Rational synthesis of resorcarenes with alternating substituents at their bridging methine carbons

Full text of DOI:10.1021/jo981864u

9618
J . Org. Chem. 1998, 63, 9618-9619
Sch em e 1. P ossible Ster eoisom er s of Alter n a tin g
Resor ca r en es w ith Th eir Sym m etr y Elem en tsa
Ra tion a l Syn th esis of Resor ca r en es w ith
Alter n a tin g Su bstitu en ts a t Th eir Br id gin g
Meth in e Ca r bon s
Giovanna Rumboldt,† Volker Bo¨hmer,*,‡
Bruno Botta,† and Erich F. Paulus§
Dipartimento di Studi di Chimica e Tecnologia delle Sostanze
Biologicamente Attive, Universita` “La Sapienza”, P.le A. Moro 5,
00185 Roma, Italy, J ohannes Gutenberg-Universita¨t,
Institut fu¨r Organische Chemie, J .-J .-Becher Weg 34, SB1,
D-5099 Mainz, Germany, and Hoechst-Marion-Roussel
Deutschland GmbH, D-65926 Frankfurt/ Main, Germany
Received September 15, 1998
Resorcarenes1,2 are macrocyclic compounds that are easily
obtained by acid-catalyzed condensation of resorcinol with
a variety of aliphatic as well as aromatic aldehydes in a
simple one-pot reaction. Of the four possible stereoisomers
(rccc, rctt, rcct, rtct), the all-cis isomer (rccc) is often the main
product (Scheme 1). This isomer has been widely used to
synthesize further elaborated molecules such as cavitands2,3
(hemi)carcerands2,4 or even larger systems.5 The rctt isomer,
sometimes a kinetically controlled product that can be
isomerized to the thermodynamically stable rccc-isomer, has
attracted less attention,6 while only a few examples of the
rcct isomer have been reported.7
In all these cases, a single aldehyde has been used and
consequently the four resorcinol units are linked via the
same -CHR bridge. We report here the first controlled
synthesis of resorcarenes in which two different aldehydes
are incorporated in alternating order.8,9
a
The σ-plane in the rccc and rtct isomer exists only in a cone
Acid-catalyzed condensation of dimer 1, available in a
rational way through condensation of 4-bromoresorcinol with
phenylpropionaldehyde (60%) and subsequent dehalogena-
tion (100%), with p-hydroxybenzaldehyde 3 gave a conden-
sation product in quantitative yield. After complete acety-
lation (acetic anhydride/pyridine), the product was separated
(crystallization from methanol, column chromatography
(CHCl3/ethyl acetate 7/3)) into three fractions (a , 10%; b,
15%; c, 34%; isolated yields), which on the basis of MS and
NMR evidence, are isomeric decaacetates 8 of the desired
alternating resorcarene 5 (Scheme 2).
conformation. On the basis of the present general experience, the
formation of the rtct isomer is highly unlikely.
Sch em e 2. Syn th esis of Alter n a tin g Resor ca r en es
† Universita` “La Sapienza”.
‡ J ohannes Gutenberg-Universita¨t.
§ Hoechst-Marion-Roussel Deutschland GmbH.
(1) For a review see: Timmerman, P.; Verboom, W.; Reinhoudt, D. N.
Tetrahedron 1996, 52, 2663.
(2) Cram, D. J .; Cram, J . M. Container Molecules and Their Guests;
Stoddart, J . F., Ed.; Monographs in Supramolecular Chemistry; Royal Soc.
Chem.: London, 1994.
(3) See, for instance: (a) Soncini, P.; Bonsignore, S.; Dalcanale, E.;
Ugozzoli, F. J . Org. Chem. 1992, 57, 4608. (b) Gibb, B. C.; Chapman, R. G.;
Sherman, J . C. J . Org. Chem. 1996, 61, 1505.
(4) For selected examples, see: (a) J acopozzi, P.; Dalcanale, E. Angew.
Chem. 1997, 109, 665; Angew. Chem. Int. Ed. Engl. 1997, 36, 613. (b) Yoon,
J .; Cram, D. J . Chem. Commun. 1997, 2065. (c) Helgeson, R. C.; Knobler,
C. B.; Cram, D. J . J . Am. Chem. Soc. 1997, 119, 3229.
(5) (a) Timmerman, P.; Verboom, W.; van Veggel, F. C. J . M. W.; van
Hoorn, P.; Reinhoudt, D. N. Angew. Chem., 1994, 106, 1313; Angew. Chem.,
Int. Ed. Engl. 1994, 33, 1292. (b) Chopra, N.; Sherman, J . C. Angew. Chem.
1997, 109, 1828; Angew. Chem., Int. Ed. Engl. 1997, 36, 1727.
(6) For rctt isomers, highly solvated in the crystalline state, see:
Shivanyuk, A.; Paulus, E. F.; Bo¨hmer, V.; Vogt, W. Angew. Chem. 1997,
109, 1358; Angew. Chem., Int. Ed. Engl. 1997, 36, 1301.
(7) (a) Abis, L.; Dalcanale, E.; Du vosel, A.; Spera, S. J . Org. Chem. 1988,
53, 5475. (b) Abis, L.; Dalcanale, E.; Du vosel, A.; Spera, S. J . Chem. Soc.,
Perkin Trans. 2 1990, 2075.
(8) A recent publication describes a statistical approach using a mixture
of two aldehydes: Hayashi, Y.; Maruyama, T.; Yachi, T.; Kudo, K.; Ichimura,
K. J . Chem. Soc., Perkin Trans. 2 1998, 981-987.
(9) Resorcarenes consisting of different resorcinol units were recently also
described: Cortes-Lopez, G.; Gutierrez Tunstad, L. M. Synlett 1998, 139
1
A preliminary structural assignment was possible by H
NMR spectroscopy. A singlet (5.66 ppm) and a triplet (3.99
ppm) for the methine protons of 8a are compatible with the
rccc isomer, although the rctt isomer cannot be entirely
excluded. Three triaryl methine signals (1:2:1) for 8b suggest
a 1:1 mixture of the two possible rcct isomers (which in fact
can be separated by further chromatography with CHCl3/
ethyl acetate/n-hexane 8/1/1). The rctt configuration of 8c
is suggested by a doublet of doublets (instead of a triplet)
10.1021/jo981864u CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/05/1998

