A nonphotochemical synthetic route to 3-hexahelicenol is reported. It involves a key [2+2+2]
cycloisomerization of CH3O-substituted triyne that is readily available from 1-methoxy-3-methylbenzene and 1-bromo-2-(bromomethyl)naphthalene. Further functional group transformations led
to 3-CO2CH3, 3-NH2, 3-PPh2, and 3-SC(O)N(CH3)2 substituted hexahelicenes.
An original approach to helicene frameworks exploiting atom economic isomerization of appropriate energy-rich aromatic cis,cis-dienetriynes has been developed. The new paradigm provides nonphotochemical syntheses of helicenes based on the easy, convergent, and modular assembly of key cis,cis-dienetriynes and their nickel(0)-catalyzed [2+2+2] cycloisomerization. The potential of the methodology is underlined by the syntheses of the parent [5]helicene (2), 7,8-dibutyl[5]helicene (23), [6]helicene (24), and [7]helicene (25). The approach can be adapted to prepare functionalized helicenes as exemplified by the eight-step synthesis of 7,8-dibutyl-2,3-dimethoxy[6]helicene (34). Density functional theory (DFT) calculations showed that bis[2-((1Z)-1-buten-3-ynyl)phenyl]acetylene (1) and isomeric [5]helicene (2) differ enormously in the Gibbs energy content (DeltaG = -136.6 kcal x mol(-1)) to favor highly the devised intramolecular simultaneous construction of three aromatic rings.
A straightforward synthetic approach to a new class of molecules
with helical chirality has been
developed involving an intramolecular [2 + 2 + 2]
cycloisomerization of triynes under
CpCo(CO)2/PPh3 catalysis. The cyclization reaction is promoted by
visible light irradiation. Starting from
1,2-diarylacetylenes with two terminal or methyl-substituted tethered
acetylene moieties (1a,b,
4,
5, and 7), the target products
(8a,b, 11, 12, and
14) are obtained in 64−89% yield. The
triynes
bearing terminal trimethylsilyl groups (1c, 2,
and 3) are less reactive and afford the products
(8c,
9a,b, and 10) in 23−71% yield.
The ability of the trimethylsilylated derivatives to
cycloisomerize
strongly depends on the tether length. The cyclized products
(8−14) with five, six, and seven
ortho-fused rings structurally resemble classical helicenes. Several
representatives (8b, 11, 12, and
14)
have been resolved into enantiomers by HPLC on a chiral column.
Thus, the methodology exhibits
a considerable versatility and allows the preparation of a variety of
helical objects.
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