Through the maze: Cross-coupling pathways to a helical hexaphenyl "Gel?nder" molecule

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DOI: 10.1002/ejoc.201403322

Through the Maze: Cross-Coupling Pathways to a Helical Hexaphenyl

“Geländer” Molecule

Michel Rickhaus,^[a]Linda Maria Bannwart,^[a]Oliver Unke,^[a]Heiko Gsellinger,^[a]

Daniel Häussinger,^[a]and Marcel Mayor*^[a,b]

Keywords: Helical structures / Cross-coupling / Conformation analysis / Chirality / Regioselectivity

This paper highlights a new concept on how to induce chiral-

ity in a hexaphenyl Geländer-type system. Bridging a ter-

phenyl backbone with a considerably longer benzyl ether

oligomer enforces a continuous twist of the molecule, while

synthetic challenges and considerations required to access

the designed target are outlined and solutions to each step

of the assembly are presented. Encountered isomerizations

are discussed as much as synthetic tools to access highly

preventing an achiral meso form. By highlighting cross-cou- functionalized intermediates with multiorthogonal moieties.

pling strategies and explored synthetic pathways, this report

aims to serve as an Ariadne’s thread for the synthesis of pre-

cisely functionalized, complex polyaromatic systems. The

A strong focus is made on the employment of Suzuki–Mi-

yaura protocols for the targeted connection of polyaromatic

fragments and ultimately the desired oligomeric structure.

sheets were obtained (Figure 1, c).^[8]Chiral naphthalene

oligomers (Figure 1, d) show extreme cisoid conformations

and demonstrate impressive state-of-the-art chiroptical

properties.^[9]Geländer oligomers (Figure 1, e)^[10]become

chiral due to a second elongated bridging structure forcing

the phenyl units of the backbone into an out-of-plane twist.

In the Geländer oligomers reported so far, the two bridging

motifs were attached in the ortho-position of the central

phenyl ring. As a consequence of this spatial remoteness,

their strain-releasing twist directions are independent and,

in most cases, the meso-form with twists of opposed chiral-

ity is favored. Expanding on the concepts found in the lit-

erature, we developed a new approach^[11](Figure 1, f) to

introduce helicity to a polymeric system: Similar to the re-

ported Geländer-oligomers, the structure is based on a ter-

phenyl backbone, but instead of solely bridging neighboring

phenyl rings (i.e., two bridges), the backbone is wrapped by

a benzyl ether oligomer (only one, continuous bridge). The

appealing design feature of this new approach is the absence

of an achiral meso-form. The central phenyl subunit of the

wrapping oligo benzyl ether acts as a rigid joint that relays

the helicity from one subunit to the other; as a consequence,

the helicity of the system must become continuous. The

geometrical molecular design considerations are sketched in

Figure 2. A ladder structure consisting of two parallel rails

and a finite numbers of cross linkages serves as a model.

The model system is, by definition, an achiral, highly

symmetrical oligomer or, depending on the length and

number of linkages, a monodimensional polymer. Cutting

one of the rails into segments (Figure 2, Panel 1) and

elongating the sections (blue) by a significant amount (Fig-

ure 2, Panel 2b) induces strain after reclosing the system.

The system may respond by wrapping the longer rail heli-

Introduction

Polycyclic aromatic compounds (PAC) have caught the

attention of material scientists and fundamental researchers

since the very beginning of molecular chemistry.^[1]Their

unique electronic properties arise from the reduced spacing

between their frontier orbitals, and their pronounced chem-

ical stability makes them interesting building blocks for the

development of components in electronics, optics, and func-

tional materials.^[2]Furthermore, such compounds offer the

opportunity to study fundamental processes such as

angular conductivity dependence, molecular motion, or

even shed light on the origin of life.^[3]Making PACs chiral

allowed increasingly delicate aspects such as circular

polarized luminescence (CPL), dynamic processes like race-

mization and controlled molecular motion to be ex-

plored.^[4,5]

Several concepts have been developed to introduce

chirality into PACs. Helically twisted acenes^[6](Figure 1, a)

were obtained by the introduction of bulky substituents

along the rim of the molecule; helicenes^[7](Figure 1, b) re-

lease the steric strain induced by the hydrogen atoms

pointing into the cavity by adopting a spring-like conforma-

tion. By inducing defects in a graphene sheet, twisted nano-

[a] Department of Chemistry, University of Basel,

St. Johanns-Ring 19, 4056 Basel, Switzerland

E-mail: marcel.mayor@unibas.ch

http://ww w .chemie.unibas.ch/~mayor/

[b] Institute for Nanotechnology (INT), Karlsruhe Institute of

Technology (KIT),

P. O. Box 3640, 76021 Karlsruhe, Germany

Supporting information for this article is available on the

WWW under http://dx.doi.org/10.1002/ejoc.201403322.

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M. Mayor et al.

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cally around the shorter rail, but if the bridge segments are

spaced far apart it also has the option to adopt a meso-

form, which is the case for most reported Geländer struc-

tures. To avoid the meso-form preference, a rotatable rigid

joint (Figure 2, Panel 2a) is introduced, which guarantees

that the helical information is propagated across the junc-

tion. Reclosing the system with the rigid joint (Figure 2,

Panel 3) induces strain, which the system will try to mini-

mize. The most efficient way to achieve this is to lengthen

the spacing between two crosslinks by wrapping them

around the principal axis. As a consequence of the length

mismatch between both rails, the oligomer (or polymer) be-

comes helical (Figure 2, Panel 4).

We have recently discussed the conceptual ideas and the

physical properties emerging from the Geländer helicity in

detail elsewhere;^[11]this full paper focuses mainly on an ex-

ploration of the synthetic pathway towards 1. In particular,

the use of Suzuki–Miyaura cross coupling as a synthetic

tool with which to assemble complex polycyclic aromatic

structures is addressed.^[12]Although a vast number of publi-

cations deal with the development and application of un-

doubtedly very complex aryl-aryl couplings, only a minority

of these go beyond the synthesis of (hetero-)biaryls. The

target structure presented here provided an excellent oppor-

tunity to contribute to the exploration of cross couplings

for the construction of complex polyaromatic systems. The

target structure requires the precise connection of aryl sub-

units and, in particular the late stage of the synthesis, of

very demanding (both electronically and sterically) systems.

Consequently, we discuss here synthetic strategies that

were explored and ultimately allowed the assembly of 1, the

synthesis of the subunits, their convergent assembly to a

suitable precursor, and its final cyclization to the target

structure 1, as well as the spectroscopic characterization of

key intermediates and their purification by chiral HPLC.

Figure 1. Various realizations of chiral polycyclic aromatic com-

pounds (PACs). (a) Twisted pentacene; (b) [5]-helicene; (c) Scott’s

nanographene; (d) chiral naphthalene; (e) Vögtle’s Geländer oligo-

mer; (f) twisted terphenyl 1 as a new type of Geländer oligomer.

Figure 2. Generalized concept for the introduction of helicity: (1) A ladder-like structure with one of the rails divided. (2a) Introduction

of a rotatable joint that relays the twist from one section to the other, and (2b) elongation of the liberated ends. (3) Stepwise reattachment

of the significantly elongated sections, which induce strain in the system. (4) The system releases strain by twisting around the original

rail and, as a consequence, becomes helical.

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Pathways to a Helical Hexaphenyl “Geländer” Molecule

Retrosynthetic Analysis

groups to a vast range of reaction conditions further fa-

vored their choice as masking group for the benzylic

hydroxyl function. A late-stage bromination of the two

available benzylic positions of the para-xylene subunit

would reduce the number of functional groups present over

a broad range of the synthesis. Thus, the open precursor

2 becomes the actual key fragment with the entire carbon

skeleton correctly connected.

The retrosynthetic analysis of the “Geländer” oligomer

1 is displayed in Figure 3. The lack of symmetry is an im-

portant structural feature that avoids the generation of

meso-forms. As a consequence, the target helical hexaphenyl

1 bears six unique benzyl units: three of the rings feature a

single aryl–aryl bond, two benzyls feature two aryl–aryl

bonds and the central ring is directly linked to three neigh-

boring aryl subunits. The end capping rings can be grouped

into two structurally similar fragments that show reversed

substitution patterns (C and D).

