Concave reagents+. New 2′-substituted m-terphenyls

Article abstract of DOI:10.1135/cccc20041325

New 2′-substituted 2,2″,6,6″-tetramethyl-1,1′: 3′,1″-terphenyls have been synthesized. Solubility of concave acids 4b-6b could be enhanced by substitution in 4 and 4″ position, allowing the study of hydrogen-bonded heterodimers. Concave acids show larger

Full text of DOI:10.1135/cccc20041325

Concave Reagents
1325
+
CONCAVE REAGENTS . NEW 2′-SUBSTITUTED m -TERPHENYLS
a
b
c
d
Michael ABBASS , Christine KÜHL , Christian MANTHEY , Anja MÜLLER and
e,
Ulrich LÜNING *
a
ChemCon GmbH, Engesserstrasse 4b, D-79108 Freiburg, Germany;
e-mail: michael.abbass@chemcon.com
Bernina Biosystems GmbH, Am Klopferspitz 19a, D-82152 Martinsried, Germany
ipal Gesellschaft für Patentverwertung Berlin mbH, Bundesallee 210, D-10719 Berlin, Germany;
b
c
e-mail: christian.manthey@ipal.de
Gilson International BV, Otto-Hahn-Str. 17, D-65520 Bad Camberg, Germany;
d
e-mail: amueller@gilson.com
Institut für Organische Chemie, Olshausenstr. 3/4, D-24098 Kiel, Germany;
e
e-mail: luening@oc.uni-kiel.de
Received Decem ber 17, 2003
Accepted February 18, 2004
Dedicated to Professor Ivan Stibor on the occasion of his 60th birthday.
New 2′-substituted 2,2′′,6,6′′-tetram eth yl-1,1′:3′,1′′-terph en yls h ave been syn th esized. Solu-
bility of con cave acids 4b–6b could be en h an ced by substitution in 4 an d 4′′ position , allow-
in g th e study of h ydrogen -bon ded h eterodim ers. Con cave acids sh ow larger bin din g con -
stan ts for 2-am idopyridin es 7 th an n on -m acrocyclic on es, probably due to th e preven tion of
h om odim er form ation by th e m acrocyclic sh ieldin g. New 2,6-diarylben zyl alcoh ols 1d , 8d
an d 9d h ave been syn th esized an d tested in proton ation reaction s. New fun ction al groups
were in troduced in to th e 2′ position : OH (ph en ols 1f an d 12f) an d NH2 (an ilin e 1j). Th e ba-
sicity of an ilin e 1j in eth an ol was determ in ed by titration an d was com pared to oth er bases.
Also sulfon ic acids 1l an d 17l were prepared, an d th e correspon din g m eth yl esters 1m an d
1
7m were tested as m eth ylatin g agen ts.
Keyw ord s: Aren es; Biaryls; Terph en yls; Ph en ols; Sulfon ic acids; Receptors; Basicity; Hydro-
gen bon ds; Macrocycles; Supram olecular ch em istry.
Th e h igh selectivity of en zym atic reaction s is largely caused by th e con cave
2
sh ieldin g of th e active site with in th e polypeptide en viron m en t (e.g. lit. ).
In artificial com poun ds, con cave structures play an in creasin gly im portan t
3
–5
6,7
role , an d con cave reagen ts an d catalysts h ave been developed . Man y of
+
Part 42 of th e series. For part 41 see: ref.1
Collect. Czech. Chem. Commun. (Vol. 69) (2004)
doi:10.1135/cccc20041325

1
326
Abbass, Kühl, Manthey, Müller, Lüning:
th ese com poun ds are m acrocyclic or oligom acrocyclic, but also tweezer-,
8
–15
clip-, cleft- or pin cer-like com poun ds
h ave been syn th esized.
An im portan t structure for con cave m olecules is th e m-terph en yl m oiety
Fig. 1). If a fun ction al group is in troduced in to th e 2′ position of a m-ter-
(
ph en yl, th e outer ben zen e rin gs sh ield th is fun ction al group. Th e sh ieldin g
is extrem ely efficien t if th e outer ben zen e rin gs carry furth er substituen ts in
th e ortho position s, i.e. in position s 2, 6, 2′′ an d 6′′.
6
6"
2
'
4
2
2"
4"
FIG. 1
Num berin g of th e 1,1′:3′,1′′-terph en yl system
m-Terph en yls of th is kin d h ave been used by m an y research groups, an d
for m an y purposes, for in stan ce for th e stabilization of h igh ly reactive fun c-
tion al groups boun d in position 2′ 16. A very con ven ien t syn th etic approach
1
7,18
to th ese m-terph en yls h as been developed by Hart
an d h as been ex-
1
9–23
ploited by us
A key in term ediate in th e syn th esis of such m-terph en yls is th e 2′-iodo-
,2′′,6,6′′-tetram eth yl-1,1′:3′,1′′-terph en yl (1a) . A variety of differen t fun c-
.
1
9
2
1
9–23
tion al groups h as been in troduced in to th e 2′ position
an d th e in flu-
en ce of th e sh ieldin g by th e m-terph en yl on th e reactivity an d selectivity of
fun ction al groups in position 2′ h as been studied in several cases. Th e
m eth yl groups h ave been also fun ction alized an d bridged to fin ally give bi-
m acrocylic con cave m-terph en yl structures 2 1
9–22
con tain in g, for in stan ce,
1
9,20
acid fun ction alities in side. Th us, con cave ben zoic acids
th iols an d con cave sulfin ic acids h ave been syn th esized (Sch em e 1).
, con cave
2
1
22
X
a
b
c
d
e
f
I
COOH
CHO
CH OH
Li
OH
X
1
2
g
h
i
COCl
CON3
NCO
NH2
j
k
l
m
SO Cl
SO H
SO Me
2
3
3
X
2
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1327
In th is work, we presen t n ew m-terph en yls. Th e solubility of som e
m-terph en yls con tain in g bim acrocycles h as been en h an ced by substitution
in position s 4 an d 4′′. Furth erm ore, th e outer aryl rin gs h ave been varied,
an d n ew fun ction al groups h ave been in troduced in to th e 2′ position .
RESULTS
All fin al com poun ds described below h ave been ch aracterized by IR, MS,
NMR an d elem en tal an alyses. In th e case of on e fin al product (9d ), a cor-
rect elem en tal an alysis could n ot be obtain ed. In stead, th e com poun d h as
been ch aracterized by h igh -resolution MS in com bin ation with a purity
ch eck by GC. Som e of th e in term ediates h ave been fully ch aracterized, oth -
ers n ot. However, subsequen t reaction s to th e fin al products are addition al
structural proofs for th e in term ediates.
Concave Acids – Hydrogen Bond Formation
Con cave ben zoic acids an d th eir m eth yl esters based on th e m-terph en yl
skeleton h ave already been syn th esized startin g from th e 2,6-bis(2,6-di-
1
9
m eth ylph en yl)ben zoic acid (1b) .
Mon obrom in ation of all four m eth yl groups was possible usin g NBS 19
.
Th e resultin g tetrabrom ide could th en be bridged with dith iols to give
1
9
bim acrocyclic esters, an d th e correspon din g acids after h ydrolysis . In or-
der to en h an ce th e solubility, tert-butyl groups h ave already been in tro-
duced in to th e 4 an d 4′′ position s of an an th racen e-con tain in g con cave
2
0
acid 6b . Perform in g an alogous tetrabrom in ation with th e tert-butylated
m eth yl ester gave tetrabrom ide 3a 20. Bis-m acrocyclization with dith iols
gave th e con cave esters 4a an d 5a, an d h ydrolysis led to th e con cave acids
2
2
4
b an d 5b in sufficien t quan tities to study th eir acid/base beh avior
(
Sch em e 2). Furth erm ore, th eir poten tial to bin d guest m olecules by h ydro-
gen bon ds could be in vestigated, n ow th at th e solubility was large en ough
for NMR titration s.
2
4
Carboxylic acids can form two h ydrogen bon ds (an exam ple: lit. ). Th e
COOH group acts as a h ydrogen bon d don or D an d as a h ydrogen bon d ac-
ceptor A. 2-Acetam idopyridin es such as 7 2
5–27
(Sch em e 3) h ave been ch o-
sen as com plem en tary partn ers, wh ich also form two (DA) h ydrogen bon ds
2
8
(
an exam ple of such in teraction s: lit. ).
