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Most notable is the fact that the former C=C bond has lost
much of its double bond character, whereas the CÀO bond is
significantly contracted, indicative of build-up of positive
charge density at this site. In the extreme, these complexes
can be thought of as consisting of an oxocarbenium motif sta-
in turn were readily prepared by Claisen condensation (see the
Supporting Information). The reactions proceeded cleanly,
scaled well and tolerated various substituents. Even halogenat-
ed substrates were cyclized without incident (entries 3, 5),
whereas a C-silylated alkyne furnished the desired 2-pyrone in
only modest yield (entry 6); this result echoes previous experi-
ences of our group with substrates of this sort.[29] The product
shown in entry 7 is the antibiotic pseudopyronine A, an inhibi-
tor of microbial fatty acid biosynthesis,[30] whereas entry 8 fea-
tures a building block for the total synthesis of the mycopyro-
nins and related RNA-polymerase inhibiting antibiotics.[31,32]
tert-Butyl ester derivatives are not the only substrates ame-
nable to 4-hydroxy-2-pyrones formation; trimethylsilylethyl 3-
oxoalkanoates are equally suitable and have the additional
bonus of being easy to make by conventional esterification
(entries 9–13). By virtue of the b-cation-stabilizing effect of the
bilized via hyperconjugation by
a flanking dimetalated
center.[25] An aurophilic interaction further supports the partic-
ular assembly mode of these unusual complexes.[26]
While complexes 12a–c invariably comprise an alkoxide sub-
stituent at the b-position, the proposed intermediates D and G
feature
a (vinylogous) b-acyloxy moiety (see Scheme 2).
Though clearly less electron releasing, even such a motif pro-
vides sufficient activation for diauration to proceed. Thus, Yu
and co-workers managed to isolate the gem-diaurated coumar-
in intermediate 18 formed upon treatment of the glucosyl al-
kynylbenzoate with [Ph3PAu]+ (Scheme 4).[27] Along similar
lines, we found that the enamide substructure of an indole is
amenable to gem-diauration, a fact that is relevant for the dis-
cussion of the N-heterocycle formations outlined below. In this
case, the mono-aurated species 14 can be formed as a discrete
species, which reacts further on exposure to an extra equiva-
lent of [(Ph3P)AuNTf2]. The contracted N1ÀC1 bond (1.378(3) )
in 15 indicates considerable N-acyliminium character inherent
to this remarkable diaurated complex (Figure 3).[25,28] In any
case, the examples shown in Scheme 4 collectively support the
notion that (moderately) electron rich p-systems are highly
prone to diauration. This bias likely represents a serious com-
petition for productive catalyst turnover and has to be taken
into consideration in any of the noble-metal catalyzed hetero-
cycle syntheses discussed herein.
silyl group,[33]
a putative intermediate of type C (R =
CH2CH2SiMe3) collapses in a fashion analogous to that for R =
tBu. This variant also allowed a set of products to be formed in
which the pyrone ring is annulated to a glucose moiety; for
the sake of the acid labile silyl ether protecting groups, these
particular cyclization reactions were performed in nitro-
methane rather than HOAc. The success of these model studies
paved the way for an application to the radicinol series (see
below).
2-Alkoxy-4-pyrones
The ready formation of the 2-benzyloxy-4-pyrone 7 from the
model compound 5b (R = Bn) under otherwise identical con-
ditions suggested that the course of the reaction is largely de-
termined by the very nature of the ester terminus in the start-
ing material (Scheme 3). Thus, substrates derived from a pri-
mary or secondary alcohol component lead to intermediates
of type C that evolve via simple proton loss to the correspond-
ing 2-alkoxy-4-pyrones F. The examples shown in Table 2 (en-
tries 1–5) prove that this reactivity pattern is general; some of
the products served as model compounds for the total synthe-
sis of the algal metabolite 2 mentioned in the Introduction.
The very mild conditions of this new method transpire from
the successful formation of the pyrones shown in entries 4 and
5 which contain a protected alcohol substituent at a homoallyl-
ic site in the tether; release of the masked “non-classical”
cation would obviously be detrimental. Moreover, the presence
of double bonds in the cyclization precursor does not obstruct
the necessary activation of the alkyne unit by the p-acidic cata-
lyst, although coordination of gold to an alkene is thermody-
namically perhaps even more favorable.[11] Equally noteworthy
is the successful cyclization of a substrate containing more
than one acetylene unit (entry 5): although the triple bond
conjugated to the carbonyl group is actually the least electron
rich and hence the least affine to the carbophilic gold catalyst,
it is the only site featuring a nucleophile at an appropriate dis-
tance and hence provides a productive outlet. The selective
formation of the polyunsaturated products shown in entries 4
and 5 is therefore thought to reflect kinetic control, which in
Figure 3. Structure of complex 15 in the solid state; only the complex cation
is depicted for clarity. Selected bond lengths []: N1ÀC1 1.378(3), C1ÀC2
1.387(3), C2ÀAu1 2.117(2), C2ÀAu2 2.127(2), Au1ÀP1 2.270(8), Au2ÀP2
2.261(7), Au1ÀAu2 2.764(4).
4-Hydroxy-2-pyrones
Entries 1–8 in Table 1 show an assortment of 4-hydroxy-2-py-
rones formed by gold-catalyzed cyclization of the correspond-
ing b-keto esters comprising a tert-butyl ester terminus, which
Chem. Eur. J. 2016, 22, 237 – 247
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