For a convergent synthetic strategy, the use of ring A

(orange ring in Figure 3) as the central unit interlinking

three aryl subunits became the focus of interest. Our plan

was to profit from Suzuki–Miyaura-type cross-coupling re-

actions to form the required aryl–aryl connections, mainly

because of the high diversity, versatility, low toxicity, and

well-established protocols.^[13]Grouping the four end-

capping phenyls into two biphenyl subunits (C and D) that

differ only in their substitution patterns, enabled the trans-

fer of obtained knowledge from one fragment to the other.

Both fragments can subsequently be attached by Suzuki–

Miyaura coupling to the core fragment E, which itself is

also accessible by coupling a suitable core A with the com-

mercially available boronic acid B. The remaining retrosyn-

thetic challenge was to identify the most promising se-

quence for the stepwise assembly of the aryl subunits. By

following a convergent strategy, it was reasonable to inter-

connect as many rings as possible prior to the attachment

to the central core structure (i.e., assembly of the biphenyl

groups C and D prior to attachment rather than attaching

one ring at a time). However the exact order of attachment

was not straightforward and the optimal synthetic route re-

mained to be deduced experimentally.

The synthetic route that we identified as most likely to

succeed was to attach the commercially available boronic

acid to the highly substituted core A, which already bears

all three required halogens, either masked or unmasked.

Having accessed the biphenyl E, the fragments C and D

(blue and pink, respectively) could be attached subsequently

over two complementary pathways: Either by attaching first

fragment C to E and then fragment D (olive arrow) or vice

versa (dark-blue arrow). Given that there have been few or

no preceding reports in this area, the choice of pathway

had to be explored empirically. Fortunately, both pathways

required the same fragments C and D. Our strategy was to

develop the central building block towards the target struc-

ture by attaching boronic derivatives whenever possible.

The structure of the central core A had to be designed

such that it allowed the selective attachment of the three

fragments B–D. A cornerstone of our synthetic strategy was

to make use of the different reactivities of halides in Su-

zuki–Miyaura cross couplings. Central building blocks with

suitable substitution patterns bearing an iodine and a

Figure 3. Retrosynthetic analysis for the stepwise assembly of 1.

The most promising disconnection was the opening of bromine substituent were expected to allow two of the three

the ether bridges in 1 such that ring B (purple ring in Fig- fragments to be introduced chemoselectively. As third sub-

ure 3) supplies the required leaving groups whereas the stituent, we planned to profit from a masked leaving group

esters, upon reduction, can provide the necessary oxygen suchasamethoxygroup,whichcouldlaterbeconvertedintoa

moieties. Esters were particularly interesting because they triflate that was suitable for cross coupling, or a nitrogen

are generally very susceptible to reductive conditions, even moiety (nitro or triazene) as a precursor of an iodine sub-

in the presence of benzylic halides. The tolerance of ester stituent.

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Results and Discussion

Synthesis of Fragments A–D

Fragments A and B

Several potential derivatives as fragment A were consid-

ered (Scheme 1). Bromination of commercially available 1-

iodo-3-methoxybenzene (3) by using a reported protocol^[14]

with N-bromosuccinimide (NBS) yielded 4 in almost quan-

titative yield. We have recently described the synthesis of 6–

8 elsewhere.^[11]In summary, nitro compound 6 was ob-

tained in excellent 97% yield from 5. In two steps, 6 could

be readily converted into the corresponding triazene 8,

giving access to three possible fragments A (4, 6, and 8)

that were suitable for subsequent cross coupling with

fragment B. 2,5-Dimethylphenylboronic acid as potential

fragment B is commercially available and was not accessed

synthetically.

Scheme 2. Reagents and conditions: (a) Pd(PPh₃)₂Cl₂, K₂CO₃,

THF/MeOH (4:1), 60 °C, 15 h, 11: 53%, 12: 54%; (b) Pd(dppf)Cl₂,

B₂pin₂, KOAc, DMF, 100 °C, 6.5 h, 13: 5%; (c) Pd(dppf)Cl₂,

B₂pin₂, KOAc, DMF, 100 °C, 2 h, Ͼ99% (75% for large scale);

(d) iPrMgCl·LiCl, B(OiPr)₃, neopentyl glycol (NPG), THF, –40 °C

to r.t., 19 h, 72%; (e) DIBAL-H, CH₂Cl₂, 0 °C to r.t., 1–2 h, 90%;

(f) DIBAL-H, CH₂Cl₂, 0 °C to r.t., 1–2 h, 94%; (g) Pd(dppf)Cl₂,

B₂pin₂, KOAc, DMF, 100 °C, 6.5 h, Ͻ5%; (h) TBSCl, imidazole,

CH₂Cl₂, r.t., 22 h, 86%; (i) iPrMgCl·LiCl, B(OiPr)₃, NPG, THF,

–40 °C to r.t., 20 h, 45%.

As a starting point, the widely used Pd(PPh₃)₄was

employed as catalyst under an oxygen-free atmosphere in a

1:2 ratio of wet tetrahydrofuran (THF) and methanol, using

K₂CO₃as base and 1.5 equiv. of 1-bromo-3-iodophenyl.

Samples were taken after 3 and 24 h, respectively, and

analyzed by GC–MS. Generally, it can be stated that

Pd(PPh₃)₂Cl₂showed superior conversions compared with

other catalysts employed. Selective cross coupling on the

iodine was observed exclusively even at 60 °C, allowing for

subsequent attachment of the next fragment (or a boronic

moiety) after the cross-coupling step. Both precatalyst

XPhos- and SPhos-palladacycle systems described by Buch-

wald and co-workers,^[15]showed a tendency to also initiate

cross coupling on the bromines, which was undesired in this

case. This observation, however, pointed to the possibility

of employing these highly active systems at a later stage in

the synthesis. The choice of solvents played a crucial role in

the success of the reaction. A significant decrease in reacti-

vity was observed without the addition of methanol. Inter-

estingly the presence of methanol seems to be important

Scheme 1. Reagents and conditions: (a) NBS, MeCN, r.t., 15 h,

96%; (b) BF₃·OEt₂, ONOtBu, THF, –30 °C to r.t., 3 h, then I₂,

KI, MeCN, r.t., 30 min, 97%; (c) Fe, HCl, EtOH, 0 °C, 2 h, 94%;

(d) BF₃·OEt₂, ONOtBu, CH₂Cl₂, –30 °C to r.t., 15 min, then pyr-

rolidine, K₂CO₃, r.t., 15 min, 95%; N₃Py = diazenylpyrrolidine.

Fragment C

The two remaining fragments C and D are both biphen- but not the exact ratio, because similar conversions were

yls, albeit with different substitution patterns. It turned out observed for THF to methanol ratios of both 2:1 and 4:1.

that the type of substitution pattern had a surprising impact

To increase the reactivity of the fragment in a subsequent

on the chemistry we were able to perform on the fragments. coupling or trans-functionalization reaction, the iodine ana-

The biphenyl fragment C features a borane in the 3-position logue 12, together with the benzylic alcohol 16 and the silyl-

and either an ester or a benzylic alcohol in the 2Ј-position. masked benzylic alcohol 18, also became a focus of interest.

For fragment D, the pattern is reversed; the borane is in the Subjecting 1,3-diiodobenzene (20) and the corresponding

2Ј-position whereas the ester or benzylic alcohol is located boronic acid to Suzuki–Miyaura conditions provided 12 in

at the 3-position. In particular, the position of the preceding up to 54% yield after optimization. Considering the statisti-

halogen was crucial for the success of the borylation. Start- cal nature of the reaction, we were pleased with the isolated

ing from 2-methoxycarbonyl phenyl boronic acid (9 in yield. The only observed side-products were the dicoupled

Scheme 2), Suzuki–Miyaura cross coupling with 1-bromo- analogue as well as starting material. It is important to

3-iodophenyl (10) was possible, rendering 11 in 53% after note, however, that by adding more than 1 equiv. of boronic

several optimizations (see Table 1 in the Supporting Infor- acid under suitable conditions [i.e., Pd(PPh₃)₂Cl₂, NaOH,

mation).

dioxane/water (4:1), 60 °C, 21 h, 88%] it was also possible

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Pathways to a Helical Hexaphenyl “Geländer” Molecule

to initiate cross coupling on the bromine. The cross cou- of iodine and bromine towards Suzuki–Miyaura coupling

pling was found to be very reliable and robust, even on large again allowed the iodine to be selectively addressed over the

scale (Ͼ20 g, 54%).

bromine, giving yields of 73% for the ester 24.