Th ese com poun ds h ave been in vestigated in NMR titration s (for in vesti-
gation of th e form ation of h ydrogen bon ds to oth er m-terph en yl acid,
2
9
see ) with th ree m-terph en ylcarboxylic acids: with th e paren t m-terph en yl-
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1
328
Abbass, Kühl, Manthey, Müller, Lüning:
Br
Br
a, R = COOMe
b, R = COOH
R
tBu
tBu
S
Br Br
4, X =
3
S
H-X-H
S
S
S
5
, X =
X
6, X =
R
X
tBu
tBu
S
4-6
SCHEME 2
O
7
a, R = H
R
N
N
H
7b, R = Me
SCHEME 3
carboxylic acid 1b, an d with carboxylic acids 4b an d 6b 20. Rem arkably, th e
3
con cave acids 4b an d 6b sh owed association con stan ts of 10 wh ile 1b pos-
sessed con stan ts of less th an 100. A possible explan ation m ay be th e com -
petin g self-dim erization of carboxylic acids because th e DA pattern is self-
com plem en tary. However, in a con cave structure, self-dim erization is pro-
h ibited, th us leadin g to a larger degree of h eterodim er form ation with acet-
am idopyridin es 7.
m-Terphenylmethanols and Protonation Reactions
Th e use of m-terph en ylm eth an ols in th e proton ation of carban ion s h as led
2
3
to predom in an t form ation of on ly on e stereoisom er (th e special cis selec-
tivity of m-terph en yl alcoh ols in proton ation reaction s is probably caused
by a selective tran sesterification 30). Two n ew m-terph en yls h ave been syn -
th esized an d in vestigated: th e m eth yl groups in th e ortho position s of th e
outer rin gs (1d ) h ave been replaced by isopropyl groups (8d ), an d th e
dim eth ylph en yl rin gs h ave been en larged to m eth yln aph th yl rin gs (9d )
(
Sch em e 4). In both cases, th e syn th esis of th e m-terph en ylm eth an ols 8d
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1329
an d 9d was carried out an alogously to th e syn th esis of th e paren t tetra-
2
3
m eth yl-m-terph en yl 1
.
a, X = I
X
1
1
2
. BuLi
. HCOOMe
iPr
iPr
c, X = CHO
X
iPr iPr
8
1. LiAlH4
. H3O+
2
d, X = CH2OH
X
9
SCHEME 4
First, th e en larged m-terph en yl structure was built up usin g iodides 8a
an d 9a. Iodide–lith ium exch an ge followed by reaction with m eth yl form ate
gave th e n ew aldeh ydes 8c an d 9c, wh ich were reduced to m eth an ols 8d
an d 9d by reaction with lith ium alum in ium h ydride.
All th ree alcoh ols 1d , 8d an d 9d were in vestigated in th e proton ation of
several substrates, for in stan ce in th e reproton ation of th e α-deproton ated
eth yl 4-tert-butylcycloh exan e-1-carboxylate (10)2
3,31
(Sch em e 5) or eth yl
COOEt
COOEt
1
. LDA
+
COOEt
2
. protonation
tBu
tBu
tBu
cis-10
trans-10
SCHEME 5
2
-m eth yl-3-ph en ylbutan oate (11)32,33 (Sch em e 6). All proton ation experi-
m en ts were carried out as described for tetram eth yl-m-terph en yl-2′-m eth a-
n ol 1d an d th e ratio of th e stereoisom ers was determ in ed by GC as de-
Ph
COOEt
1. LDA
. protonation
Ph
COOEt
2
11
threo- and erythro-11
SCHEME 6
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1
330
Abbass, Kühl, Manthey, Müller, Lüning:
scribed in 23. As with 1d 23, th e cis an d erythro products were foun d in excess
wh en th e m odified m eth an ols 8d an d 9d were used. With th e cycloh exan e
ester 10 an d th e m eth yln aph th ylated alcoh ol 9d , also a very good cis/trans
ratio of >97:3 was foun d. In con trast, th e isopropylated m eth an ol 8d was
less selective, an d even less reproducible. Varyin g ratios were foun d for
cis-10/trans-10, from 80:20 to >97:3. Th is fin din g is supported by th e data
obtain ed for acyclic butan oate 11. Th e threo/erythro ratios obtain ed with 8d
(
22:78) were sm aller th an th ose obtain ed with 1d an d 9d (both 15:85).
Other Acids and Bases: m-Terphenyl Phenols and Aniline
With m-terph en ylm eth an ols, an d th e respective carboxylic an d sulfin ic ac-
1
9–22
ids
, on ly a sm all pK ran ge of acids an d bases was covered. Th erefore,
a
altern ative reaction s to in troduce furth er fun ction al groups in to th e 2′ posi-
tion of th e m-terph en yl h ave been in vestigated.
1
9
In th e first reaction , th e 2′-iodo-m-terph en yl 1a
was lith iated, an d th e
in term ediate 1e was oxidized to give th e ph en ol 1f (Sch em e 7). Oxygen an d
lith ium tert-butyl peroxide could be used as oxidan ts. Furth erm ore, th e lith -
ium com poun d 1e was also quen ch ed with boran e an d th en oxidized with
h ydrogen peroxide. In all cases, th e ph en ol 1f could be obtain ed, but on ly
in m oderate yields (m ax. 25%).
1
. O
. H
2
2
3
O+
or
1
. LiOOtBu
. H
O+
2
3
nBuLi
I
Li
or
. BH
OH
1
3
1a
1e
2
2. H O
2
, NaOH
1f
1. nBuLi
I
2. O
. H
2
OH
3
3
O+
12a
12f
SCHEME 7
Th e sam e reaction was possible for th e 3,5-dim eth ylated an alog 12f start-
1
9
in g from iodide 12a . In proton ation reaction s, h owever, n o special selec-
tivity is expected for ph en ols 1f an d 12f because ph en ols are m ore acidic
th an alcoh ols (Sch em e 7). Th e com petition between a gen eral an d specific
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1331
proton ation – proton ation by an y acid or specifically by proton ated solven t
m olecules – is determ in ed by th e con cen tration of proton ated solven t m ol-
7
,34
ecules, th us by th e acidity of th e proton source
(for gen eral an d specific
3
5
36
acid catalysis, see , for gen eral an d specific proton ation , see ). In deed, n o
special cis or erythro selectivity was foun d.
So far, m-terph en yls h ad on ly been syn th esized as acids, n o basic fun c-
tion alities like an am in o group were in troduced. We h ave realized two ways
to obtain m-terph en yl-2′-am in e 1j. Th e first approach exploits a rearran ge-
m en t reaction . Startin g from acid 1b 19, acid ch loride 1g was syn th esized
an d reacted with an azide source (trim eth ylsilyl azide or sodium azide). Th e
resultin g m-terph en yl azide 1h was allowed to decom pose at elevated tem -
perature an d rearran ged to give isocyan ate 1i. Subsequen t h ydrolysis re-
sulted in th e form ation of th e an ilin e 1j (Sch em e 8).
1b, X = COOH
1g, X = COCl
1h, X = CON3
1i, X = NCO
1j, X = NH2
SOCl2
N3-SiMe3 or NaN3
∆
X
H2O
SCHEME 8
Altern atively, th e 2′-am in o-m-terph en yl 1j can also be built up startin g
from 2,6-dibrom oan ilin e (14). A double Suzuki couplin g of two equivalen ts
3
7
of boron ic acid 13 with 2,6-dibrom oan ilin e (14) resulted in th e form ation
of th e sam e an ilin e 1j (Sch em e 9).
B(OH)
2
[
3 4
Pd(PPh ) ]
+
Br
Br
1j
2
NH
2
13
14
SCHEME 9
Th e basicity of th e n ew an ilin e 1j was in vestigated in eth an olic solution
usin g a m eth od wh ich was establish ed to determ in e relative basicities for a
large n um ber of oth er sterically h in dered bases3
8,39
. A dilute solution of
Th ym ol Blue was slowly titrated with a base, an d th e UV spectrum was re-
corded. Th e resultin g log K values are relative basicities. Table I com pares
differen t bases. Th e dim eth ylaryl rin gs ortho to th e am in o fun ction lower
th e basicity of th e n ew an ilin e 1j by m ore th an on e order of m agn itude.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1
332
Abbass, Kühl, Manthey, Müller, Lüning:
m-Terphenylsulfonic Acids and Esters – Methylation Reactions
As observed in m an y cases, th e reactivity of th e fun ction al group in posi-
tion 2′ of a sterically sh ielded m-terph en yl is reduced, for in stan ce th e reac-
tivity of sulfon yl ch loride 1k 21. On ly un der h arsh con dition s th is ch loride
can be h ydrolyzed to give sulfon ic acid 1l (Sch em e 10). Th e use of eth an ol
to en h an ce th e solubility was crucial.
