with both contiguous and alternating donor/acceptor ele-
ments, and how stable the resulting complexes would be. In
view of the importance and wide utility of coplanar AADD
arrays in the development of supramolecular polymers and
materials,[11] we anticipate an array based on our double-hel-
ical design containing this sequence could be utilized in sim-
ilar applications, if the dimerization constant is comparable.
Herein, we describe the synthesis and characterization of a
series of four AADD hydrogen-bond arrays that form self-
complementary double-helical complexes exhibiting Kdimer
values from 102 to >107 mÀ1.
Results and Discussion
Scheme 1. Synthesis of the dipyridyl containing fragments of the AADD
arrays. a) tBuLi/Et2O (1.2 equiv), À788C, 0.5 h, N,N-dimethyl acetamide
(1 equiv; 3a) or N,N-dimethylpropionamide (3b), À788C, 1.5 h, 80–85%;
Design and synthesis: The four AADD arrays synthesized
were chosen to elucidate the importance of several factors
that were anticipated to affect dimer formation and stability.
The presence or absence of a methyl substituent (R2) on the
thiazine donor was intended to indicate the importance of
sterics in preventing any potentially undesired intramolecu-
lar hydrogen bonding with the adjacent pyridyl acceptor
(Scheme 3). Similarly, the installation of a trimethylene
tether between the two donor heterocycles (R3) was antici-
pated to improve dimerization as a result of its preorganiz-
b) [PdACHTNUGTRNEGNU(PPh3)4] (3 mol%), toluene, reflux 18 h, 85–95%; c) Br2 (1.2 equiv)
and HBr in acetic acid (2 equiv, 33%; 3a) or AlCl3 in Et2O (2%; 3b),
12–18 h, 70–82%.
ing effect on the arrayꢂs conformation. The installation of
4
electron-donating R1 ( CH3) and electron-withdrawing R
À
À
À
( CO2Et, NO2) group were expected to improve the ac-
ceptor and donor character of their respective heterocy-
cles.[10c]
The final AADD arrays were generated by using a con-
vergent approach, in which two halves of the molecule were
synthesized and joined to provide a thioether intermediate
that is further oxidized and cyclized to give the thiazinediox-
ide ring system.[12] The reaction scheme involves readily
available and inexpensive starting materials and conversions
are executed in moderate-to-excellent yields by using six
linear steps.
Scheme 2. Synthesis of the indole-containing fragments of the AADD
arrays. a) (i) KOH, EtOH, H2O, 0 8C to RT; (ii) HCOOH, reflux 2–20 h,
80–90%; b) phenyltrimethylammonium tribromide (1 equiv), dry THF,
408C, 1–12 h, 75–80%; c) (i) KSAc (1 equiv), DMF, 4–12 h; 90–95%; (ii)
cysteamineHCl (1 equiv), NaHCO3 (1.2 equiv), MeCN, 24 h, 85–92%.
Synthesis of the dipyridine fragment 4 was initiated by
monolithiating 2,6-dibromo-3,5-lutidine[13] and acylating the
resulting anion by using an appropriate dimethylamide to
give 1 (Scheme 1). Palladium coupling with 2a/b led to 3a–c
that are easily brominated to yield dipyridyl fragments 4a–c.
Synthesis of the indole-containing fragments was straight-
forward by using a modification of the protocol that we pre-
viously employed.[14] The cyclic heptanoyl indole 9 was gen-
erated in a similar manner to that of the acyclic skatoles 6
The AADD arrays were assembled by connecting the two
fragments to form thioethers 12 (Scheme 2). The thioethers
were then oxidized to their analogous sulfones 13 and ulti-
mately condensed with NH4OAc to give the final products
14 (Scheme 3). Although the syntheses of only four arrays
are presented herein, the synthetic approach is amenable to
give derivatives incorporating a wide variety of R1–R4,
should they be desired.
by using
a
Japp–Klingemann–Fischer indole synthesis
X-ray analysis of AADD complexes: Single crystals suitable
for X-ray diffraction analysis were grown for all four of the
AADD arrays synthesized. Of the four sets of crystals ana-
lyzed, satisfactory solutions were obtained for those contain-
ing 14a°, 14c§, and 14d†.[16] The solid-state structures are
instructive and shed light on the solution studies that follow.
The unsubstituted array 14a crystallizes in space group
P21/c including two molecules per asymmetric unit
(Figure 2). The two molecules form zigzag one-dimensional
(Scheme 2).[15] These intermediates were then brominated
and converted to their corresponding mercaptans by substi-
tution with thioacetate and subsequent hydrolysis to give 8
and 11. It is notable that the manipulations to produce both
8 and 11 from the initial diazonium salts can be executed
without the aid of chromatography if desired, considerably
simplifying their syntheses.
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
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