The synthetic strategy relies on a reduction of the methyl

esters at a late stage of the synthesis. Compounds 11 and

12 were considered as model compounds with which to in-

vestigate the required reaction conditions. Subjecting either

11 or 12 to reductive conditions using diisobutylaluminum

hydride (DIBAL-H), the desired benzylic alcohols 15 and

16 were obtained in promising yields of 90 and 94%, respec-

tively, corroborating the potential of these esters as masked

benzylic alcohols. In case the reduction should fail on the

further advanced (more crowded) precursor, a masked

benzylic alcohol might be an alternative building block.

Treating the obtained benzylic alcohol 16 with TBSCl un-

der basic conditions provided the TBS-protected alcohol 18

in a pleasing 86% yield.

According to our convergent strategy, borylation of the

biphenyl building block was investigated next (Table 2 in

the Supporting Information). Reaction conditions were de-

veloped starting from reported protocols^[16]with the ester-

bearing biphenyls 11 and 12, the free alcohols 15 and 16,

as well as the TBS-protected alcohol 18 as potential starting

materials. Similar to the trends observed for Suzuki–

Miyaura couplings, iodines were found to show signifi-

Scheme 3. Reagents and conditions: (a) Pd(PPh₃)₂Cl₂, K₂CO₃,

THF/MeOH (4:1), 60 °C, 15 h; 21 + 22Ǟ24: 73%; Pd(PPh₃)₂Cl₂;

30 + 22Ǟ25: 41%; Pd(PPh₃)₄, Cs₂CO₃, THF/EtOH (4:1), 60 °C,

4 h; 21 + 23Ǟ27, 71%; (b) Pd(dppf)Cl₂, B₂pin₂, KOAc, dioxane,

100 °C, 1 h, 57% as regioisomers; (c) DIBAL-H, CH₂Cl₂, 0 °C to

r.t., 2 h, Ͼ99%; (d) Pd(dppf)Cl₂, B₂pin₂, KOAc, DMF, 100 °C, 1 h,

59% as regioisomers.

In contrast to the observations made for fragment C, it

cantly increased reaction rates towards Hosomi–Miyaura was also possible to directly cross couple the free alcohol

borylation (quantitative conversions for iodines vs. 5% for without prior protection, giving 27 in comparable yield

bromines). The conversion of the iodine worked most (71%). To benefit from the increased reactivity of iodines

reliably on large scale (Ͼ14 g) when heating to approxi- over bromines in Hosomi–Miyaura borylations, we also

mately 112 °C in dioxane overnight (sealed flask). Lithi- prepared the iodinated analogues 25 and 28. Statistically

ation of ester 11 by using sBuLi, tBuLi or lithium diiso- subjecting 1,2-diiodobenzene (30) and the corresponding

propylamide (LDA) as lithium source^[17]resulted in decom- boronic acid to Suzuki–Miyaura conditions allowed 25 to

position of the starting material. Another explored possibil- be accessed in 41% yield, which is a reasonable yield for a

ity to introduce the boronic moiety by metalation was the statistical reaction. The only observed side-products were,

use of conditions developed by Knochel and co-workers in as in the case for fragment C, the dicoupled analogue as

which the corresponding halide is subjected to Grignard well as the starting material. Subjecting 25 to reductive con-

conditions and the formed magnesium intermediate is ditions using DIBAL-H again allowed access to the desired

quenched with a boron source. In our hands the Knochel benzylic alcohol 28 quantitatively in 2 h.

conditions^[18]turned out to be generally lower yielding

From the four precursors for the subunit C (24, 25, 27,

compared to the classical Hosomi–Miyaura borylation. and 28), precursors 25 and 27 were initially selected and

Furthermore, upscaling to multigram batches resulted in a subjected to Hosomi–Miyaura conditions. Borylation of 27

substantial drop in yield and the reaction required extended provided a crude boronic ester derivative in reasonable 59%

reaction times (72% for small scale, 31% for large scale). isolated yield. Interestingly, we were now able to obtain the

For the free alcohol 15, only low yields were obtained borylated free hydroxy in good yields, whereas with re-

(Ͻ5%) with the Knochel system,^[18]because decomposition versed substitution patterns, the obtained boronic ester 17

of the free alcohol 17 was observed under basic conditions was not stable. We found a strong dependence of the iso-

even without the presence of a metal source. The TBS-pro- lated yield on the concentration, and significantly lower

tected alcohol 18 could, however, be successfully borylated yields tended to be obtained upon dilution. To our surprise,

(45%).

the isolated boronic ester derivative was not a pure com-

pound, but an inseparable mixture of two regioisomers

(Scheme 4). GC–MS, ¹H and ¹³C NMR analyses confirmed

the presence of exactly two regioisomers in a 1:1 ratio. 2-D

Synthesis of Fragment D

Building on the knowledge obtained for fragment C, we NMR spectroscopy allowed the identification of both com-

turned our attention to the structurally related fragment D pounds as the expected biphenyl 29, and 31 as the second

(Scheme 3). Starting from 1-bromo-2-iodobenzene (21) and isomer. Intriguingly, the boronic moiety in 31 is located

[3-(methoxycarbonyl)phenyl]boronic acid (22) or [3- para to the hydroxyl group on the opposite phenyl ring.

(hydroxymethyl)phenyl]boronic acid (23), access to 24 and Whether the formation of that second isomer occurs by de-

27 was achieved in good yields. The difference in reactivity borylation and reborylation of the C–H bond at the 2-posi-

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tion or whether the boronic moiety escapes the steric con- tered conditions promoted the formation of the rearranged

straint it undoubtedly suffers from and directly isomerizes, side-product 32 over the expected product 26 (entry 2; 84

is still under investigation. Similar observations have been and 16%, respectively). It thus appears that the choice of

reported for corannulene and biphenyl using an iridium- solvent can influence the formation of the regioisomer sig-

catalyzed system.^[19]We wondered whether the observed nificantly. Lowering the temperature to 80 °C resulted in

isomerization was a unique feature of alcohol 27. Sub- formation of the undesired isomer 32 in 71% yield (entry 3),

jecting ester 25 to the same conditions, however, rendered demonstrating that temperature can also influence the ex-

a similar picture (Table 1): The yield was as high as for 27 tent of the rearrangement.

(isolated yield: 57%) again with a 1:1 ratio of similar re-

gioisomers (entry 1, 26 and 32). Both regioisomers could be

Table 1. Formation of regioisomers during the Hosomi–Miyaura

borylation of 25.^[a]

separated by normal-phase HPLC (column: semiprepar-

ative Reprosil 100 Si, 5 μm, 250ϫ16 mm, eluent: CH₂Cl₂,

8 mL/min) and both were fully assigned based on ¹H NMR

and 2D NMR spectroscopy. GC–MS showed the same

mass and fragmentation pattern for both compounds as ex-

pected for regioisomers (see Figure 4). It appears that an

ester is equally capable to direct this unexpected rearrange-

ment. However, we never observed the rearrangement when

exchanging the positions of the halogen and the ester or

alcohol (i.e., for the fragment C homologues), further indi-

cating that steric strain plays an essential role in promoting

this unexpected rearrangement. The use of dioxane instead

of N,N-dimethylformamide (DMF) under otherwise unal-

[a] Reaction conditions: Pd(dppf)Cl₂, B₂pin₂, KOAc, 15 h. [b] By

GC–MS analysis. [c] Significant amount of side-products observed.

This unexpected and intriguing rearrangement prevented

the synthetic availability of borylated building block D and

challenged the envisaged synthetic strategy. In addition,

borylation of the bromine analogue 24 showed significantly

reduced reaction rates compared with those of 25. We there-

fore decided to alter our synthetic strategy by exchanging

the positions of the boronic acid derivative and of the halo-

gen leaving group for the bond formation between the frag-

ments D and A. The iodinated precursors 25 and 28 were

thus considered as potential fragments C.

Scheme 4. Formation of the two regioisomers 29 and 31 upon

borylation of bromobiphenyl 27, yields were determined by GC–

MS analysis.

Figure 4. (a) GC–MS trace from the reaction mixture of the borylation of 25 displaying both regioisomers (26 and 32), which were

formed in a 1:1 ratio. (b) Mass-spectrometric analysis of both GC signals. Both regioisomers give closely related patterns because of their

structural similarity.