23
1. KOH, EtOH/H2O
SO2Cl
SO3H
2. conc. HCl
1k
1l
SCHEME 10
Due to th e stron g acidity of sulfon ic acids, th e steric effect of th e m-ter-
ph en yl m oiety will probably h ave n o large in fluen ce on th e beh aviour of
th is acid. However, th e sh ieldin g sh ould h ave an in fluen ce on th e ch em is-
try of th e sulfon ic acid derivatives, for in stan ce esters. Meth yl ester 1m is a
sterically sh ielded an alog of dim eth yl sulfate or m eth yl tosylate, well-
kn own alkylatin g agen ts. It was syn th esized by reaction of sulfon ic acid 1l
with diazom eth an e (Sch em e 11).
CH2N2
1l
SO3Me
1m
SCHEME 11
TABLE I
log K values (relative basicities) for differen t bases obtain ed by UV titration of Th ym ol Blue
ca. 50 µm ol/l) in eth an ol (log K(Th ym ol Blue) ≡ 0)
(
Base
log K
Pyridin e
,6-Dim eth ylpyridin e
An ilin e
,6-Dim eth ylan ilin e
Com poun d 1j
0
... –0.2
2
1.2 ... 1.3
0.6
2
–0.3
–1.0
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1333
To en h an ce th e solubility of acid 1l an d m eth yl ester 1m , again , th e
outer ben zen e rin gs of th e m-terph en yl m oiety were substituted by tert-
butyl groups in position s 4 an d 4′′. Th e tert-butyl-substituted m-terph en yl
1
7a was built up by th e Hart reaction 17 usin g tert-butylated aryl brom ide 15
(
Sch em e 12) an d 1,3-dich loro-2-iodoben zen e (16).
tBu
1. 3 Mg
3
2.
I
tBu
tBu
Br
Cl
Cl
15
I
17a
16
SCHEME 12
Startin g from iodide 17a, lith iation an d followin g reaction of th e
lith iated com poun d 17e with sulfuryl ch loride gave sulfoch loride 17k .
Hydrolysis to acid 17l an d reaction with diazom eth an e yielded m eth yl
sulfon ate 17m (Sch em e 13).
nBuLi
SO2Cl2
I
Li
tBu
tBu
tBu
tBu
17a
17e
1. KOH, EtOH/H2O
SO2Cl
7k
SO3H
2. conc. HCl
tBu
tBu
tBu
tBu
1
17l
CH2N2
SO3Me
7m
tBu
tBu
1
SCHEME 13
Th en , esters 1m an d 17m were in vestigated as alkylatin g reagen ts in a
diastereoselective m eth ylation of th e ester en olate of 10 (Sch em e 14). Both
axial an d equatorial attacks on th e carban ion are possible, an d two diastereo-
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1
334
Abbass, Kühl, Manthey, Müller, Lüning:
isom ers of 18 are form ed. Th e relative orien tation of th e tert-butyl an d ester
groups defin e cis-18 an d trans-18. Th e predom in an t equatorial attack leads
to m ore cis- th an trans-18.
COOEt
COOEt
1
. LDA
COOEt
+
2
. methylation
tBu
tBu
tBu
10
cis-18
trans-18
SCHEME 14
In deed, th e sh ieldin g of th e m eth yl sulfon ate group in m-terph en yl esters
m an d 17m h ad an in fluen ce on th eir alkylatin g ability. Th e sm aller
1
m eth yl m-terph en ylsulfon ate 1m sh owed a cis/trans selectivity for th e
m eth ylation of deproton ated cycloh exan ecarboxylate 10 (87:13) wh ich
h ardly differed from th at foun d for m eth yl tosylate (90:10). However, th e
sterically m ore sh ielded m eth yl 4,4′′-di-tert-butyl-m-terph en ylsulfon ate
1
7m did n ot m eth ylate th e substrate at all. Th e ch an ge from th e h ydrogen
atom s in 4 an d 4′′ position s to th e tert-butyl groups h ad an un expectedly
dram atic in fluen ce on th e m eth ylatin g ability. Figure 2 sh ows th e steric in -
teraction s th at m ay be respon sible for th e in h ibition of th e m eth ylation of
en olate of 10 by m-terph en ylsulfon ate 17m . In order to fin d a special selec-
tivity, a fin e-tun in g of th e steric sh ieldin g will be n ecessary.
H3C
H3C
H
CH3
CH3
H
S
O
H
S
O
H
C
C
H
C
C
H
O
C
H
O
O
C
H
O
H
H
C
H
H
O
O
O
H
H
H
H
H
H3C CH3 H
C
C
C
O
H3C CH3
10 ·1m
10 ·17m
FIG. 2
Steric in teraction s in th e m eth ylation of deproton ated eth yl 4-tert-butylcycloh exan e-
ᮎ
1
-carboxylate 10 by two differen t m eth yl m-terph en ylsulfon ates (left: 1m , righ t: 17m ). Th e
large tert-butyl groups in 17m m ay repulse th e en olate, th us proh ibitin g th e alkylation
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1335
EXPERIMENTAL
Gen eral Rem arks
Colum n ch rom atograph y was carried out on silica gel. Meltin g poin ts are un corrected. Ele-
m en tal an alyses were carried out with VarioEl, Elem en taran alysen system e Gm bH. In som e
cases, th e an alyzed com poun ds con tain ed solven t, wh ich was also detected in th e NMR.
~
–1
1
IR spectra were recorded on a Perkin –Elm er 1600 Series ( ν is given in cm ). H an d
1
3
1
C NMR spectra were recorded on a Bruker AC 200 or Bruker AM 300 (200–300 MHz for H,
0–75 MHz for 13C). Ch em ical sh ifts (δ) are given in ppm relative to tetram eth ylsilan e, cou-
5
plin g con stan ts (J) are given in Hz. MS spectra were recorded on a Fin n egan MAT 8230.
Safety remark: Azide 1h was n ever isolated but decom posed in solution .
2
,2′′,6,6′′-Tetram eth yl-1,1′:3′,1′′-terph en yl-2′ol (1f)
Method A) By lithiation and reaction with oxygen. Un der n itrogen , iodide 1a 19 (1.00 g,
.42 m m ol) in cycloh exan e (15 m l) was reacted with butyllith ium (2.5 M solution in h exan e,
.0 m l, 2.5 m m ol). After a few m in utes, th e m ixture turn ed turbid an d was th en stirred at room
2
1
tem perature for addition al 15 h . Th en oxygen gas was bubbled th rough th e m ixture for 2–3 h .
After addition of 2 M h ydroch loric acid (10 m l), th e layers were separated an d th e aqueous
layer was extracted twice with dieth yl eth er. Th e com bin ed organ ic layer was dried with an -
h ydrous m agn esium sulfate, th e solven ts were evaporated in vacuo an d th e crude product
was purified by ch rom atograph y (silica gel, dich lorom eth an e/cycloh exan e, 1:1), givin g 148
m g (20%) of 1f.
Method B) By lithiation and reaction with lithium tert-butyl peroxide. Lith ium tert-butyl perox-
ide was prepared by reaction of 2.5–3
M h ydrogen peroxide in n on an e (420 µl, 2.1–
2
.5 m m ol) with 2.5 M butyllith ium in h exan e (10.0 m l, 25.0 m m ol) at –70 °C in THF
1
9
(
10 m l). Separately, iodo-m-terph en yl 1a
(366 m g, 0.888 m m ol) was reacted with 2.5 M
butyllith ium in h exan e (360 µl, 0.900 m m ol) in THF (10 m l). At –75 °C, th is solution was
added dropwise to th e THF solution of lith ium tert-butyl peroxide, th e m ixture was stirred at
th is tem perature for addition al 2 h , an d stirrin g was con tin ued at room tem perature for
3
1
days. After work-up described above, GC an alysis (SE 30, 25 m ) determ in ed a yield of ca.
0% of 1f. An an alogous reaction in cycloh exan e at 0 °C gave ca. 11% of 1f. Th e reaction of
lith iated m-terph en yl 1e (409 m g, 1.40 m m ol) with a solution of lith ium tert-butyl peroxide
prepared from a 75% solution of h ydrogen peroxide in di-tert-butyl peroxide (0.33 m l,
.5 m m ol) with 2.5 M butyllith ium in h exan e (720 µl, 1.80 m m ol)) in cycloh exan e (25 m l)
(
2
at room tem perature gave ca. 25% of 1f (GC an alysis).
