Notes
J . Org. Chem., Vol. 62, No. 21, 1997 7501
Sch em e 5. Mor i’s Stu d y
Under otherwise identical conditions, carrying out the
reaction in pure THF gave but an 8% yield, whereas use
of HMPA in place of the DMSO (again 8:1) led to a 16%
yield. If KF was used in place of CsF, only a 5% yield
was obtained. Attempts to substitute other ethereal
solvents, such as diethyl ether, dioxane, or diglyme, for
THF also led to much poorer results.
It is believed that the active reducing agent in this
reaction is generated in situ by the reaction of fluoride
ion, F-, with TMSTBT. Because Me3SiF and Bu3SnBr
are formed as a result of the overall reaction, it is
assumed that the process begins by attack of the TM-
STBT by fluoride ion. That being the case, the actual
active reducing agent could be either the complex anion
4 or the tributyltin anion itself, 5 (Scheme 7).
Sch em e 6. New AF 4 Syn th esis
able conformational change to the syn conformer, 3-syn ,
before it can undergo unimolecular cyclization to the
desired paracyclophane product, AF4. If 3 encounters
another molecule of monomer 1 before it can cyclize, it
will react to form the linear trimer diradical which,
having an even smaller probability of undergoing cycliza-
tion, usually, but not always, continues on to form AF4
polymer. This polymer has no appreciable solubility in
any solvent yet tested. The high dilution conditions are
designed to provide the optimal kinetic environment for
allowing unimolecular cyclization of 3 to compete ef-
fectively with bimolecular oligomerization.
The suggestion that 4 is the possible active agent which
effectively “delivers” Bu3Sn- to dibromide 2 has precedent
in that Olah has found that CF3SiMe3 + fluoride ion
-
effectively “delivers” a CF3 anion in reactions with
carbonyl compounds without apparently passing thor-
ough a free CF3 anionic species (Scheme 8).13
-
Indeed we have found, in a control study, that treat-
ment of 2 with pregenerated Li+SnBu3 under high
-
dilution conditions does not lead to formation of signifi-
cant amounts of AF4. Mori also made the same type of
observation in his Diels-Alder study depicted in Scheme
5.11
Recognizing the need for an improved synthesis of AF4,
we have continued to pursue new reductive methodolo-
gies toward that end, with the result that we now wish
to report a new and improved method for synthesis of
AF4, using as a reductant the active species generated
in situ by reaction of (trimethylsilyl)tributyltin (TM-
STBT) with cesium fluoride (CsF). Furthermore, it has
been demonstrated that this method is scaleable and thus
should be able to be utilized to readily make kilogram
quantities of AF4.
It is believed that the success of our new procedure
derives from the limited solubility of CsF in the solvent
mixture at 70 °C and that the required slow but consis-
tent generation of the active reducing agent is controlled
by the slow, steady dissolution of the CsF which gener-
ates this active agent.
The actual nature of the debrominative process also
remains ambiguous as to whether there is a direct
formation of Bu3SnBr by a bimolecular reaction of the
active reducing agent with dibromide 2, or there is a
single electron transfer (SET) process involved between
4 (or 5) with 2. Consistent with this latter possibility is
the fact that the two best cosolvents with THF have been
found to be DMSO and HMPA, both recognized to be
excellent facilitators of SET reactions. The truth is,
though, that the emphasis in this work has been develop-
ment of a good synthesis, with little effort of a mecha-
nistic nature having been made.
The fact that the major competing reaction in this new
process is formation of polymer, with most of the remain-
ing material being accounted for as “reduction” products,
where one or both of the CF2Br groups of 2 have been
reduced to CF2H groups, provides good evidence for the
intermediacy of monomer 1 in the reaction. Another
piece of evidence along that line derives from an experi-
ment in which pure DMSO was used as the solvent at
70 °C, with gradual addition of CsF. In this case no AF4
was observed, but there was instead a high yield conver-
sion to the pentafluoro-p-xylene, 6, most likely via
fluoride interception of monomer 1, followed by abstrac-
tion of a proton from DMSO (Scheme 9).
The use of TMSTBT/CsF for the purpose of debromi-
nation has been previously reported in Mori’s study of
the generation of o-quinodimethanes for use in Diels-
Alder reactions (Scheme 5).11,12
The new method uses a unique approach to circumvent
the need for conventional high dilution technology. It
allows one to add in most of the ingredients together
rather quickly, while maintaining the necessary low
concentration of monomer via control of its rate of in situ
generation. As was the case for the earlier two methods,
2 is the preferred precursor to monomer 1 in the new
synthesis. In a typical reaction, 55 g (0.36 mol) of CsF,
105.5 g (0.28 mol) of TMSTBT, and 100 g (0.32 mol) of
dibromide 2 were added consecutively to a mixture of 8
L of THF and 2 L of DMSO at 78 °C. After stirring and
refluxing for 12 h, another 57.5 g (0.16 mol) of tinsilane
was added, followed by a third 52.5 g (0.14 mol) dose after
6 h more. After an additional 10 h of reflux, the reaction
was worked up to give 25 g of crude AF4 product, which
upon recrystallization from 10:1 CHCl3-hexane provided
22.7 g (40%) of >99% pure AF4 (Scheme 6). In subse-
quent development studies, the reaction has been able
to be scaled up to produce as much as 1 kg of AF4 in a
single run.
Exp er im en ta l Section
Anhydrous THF and DMSO were obtained from Fisher
Scientific, cesium fluoride (anhydrous, 99%) from CM Chemical
Products, Inc., and tri-n-butyltin chloride and trimethylsilyl
chloride from Aldrich Chemical Co.
The above-described conditions have been optimized
with respect to choice of solvent and reaction conditions.
(11) Sato, H.; Isono, N.; Okamura, K.; Date, T.; Mori, M. Tetrahedron
Lett. 1994, 35, 2035-2038.
(12) Sato, H.; Isono, N.; Miyoshi, I.; Mori, M. Tetrahedron 1996, 52,
8143-8158.
(13) Prakash, G. K. S.; Krishnamurti, R.; Olah, G. A. J . Am. Chem.
Soc. 1989, 111, 393-395.