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Pathways to a Helical Hexaphenyl “Geländer” Molecule

With all building blocks for a convergent synthesis in tiated bond formations are widely used in polyaromatic syn-

hand, our attention moved towards the assembly of the thesis (e.g., Scholl-type reactions),^[21]the inability to depro-

target structure 1.

tect the methoxy group forced us to search for alternative

routes. The nitro derivative 6 is ideally suited for cross-cou-

pling reactions because of its electronic nature. Indeed,

when subjected to the same cross-coupling conditions as

applied above for 4, compound 6 and phenyl boronic acid

Stepwise Connection of the Fragments I: Preliminary

Studies with Model Compounds

With all fragments in hand, we aimed to establish a were converted into 37 in 68% yield. The electron-with-

viable sequence for their combination to give the target drawing effect of the nitro group has an even larger activa-

structure. Fragment A, that is 4, 5 and ultimately 8, allowed ting effect on the engagement of the bromine in the para-

for the envisaged stepwise attachment of the other frag- position in cross-coupling reactions. Subsequent coupling

ments. At this point we were mainly interested in exploring of the remaining bromine of the formed biphenyl 37 as a

the synthetic strategy as far as possible. It was therefore of major side-reaction clearly reflected this effect. The in-

interest to attach a fragment B with diminished steric bulk. creased activity of the bromine leaving group was also

Coupling of 4 with commercially available phenyl boronic promising for the subsequent attachment of fragment C. We

acid gave 33 in excellent 93% yield over 21 h using partially decided to directly subject the only marginally purified 37

optimized conditions (Scheme 5). A solvent system con- together with 19 to cross-coupling conditions, giving the

sisting of dioxane/water (4:1) was found to promote cross tetraphenyl building block 38 in excellent 84% yield. Purifi-

coupling on both halides to a significant amount (up to cation of the test system 38 was very challenging and we

26% according to GC–MS analysis). Cross coupling 33 decided to focus instead on the similar reaction between

with crude 14 under similar conditions to those described 37 and 14, which provided the methyl ester functionalized

before gave tetraphenyl 34 in reasonable 51% yield. To en- tetraphenyl building block 39. To enable the attachment of

able the introduction of the last fragment D, the hydroxy the remaining fragment D, the nitro groups of 38 and 39

group needed to be liberated. Typically a strong Lewis acid had to be transformed into a leaving group. Reductive con-

such as BBr₃is capable of demethylating the methoxy ditions using SnCl₂are known to promote the reduction of

group.^[20]When subjecting 34 to Lewis-acidic conditions at nitro groups selectively, while leaving ester groups un-

–78 °C, we observed the formation of a single isolable prod- touched.^[22]Indeed, we were able to reduce the nitro group

uct in 56% yield. 1D ¹H NMR and 2D NMR spectroscopy of both 38 and 39 to the corresponding amines 40 and 41,

(namely selective TOCSY), as well as GC–MS analysis al- albeit in low yields of Ͻ27% for the TBS-protected alcohol

lowed the isolated compound to be identified as cyclic 40 and Ͻ50% for the methyl ester 41. Reduction using Pd/

ketone 36, instead of the desired complex quarterphenyl 35 C and H₂as an alternative protocol resulted in decomposi-

with a liberated phenolic OH group. Apparently, BBr₃is tion of the starting material. Nevertheless, because 41 was

capable of activating the ester such that cyclization is pre- accessible in sufficient purity, we attempted to substitute the

ferred to the desired methylation. Although Lewis-acid ini- amine group with an iodine, which would allow the remain-

Scheme 5. Reagents and conditions: (a) phenyl-B(OH)₂, Pd(PPh₃)₂Cl₂, K₂CO₃, toluene/EtOH (4:1), 80 °C, 21 h, 93%; (b) 14, Pd(PPh₃)₂-

Cl₂, K₃PO₄, dioxane/water (4:1), 80 °C, 4 h, 51%; (c) BBr₃, CH₂Cl₂, –78 °C to 0 °C, 4 h, 56% of 36; (d) phenyl-B(OH)₂, Pd(PPh₃)₂Cl₂,

K₂CO₃, toluene/EtOH (4:1), 80 °C, 18 h, 68%; (e) 19, Pd(PPh₃)₂Cl₂, K₃PO₄, dioxane/water (4:1), 80 °C, 5.5 h, 84%; (f) 14, Pd(PPh₃)₂Cl₂,

K₃PO₄, dioxane/water (4:1), 80 °C, 3 h, 81%; (g) SnCl₂, EtOAc, reflux, 8 h, Ͻ27; (h) SnCl₂, EtOAc, reflux, 6 h, Ͻ50%; (i) 1. BF₃·OEt₂,

ONOtBu, THF, –30 °C to r.t., 3 h; 2. I₂, KI, MeCN, r.t.

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ing fragment D to be attached. By using the established borane 48 in low yields of 32% for the unsubstituted bi-

conditions to convert anilines into iodines by forming the phenyl model compound. As this served merely as a test

corresponding diazonium salt, the ester 41 was subjected to system, the conditions were not improved. As a conse-

the iodination protocol. Unfortunately, the only observed quence, however, the palladium-catalyzed Hosomi–Miyaura

product was the dehalogenated tetraphenyl 43 and in none borylation protocol that we have already established was

of the attempts was the desired iodinated derivative 42 de- used for the dimethylated iodobiphenyl 47, providing

tected.

pinacol borane 49 in an improved yield of 53%. Given the

metastable nature of the intermediate, the obtained borane

was typically used directly in the next step.

Stepwise Connection of the Fragments II: The End Game

The synthetic routes exploited so far mainly focused on

the stepwise attachment of fragments C and D to E follow-

ing the olive path of the retrosynthetic analysis (Figure 3).

Thereby, we faced severe challenges with the attachment of

fragment D, in particular its troublesome isomerization dur-

ing borylation. Furthermore, the challenging introduction

of a suitable leaving group at the quaterphenyl structure

required for the attachment of the fragment D raised ques-

tions concerning the viability of this route. At this stage we

reconsidered our synthetic strategy, building on the insights

gained over the course of the various attempts.

The new plan was to profit from the fact that fragment A

can already feature a masked iodine. Particularly interesting

were triazenes, which can be converted into iodines without

the need for a reduction/iodination sequence. The iodine

was appealing because it would allow for selective

borylation in the presence of less reactive bromines. By

introducing the boronic ester to the assembled biphenyl

system, the troublesome fragment D could then be intro-

duced as a halide (iodine), thus potentially preventing the

isomerization as well as moving the challenging attachment

of the fragment to an earlier point in the synthesis. Thus,

the blue path of the retrosynthetic analysis (Figure 3) be-

came more appealing. As fragment B, a para-xylene deriva-

tive was envisaged, which should allow benzylic bromina-

tion in a late stage of the synthesis. The conceptual idea

was to minimize the number of functional groups present

over a large extent of the synthesis. Having all rings in place

would allow the investigation and the full characterization

of the structure before introducing the required bromines

and reducing the ester moieties to benzylic alcohols. As a

last step, basic cyclization should then provide the target

structure 1.

Scheme 6. Reagents and conditions: (a) phenyl-B(OH)₂, Pd(PPh₃)₂-

Cl₂, K₂CO₃, toluene/EtOH (1:1), 80 °C, 23 h, 62%; (b) 2,5-dimeth-

ylphenyl-B(OH)₂, Pd(PPh)₂Cl₂, K₂CO₃, THF/H₂O (4:1), 60 °C,

15 h, 88% to Ͼ99%; (c) MeI, 120 °C, 15 h, 83%; (d) MeI, 120 °C,

15 h, 77–96%; (e) iPrMgCl·LiCl, B(OiPr)₃, NPG, THF, –40 °C to

r.t., 19 h, 32%; (f) Pd(dppf)Cl₂, KOAc, B₂pin₂, dioxane, 100 °C,

15 h, 53%; (g) 25, Pd(PPh₃)₂Cl₂, K₂CO₃, toluene/EtOH (4:1),

80 °C, 5.5 d, 33%; (h) 25, XPhos Pd G2, K₂CO₃, toluene, 110 °C,

1–2 d, 58–94%; (i) 14, Pd(PPh₃)₂Cl₂, K₃PO₄, dioxane/H₂O (4:1),

80 °C, 4 h, 90%; (j) 13, SPhos Pd G2, K₂CO₃, toluene/H₂O (20:1),

110 °C, 1–3 d, 50%; (k) NBS, DBP, CCl₄, 75 °C, 1 h, 87% to

Ͼ99%; (l) DIBAL-H, CH₂Cl₂, r.t., 30 min, Ͼ99%; (m) 1. NaH,

THF, reflux, 12 h, 30% for the monocyclized intermediate; 2. NaH,

[D₈]THF, 60 °C, 2–3 d, 28%.