Method C) By reaction with borane and oxidation with hydrogen peroxide. In THF (15 m l),
1
9
iodo-m-terph en yl 1a (412 m g, 1.00 m m ol) was reacted with 2.5 M butyllith ium in h exan e
650 µl, 1.63 m m ol). After 4 h of stirrin g at room tem perature, th is m ixture was cooled to
78 °C, an d 1 N boran e in THF (5.0 m l, 5.0 m m ol) was added. After stirrin g at room tem per-
(
–
ature for 15 h , th e m ixture was carefully h ydrolyzed at 0 °C usin g a m ixture of 30% h ydro-
gen peroxide (4.5 m l) an d 3 M sodium h ydroxide (4.5 m l). After stirrin g th e m ixture at room
tem perature for 4 days, potassium carbon ate (8.0 g) was added an d th e m ixture was ex-
tracted th ree tim es with THF. Th e organ ic layer was dried with an h ydrous m agn esium sul-
fate, th e solven t was evaporated an d th e yield was determ in ed by GC: 17 an d 25% in two
batch es.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1
336
Abbass, Kühl, Manthey, Müller, Lüning:
For C22H22O (302.4) calculated: 87.38% C, 7.33% H; foun d: 87.36% C, 7.35% H. IR (KBr):
3
1
482, 3431 (OH); 3057 (CH arom .); 2945, 2917, 2854 (CH aliph .); 1582 (arom .); 1448, 1375,
320, 1217, 1162, 1116, 1070, 830, 798, 770. 1H NMR (300 MHz, CDCl ): 2.10 s, 12 H
3
(
(
3
CH ); 4.52 br s, 1 H (OH); 7.05 m , 3 H (Ar-H); 7.1–7.3 m , 6 H (Ar-H). MS (EI, 70 eV), m/z
3 c
%): 302 (100) [M ], 287 (41) [M – CH ], 272 (8) [M – 2 CH ]. MS (CI, isobutan e), m/z (%):
3 3
03 (100) [M+ + H].
+
+
+
2
,2′′,6,6′′-Tetram eth yl-1,1′:3′,1′′-terph en yl-2′-am in e (1j)
Method A) From acid 1b by rearrangement. 2,2′′,6,6′′-Tetram eth yl-1,1′:3′,1′′-terph en yl-
1
9
2
′-carboxylic acid (1b; 100 m g, 0.300 m m ol) was m ixed with fresh ly distilled th ion yl ch lo-
ride (53 m g, 0.450 m m ol) an d th e m ixture was h eated to reflux for 1 h . Excess th ion yl ch lo-
ride was distilled off an d its rem ain in g traces were rem oved in vacuo (<0.1 m bar). IR ch eck
sh owed com plete con version of acid 1b to acid ch loride 1g. IR (KBr): 1786 (COCl).
1
. With trim eth ylsilyl azide. Un der n itrogen , crude acid ch loride 1g was dissolved in dry
toluen e (5 m l), trim eth ylsilyl azide (0.5 m l, 4 m m ol) was added, an d after 3 h of stirrin g at
room tem perature, th e m ixture was h eated to reflux for 10 h . After evaporation of th e sol-
ven t in vacuo, IR ch eck sh owed th e production of isocyan ate 1i besides sm all am oun ts of
acid ch loride 1g. IR (KBr): 2916 (CH ); 2245 (N=C=O); 1786 (COCl). Hydrolysis of th e crude
3
isocyan ate 1i was ach ieved by addin g a sm all am oun t of aceton e (ca. 100 µl) an d con cen -
trated sodium h ydroxide (2 m l). Th e m ixture was h eated to reflux for 2 h , th e solven t was
evaporated in vacuo an d th e yellowish residue was dissolved in dieth yl eth er an d extracted
four tim es with sem i-con cen trated h ydroch loric acid. 30% Sodium h ydroxide was added
carefully un til th e m ixture was stron gly alkalin e, an d th e m ixture was extracted four tim es
with dieth yl eth er. Th e com bin ed eth er layer was dried with an h ydrous m agn esium sulfate
an d evaporated in vacuo givin g a sligh tly yellow residue. Recrystallization from cycloh exan e
gave 1j (58 m g, 64% based on acid 1b) as wh ite crystals. M.p. 98 °C.
2
. With sodium azide. Crude acid ch loride 1g was dissolved in dry DMF (5 m l). Un der n i-
trogen , sodium azide (30 m g, 0.460 m m ol) was added at 0 °C. After stirrin g at room tem per-
ature for 1 h , at reflux for 2 h an d at room tem perature for addition al 15 h , th e m ixture was
h ydrolyzed with water (7.5 m l) (exoth erm ic reaction ), an d a wh ite precipitate form ed. Th e
m ixture was cooled an d extracted four tim es with dieth yl eth er (5 m l). Th e com bin ed or-
gan ic layer was dried with an h ydrous m agn esium sulfate, th e solven t was evaporated an d
th e rem ain in g yellowish crystals were recrystallized from cycloh exan e givin g 1j (67 m g, 73%
based on acid 1b). M.p. 98 °C.
Method B) By Suzuki coupling.
1
. 2,6-Dim eth ylben zen eboron ic acid (13). Un der n itrogen , 2-brom o-1,3-dim eth ylben zen e40
(
5.00 g, 27 m m ol) in dry THF (5 m l) was added dropwise to m agn esium (690 m g, 28 m m ol)
in dry THF (20 m l). Th e m ixture was stirred at 50 °C for 12 h , before it was added dropwise
to trim eth yl borate (4.0 m l, d20 = 0.997 g/m l, 36 m m ol, dried with lith ium ch loride) in di-
eth yl eth er (20 m l) at –50 °C. A wh ite precipitate form ed, addition al dieth yl eth er (7 m l) was
added an d stirrin g was con tin ued at –75 °C for 30 m in . Th e m ixture was allowed to warm to
0
°C durin g 1.5 h , first water (7 m l) an d th en 10% sulfuric acid (6 m l) was slowly added
wh ile keepin g th e tem perature between 0 an d 15 °C. After addition of water (8 m l), th e or-
gan ic layer was separated, an d th e aqueous layer was extracted th ree tim es with dieth yl
eth er. Th e com bin ed organ ic layer was dried with an h ydrous m agn esium sulfate an d th e sol-
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1337
ven t was rem oved in vacuo. Th e sligh tly yellow residue was recrystallized several tim es from
3
7
37
water an d dried givin g 916 m g (23%, lit. : 50%). M.p. 121–124 °C, lit. : 125 °C.
. Couplin g. 2,6-Dim eth ylben zen eboron ic acid (13; 920 m g, 7.5 m m ol) in eth an ol (6 m l)
was added to a solution of 2,6-dibrom oan ilin e (14; Fluka, 620 m g, 2.5 m m ol) in ben zen e
30 m l). Aqueous 2 M sodium carbon ate (10 m l) was added, th e reaction vessel was flush ed
with n itrogen , degassed with ultrasoun d an d flush ed again with n itrogen . Th en tetrakis-
triph en ylph osph in e)palladium (0) (ca. 0.42 g, 0.36 m m ol) was added an d th e m ixture was
2
(
(
h eated to reflux for 1.5 days an d stirred at room tem perature for 7 days. Th e layers were sep-
arated an d th e aqueous layer was extracted twice with dieth yl eth er (10 m l). Th e com bin ed
organ ic layer was dried with an h ydrous m agn esium sulfate an d th e solven t was evaporated
in vacuo. Th e dark brown residue was dissolved in sm all am oun t of dich lorom eth an e an d
purified by ch rom atograph y (silica gel, cycloh exan e/dich lorom eth an e, 1:1), givin g 98 m g
(
13%) of 1j. M.p. 104–106 °C. For C22H23N (301.4) calculated: 87.66% C, 7.68% H, 4.55% N;
foun d: 87.55% C, 7.60% H, 4.59% N. IR (KBr): 3460, 3368, 2916, 1603, 1446, 1376, 1260,
7
1
3
73, 551. Ram an : 3040, 3021, 2951, 2913, 2860, 1599, 1448, 1378, 1293, 1247, 1167, 1074,
006, 614, 554, 513, 347, 328, 213. 1H NMR (200 MHz, CDCI ): 2.1 s, 12 H (CH ); 6.85–6.9 m ,
3
3
H (4′-H, 5′-H, 6′-H); 7.1–7.2 m , 6 H (3-H, 3′′-H, 4-H, 4′′-H, 5-H, 5′′-H). MS (EI, 70 eV), m/z
+
(
(
%): 301 (100) [M ], 300 (10), 286 (35), 284 (13), 271 (13), 269 (14). MS (CI, isobutan e), m/z
%): 302 (10) [M+ + H], 190 (6), 75 (100).
