Synthesis of stemofurans C, L and T using organomanganese arene
chemistry; Revised structure for stemofuran L
William H. Miles
a, *
, Cassidy M. Madison
a
, Christopher Y. Kim
a
, Daniel J. Sweitzer
a
,
Shelby D. Valent
a
, Dasan M. Thamattoor
b
a
Department of Chemistry, Lafayette College, Easton, PA 18042, USA
b
Department of Chemistry, Colby College, Waterville, ME 04901, USA
article info
Article history:
Received 28 June 2017
Received in revised form
19 September 2017
Accepted 21 September 2017
Available online 23 September 2017
Keywords:
Organomanganese arene
Stemofuran
Benzofuran
Nucleophile
abstract
The synthesis of stemofurans C, L and T was achieved using organomanganese arene complexes. The
critical carbon-carbon bond between the C-2 position of benzofuran and the arene was established in a
regioselective manner directed by the cationic manganese tricarbonyl moiety. Oxidation of the resulting
dienyl complexes and cleavage of the methyl ethers gave the desired stemofuran products. The spec-
troscopic data for the originally proposed structure for stemofuran L did not match the synthesized
material, which prompted the synthesis of an isomer that did match the spectroscopic data. This revised
structure has been proposed as the correct structure for stemofuran L.
© 2017 Elsevier B.V. All rights reserved.
1. Introduction
Nucleophilic attack on arenes coordinated to transition metals is
one of the most important modes of reactivity in organometallic
chemistry [1]. Organomanganese arene complexes, which have
been exploited in many studies [1b,2-7], are notable for their
greater reactivity compared to the more extensively studied orga-
nochromium arene complexes [1a,1c]. The reactivity of nucleo-
philes with h
6
-arene complexes, in which electron-donating
groups such as alkoxy and amino groups direct the nucleophile to
the meta-position, complements the standard electrophilic aro-
matic addition reactions to arenes [1e 7]. The addition of carbon
nucleophiles to organomanganese arene complexes possessing
electron-donating substituents typically follows this pattern, but
there are a couple of noteworthy exceptions [3b,6]. Steric repulsion
inherent in more highly substituted arenes complexes (such as the
(3-methoxyestrone)Mn(CO)
3
þ
) [3b] and/or the nature of the car-
bon nucleophile [6] leads to diminished selectivity. Even with these
potential complications, the general selectivity of these reactions
for nucleophilic attack at the meta-position to alkoxy groups sug-
gested a straightforward method for the synthesis of some 2-
arylbenzofurans, compounds that have become increasingly
important [8e10].
Benzofurans represent a broad class of biologically important
compounds [8]. 2-Arylbenzofurans, an important subset of ben-
zofurans, have been isolated from various plants, and possess bio-
logical activity including antifungal, antibacterial, and anticancer
properties [9,10]. The Stemona genus is a particularly rich source of
2-arylbenzofurans named stemofurans. The stemofurans are char-
acterized by C-3
0
and C-5
0
oxygenation on the arene ring, and
methylation on the arene and/or benzofuran rings, with additional
oxygenation frequently occurring on the benzofuran moiety [9].
Some representative examples include stemofurans C (1a), T (1b),
and L (1c; originally proposed structure). In the course of our
synthetic studies, we suspected that 1c, the originally proposed
structure for stemofuran L, was incorrect based on the comparison
between the literature values of the NMR peaks and compound 1c
that we synthesized, and that isomeric 1d was the correct structure
(Fig. 1).
There have been many synthetic strategies employed for the
synthesis of 2-arylbenzofurans, in particular the SuzukieMiyaura
coupling of 2-(boronic acid)benzofurans with the appropriate aryl
bromide [11,12]. This method depends on ready access to the
necessary aryl bromide, which sometimes poses synthetic chal-
lenges with standard electrophilic aromatic substitution chemistry.
We recognized that a subset of stemofurans and related 2-
* Corresponding author.
E-mail address: milesw@lafayette.edu (W.H. Miles).
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
https://doi.org/10.1016/j.jorganchem.2017.09.034
0022-328X/© 2017 Elsevier B.V. All rights reserved.
Journal of Organometallic Chemistry 851 (2017) 218e224