Starting from triazene 8, two different fragments B were

attached (Scheme 6): Either an unsubstituted phenyl ring,

giving 44 as a test system, or 2,5-dimethyl phenyl, which

results in 45. The only difference in reactivity between both

fragments might be some steric constrains from the two

methyl groups. Both biphenyl fragments 44 and 45 were ob-

With 48 and 49 in hand, the attachment of fragment D

tained: 62% for 44, and excellent yields of up to Ͼ99% became the focus of interest. Suzuki–Miyaura cross cou-

for 45 under optimized conditions. In both cases, selective pling of the phenyl-bearing model system 48 with 25 under

substitution of the iodine was observed. Both triazenes 44 the conditions optimized for the assembly the tetraphenyls

and 45 were converted into the corresponding iodines 46 38 and 39 gave the desired tetraphenyl 50 in modest 33%

and 47 in very good yields of 83 and 77–96%, respectively, yield. Relying on the observations made while screening for

by treatment with MeI at 120 °C overnight.^[23]Subsequent optimal Suzuki conditions for the assembly of fragment C,

borylation of iodines 46 and 47 was more challenging. The we decided to employ a catalyst system that showed a high

application of Knochels protocol gave access to neopentyl tendency for cross coupling of sterically challenging

8

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Pathways to a Helical Hexaphenyl “Geländer” Molecule

systems.^[24]XPhos Pd G2 was found to be ideal for the suc- straightforward and comparably facile final step. This as-

cessful promotion of the desired cross coupling of 49 with sumption was based on the observation that, in 54, the two

25, giving the desired quaterphenyl system 51 in up to 94% benzylic alcohols as nucleophiles and the two benzylic

yield based on GC–MS analysis. At this stage of the synthe- bromides as substrates are ideally preorganized for two sub-

sis, the obtained crude material was very challenging to pu- sequent intramolecular substitution reactions. Potential

rify and it was best used as obtained in the next step. The polymerization reactions can be avoided by performing

cross-coupling reaction was monitored by GC–MS analysis both ring-closing reactions under high-dilution conditions.

and full conversion was observed within 1–2 days. By plac- Much to our surprise, the double ring-closing reaction of

ing the borane on the assembled structure rather than on 54 to 1 turned out to be very challenging. Initial attempts

the biphenyl fragment D, its troublesome isomerization was to cyclize 54 to 1 under basic conditions resulted in traces

prevented entirely. Both quarterphenyls 50 and 51 were of 1 at best, regardless of full consumption of the starting

suitably functionalized for the attachment of the last material. The only promising signs were obtained by

fragment C.

DART-MS of the reaction mixture, which revealed at least

Whereas slightly modified standard Suzuki–Miyaura partial formation of the desired structure. Attempts to iso-

conditions were used for the coupling between the sterically late 1 failed; instead, substantial loss of mass was observed

less demanding 50 and 14, the sterically encumbered 51 to- when exposing the reaction mixture to either silica (acidic

gether with the pinacol borane C fragment 13 were sub- or pH-neutral) or aluminum oxide. Closer inspection of the

jected to a previously reported, highly active catalyst system course of the double ring-closing reaction by TLC revealed

[Pd(OAc)₂/SPhos or SPhos Pd G2].^[25]The less hindered the rapid formation of a new spot, which was subsequently

model compound 52 was isolated in excellent 90% yield, consumed with the addition of more base. The working

while the sterically more challenging coupling product 2 hypothesis was that this rapidly formed new spot might be

was still obtained in a reasonable yield of 50%. Both hexa- a monocyclized intermediate; indeed, DART-MS analysis

1

phenyl systems 52 and 2 were fully characterized by H, of the TLC spot revealed a molecular mass supporting the

¹³C, as well as 2D NMR spectroscopy, confirming not only hypothesis. Given that we failed to cyclize 54 directly to 1,

the presence of all required rings, but also the desired sub- our desperate final strategy was to isolate the monocyclized

stitution patterns. DART-MS as well as HRMS (ESI) pro- derivative of 54 and to investigate its ability to close the

vided further evidence for the molecular identity of 2.

second ring. The hope was that cleaner reaction conditions

With compound 2 in hand, our attention turned to the might prevent the formation of side products and thereby

bromination of its methyl groups. A bromination procedure favor the second intramolecular ring closure of the inter-

adapted from a reported protocol was applied.^[26]Treat- mediate to 1. By reducing the amount of sodium hydride

ment of 2 with NBS and dibenzoylperoxide in CCl₄pro- and carefully monitoring the course of the reaction,

vided the dibrominated hexaphenyl 53 in up to quantitative selective monocyclization was possible. According to ¹H

yield. The reaction times varied with the batch size, and the NMR analysis, a pure monocyclized derivative was isolated

course of the reaction had to be closely monitored to avoid and, although we could not identify which, it seemed that

over-bromination. All brominated species were structurally exclusively one of the four possible regioisomers was

and electronically very similar, resulting in comparable formed. Considering the proximity of the functional sub-

retention values in all investigated chromatographic units, we were confident that we obtained one of the two

systems; thus, monitoring was best performed by DART- correctly closed systems, because we reasoned that the de-

MS. The mono- and tri-brominated species were sub- signed target structure is the energetically most favored

sequently removed efficiently by semipreparative HPLC spatial arrangement. Even though the isolation of the

(column: semipreparative Reprosil 100 Si, 5 μm, monocyclized compound was yield diminishing (30% iso-

250ϫ16 mm, eluent: 60:40 hexane/CH₂Cl₂, 8 mL/min). lated yield), we hoped that in the monocyclized derivative

Conventional flash column chromatography (CC) could be the remaining functional groups might be even better pre-

used to enrich the dibrominated species 53, but only after organized, further favoring the second ring closing over

1

several repeated columns. Interestingly, the H NMR spec- competing reaction pathways such as intermolecular substi-

trum revealed diastereotopic hydrogen signals for all benz- tution reactions. To monitor the course of the second ring

ylic positions, indicating that, on the NMR timescale, the closure, the reaction was directly performed in an NMR

structure was already subject to hindered rotation. For the tube. The tube was charged with the monocyclized re-

reduction of diester 53, the protocol established for frag- gioisomer in deuterated THF, and sodium hydride was

ment C was applied. Treatment of 53 with DIBAL-H in added as base. The reaction mixture was heated to 60 °C

1

dichloromethane at room temperature for 30 min provided and the formation of 1 was monitored by H NMR spec-

hexaphenyl diol 54 in almost quantitative yield. The latter troscopy.

diol displayed limited stability and thus subsequent cycliza-

Much to our delight, we observed an almost clean trans-

tion was best carried out immediately after purification.

formation of the monocyclized intermediated into a new

During the development of the synthetic strategy, we compound with NMR signals matching the expectations

judged the assembly of the suitably functionalized hexa- for the desired target structure 1 over a period of 2–3 days

phenyl system to be the major challenge and assumed that (Figure 5). In particular, for each of the eight diastereotopic

once 54 became available, its double cyclization would be a benzylic hydrogen atoms, an individual signal was observed

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(each as a doublet) due to geminal coupling to the second yield the target compound 1 in a combined yield of 28%

hydrogen at the corresponding benzylic carbon atom. In (14% of each enantiomer). Although the yield was some-

spite of the clean transformation observed in the NMR what sobering considering the clean transformation

spectra, all attempts to isolate the formed species by con- monitored by ¹H NMR analysis, we were at this point more

ventional column chromatography or by normal-phase than pleased to finally have been able to isolate 1 as pure

HPLC failed; in other words, the results further documen- enantiomers. Interestingly, the purified samples of 1 were

ted the delicate stability properties of the compound at least reasonably stable; the compounds tolerated air and

on these solid phases. Given that the target structure 1 is moisture as well as evaporation of the solvents at elevated

formed as a racemate, we considered purification by chiral temperatures under reduced pressure.