2
,2′′,6,6′′-Tetram eth yl-1,1′:3′,1′′-terph en yl-2′-sulfon ic Acid (1l)
Th e sulfoch loride 1k 21 (105 m g, 0.285 m m ol) an d potassium h ydroxide (140 m g, 2.50 m m ol)
were h eated to reflux in an eth an ol/water m ixture (1:1, 4 m l) for 2 days. After evaporation
of large part of th e solven t, th e residue was acidified with con cen trated h ydroch loric acid.
Th e m ixture was extracted th ree tim es dieth yl eth er (3 m l). Th e com bin ed organ ic layer was
dried with an h ydrous m agn esium sulfate. Evaporation of th e solven t in vacuo gave 1l (86 m g,
8
1
6%) as a sligh tly yellow solid. M.p. 220 °C (dec.). IR (KBr): 3440 (OH); 2916 (CH aliph .);
581 (arom .); 1458, 1396, 1376, 1226 (S=O); 1130, 1069, 1023, 774, 756, 745. 1H NMR
(
(
6
(
200 MHz, CDCl ): 2.01 s, 12 H (CH ); 2.97 br s, 3 H (SO H + H O); 6.9–7.0, 7.4–7.7 2 m , 9 H
3 3 3 2
1
Ar-H). H NMR (200 MHz, DMSO-d ): 1.98 s, 12 H (CH ); 6.77 d, 2 H, J = 7.5 (3, 5-H);
6 3
+
.8–7.0 m , 6 H (Ar-H); 7.36 t, 1 H, J = 7.5 (4-H). MS (EI, 70 eV), m/z (%): 366 (87) [M ], 284
+
+
63) [M – H SO ], 269 (100) [M – H SO – CH ], 253 (69), 239 (27). MS (CI, isobutan e),
2 3 2 3 3
+
+
m/z (%): 367 (25) [M + H], 287 (39) [M + H – SO ], 214 (16), 197 (15), 69 (100). HR-MS:
C22H22SO3 calculated: 366.12897; foun d: 366.12870; C21 CH22SO3 calculated: 367.13232;
foun d: 367.13220.
3
1
3
Meth yl 2,2′′,6,6′′-Tetram eth yl-1,1′:3′,1′′-terph en yl-2′-sulfon ate (1m )
Un der n itrogen , a solution of sulfon ic acid 1l (38 m g, 0.104 m m ol) in THF (5 m l) was added
to a 0.31 M solution of diazom eth an e in dieth yl eth er (500 µl, 0.155 m m ol). After stirrin g
for 5 h , th e solven ts were evaporated in vacuo. Spectroscopically, n o im purities could be de-
tected. For C23H24O S calculated: 72.60% C, 6.36% H; for C23H24O S·0.1CH Cl calculated:
3
3
2
2
1
7
1.33% C, 6.27% H; foun d: 71.38% C, 6.29% H. H NMR (200 MHz, CDCl ): 2.07 s, 12 H
3
(
7
[
3
Ar-CH ); 3.18 s, 3 H (SO CH ); 7.0–7.3 m , 8 H (Ar-H); 7.69 t, 1 H, J = 7.8 (4-H). MS (EI,
3 3 3
+
+
+
0 eV), m/z (%): 380 (100) [M ], 348 (10) [M – CH O], 284 (80) [M – HSO CH ], 269 (74)
4 3 3
+
M
– HSO CH – CH ], 253 (33), 179 (13), 126 (18). HR-MS: C23H24SO3 calculated:
3 3 3
1
3
80.14462; foun d: 380.14450; C22 CH24SO3 calculated: 381.14798; foun d: 381.14770.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1
338
Abbass, Kühl, Manthey, Müller, Lüning:
Syn th esis of Con cave Esters 4a an d 5a. Gen eral Procedure
Un der n itrogen , tetrabrom ide 3 20 an d two equivalen ts of a ph en ylen edith iol dissolved in an
eth an ol/toluen e m ixture (1:1, 800 m l) were added dropwise to an in ten sively stirred,
refluxin g solution of potassium h ydroxide (ca. 130 m m ol) in dry eth an ol (500 m l) durin g
1
0 h . After 15 h at room tem perature, th e solven ts were evaporated in vacuo, th e residue
was dissolved in water (200 m l) an d dich lorom eth an e (200 m l), an d th e aqueous layer was
extracted four tim es with dich lorom eth an e (50 m l). Th e com bin ed organ ic layer was dried
with an h ydrous m agn esium sulfate an d th e solven t was evaporated in vacuo, th e residue
was dissolved in dich lorom eth an e, an d th e solution was filtered th rough basic alum in ium
oxide (4 × 10 cm ). Wash in g with dich lorom eth an e was con tin ued un til TLC (silica gel, di-
ch lorom eth an e) sh owed n o m ore product. After evaporation of th e solven t in vacuo, th e res-
idue was purified twice by ch rom atograph y (silica gel, dich lorom eth an e; dich lorom eth an e/
cycloh exan e, 3:1) an d recrystallized from dieth yl eth er.
5
5
Methyl 1 ,7 -di-tert-butyl-2,6,8,12-tetrathia-1(1,3,2),4(1,4),7(1,3,2),10(1,4),13(1,3)-penta-
2
20
benzenabicyclo[5.5.1]tridecaphane-13 -carboxylate (4a). Tetrabrom ide 3
(2.40 g, 3.11 m m ol)
4
1
an d 1,4-ph en ylen edith iol (1.06 g, 6.22 m m ol) with potassium h ydroxide (7.00 g, 125 m m ol).
Yield 418 m g (17%) of a wh ite solid. M.p. > 250 °C (dec.). For C48H52O2S4 (788.9) calcu-
lated: 73.05% C, 6.64% H; foun d: 72.52% C, 6.76% H. IR (KBr): 2961 (CH aliph .); 1736
C=O); 1607 (arom .); 1439 (CH aliph .); 1265, 1117 (C–O). 1H NMR (300 MHz, CDCl ): 1.29 s,
(
3
1
8 H (C(CH ) ); 2.29 d, 4 H, J = 10.0 (ArCH H ); 2.70 s, 3 H (OCH ); 3.09 d, 4 H, J = 10.0
3 3 a b 3
(
(
(
ArCH H ); 3.67 d, 4 H, J = 13.5 (Ar′CH H ); 3.74 d, 4 H, J = 13.5 (Ar′CH H ); 6.89 s, 4 H
a b a b a b
Ar-H); 7.26 m , 8 H (Ar-H); 7.4–7.5 m , 3 H (Ar-H). MS (EI, 70 eV), m/z (%): 789 (56), 788
c
100), 756 (67), 620 (35), 588 (24), 483 (17), 451 (24).
5
5
Methyl 1 ,7 -di-tert-butyl-2,6,8,12-tetrathia-1(1,3,2),4(1,3),7(1,3,2),10(1,3),13(1,3)-penta-
2
20
benzenabicyclo[5.5.1]tridecaphane-13 -carboxylate (5a). Tetrabrom ide 3
an d 1,3-ph en ylen edith iol (1.10 g, 6.48 m m ol) with potassium h ydroxide (7.30 g, 130 m m ol).
(2.50 g, 3.24 m m ol)
1
9
Yield 560 m g (22%) of a wh ite solid. M.p. > 250 °C (dec.). IR (KBr): 2960 (CH aliph .); 1730
1
(
C=O); 1604 (arom .), 1443 (C-H aliph .); 1266, 1118 (C–O). H NMR (300 MHz, CDCl ): 1.32 s,
3
1
8 H (C(CH ) ); 2.87 s, 3 H (OCH ); 2.88 d, 4 H, J = 10.5 (ArCH H ); 3.44 d, 4 H, J = 10.5
3 3 3 a b
(
(
ArCH H ); 3.48 d, 4 H, J = 14.0 (Ar′CH H ); 3.59 d, 4 H, J = 14.0 (Ar′CH H ); 6.64 br s, 2 H
a b a b a b
Ar-H); 6.73 m , 1 H (Ar-H); 6.91 d, 2 H, J = 7.5 (Ar-H); 7.13 d, 4 H, J = 8.0 (Ar-H); 7.2–7.3 m ,
c
6
4
H (Ar-H). MS (EI, 70 eV), m/z (%): 789 (8), 788 (15), 756 (100), 620 (16), 588 (18), 483 (9),
51 (17).
