10.1002/anie.201908693
Angewandte Chemie International Edition
COMMUNICATION
a stronger base catalyst, i.e. amidine (DBU) or guanidine (MTBD),
was necessary. Accordingly, the stereochemical outcome of this
catalytic carbocyclization process appears to be fully substrate-
controlled. In support of this assumption, the energies of the TS
for the four possible nitronate-dienone face combinations were
calculated. The energy barrier for the re,re approach was found
to be 9.6 kcal/mol (about 2 kcal/mol lower than any of the other
three possible approaches) which nicely explains the essentially
perfect stereoinduction observed in all but one case (compound
15g).
route to complementary cyclohexene systems and products
derived thereof. Given that both proton transfer and H-bonding
are general activation modes, new enantioselective reactions
involving trienolate-like -extended systems from carbonyl and
non-carbonyl substrates might be predictable.
Acknowledgements
Support has been provided by the University of the Basque
Country UPV/EHU (UFI QOSYC 11/22), the Basque Government
(GV grant No IT-1236-19), and the Ministerio de Economía y
Competitividad (MEC Grant CTQ2016-78487-C2), Spain. I.I. and
O.O. thank GV for a fellowship. G.Z. and E.G.-B thank the
European Funding Horizon 2020-MSCA (ITN-EJD CATMEC
14/06-721223). We also thank SGIker (UPV/EHU) for providing
NMR, HRMS, X-ray facilities and computational resources.
Several transformations of these polysubstituted
cyclohexene adducts were explored (Scheme 2). Selective
reduction of the C–C double bond in thioester 6Ae was achieved
by simply using an excess of NaBH4 in isopropyl alcohol and
CH2Cl2 mixture, affording cyclohexane 21 as the only isomer in
68% isolated yield. In its turn, the reduction of enone 15b to 22
could be achieved in 72% yield and without affecting the carbonyl
group by using Et3SiH in the presence of Pd/C.[18] Interestingly,
these cyclohexene adducts also resulted well suited for
expanding the Nazarov cyclisation,[19] as demonstrated by the
conversion of adducts 17b, 17f and 18a into products 23-25 in
good yields and as essentially single diastereomer. The structure
of these polycyclic products were established by NMR
experiments and corroborated by X-ray analysis of 24.[14]
Keywords: Brønsted bases • 1,6-conjugate additions •
organocatalysis • trienolates • synthetic methods
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A
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In summary,
a
catalytic one-pot process to assemble
stereodefined tetrasubstituted six membered carbocycles from
polyunsaturated thioesthers or ketones is developed. The new
method features: (i) a highly enantioselective -addition of
transiently generated trienolates to nitrolefins, (ii) a catalytic
intramolecular 1,6-addition that proceeds with essentially perfect
stereocontrol and has almost no precedents, and (iii) two
intermediate C=C isomerizations, with Brønsted base catalysts as
the only promoters. Importantly, the -addition pathway observed
for trienolates is divergent from the [4+2] cycloaddition pathways
dominant in trienamine mediated chemistry,[3h, 15] and provides a
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