HPLC with the hope of isolating pure enantiomers. Inter-

The target structure 1 is a colorless solid that is soluble

estingly, both Chiralpak IA and AD-H analytical columns in common organic solvents (ethers, chlorinated hydro-

1

were suitable (eluent: n-hexane/2-propanol, 99:1; flow rate carbons, aromatics, etc.). It was fully characterized by H

1 mL/min; T = 25 °C) to successfully separate 1 into its M and ¹³C NMR spectroscopy and by high-resolution mass

and P enantiomers. The injected sample contained the reac- spectrometry. 2D NMR experiments enabled the full as-

tion mixture as obtained directly after filtration and change signment of all the peaks, confirming the identity of the

of solvents. The obtained UV trace of one representative structure. ¹H NMR spectra were identical for both enantio-

run is displayed in Figure 6, which clearly displays the mers, which clearly demonstrated the diastereotopic benz-

enantiomeric peaks as major components in the mixture. ylic protons (see Figure 5, c). The identity of 1 was finally

No significant plateau between the peaks was observed, corroborated without a doubt by X-ray diffraction, which

pointing to a relatively slow racemization process at room was presented in detail in the preceding communication.^[11]

temperature on the timescale of a single run (ca. 20 min). All compounds synthesized over the course of this work

1

The obtained fractions of numerous runs were combined to were characterized by H and ¹³C NMR spectroscopy and

Figure 5. Conversion of the monocyclized intermediate into 1 with NaH in [D₈]THF at 60 °C, monitored by ¹H NMR spectroscopic

analysis. (a) Selected ¹H NMR region of the open-chain precursor 54. The observed benzylic hydrogen atoms are diastereotopic.

(b) Monocyclized intermediate at the beginning of the second cyclization. (c) Spectra of the reaction with almost complete conversion

into target structure 1. The topmost spectrum shows the isolated Geländer oligomer 1 after chiral HPLC.

10

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Pathways to a Helical Hexaphenyl “Geländer” Molecule

with a 5 mm BBI probe head with Z-gradients. ¹³C NMR and all

2D spectra were recorded with a Bruker Ascend 600 MHz Avance

III HD equipped with a 1.7 mm TCI cryo probe head. The chemi-

cal shifts are reported in parts per million (ppm) relative to

tetramethylsilane or a residual solvent peak, and the J values are

given in Hz. DART-MS was measured with an IonSense DART-

SVP100 (He, 450 °C) connected to a Shimadzu LC-2020. GC–MS

analysis was performed with

a Shimadzu GC–MS-2010 SE

equipped with a Zebron 5 MS Inferon column, which allowed tem-

peratures up to 350 °C to be achieved. High-resolution mass spec-

tra (HRMS) were measured as HR-ESI-ToF-MS with a Maxis 4G

instrument from Bruker with the addition of NaOAc. For column

chromatography, usually silica gel Siliaflash p60 (40–63 μm) from

Silicycle was used, and TLC was performed on silica gel 60 F254

glass plates with a thickness of 0.25 mm purchased from Merck.

Buffered silica was prepared by using buffer solution pH 7 by

Fluka and diluting 1:25 with water. 10 mL of the prepared solution

was added to 100 g of silica and allowed to adsorb under mixing

overnight. For HPLC, a Shimadzu LC-20AT HPLC was used

equipped with a diodearray UV/Vis detector (SPD-M10A VP from

Shimadzu, λ = 200–600 nm) equipped with the corresponding col-

umn (regular: Reprosil 100, 5 μm, 250ϫ16 mm; chiral: Chiralpak

IA 0.46ϫ25 cm; Daicel Chemical Industries Ltd.). All solutions

were prepared and measured under air-saturated conditions.

Figure 6. UV trace of a representative chiral HPLC run of the

crude reaction mixture after filtration (Chiralpak IA; n-hexane/2-

propanol (99:1), flow rate 1 mL/min, T = 25 °C). The chart reveals

the two enantiomeric peaks (blue) as major compounds. The

enantiomeric fractions were collected and combined to give 28%

combined yield of the desired target structure 1.

by mass spectrometry. The intermediates obtained on the

synthetic route resulting in the successful assembly of 1

were also characterized by high-resolution ESI mass spec- 1-Bromo-2-iodo-4-methoxybenzene (4) was synthesized from 1-

iodo-3-methoxybenzene according to a reported procedure.^[27]The

experimental data for the successful route including each interme-

trometry.

diate step to access 1 (i.e., 6–8, 12, 13, 25, 45, 47, 49, 51, 53, 54

and 1) were described previously.^[11]

Conclusions

Methyl 3Ј-Bromo-[1,1Ј-biphenyl]-2-carboxylate (11): To an oven-

dried and argon-flushed Schlenk tube were consecutively added

potassium carbonate (2.32 g, 16.6 mmol, 3.00 equiv.), 2-methoxy-

carbonylphenylboronic acid (9; 1.00 g, 5.56 mmol, 1.00 equiv.),

Pd(PPh₃)₂Cl₂(82.8 mg, 2 mol-%), and 1-bromo-3-iodobenzene (63;

1.42 mL, 11.1 mmol, 2.00 equiv.). Anhydrous THF (20 mL) and

We have discussed the synthesis of the new “Geländer”

structure 1 as a model compound to demonstrate a new

concept to induce helicity in polyaromatic systems. The syn-

thesis of 1 is based on a broad range of Miyuara–Hosomi

borylation/Suzuki–Miyaura cross-coupling protocols. In a

convergent assembly strategy, suitable precursors were as- anhydrous MeOH (5 mL) were added and the solution was de-

gassed for 15 min before heating to 60 °C and stirring overnight.

EtOAc and water were added, the aqueous phase was extracted

with EtOAc (2ϫ), and the combined organic phases were washed

with brine (1ϫ). After drying over Na₂SO₄, the solvent was re-

moved under reduced pressure. Column chromatography (SiO₂;

EtOAc/cyclohexane, 1:15) gave 11 (859 mg, 2.95 mmol, 53%) as a

yellow solid. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.86 (dd,

sembled and interlinked to increasingly complex oligo-

phenyl systems to finally yield the suitably functionalized

hexaphenyl precursor. The “Geländer” motif was installed

by two subsequent intramolecular substitution reactions to

build up the elongated benzyl ether oligomer. Whereas care-

ful choice of masking substrates and placement of the

boronic moieties allowed the stepwise assembly of the hexa-

phenyl precursor, persistence was required to close the

benzyl ether banister and to isolate the obtained target

4

3

4

³J_H,H= 7.7, J_H,H= 1.1 Hz, 1 H), 7.54 (td, J_H,H= 7.5, J_H,H

=

3

4

1.3 Hz, 1 H), 7.50–7.41 (m, 3 H), 7.34 (dd, J_H,H= 7.6, J_H,H

0.7 Hz, 1 H), 7.29–7.20 (m, 2 H), 3.67 (s, 3 H) ppm. ¹³C NMR

structure. In spite of numerous obstacles, the “Geländer” (101 MHz, CDCl₃): δ = 168.6, 143.4, 141.1, 131.5, 131.3, 130.7,

130.6, 130.2, 130.1, 129.5, 127.7, 127.1, 122.1, 52.1 ppm. MS (EI,

+): m/z (%) = 292 (48), 291 (12), 290 (49), 261 (52), 259 (53), 181

(20), 180 (100), 152 (48), 151 (18), 76 (22).

oligomer 1 was assembled in an overall yield of 8%, con-

sidering only the convergent ten steps interlinking the frag-

ments and installing the “Geländer” motif. Pure enantio-

mers of 1 were obtained by chiral HPLC.

Methyl 3Ј-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-[1,1Ј-biphenyl]-2-

carboxylate (14): In an oven-dried and argon-flushed Schlenk tube,

We now intend to investigate various types of bridges

and their influence on the chiroptical properties and race- isopropylmagnesium chloride lithium chloride complex solution

(1.13 mL, 1.47 mmol, 1.10 equiv.) was added to a degassed solution

of 12 (451 mg, 1.33 mmol, 1.00 equiv.) in THF (8.5 mL) at –40 °C,

followed by stirring for 40 min. After GC–MS analysis revealed full

conversion, a solution of triisopropyl borate (380 μL, 1.6 mmol,

1.20 equiv.) in THF (1 mL) was added and the mixture was stirred

at –40 °C for 2 h before warming to room temperature and stirring

for an additional 2 h. After adding 2,2-dimethyl-1,3-propanediol

(175 mg, 1.67 mmol, 1.25 equiv.), the mixture was stirred for 14 h

at room temperature. CH₂Cl₂and satd. aq. NH₄Cl were added, the

mization behavior.

Experimental Section

General Procedures: All commercially available compounds were

purchased and used as received unless explicitly stated otherwise.

[D₈]THF was purchased from Acros. ¹H NMR spectra were re-

corded with a Bruker UltraShield 500 MHz Avance III equipped

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M. Mayor et al.