Syn th esis of Con cave Acids 4b an d 5b. Gen eral Procedure
Un der n itrogen , ester 4a or 5a, lith ium iodide an d 12-crown -4 were dissolved in dry pyridin e
70 m l). Th e m ixture was h eated to reflux un til two-dim en sion al TLC (silica gel, 1. dich loro-
(
m eth an e, 2. dieth yl eth er) sh owed alm ost total con version (264–329 h ). Th en , con cen trated
h ydroch loric acid/ice (ca. 250 m l, 1:1) was added an d th e m ixture was extracted four tim es
with dich lorom eth an e (50 m l). Th e com bin ed organ ic layer was extracted twice with 6 M h y-
droch loric acid (50 m l) an d on ce with water (50 m l). After dryin g with an h ydrous m agn e-
sium sulfate, th e solven t was evaporated in vacuo, th e residue was purified by ch rom atogra-
ph y (silica gel, dich lorom eth an e/dieth yl eth er, 40:1) an d recrystallized from toluen e.
5
5
1
,7 -Di-tert-butyl-2,6,8,12-tetrathia-1(1,3,2),4(1,4),7(1,3,2),10(1,4),13(1,3)-pentabenzenabi-
2
cyclo[5.5.1]tridecaphane-13 -carboxylic acid (4b). Ester 4a (363 m g, 0.460 m m ol), lith ium io-
dide (1.23 g, 9.2 m m ol) an d 12-crown -4 (ca. 460 µl) were reacted as described for ca. 329 h .
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1339
Yield 184 m g (52%) of a wh ite solid. M.p. > 310 °C (dec.). For C47H50O S ·C H (774.9 +
2
4
7
8
9
2
2.1) calculated: 74.78% C, 6.74% H; foun d: 74.44% C, 6.83% H. IR (KBr): 3050–2800 (OH);
961 (CH aliph .); 1701 (C=O); 1605, 1508 (arom .); 1442 (CH aliph .). 1H NMR (200 MHz,
CDCl ): 1.31 s, 18 H (C(CH ) ); 2.29 d, 4 H, J = 10.1 (ArCH H ); 2.36 s, 3 H (ArCH , tolu-
3
3
3
a
b
3
en e); 3.11 d, 4 H, J = 10.1 (ArCH H ); 3.65 d, 4 H, J = 13.4 (Ar′CH H ); 3.74 d, 4 H, J = 13.4
a
b
a
b
(
Ar′CH H ); 6.86 s, 4 H (Ar-H); 7.1–7.3 m , 8 H (Ar-H) + 5 H (toluen e); 7.4–7.6 m , 3 H (Ar-H).
a b
MS (EI, 70 eV), m/z (%): 775 (37), 774 (67), 756 (37), 637 (47), 606 (32), 573 (27), 469 (25),
4
23 (100).
5
5
1
,7 -Di-tert-butyl-2,6,8,12-tetrathia-1(1,3,2),4(1,3),7(1,3,2),10(1,3),13(1,3)-pentabenzenabi-
2
cyclo[5.5.1]tridecaphane-13 -carboxylic acid (5b). Ester 5a (556 m g, 0.705 m m ol), lith ium io-
dide (1.88 g, 14.1 m m ol) an d 12-crown -4 (ca. 700 µl) were reacted as described for ca. 264 h .
Yield 228 m g (42%) of a wh ite solid. M.p. > 320 °C (dec.). For C47H50O2S4 (774.9) calcu-
lated: 72.83% C, 6.50% H; foun d: 72.78% C, 6.48% H. IR (KBr): 3055–2900 (OH); 2962
1
(
CH aliph .); 1751 (C=O); 1604 (arom .); 1444 (CH aliph .). H NMR (200 MHz, CDCl ): 1.33 s,
3
1
4
8 H (C(CH ) ); 2.90 d, 4 H, J = 10.9 (ArCH H ); 3.48 d, 4 H, J = 14.2 (Ar′CH H ); 3.49 d,
3 3 a b a b
H, J = 10.9 (ArCH H ); 3.59 d, 4 H, J = 14.2 (Ar′CH H ); 6.69 br s, 2 H (Ar-H); 6.76 m , 1 H
a
b
a
b
c
(
Ar-H); 6.90 d, 2 H, J = 6.9 (Ar-H); 7.11 brs, 4 H (Ar-H); 7.2–7.4 m , 6 H (Ar-H). MS (EI, 70 eV),
m/z (%): 775 (5), 774 (8), 756 (100), 637 (30), 606 (13), 573 (11), 469 (15), 436 (18), 423 (93).
Syn th esis of Iodo-m-terph en yls 8a an d 9a. Gen eral Procedure
To obtain 300 m m ol of an aryl Grign ard reagen t, 302 m m ol of an aryl brom ide in dry THF
(
220 m l) was slowly added to m agn esium (7.35 g, 302 m m ol) in dry THF (80 m l). At room
tem perature an d un der n itrogen , 1,3-dich loro-2-iodoben zen e (16; 20.5 g, 75.0 m m ol) in THF
300 m l) was added to th is solution durin g 2 h an d th e m ixture was stirred for 6 h . Wh ile
(
coolin g with ice, iodin e (88.8 g, 0.35 m ol) in THF (300 m l) was added slowly an d th e m ix-
ture was stirred for 15 h . Excess iodin e was destroyed with aqueous sodium dith ion ite an d
m ost of th e solven t was evaporated in vacuo. Th e aqueous residue was extracted four tim es
with dieth yl eth er (1 l total). After dryin g of th e com bin ed organ ic layer with an h ydrous
m agn esium sulfate, th e solven ts were evaporated in vacuo an d volatile by-products were dis-
tilled off at 100 °C an d 0.1 m bar.
2
′-Iodo-2,2′′,6,6′′-tetraisopropyl-1,1′:3′,1′′-terph en yl (8a)
2
6
-Brom o-1,3-diisopropylben zen e42 (2.88 g, 11.9 m m ol), 1,3-dich loro-2-iodoben zen e43 (16;
80 m g, 2.49 m m ol), m agn esium (252 m g, 10.4 m m ol), iodin e (2.84 g, 11.2 m m ol) an d THF
(
30 m l total) were reacted accordin g to th e gen eral procedure. Th e brown residue was dis-
solved in cycloh exan e an d filtered th rough silica gel. Th e solven t was evaporated an d th e
residue was recrystallized from eth an ol. Yield 750 m g (59%). M.p. 151–153 °C. GC purity (SE
3
1
0, 25 m ): 95%. IR (KBr): 3065 (CH arom .); 2957, 2865 (CH aliph .); 1578 (arom .); 1461,
1
382, 1360, 1057, 1002, 802, 791, 756. H NMR (200 MHz, CDCl ): 1.24 d, 12 H, J = 6.8
3
(
5
(
CH ); 3.49 sept, 4 H, J = 6.8 (CH(CH ) ); 7.0–7.3 m , 9 H (Ar-H). MS (EI, 70 eV), m/z (%):
3 3 2
+
+
24 (100) [M ], 481 (11) [M – C H ], 381 (18), 339 (32). MS (CI, isobutan e), m/z (%): 525
3 7
100) [M+ + H], 397 (16) [M – I].
+
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1
340
Abbass, Kühl, Manthey, Müller, Lüning:
2
-Iodo-1,3-bis(2-m eth yl-1-n aph th yl)ben zen e (9a)
1
-Brom o-2-m eth yln aph th alen e (Jan ssen , 3.67 g, 15.8 m m ol), 1,3-dich loro-2-iodoben zen e43
(
16; 1.08 g, 3.96 m m ol), m agn esium (385 m g, 15.8 m m ol), iodin e (4.39 g, 17.3 m m ol) an d
THF (60 m l total) were reacted accordin g to th e gen eral procedure. Th e residue was
recrystallized from toluen e/m eth an ol. Yield 921 m g (48%). M.p. > 210–215 °C. IR (KBr):
1
3
047 (CH arom .); 1617, 1594, 1564, 1506 (arom .); 1372, 1261, 1009, 811, 798, 743. H NMR
(
(
(
200 MHz, CDCl ): 2.30 s, 6 H (CH ); 7.3–7.5 m , 10 H (Ar-H); 7.62 m (AB ), 1 H, J ≈ 7.6
3 3 c 2
+
+
4-H); 7.8–7.9 m , 4 H (Ar-H). MS (EI, 70 eV), m/z (%): 484 (100) [M ], 357 (18) [M – I], 342
+
+
20) [M – I – CH ], 242 (14). MS (CI, isobutan e), m/z (%): 485 (100) [M + H].
