Received: April 15, 2015 | Accepted: May 14, 2015 | Web Released: May 21, 2015
CL-150351
Cavity-promoted Diels-Alder Reactions of Unsubstituted
Naphthalene: Fine Reactivity Tuning by Cavity Shrinkage#
Yu Fang,1 Takashi Murase,2 and Makoto Fujita*1
1Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656
2Department of Material and Biological Chemistry, Faculty of Science, Yamagata University,
1-4-12 Kojirakawa-machi, Yamagata 990-8560
(E-mail: mfujita@appchem.t.u-tokyo.ac.jp)
O
R2
By finely tuning the cavity volume of a coordination cage,
R2
N
N
R1
R1
cage 1a or 1b
the Diels-Alder reactivity of aromatic compounds was
enhanced. Even unsubstituted naphthalene could be made to
undergo the Diels-Alder reaction with N-tert-butylmaleimide,
with perfectly controlled syn-selectivity. M6L4 cages with
standard and contracted cavities had opposite effects on the
reaction: the former favored larger Diels-Alder substrates,
whereas the latter favored smaller ones.
+
O
O
O
R1
R1
2a : R1 = H
3a : R2 = t-Bu
3b: R2 = c-C6H11
4a : R1 = H, R2 = t-Bu
2b: R1 = Me
2c : R1 = Et
4b: R1 = Me, R2 = t-Bu
4c : R1 = Et, R2 = t-Bu
4d: R1 = H, R2 = c-C6H11
4e : R1 = Me, R2 = c-C6H11
4f : R1 = Et, R2 = c-C6H11
Well-defined cage cavities can activate otherwise inert
substrates to accelerate chemical reactions with high regio- and
stereoselectivity.1 The close proximity of the substrates’ reaction
sites in the cavity is indispensable, and fine tuning of substrate
structures is often required to achieve highly efficient reactions.
In our previous studies on the Diels-Alder reactions of aromatic
compounds within M6L4 cage 1b (Figure 1),2 unnecessary alkyl
substituents had to be introduced into the substrates to enhance
their reactivity.2c Here, we report that the substrate reactivity
can be changed dramatically without modifying the substrate
structures but by finely tuning the cavity volume of cage 1.
Recently, we have shown that the effective cavity volume
of cage 1 is easily contracted by functionalizing the 1,10-
phenanthroline ancillary ligand on the Pd(II) units with sterically
demanding groups.3 The cavity volume is, in particular,
significantly reduced (by as much as ca. 20%) with mesityl
(Mes) group functionalization (Figure 1).4 Contracted cage 1a
showed binding behavior different from that of 1b toward large
organic guests, but we have not previously examined the effect
of the cavity contraction on reactivity control. Here, we show
Scheme 1. Cavity-promoted Diels-Alder reactions of naphthalene 2
with N-alkyl maleimide 3.
that in the contracted cavity, even unsubstituted naphthalene
smoothly undergoes the Diels-Alder reaction, and suggest a
catalytic cycle for the reaction (Scheme 1).5
Expecting enhanced reactivity for the Diels-Alder reaction,
unsubstituted naphthalene 2a (20 ¯mol), which was inert in cage
1b,2c was treated with N-tert-butylmaleimide (3a, 10 ¯mol) in
an aqueous solution of cage 1a (1.0 mM, 10.0 mL, 10 ¯mol) at
80 °C.6 Unlike its inclusion in cage 1b, in which a ternary
complex [namely, 1b¢(2a¢3a)] is easily formed, after 1 h
stirring, contracted cage 1a bound only one molecule of 2a to
form inclusion complex 1a¢2a in 60% yield. Maleimide 3a,
though slightly soluble in water, remained largely unbound and
suspended in the reaction solution. A small portion of dissolved
3a may have formed ternary complex 1a¢(2a¢3a), as the signals
of 3a were slightly shifted upfield (¦¤ = ¹0.24 ppm for the
olefin protons). When this mixture was heated at 100 °C for 24 h,
however, the pale yellow solution turned cloudy. In a control
experiment in D2O, a new set of signals appeared in the 1H NMR
spectrum at this stage, strongly indicating that the Diels-Alder
reaction started to occur at 100 °C. The reaction mixture was
filtered, and the filtrate was extracted with chloroform. 1H NMR
spectroscopy of the filtrate showed the formation of Diels-Alder
product 4a. The filtered solid also included 4a as a major
component. The combined crude product was purified by
column chromatography and gel permeation chromatography
to give pure 4a in 46% isolated yield. When the reaction was
carried out at 110 °C, the yield was increased to 58%.
N
N
Pd
12+
–
Pd =
Pd
Pd =
Pd
N
N
N
N
12NO3
N
N
N
N
N
N
N
Pd
N
N
N
N
Pd
Pd
N
N
Pd
N
N
N
N
N
N
N
N
N
Pd
1
The syn stereochemistry of 4a was deduced from the
upfield-shifted N-tert-butyl protons (¤ = 1.17 ppm), which are
located above the benzene ring. An NOE correlation between
the vinyl protons and the bridgehead protons also supported the
stereochemistry. No anti isomer was detected by NMR spec-
troscopy. With the sterically unbiased cage 1b, 2a, and 3a were
coencapsulated to give ternary complex 1b¢(2a¢3a) in 71%
1a
(380 Å3)
1b
(462 Å3)
Figure 1. Self-assembled coordination cages 1. The cavity volume
of 1 shown in parentheses was calculated based on each X-ray crystal
structure using the VOIDOO program (probe radius: 3.36 ¡). For
details, see ref 3.
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