Alkynyliodonium salts in organic synthesis. Preparation of 2-substituted-3-p-toluenesulfonyldihydrofurans from 1-hydroxybut-3-ynyliodonium ethers via a formal stevens shift of a carbon group

Article abstract of DOI:10.1021/ol006115p

(equation presented) p-Toluenesulfinate addition to 1-hydroxybut-3-ynyliodonium ethers triggers a sequence of reactions which ultimately delivers 2-substituted-3-p-toluenesulfonyldihydrofuran products along with 3-p-toluenesulfonyldihydrofuran as a major byproduct. A putative 1,2-alkyl shift within an unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of the alkyl group.

Full text of DOI:10.1021/ol006115p

ORGANIC
LETTERS
2000
Vol. 2, No. 17
2603-2605
Alkynyliodonium Salts in Organic
Synthesis. Preparation of
2-Substituted-3-p-toluenesulfonyldihydrofurans
from 1-Hydroxybut-3-ynyliodonium
Ethers via a Formal Stevens Shift of a
Carbon Group
Ken S. Feldman* and Michelle Laci Wrobleski
Department of Chemistry, The PennsylVania State UniVersity,
UniVersity Park, PennsylVania 16802
Received May 26, 2000
ABSTRACT
p-Toluenesulfinate addition to 1-hydroxybut-3-ynyliodonium ethers triggers a sequence of reactions which ultimately delivers 2-substituted-
3-p-toluenesulfonyldihydrofuran products along with 3-p-toluenesulfonyldihydrofuran as a major byproduct. A putative 1,2-alkyl shift within an
unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of the alkyl group.
The utility of alkynyliodonium salts in organic synthesis
stems largely from their role as alkylidene carbene precursors
upon combination with select nucleophiles.1 These reactive
monovalent carbenes participate in a range of C-C, C-H,
and C-X bond-forming processes which all appear to
originate with an interaction between the empty p orbital at
the terminus of the electrophilic carbene and a proximate
source of electron density (e.g., C-H, CdC, or X-H bond).2
In contrast, the formal combination of an alkylidene carbene
with a heteroatom lone pair (cf. 1 f 2, eq 1) has been much
these instances, dihydrofuran derivative 3 is produced,
presumably via Stevens rearrangement4 (1,2 R shift) within
the oxonium ylide 2. Attempts at detecting a similar shift
with a carbon group (R ) allyl or benzyl) by Kim et al.
were frustrated by intervention of uncharacterized reaction
channels which diverted the ylide intermediate.3a
A recent observation of alkylidene carbene addition to the
lone pair of a carbamate nitrogen suggested that this process
may be more general than otherwise suspected5 and that by
proper choice of the migrating group R in 1, efficient Stevens
rearrangement of a carbon-based group might be realized.
In this vein, we report the successful conversion of the simple
alkynyliodonium salts 4 into the 2,3-disubstituted dihydro-
furan products 7 by treatment with the mild nucleophile
p-toluenesulfinate (eq 2). These transformations presumably
(3) (a) Kim, S.; Cho, C. M. Tetrahedron Lett. 1995, 36, 4845. (b) Ito,
Y.; Aoyama, T.; Shioiri, T. Synlett 1997, 1163. (c) Miwa, K.; Aoyama, T.;
Shioiri, T. Synlett 1994, 461. (d) see also Sueda, T.; Nagaoka, T.; Goto, S.;
Ochiai, M. J. Am. Chem. Soc. 1996, 118, 10141.
less thoroughly investigated, and productive reactions have
heretofore been limited to cases where R ) H or SiR′3.3 In
(4) Marko´, I. E. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford 1991; Vol. 3, Chapter 3.10.
(5) Feldman, K. S.; Mingo, P. A.; Hawkins, P. C. D. Heterocycles 1999,
51, 1283.
(1) (a) Stang, P. J.; Zhdankin, V. V. Tetrahedron 1998, 54, 10927. (b)
Varvoglis, A. Tetrahedron 1997, 53, 1179.
(2) Kirmse, W. Angew. Chem., Int. Ed. Engl. 1997, 36, 1164.
10.1021/ol006115p CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/26/2000