3
Syn th eses of 2,6-Diarylben zaldeh ydes 8c an d 9c. Gen eral Procedure
Un der n itrogen , th e 2,6-diaryl-1-iodoben zen e 8a or 9a in cycloh exan e was reacted with
butyllith ium . After several m in utes a wh ite precipitate was form ed. Th e m ixture was stirred
at room tem perature for 15 h before excess m eth yl form ate was added. Th e m ixture turn ed
viscous an d th e precipitate began to dissolve. After stirrin g for 3 h , water (20 m l) was added
an d th e m ixture was extracted th ree tim es with dieth yl eth er (100 m l total). Th e com bin ed
organ ic layer was wash ed with water an d dried, th e solven t was evaporated an d th e yellow-
ish residue was recrystallized from h exan e.
2
,6-Bis(2,6-diisopropylphenyl)benzaldehyde (8c). 8a (described in 44, but syn th esized accord-
1
7,18
in g to
) (112 m g, 214 µm ol), butyllith ium (300 µm ol), m eth yl form ate (120 µl,
1
.94 m m ol) in cycloh exan e (1.2 m l). Yield 28 m g (31%) of 8c. IR (KBr): 2958, 2864 (CH
aliph .); 1698 (C=O); 1577 (arom .); 1459, 1381, 1361, 1326, 1250, 1191, 1055, 804, 792, 757.
1
H NMR (300 MHz, CDCl ): 1.02, 1.12 2 d, 24 H, J = 6.9 (CH(CH ) ); 2.52 sept, 4 H, J = 6.9
3
3 2
(
(
CH(CH ) ); 7.2–7.3 m , 6 H (Ar-H); 7.38 m , 2 H (3, 5-H); 7.64 t, 1 H, J = 7.6 (4-H); 9.70 s, 1 H
3 2 c
+
+
CHO). MS (Cl, isobutan e), m/z (%): 427 (100) [M + H], 415 (11), 399 (51) [M + H – CO].
,6-Bis(2-methyl-1-naphthyl)benzaldehyde (9c). 9a (550 m g, 1.14 m m ol), butyllith ium
1.5 m m ol), m eth yl form ate (500 µl, 8.08 m m ol) in cycloh exan e (5 m l). Crude yield of 9c:
40 m g. GC purity (SE 30, 25 m ): 75%. IR (KBr): 2920 (CH arom .); 1697 (C=O); 1567, 1507
2
(
4
(
arom .); 1375, 1262, 1028, 811.
Syn th eses of 2,6-Diarylben zyl Alcoh ols 8d an d 9d . Gen eral Procedure
A solution of 2,6-diarylben zaldeh yde 8c or 9c in THF was added dropwise to a m ixture of
lith ium alum in ium h ydride in dry THF (10 m l). Th e m ixture was h eated to reflux for 2–4 h ,
an d th en h ydrolyzed carefully with water. After acidification with 1 M sulfuric acid, th e m ix-
ture was extracted twice with dieth yl eth er (150 m l total). After dryin g of th e organ ic layer
with an h ydrous m agn esium sulfate an d evaporation of th e solven t, th e rem ain in g yellowish
oil was recrystallized from h exan e. For n o ben zylic alcoh ol 8d an d 9d could an OH proton
1
be observed in th e H NMR.
2
,6-Bis(2,6-diisopropylphenyl)benzyl alcohol (8d ). Ben zaldeh yde 8c (85 m g, 0.20 m m ol),
lith ium alum in ium h ydride (35 m g, 0.92 m m ol), THF (8 an d 10 m l). Yield 54 m g (63%).
M.p. 193–196 °C. For C31H40O (428.7) calculated: 86.86% C, 9.41% H; foun d: 86.79% C,
9
1
.48% H. IR (KBr): 3569 (OH); 3060 (CH arom .); 2960, 2865 (CH aliph .); 1577 (arom .); 1459,
381, 1360, 1326, 1261, 1055, 1013, 805, 792, 759. 1H NMR (200 MHz, CDCl ): 1.09 d, 6 H,
3
J = 6.8 (CH ); 1.13 d, 6 H, J = 6.9 (CH ); 2.59 sept, 4 H, J = 6.9 (CH(CH ) ); 4.05, 4.08 2 s,
3
3
3 2
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1341
+
+
2
H (CH OH); 7.1–7.4 m , 9 H (Ar-H). MS (EI, 70 eV), m/z (%): 428 (2) [M ], 410 (100) [M
–
2
+
H O], 353 (28) [M – H O – C H ], 311 (37), 283 (24), 269 (26).
2
2
4
9
2
,6-Bis(2-methyl-1-naphthyl)benzyl alcohol (9d). Crude 9c (300 m g, m ax. 776 µm ol), lith ium
alum in ium h ydride (150 m g, 3.95 m m ol), THF (10 m l). Yield 99 m g (33%, based on 9a).
M.p. 210–215 °C. GC purity (SE 30, 25 m ): 98%. IR (KBr): 3582 (OH); 3048 (CH arom .); 2929
1
(
CH aliph .); 1618, 1506 (arom .); 1376, 1189, 998, 811, 783, 743. H NMR (200 MHz, CDCl ):
3
2
.29, 2.35 2 s, 6 H (CH ); 3.9–4.0 m , 2 H (CH OH); 7.2–7.6, 7.8–7.9 2 m , 15 H (Ar-H).
3 2
+
+
+
MS (EI, 70 eV), m/z (%): 388 (45) [M ], 370 (100) [M – H O], 355 (36) [M – H O – CH ],
3
3
2
2
3
+
+
39 (25), 228 (14), 170 (19). MS (CI, isobutan e), m/z (%): 389 (8) [M + H], 388 (22) [M ],
71 (100) [M + H – H O]. HR-MS: C29H24O calculated: 388.18271; foun d: 388.18250;
+
2
1
3
C28 CH24O calculated: 389.18607; foun d: 389.18600.
3
,3′′,5,5′′-Tetram eth yl-1,1′:3′,1′′-terph en yl-2′-ol (12f)
By lith iation an d reaction with oxygen : th e syn th esis was carried out in an alogy to th e syn -
1
9
th esis of 1f. An am oun t of 500 m g (1.21 m m ol) of 12a
rity (SE 30, 25 m ): >99%. For C22H22O (302.4) calculated: 87.67% C, 7.02% H; foun d:
7.70% C, 7.26% H. IR (KBr): 3533 (OH); 3023 (CH arom .); 2918, 2857 (CH aliph .); 1598
gave 102 m g (28%) of 12f. GC pu-
8
1
(
arom .); 1462, 1454, 1205, 849, 793, 700. H NMR (300 MHz, CDCl ): 2.37 s, 12 H (CH );
3 3
5
7
2
.51 s, 1 H (OH); 7.01 t, 1 H, J = 7.8 (4-H); 7.02 m , 2 H (4′-H); 7.12 br s, 4 H (2′, 6′-H);
c
+
+
.24 d, 2 H, J = 7.8 (3, 5-H). MS (EI, 70 eV), m/z (%): 302 (100) [M ], 287 (24) [M – CH ],
3
+
72 (8) [M – 2 CH ], 151 (10), 129 (11), 83 (42). MS (CI, isobutan e), m/z (%): 303 (100)
3
+
[
M
+ H], 163 (13), 157 (29), 117 (60), 99 (78).
4
,4′′-Di-tert-butyl-2′-iodo-2,2′′,6,6′′-tetram eth yl-1,1′:3′,1′′-terph en yl (17a)
Un der n itrogen , a solution of 2-brom o-5-tert-butyl-1,3-dim eth ylben zen e45,46 (12 g, 50 m m ol)
in dry THF (30 m l) was added to m agn esium (1.2 g, 50 m m ol) previously warm ed to ca. 70 °C.
Th e resultin g m ixture was h eated to reflux for 2 h an d, durin g 2 h , a solution of 1,3-di-
ch loro-2-iodoben zen e (3.4 g, 13 m m ol) in dry THF (50 m l) was added dropwise at room
tem perature. After 8 h of reflux, th e m ixture was cooled with an ice bath an d iodin e (15 g,
6
0 m m ol) dissolved in dry THF (50 m l) was added dropwise. Stirrin g was con tin ued at room
tem perature for 2 days an d aqueous sodium disulfite was added un til th e color of th e solu-
tion turn ed to oran ge. A m ajor part of th e solven t was evaporated in vacuo, an d th e aque-
ous layer was extracted th ree tim es with dieth yl eth er (80 m l). After dryin g with an h ydrous
m agn esium sulfate, th e solven t was evaporated in vacuo, an d volatile by-products were dis-
tilled off at ca. 100 °C an d ca. 0.5 m bar. Th e brown residue was dissolved in cycloh exan e an d
purified by filtration th rough silica gel. Yield 5.0 g (76%). M.p. 158 °C. GC purity: 98.5%.