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organic phase was washed with water and brine, the organic layer

was dried over Na₂SO₄, and the solvent was removed under re-

duced pressure. Column chromatography (SiO₂; EtOAc/cyclohex-

ane, 1:20) gave 14 (312 mg, 962 μmol, 72%) as a yellow oil. ¹H

NMR (400 MHz, CDCl₃, 25 °C): δ = 7.84–7.80 (m, 1 H), 7.78 (dd,

3.01 equiv.), and TBSCl (181 mg, 1.18 mmol, 1.20 equiv.) in anhy-

drous CH₂Cl₂(3 mL) and the mixture was stirred at room tempera-

ture for 7 h, before adding more TBSCl (154.1 mg, 0.983 mmol,

1.0 equiv.) and stirring overnight. The mixture was diluted with

CH₂Cl₂(30 mL) and washed with water (2ϫ 20 mL), aq. HCl (1 m,

3ϫ 20 mL) and brine (50 mL). The organic layer was dried with

3

³J_H,H= 5.9, J_H,H= 2.1 Hz, 2 H), 7.57–7.45 (m, 1 H), 7.44–7.34

(m, 4 H), 3.77 (s, 4 H), 3.61 (s, 3 H), 1.03 (s, 6 H) ppm. ¹³C NMR Na₂SO₄and adsorbed on Celite before subjecting to column

(63 MHz, CDCl₃): δ = 169.5, 143.0, 140.6, 134.0, 132.9, 131.4, chromatography (SiO₂; EtOAc/cyclohexane, 1:20) to give 18

131.4, 131.1, 131.0, 130.8, 129.9, 127.4, 127.2, 72.6, 52.1, 32.1,

22.2 ppm. MS (EI, +): m/z (%) = 325.1 (21), 324.1 (99), 323.1 (44),

294.1 (20), 293.1 (99), 292.1 (26), 208.0 (15), 207.0 (100), 206.1 (27),

181.0 (17), 179.0 (22), 178.0 (25), 177.0 (10), 152.1 (27), 151.1 (12),

69.1 (13), 56.1 (12).

(358 mg, 844 μmol, 86%) as a colorless oil. ¹H NMR (400 MHz,

4

CDCl₃, 25 °C): δ = 7.75 (t, J_H,H= 1.7 Hz, 1 H), 7.69 (dd, ³J_H,H

=

4

3

4

7.9, J_H,H= 1.7 Hz, 1 H), 7.55 (dd, J_H,H= 7.7, J_H,H= 1.5 Hz, 1

H), 7.38 (td, ³J_H,H= 7.5, ⁴J_H,H= 1.5 Hz, 1 H), 7.36–7.29 (m, 2 H),

7.20 (dd, ³J_H,H= 7.7, ⁴J_H,H= 1.5 Hz, 1 H), 7.14 (t, ³J_H,H= 7.9 Hz,

1 H), 4.56 (s, 2 H), 0.90 (s, 9 H), 0.04 (s, 6 H) ppm. MS (EI, +):

m/z (%) = 367.9 (22), 366.9 (100), 336.9 (11), 292.9 (14), 167.1 (13),

166.0 (73), 165.0 (72), 75.0 (62).

(3Ј-Bromo-[1,1Ј-biphenyl]-2-yl)methanol (15): An oven-dried and

argon-flushed round-bottomed flask was charged with 11 (408 mg,

1.40 mmol, 1.00 equiv.) and anhydrous CH₂Cl₂(20 mL) before

cooling to 0 °C. DIBAL-H (1 m in hexanes, 4.90 mL, 3.50 equiv.)

was slowly added while maintaining the temperature. After stirring

for 30 min at 0 °C, the mixture was warmed to room temperature

and stirring was continued for an additional 1 h. MeOH (10 mL)

was slowly added to the yellow solution (which became dark), fol-

lowed by tBME and aq. HCl (1 m). The organic layer was washed

with water and the aqueous layer was extracted three times with

tBME. The combined organic layers were washed with brine, dried

with Na₂SO₄, concentrated under reduced pressure, and the resid-

ual oil was passed through a plug of silica (eluent: EtOAc) to give

15 (332 mg, 1.26 mmol, 90%) as an orange oil. ¹H NMR

(400 MHz, CDCl₃, 25 °C): δ = 7.58–7.53 (m, 2 H), 7.53–7.49 (m, 1

tert-Butyl{[3Ј-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-(1,1Ј-biphen-

yl)-2-yl]methoxy}dimethylsilane (19): In an oven-dried and argon-

flushed Schlenk tube, isopropylmagnesium chloride lithium chlor-

ide complex solution (700 μL, 911 μmol, 1.10 equiv.) was added to

a degassed solution of 18 (351 mg, 828 μmol, 1.00 equiv.) in THF

(6.5 mL) at –40 °C before stirring for 40 min. After GC–MS analy-

sis revealed full conversion, a solution of triisopropyl borate

(230 μL, 994 μmol, 1.20 equiv.) in THF (1 mL) was added. Stirring

was continued at –40 °C for 2 h before warming to room tempera-

ture and stirring for another 2.5 h. After adding 2,2-dimethyl-1,3-

propanediol (109 mg, 1.03 mmol, 1.25 equiv.), the reaction was

stirred for 14 h. CH₂Cl₂and satd. aq. NH₄Cl were added and the

organic phase was washed with water and brine. After drying over

Na₂SO₄, the solvent was removed under reduced pressure. Column

chromatography (SiO₂; EtOAc/cyclohexane, 1:20) gave 19 (243 mg,

604 μmol, 45%) as a brown oil. ¹H NMR (400 MHz, CDCl₃,

3

4

3

H), 7.41 (td, J_H,H= 7.5, J_H,H= 1.5 Hz, 1 H), 7.36 (td, J_H,H

=

4

3

7.5, J_H,H= 1.5 Hz, 1 H), 7.34–7.24 (m, 3 H), 4.61 (d, J_H,H

5.7 Hz, 2 H), 1.57 (t, J_H,H= 5.7 Hz, 1 H) ppm. ¹³C NMR

(101 MHz, CDCl₃): δ = 143.1, 140.2, 138.3, 132.5, 130.7, 130.5,

130.2, 129.0, 128.6, 128.3, 128.2, 122.8, 63.4 ppm. MS (EI, +): m/z

(%) = 264 (45), 262 (46), 183 (56), 182 (11), 181 (17), 166 (19), 165

(100), 155 (18), 154 (32), 153 (17), 152 (26), 76 (13).

3

4

25 °C): δ = 7.77 (tt, J_H,H= 3.2, 1.2 Hz, 2 H), 7.59–7.54 (m, 1 H),

7.42–7.36 (m, 2 H), 7.36–7.32 (m, 1 H), 7.28 (td, ³J_H,H= 7.4, ⁴J_H,H

3

4

= 1.5 Hz, 1 H), 7.22 (dd, J_H,H= 7.5, J_H,H= 1.5 Hz, 1 H), 4.59

4

(s, 2 H), 3.75 (s, 4 H), 1.02 (s, 6 H), 0.88 (s, 9 H), –0.01 (d, J_H,H

(3Ј-Iodo-[1,1Ј-biphenyl]-2-yl)methanol (16): An oven-dried, argon-

flushed Schlenk tube was charged with 12 (369 mg, 1.09 mmol,

1.00 equiv.) and anhydrous CH₂Cl₂(3 mL) and cooled to 0 °C be-

fore adding DIBAL-H (1 m in hexanes, 2.30 mL, 5.91 mmol,

4.20 equiv.) dropwise over 15 min. The mixture was stirred for

30 min at room temperature and cooled to 0 °C before adding more

CH₂Cl₂. The reaction was carefully quenched with brine and the

mixture was stirred for an additional 30 min. The solution was neu-

tralized with satd. aq. NH₄Cl, the precipitate was filtered off and

discarded, and the filtrate was extracted with CH₂Cl₂(3ϫ). The

combined organics were washed with brine and dried over Na₂SO₄.

