propargylic
fluoride 2a was obtained within 96 hours in 50% yield when the
reaction was carried out in acetone and in the presence of 1.5 eq. of
NaHCO3. The base was used primarily to avoid possible
protodesilylation.14 Under these conditions, a side-product was
isolated in 13% yield and unambiguously identified as the
fluorinated allenylsilane 3a. The base was found unnecessary as
a similar yield of 51% was obtained in its absence, with no trace of
a non-fluorinated alkyne resulting from a protodesilylation
process. Further studies revealed that acetonitrile was a better
solvent than acetone for this transformation, allowing a shorter
reaction time (6 h) and a higher isolated chemical yield for 2a
(78%). Under these conditions, the side-product 3a could not be
detected in the crude reaction mixture (Scheme 2).
We report in this communication the first route to propargylic
monofluorides based on the use of an electrophilic fluorinating
reagent (Fig. 1). We reasoned that exposure of allenylsilanes to
commercially available and easy to handle N–F reagents would
result in the formation of the corresponding propargylic fluorides.
This idea was substantiated by the recent advances in the area of
electrophilic fluorodesilylation of structurally diverse organosilanes
for the preparation of fluorinated targets10 and the established
reactivity of allenylsilanes with other electrophiles.11
Having established the optimal conditions for the electrophilic
fluorodesilylation of 1a, we examined the scope and limitations of
this reaction with allenylsilanes 1b–h featuring various substitution
patterns. The fluorodesilylations were carried out in acetonitrile at
room temperature (Table 1). As is evident from the examples of
For this study, various allenylsilanes were prepared in high
yields from the corresponding silylated propargylic alcohols using
one of two procedures (Scheme 1).{ The first procedure began
with the mesylation of the silylated propargylic alcohol followed
by organocuprate substitution using the requisite organolithium
combined with CuCN and LiCl (eqn (1), Scheme 1).12 The yields
Fig. 1 Two approaches towards propargylic fluorides.
University of Oxford, Chemistry Research Laboratory, 12 Mansfield
Road, Oxford, UK OX1 3TA.
E-mail: veronique.gouverneur@chem.ox.ac.uk; Fax: +44 1865 275 644
{ Electronic supplementary information (ESI) available: Procedures for
the preparation of the allenylsilanes and propargylic fluorides are provided
as well as full characterisation of all new compounds. See DOI: 10.1039/
b610013a
Scheme 1 Synthesis of allenylsilanes 1a–h.
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Scheme 3 Suggested mechanism for the fluorodesilylation of 1a.
direct stabilisation to the transition state resulting from electro-
philic addition of Selectfluor at C3. This process provides a
stabilised fluorinated vinyl cation, which upon desilylation affords
the desired propargylic fluoride 2a. If a 1,2-shift of the
trimethylsilyl group occurs prior to the desilylation,15 an isomeric
vinyl cation is formed and eliminates to give a terminal
allenylsilane which does not react further under the reaction
conditions as seen for 1e. This secondary reaction pathway
accounts for the formation of the side-product 3a observed during
our optimisation studies. The presence of this compound further
testifies to the formation of the carbocationic intermediate 5a
(Scheme 3).
Scheme 2 Fluorination of allenylsilane 1a.
Table 1, the method is suitable for the preparation of various
terminal and non-terminal secondary propargylic fluorides with
isolated yields ranging from 40% to 78%. The reaction tolerates
alkyl, alkenyl and silyloxy groups (entries 1–6). However, only
traces of the primary propargylic fluoride 2e (entry 7) were
observed using this method due to the lack of reactivity of the
disubstituted allenylsilane 1e, which was recovered almost intact
after work-up. In contrast, tetrasubstituted allenylsilane 1f reacted
rapidly but the corresponding propargylic fluoride 2f featuring a
quaternary fluorinated carbon could not be isolated due to the
propensity of this compound to eliminate HF rapidly under
the reaction conditions, a process resulting in the formation of the
corresponding enyne (entry 8).{
In summary, we have established a new reaction that leads to
propargylic monofluorides. This mild and operationally simple
reaction based on the use of an electrophilic source of fluorine and
carried out at room temperature is suitable for the formation of
secondary propargylic fluorides. Further studies on this novel
transformation are ongoing in our laboratory with a focus on the
preparation of enantiopure functionalised propargylic fluorides
from the corresponding non-racemic chiral allenylsilanes.{
Mechanistically, the C–Si bond in trimethylsilylallenes such as
1a is oriented cis coplanar to the allylic p bond and thus can afford
Table 1 Fluorodesilylation of allenylsilanes 1a–h
Yield
(%)a
Notes and references
Entry Allenylsilane
1
Product
{ The authors thank Dr B. Greedy for preliminary synthetic efforts on this
project. This work was generously supported by the European Community
(MEIF-CT-2004-515589, M.P.). We also acknowledge generous support
from AstraZeneca.
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2
3
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Isolated yields. Reaction in acetone with 1.5 eq. of NaHCO3.
No propargylic fluoride could be isolated.
4114 | Chem. Commun., 2006, 4113–4115
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