Table 1. 2-Substituted-3-p-toluenesulfonyldihydrofuran
Products 7 Prepared from Alkynyliodonium Salts 4 in THF at
Reflux
pass through a formal Stevens 1,2-shift of R within the ylide
6 to fashion the new C-C bond in 7. Variable but significant
quantities of the proton-trapping product 8 are formed as
well, and formation of this compound constitutes the major
yield-limiting competition in the sequence. The choice of
sulfinate as a nucleophile was predicated on a desire to
prepare an enol ether product 3 whose alkene would not be
sensitive to hydrolysis upon isolation/chromatography. In
principle, the range of nucleophiles with reported utility in
converting an alkynyliodonium salt into the derived carbene
(sulfonamide anion, azide, â-dicarbonyl enolate, etc.)1 may
be applicable to this transformation as well.
A series of alkynyliodonium salts 4a-4g was prepared
and examined in this dihydrofuran-forming reaction, Table
1. These salts were readily available by treatment of the
corresponding alkynyltributylstannanes with Stang’s reagent,
PhI(CN)OTf. The thermal lability of these species required
that temperatures did not exceed -30 °C during their
preparation and handling. Optimization studies with sub-
strates 4a and 4d spanned a range of experimental variables,
including order and rate of addition, concentration (0.15-
0.30 M in iodonium salt), temperature (room temperature
f refluxing solvent), and solvents (CH2Cl2, ClCH2CH2Cl,
THF, DME, t-BuOMe, DMF), to maximize production of
the dihydrofuran products 7a and 7d, respectively. Eventu-
ally, a procedure by which a chilled (-42 °C) THF solution
of the alkynyliodonium salt 4d was rapidly cannulated into
refluxing THF containing a suspension of 1.3 equiv of
anhydrous sodium p-toluenesulfinate (final concentration
∼ 0.15 M alkynyliodonium salt) was found to provide the
desired cyclized/rearranged dihydrofuran product 7d in
optimal yield. Further experimental details can be found in
the Supporting Information.
Verification of Kim’s observations that silicon migrates
effectively (entry a) while benzyl does not (entry b) provided
a baseline for subsequent studies. Better carbon migration
results are obtained with the tetrahydrofuran and tetra-
hydropyran series, entries c-f. With both the simple unsub-
stituted rings (entries c and d, respectively), the desired
2-tetrahydrofuranyl- and 2-tetrahydropyranyldihydrofurans
are formed in moderate yields. The formal Stevens rear-
rangement appears to proceed with reasonable levels of
stereochemical fidelity in the tetrahydropyran series, entries
e and f. Each pure diastereomer of the 3-methyl-substituted
substrates 4e and 4f provides a diastereomeric mixture of
2-dihydrofuranyltetrahydropyran products that strongly favors
retention of the stereochemical relationship present in the
starting material. The ratios of diastereomers were determined
by integration of diagnostic signals in the 1H NMR spectra.
The stereochemical assignments were predicated upon
analysis of the coupling constants between protons on the
stereogenic centers (7e, J1,2 ) 3.6 Hz; 7f, J1,2 ) 10.0 Hz).
Treatment of orthoester-containing substrate 4g with p-
toluenesulfinate provided acetal 7g in superior yield, and
none of the protonated dihydrofuran 8 was detected. This
observation draws attention to the possible role that the C(3)
THP proton (H in 4d) plays in the formation of the
dihydrofuran byproduct 8.
The mechanistic course of this transformation is believed
to proceed through the oxonium ylide 6 en route to
dihydrofuran product 7. Evidence that has been interpreted
as supporting either homolytic or heterolytic scission of the
C-O bond within trivalent oxonium ylides has been
recorded,6 but no mechanistic investigations that factor in
(6) (a) Roskamp, E. J.; Johnson, C. R. J. Am. Chem. Soc. 1986, 108,
6062. (b) Eberlein, J. H.; West, F. G.; Tester, R. W. J. Org. Chem. 1992,
57, 3479. (c) Doyle, M. P.; Griffin, J. H.; Chinn, M. S.; van Leusen, D. J.
Org. Chem. 1984, 49, 1917.
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Org. Lett., Vol. 2, No. 17, 2000

the influence of a divalent carbanion (cf. 6) in the Stevens
rearrangement have been reported. A priori, two limiting
mechanisms proceeding through either homolytic C-O
cleavage (e.g., 9) or heterolytic C-O cleavage (e.g. 10) can
be envisioned (eq 3). On the basis of the limited structure/
illuminate allied issues regarding the intra- vs intermolecular
nature of the formal 1,2-shift and the source of the proton at
C(2) in 8.
In summary, a novel application of arylalkynyliodonium
salts bearing terminal ether functionality to the synthesis of
dihydrofurans is reported. This sequence likely involves a
sequence of events which generates, in turn, reactive
intermediate alkylidene carbenes and oxonium ylides. In
essence, this transformation converts an easy-to-make O-R
bond in the alkynyliodonium salt precursor into a more
difficult-to-make C-C bond in the product dihydrofuran.
Efforts to expand the scope and define the limitations of this
reaction are in progress, and results will be reported in due
course.
Acknowledgment. We thank the national Institutes of
health (GM37681) for financial support of this work.
reactivity data gleaned from Table 1, it is tempting to suggest
that the heterolytic scission pathway is favored in these
rearrangements. Thus, substituents R in 6 which were
anticipated to promote homolytic cleavage perform poorly
(i.e., benzyl, allyl, and p-methoxybenzyl (not shown, 7 not
formed), while, in contrast, substrates whose substituent R
has a documented capacity to stabilize cationic character
(silyl, R-THF, R-THP) fare much better. Further studies to
probe this point are planned, as are experiments designed to
Supporting Information Available: A representative
experimental procedure for the formation of 7d and char-
acterization data (1H NMR, 13C NMR, IR, LRMS, and
combustion analysis) for 7a, 7c-g, and 8. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL006115P
Org. Lett., Vol. 2, No. 17, 2000
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