1
IR (KBr): 2962 (CH aliph .); 1606 (arom .); 1573 (arom .); 1453 (CH ). H NMR (200 MHz,
3
CDCl ): 1.35 s, 18 H (C(CH ) ); 2.01 s, 12 H (Ar-CH ); 7.07–7.12 m , 6 H (Ar-H); 7.44 t, 1 H,
3
3
3
3
+
+
J = 7.5 (5′-H). MS (EI, 70 eV), m/z (%): 524 (86) [M ], 509 (100) [M – CH ]. HR-MS: C30H37
calculated: 524.19403; foun d: 524.19370; C29 CH37
25.19710.
I
3
1
3
I
calculated: 525.19739; foun d:
5
4
,4′′-Di-tert-butyl-2,2′′,6,6′′-tetram eth yl-1,1′:3′,1′′-terph en yl-2′-sulfon yl Ch loride (17k)
Un der n itrogen , 2.5 M butyllith ium in h exan e (2.0 m l, 5.0 m m ol) was added to a solution of
iodo-m-terph en yl 17a (2.6 g, 5.0 m m ol) in dry cycloh exan e (30 m l). Th e m ixture turn ed yel-
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1
342
Abbass, Kühl, Manthey, Müller, Lüning:
low an d a fin e, colorless solid precipitated after ca. 30 m in . After stirrin g for 20 h , th e sol-
ven t was evaporated in vacuo. Th e rem ain in g lith ium com poun d 17e was dissolved in dry
THF (30 m l) at –78 °C an d stirred for 10 m in . With in 1 m in , fresh ly distilled sulfuryl ch lo-
ride (0.47 m l, 5.8 m m ol) was added. Th e m ixture turn ed red an d th en yellow, an d was
stirred at 60 °C for 1 h an d at room tem perature for 2 days. Th en , th e m ixture was poured
on to saturated aqueous sodium h ydrogen sulfate (30 m l) an d extracted th ree tim es with
dieth yl eth er (25 m l). Iodin e was rem oved by wash in g with a sodium th iosulfate solution ,
th e organ ic layer was wash ed with water (50 m l) an d th en dried with an h ydrous m agn esium
sulfate. After evaporation of th e solven t in vacuo, th e crude product was purified by ch ro-
m atograph y to rem ove th e side product, a 2′-ch loro-m-terph en yl (silica gel, dich loro-
m eth an e/cycloh exan e, 1:2) givin g 379 m g (15%) of 17k. M.p. 110 °C. GC purity: 95.2%.
IR (KBr): 2962 (CH aliph .); 1606 (arom .); 1572 (arom .); 1452 (CH ); 1385 (S=O); 1190 (S=O).
3
1
H NMR (200 MHz, CDCl ): 1.34 s, 18 H (C(CH ) ); 2.07 s, 12 H (Ar-CH ); 7.10–7.30 m , 6 H
3
3
3
3
+
(
(
Ar-H); 7.73 t, 1 H, J = 7.5 (5′-H). MS (EI, 70 eV), m/z (%): 498, 496 (22, 49) [M ], 483, 481
+
+
+
41, 100) [M – CH ], 414 (31) [M – SOCl], 399 (44) [M – SOCl – CH ]. HR-MS:
3
3
C30H37 ClO S calculated: 496.22028; foun d: 496.22020; C 13CH
3
5
35
ClO S calculated:
2
29
37
2
3
7
4
97.22363; foun d: 497.22340; C30H37 ClO S calculated: 498.21732; foun d: 497.21720.
2
4
,4′′-Di-tert-butyl-2,2′′,6,6′′-tetram eth yl-1,1′:3′,1′′-terph en yl-2′-sulfon ic Acid (17l)
Sulfon yl ch loride 17k (248 m g, 0.500 m m ol) an d potassium h ydroxide (280 m g, 5.00 m m ol)
in eth an ol/water (1:1, 8 m l) were h eated to reflux for 1 day. After evaporation of a m ajor
part of th e solven ts, th e residue was acidified with con cen trated h ydroch loric acid. After
th ree extraction s with dieth yl eth er (3 m l), th e com bin ed organ ic layer was dried with an -
h ydrous calcium ch loride, an d th e solven t was evaporated in vacuo givin g 242 m g (100%)
of a sligh tly yellow solid. M.p. 72 °C. IR (KBr): 3438 (OH); 2963 (CH aliph .); 1636 (arom .);
1
1
452 (CH ); 1361 (S=O). H NMR (200 MHz, CDCl ): 1.32 s, 18 H (C(CH ) ); 2.02 s, 12 H
3
3
3 3
(
7
Ar-CH ); 6.32 s, 1 H (SO H); 7.06–7.13 m , 6 H (Ar-H); 7.55 t, 1 H, J = 7.5 (5′-H). MS (EI,
3 3
0 eV), m/z (%): 478 (16) [M ], 463 (38) [M – CH ], 414 (56) [M – SO ], 399 (100) [M –
3 2
+
+
+
+
SO2 – CH ].
3
Meth yl 4,4′′-Di-tert-butyl-2,2′′,6,6′′-tetram eth yl-1,1′:3′,1′′-terph en yl-2′-sulfon ate (17m )
Un der n itrogen , 0.3 M diazom eth an e in dieth yl eth er (2.5 m l, 0.75 m m ol) was added to a
solution of th e sulfon ic acid 17l (236 m g, 0.49 m m ol) in dry THF (25 m l). After stirrin g
at room tem perature for 15 h , th e solven ts were evaporated in vacuo givin g 235 m g (98%)
of crude 17m . Ch rom atograph y (silica gel, dich lorom eth an e) gave 137 m g (57%) of 17m .
M.p. 166 °C. GC purity: 99.9%. For C31H40O S calculated: 75.57% C, 8.18% H; for
3
C31H40O S·0.1CH Cl calculated: 74.53% C, 8.08% H; foun d: 74.32% C, 8.17% H. IR (KBr):
3
2
2
1
2
959 (CH aliph .); 1606 (arom .); 1574 (arom .); 1454 (CH ); 1351 (S=O); 1178 (S=O). H NMR
3
(
7
200 MHz, CDCl ): 1.33 s, 18 H (C(CH ) ); 2.06 s, 12 H (Ar-CH ); 3.07 s, 3 H (SO CH );
3 3 3 3 3 3
.11–7.21 m , 6 H (Ar-H); 7.63 t, 1 H, J = 7.5 (5′-H). C NMR (50 MHz, CDCl ): 21.0 q
3
1
3
(
(
(
Ar-CH ); 31.4 q (C(CH ) ); 34.3 s (C(CH ) ); 53.8 q (SO CH ); 123.9 d (C arom .); 131.2 d
3 3 3 3 3 3 3
C arom .); 133.0 d (C arom .); 135.2 s (C arom .); 135.6 s (C arom .); 137.1 s (C arom .); 142.6 s
+
+
C arom .); 150.1 (s, C arom .). MS (EI, 70 eV), m/z (%): 492 (56) [M ], 477 (100) [M – CH ],
3
+
4
45 (5) [M – CH3 – CH OH]. HR-MS: C31H40O S calculated: 492.26981; foun d: 492.26940;
3
3
1
3
C30 CH40O S calculated: 493.27316; foun d: 493.27280.
3
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

Concave Reagents
1343
Meth ylation of th e En olate of Eth yl 4-tert-Butylcycloh exan e-1-carboxylate (10)
Eth yl 4-tert-butylcycloh exan e-1-carboxylate (10; 212 m g, 1.00 m m ol) was dissolved in dry
THF (2 m l). At –78 °C, th is solution was added dropwise to a solution of 2 M LDA (1 m l)
in dry THF (10 m l). After stirrin g for 2 h , m eth ylatin g agen t (3 m m ol) was added an d stir-
rin g was con tin ued at –78 °C for 1 h . After stirrin g at room tem perature for 10 h , water
(
5 m l) an d 2 M h ydroch loric acid (2 m l) was added, an d th e layers were separated. Th e aque-
ous layer was extracted th ree tim es with dieth yl eth er (20 m l), an d th e com bin ed organ ic
layer was dried with an h ydrous m agn esium sulfate. An alysis by GC (SE 30, 25 m , 10 m in at
8
2
0 °C, h eatin g with 5 °C/m in un til 200 °C): 18.19 (cis-10 an d cis-18), 20.11 m in (trans-10),
0.88 m in (trans-18).
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3
3
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Collect. Czech. Chem. Commun. (Vol. 69) (2004)