Communications
J . Org. Chem., Vol. 63, No. 26, 1998 9619
F igu r e 2. Section of the 1H NMR spectra of the three isomeric
resorcarenes 6a -c (400 MHz, CDCl3). The assignment of R/â, δ/γ,
and η/æ is sometimes tentative (6a at 60 °C, 6b,c at rt).
b, 7%; c, 40%; isolated yields) were separated chromato-
graphically from the mixtures 6a -c or 9a -c, respectively.
In this case, only one rcct isomer (6b), with two identical
p-nitrophenyl groups, was observed, in addition to the rccc
(6a ) and rctt (6c) isomers. Its 1H NMR spectrum is shown
and interpreted in Figure 2, and this structural asssignment
is confirmed by its decaacetate 9b, showing six methyl
singlets in the ratio of 1:1:2:2:2:2.
The less reactive propionaldehyde 4 gave with 1 only 15%
of a condensation product 7, which after acetylation could
be split into four isomeric compounds 10, namely the rccc,
the rctt, and the two rcct isomers.
In conclusion, we have shown for the first time that
resorcarenes bearing aldehyde residues in alternating order
can be prepared by fragment condensation of resorcinol
derived dimers with a second aldehyde. Further analogous
compounds should be available, using various aldehydes in
various combinations.
F igu r e 1. Molecular conformation of 8c seen from two different
directions, showing the alternating order of the methine bridge
residues (above) and the chair conformation of the rctt isomer
(below).
for the methine protons at 4.08 ppm (in addition to the
singlet at 5.58 ppm), as the diastereotopicity of the adjacent
CH2 protons is much more pronounced than for the boat
conformation of 8a , thus leading to different coupling
constants. The stronger separation of the singlets of the
endo-aryl protons (6.11 and 6.68 ppm) is also expected for
the chair conformation of the rctt isomer.
Both the general structure of the resorcarene skeleton
with alternating substituents at the methine bridges and
the configurational/conformational assignment for 8c were
confirmed by the single-crystal X-ray analysis10 shown in
Figure 1.
Condensation of the dimer 2 with p-hydroxybenzaldehyde
3 was also quantitative, and three different isomers (a , 40%;
Thus far, the condensations were carried out under mild
conditions, while the rccc isomer often forms preferably at
high temperatures. Such an acid-catalyzed isomerization rctt
f rccc requires the cleavage of Ar-CHR bonds, a reaction
that could lead to a “scrambling” of residues X and Y.
However, no compounds with a different composition could
be detected, and we are presently attempting to modify the
conditions in order to shift the product distribution toward
the rccc isomer.
(10) Crystal data for 8c: C76H68O20‚2CH3CN; Mr ) 1383.41, triclinic,
space group P-1, Z ) 1, a ) 10.745(1) Å, b ) 12.450(1) Å, c ) 14.244(1) Å;
R ) 76.49(1)°, â ) 85.39(1)°, γ ) 83.87(1)°, V ) 1839.1(3) Å3, Dc ) 1.249 g
cm-3; crystals from CH3CN/CH2Cl2, dimensions 0.35 × 0.1 × 0.07 mm;
computer-controlled four-circle diffractometer with CCD area detector and
low-temperature device, X-ray generator with rotating anode (Siemens), λ-
(Mo KR) ) 0.71073 Å, µ ) 0.090 mm-1, F(000) ) 728, T ) 238(2) K; 6894
reflections measured, 4066 of which were unique (Rint ) 0.0465, Rσ ) 0.1026)
and used for the structure determination. Direct methods (SHELXS-90),
refinement by least-squares methods (SHELXS-90, SHELXL-93), minimiza-
Su p p or tin g In for m a tion Ava ila ble: Crystallographic details
of compound 8c and preparation and characterization of com-
pounds 6 and 9 (14 pages).
2
tion of (Fo - Fc2)2; R ) 0.0811 and Rw ) 0.2022 for 2351 reflections with I
> 2σ(I), R ) 0.1408 and Rw ) 0.2417 for all unique CCD data; the
coordinates of the H-atoms were calculated, S ) 1.021, ∆Fmin ) -0.270,
∆Fmax′ ) 0.517 e Å-3
.
J O981864U