Cycloadditions with [n]Cyclophanes

Abstract

Benzene and its simple derivatives generally do not tend to play the role of the diene component in Diels-Alder reactions[ '1. However, this passive nature can occasionally be overcome by drastic experimental conditions, Lewis acid catalysis, or by the use of strong dienophiles such as dicyanoacetylene, perfluoro-2-butyne, or tetrafluor~dehydrobenzene [~].Another possibility of increasing reactivity consists in the use of sterically strained arenes. Thus, e. g. [2.2]paracyclophane (strain energy ca. 31 kcal/mol) reacts with dicyanoacetylene["l and with tetrafl~orodehydrobenzene~~~~ to give 1 : 1 and 1 : 2 adducts. No cycloaddition takes place with the less reactive dimethyl acetylenedicarboxylate ; however, this dienophile does add to the more highly strained [2.2.2](1,2,4)cyclophane (170°C, 1 h, 61 %)I4]. Since [n]cyclophanes with small numbers of bridging members have become readily accessible recentlyr5], the question of their behavior in [2+4] cycloadditions has attracted interest. We report here on the Diels-Alder reactions of [7]-(1 a) and [Slparacyclophane ( I b) and of [7]metacyclophane ( 4 ) . n + R -C S -R (2) * i L& ~ CHC ' ( C H i ) L n = 7: ( I a j n = 8 : ( I b ) R = CF,, n = I: (3aj R = CF,, n = 8: (36) R = CN, n = 8: ( 3~)3 h to give 1 : 1 adducts (MS analysis) in 52 and 12.5 % yield, respectively, whose structures (3 a) and (3 b ) follow from spectroscopic data. The 'H-NMR spectra of these bridged barrelenes are highly informativec6]. In the more complex spectrum (CDC13) of the solid (36) (m.p. 53°C) the olefin protons Ha appear as a pseudo double-doublet at 6=6.45 (2H, J1 = 6.0, J 2 = 2.0 Hz, coupling with H' no longer resolved), the bridgehead protons Hb as a sharp double doublet at 4.59 (2H, J1 =6.0, J2=2.0Hz), the methylene protons H" at 2.25 (4H, ps-t, J = 6.5 Hz) and the remaining bridge protons as an unstructured multiplet between 1.7 and 0.8 (12H). For the oily adduct ( 3 a ) the corresponding signals are observed at 6=6.52 (2H, ps-d, J=5.5Hz, Ha), 4.64 (2H, dd, J1=5.5, J z = I S H z , Hb), 2.24 (4H, m, H') and 1.26 (IOH, m, Hd). If the reaction time is prolonged to 24 h in the case of (1 b ) , the yield of ( 3 b ) increases to 76.5 %. The shorter-bridged phane thus proves to be more suitable for addition; this can be explained in terms of its higher strain energy in comparison to ( 1 b)[']. Under comparable conditions (o-dichlorobenzene, 170°C, 24 h), dicyanoacetylene (2), R = CN, does not react with (1 b); cycloaddition to the solid ( 3 c ) (m.p. 186°C) C24.6 % ; NMR[6' (CDC13): F = 6.45 (2 H, ps-dd, J 1 = 2.0 Hz, Ha), 4.58 (2H, dd, J 1~6 . 0 , J2=2.0Hz, Hb), 2.27 (4H, ps-t, J=7.0Hz, H"), 0.8-1.7 (12H, m, Hd)] takes place only on addition of aluminum trichloride (o-dichlorobenzene, 120"C, 24 h). Finally since dimethyl acetylenedicarboxylate (2), R=COOCH3, does not add to (1 b), even with this type of activation (A1C13/o-dichlorobenzene, 120"C, 24 h) the dienophilicity of the triple bond dienophiles (2) towards the arenes ( I ) decreases along the series R=CF3 >CN $ COOCH3.If (1 a) is tr...

Dual Activation of Aromatic Diels–Alder Reactions

“…Contrary to intuition, there is ad ecrease in p*-p*o verlap S 0 pÀp upon bending ( Table S3 in the Supporting Information). [30] Thus, structural distortion reduces the H-L energy gap within P and accelerates its Diels-Alder cycloaddition because of the enhanced P-A orbital interaction, as reflected in DE oi (red curves in Figure 6). Thus, the H-L energy gap within B decreases upon out-of-planed istortion by 1) increased p-p overlap thatd estabilizes theH OMO,a nd 2) enhanced electrostatic stabilization that stabilizes the LUMO despite an unanticipated reduction in p* + p*o verlap.F urthermore, an increase in the bending of the benzylic CÀCb ond b (see Figure 1a)r esults in mixingo ft he s and p fragment orbitals of the ring substituents and the aromatic core, respectively,which therebyenhances both the destabilization of the antibonding p-HOMO andt he stabilization of the bonding p* LUMO and thus contributes to decreasing the H-L gap even further( Figure8and Figure S3 in the Supporting Information).…”

“…The outlined relationship between structural distortion (geometrical strain) and the H-Lg ap sheds new light on the findings of Hopf and co-workers,w ho attributed the enhanced reactivity of [n]paracyclophanes over B solely to the sterically strained geometries. [30] Thus, structural distortion reduces the H-L energy gap within P and accelerates its Diels-Alder cycloaddition because of the enhanced P-A orbital interaction, as reflected in DE oi (red curves in Figure 6). Cyclophane M exhibits as maller M-A orbital-energy gap than the parent system B-A at the start of the cycloaddition (blue and black curve, respectively,i n Figure 6).…”

Some Investigations on [6]Metacyclophanes

“…[17] At room temperature, [6]metacyclophanes undergo a second conformational movement, a pseudorotation of the hexamethylene bridge on the same side of the ring [11] (Figure 1). This dynamic process can be frozen on the NMR time scale, and we have determined the energy barrier from variable-temperature 13 C NMR measurements and lineshape analysis. For the dichloro [6]metacyclophane (2c), the parameters are ∆H ‡ ϭ 10.9 kcal·mol Ϫ1 and ∆S ‡ ϭ Ϫ5 cal·mol Ϫ1 ·K Ϫ1 (CDCl 3 ); this is in good agreement with previously determined data for three derivatives of 2 [∆G ‡ ϭ 11.1Ϫ12.7 kcal·mol Ϫ1 (CFCl 3 , T c ϭ Ϫ 31.5 to Ϫ1.0°C)].…”

“…Scheme 1 homologue [7]metacyclophane (3) did undergo a DielsϪAlder reaction with hexafluoro-2-butyne at 150°C to furnish 4. [13] More recently, 2a, inadvertently formed in situ from [6]paracyclophane (5), was shown to react with dicyanoacetylene with formation of the adduct 6 in 6% yield [14] (Scheme 2).…”

Some Investigations on [6]Metacyclophanes

“…Scheme 1 homologue [7]metacyclophane (3) did undergo a DielsϪAlder reaction with hexafluoro-2-butyne at 150°C to furnish 4. [13] More recently, 2a, inadvertently formed in situ from [6]paracyclophane (5), was shown to react with dicyanoacetylene with formation of the adduct 6 in 6% yield [14] (Scheme 2).…”