Removal of the solvent under reduced pressure gave 16 (317.3 mg,

1.02 mmol, 94%) as a colorless solid. ¹H NMR (400 MHz, CDCl₃,

25 °C): δ = 7.75 (t, J_H,H= 1.8 Hz, 1 H), 7.71 (ddd, J_H,H= 7.8,

⁴J_H,H= 1.8, 1.1 Hz, 1 H), 7.58–7.53 (m, 1 H), 7.45–7.31 (m, 3 H),

7.27–7.22 (m, 1 H), 7.16 (t, ³J_H,H= 7.8 Hz, 1 H), 4.60 (s, 2 H) ppm;

the hydroxy peak is most likely located underneath the broadened

water peak at δ = 1.55 ppm. ¹³C NMR (63 MHz, CDCl₃): δ =

143.0, 140.0, 138.2, 138.1, 136.5, 130.1, 130.1, 128.8, 128.7, 128.4,

128.0, 94.4, 63.2 ppm. MS (EI, +): m/z (%) = 311.1 (11), 310.1 (61),

183.1 (63), 182.1 (11), 181.1 (25), 166.0 (28), 165.1 (100), 164.1 (13),

163.1 (10), 155.2 (46), 154.1 (39), 153.1 (40), 152.1 (49), 151.1 (19),

139.1 (11), 128.1 (12), 127.0 (14), 115.1 (18), 91.2 (11), 82.5 (15),

77.0 (27), 76.1 (23), 75.1 (10), 63.0 (15), 51.0 (14).

= 1.9 Hz, 6 H) ppm. ¹³C NMR (63 MHz, CDCl₃): δ = 141.0, 140.2,

138.6, 134.8, 132.7, 131.6, 130.0, 127.8, 127.5, 127.4, 127.0, 72.5,

63.3, 32.1, 26.2, 22.1, 18.6, –5.1 ppm. MS (EI, +): m/z (%) = 354.1

(16), 353.1 (60), 352.2 (15), 225.9 (14), 225.0 (70), 193.0 (51), 192.1

(11), 191.0 (11), 180.0 (16), 179.0 (100), 167.0 (48), 166.1 (18), 165.0

(65), 119.0 (21), 75.0 (36), 73.1 (11), 69.1 (63), 57.1 (13).

Methyl 2Ј-Bromo-[1,1Ј-biphenyl]-3-carboxylate (24): To an argon-

flushed Schlenk tube was consecutively added potassium carbonate

(464 mg, 3.32 mmol, 2.98 equiv.), 3-methoxycarbonylphenylbor-

onic acid (22; 201 mg, 1.12 mmol, 1.00 equiv.), Pd(PPh₃)₂Cl₂

(16.0 mg, 2 mol-%), and 1-bromo-2-iodobenzene (21; 284 μL,

2.19 mmol, 1.96 equiv.). Wet THF (4 mL) and MeOH (1 mL) were

added and the solution was degassed for 10 min before heating to

60 °C and stirring overnight. EtOAc and water were added, the

aqueous phase was extracted with EtOAc (2ϫ) and the combined

organic phases were washed with brine (1ϫ). After drying over

Na₂SO₄, the solvent was removed under reduced pressure. Column

chromatography (SiO₂; EtOAc/cyclohexane, 1:15) gave 24 (238 mg,

817 μmol, 73%) as a yellow oil. ¹H NMR (400 MHz, CDCl₃,

4

3

4

25 °C): δ = 8.10–8.05 (m, 2 H), 7.68 (dd, J_H,H= 8.0, J_H,H

=

1.2 Hz, 1 H), 7.62 (dt, ³J_H,H= 7.7, ⁴J_H,H= 1.6 Hz, 1 H), 7.54–7.48

3

4

(m, 1 H), 7.38 (td, J_H,H= 7.4, J_H,H= 1.2 Hz, 1 H), 7.33 (dd,

³J_H,H= 7.6, J_H,H= 2.0 Hz, 1 H), 7.26–7.21 (m, 1 H), 3.93 (s, 3

4

tert-Butyl{[3Ј-iodo-(1,1Ј-biphenyl)-2-yl]methoxy}dimethylsilane (18):

An argon-flushed round-bottomed flask was charged with 16

(305 mg, 983 μmol, 1.00 equiv.), imidazole (203.5 mg, 2.96 mmol,

H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 166.9, 141.6, 141.3,

134.0, 133.2, 131.2, 130.5, 130.1, 129.2, 128.8, 128.1, 127.5, 122.5,

52.2 ppm. MS (EI, +): m/z (%) = 293 (14), 292 (95), 291 (15), 290

12

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Pathways to a Helical Hexaphenyl “Geländer” Molecule

(96), 262 (13), 261 (97), 260 (13), 259 (98), 153 (13), 152 (100), 151

(18), 76 (28).

(2Ј-Iodo-[1,1Ј-biphenyl]-3-yl)methanol (28): An oven-dried, argon-

flushed Schlenk tube was charged with 25 (477 mg, 1.41 mmol,

1.00 equiv.) and anhydrous CH₂Cl₂(4 mL) and cooled to 0 °C be-

fore adding DIBAL-H (1M in hexanes, 5.91 mL, 5.91 mmol,

4.20 equiv.) dropwise over 15 min. The mixture was stirred for

30 min at room temperature before adding more CH₂Cl₂, then the

reaction was carefully quenched with brine and the mixture was

stirred for an additional 30 min. The solution was neutralized with

satd. aq. NH₄Cl, the precipitate was filtered off and discarded, and

the filtrate was extracted with CH₂Cl₂(3ϫ). The combined or-

ganics were washed with brine and dried with Na₂SO₄. Removal

of the solvent under reduced pressure gave 28 (437 mg, 1.41 mmol,

Regioisomers 26 and 32: A solution of 25 (202 mg, 597 μmol,

1.00 equiv.), Pd(dppf)Cl₂(38.7 mg, 47.3 μmol, 8 mol-%), bis-

(pinacolato)diboron (166 mg, 653 μmol, 1.10 equiv.), and potas-

sium acetate (175 mg, 1.79 mmol, 3.00 equiv.) in degassed dioxane

(4 mL) was prepared in a dry round-bottomed flask under an argon

atmosphere and heated to 100 °C. After stirring for 1 h, the solvent

was removed under reduced pressure and the residue was purified

by column chromatography (SiO₂; EtOAc/cyclohexane, 1:20). The

isolated mixture of regioisomers (26 and 32, 57%) was purified by

HPLC (column: semipreparative Reprosil 100 Si, 5 μm,

250ϫ16 mm, eluent: CH₂Cl₂).

1

Ͼ99%) as a brown solid. H NMR (400 MHz, CDCl₃, 25 °C): δ =

3

4

7.96 (dd, J_H,H= 7.9, J_H,H= 1.2 Hz, 1 H), 7.45–7.36 (m, 3 H),

7.34 (t, ⁴J_H,H= 1.8 Hz, 1 H), 7.30 (dd, ³J_H,H= 7.8, ⁴J_H,H= 1.8 Hz,

Methyl

2Ј-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1Ј-bi-

1

3

phenyl]-3-carboxylate (26): H NMR (500 MHz, CDCl₃, 25 °C): δ

= 8.00 (td, J_H,H= 1.8, 0.5 Hz, 1 H), 7.95 (ddd, J_H,H= 7.8, J_H,H

= 1.8, 1.2 Hz, 1 H), 7.71 (dd, J_H,H= 7.7, J_H,H= 1.2 Hz, 1 H),

7.53 (ddd, J_H,H= 7.8, J_H,H= 1.8, 1.2 Hz, 1 H), 7.43–7.38 (m, 1

1 H), 7.28 (d, J_H,H= 5.2 Hz, 1 H), 7.04 (ddd, J_H,H= 7.9, 7.3,

4

3

4

⁴J_H,H= 1.8 Hz, 1 H), 4.77 (d, J_H,H= 5.8 Hz, 2 H) ppm; 1.71 (t,

3

4

³J_H,H= 5.8 Hz, 1 H) ppm. ¹³C NMR (63 MHz, CDCl₃): δ = 146.6,

144.6, 140.8, 139.7, 130.3, 129.1, 128.8, 128.4, 128.4, 128.1, 126.4,

98.7, 65.5 ppm. MS (EI, +): m/z (%) = 310.8 (44), 309.9 (97), 183.1

(20), 182.1 (12), 181.1 (24), 166.1 (21), 165.2 (100), 155.1 (40), 154.1

(84), 153.1 (76), 152.2 (97), 151.1 (37), 150.1 (14), 139.1 (10), 128.1

(12), 127.1 (17), 126.1 (14), 115.1 (14), 77.1 (26), 76.0 (17), 75.0

(12), 63.0 (14), 51.0 (14).

3

4

3

4

H), 7.37 (dd, J_H,H= 7.7, J_H,H= 0.5 Hz, 1 H), 7.33–7.27 (m, 2

H), 3.85 (s, 3 H), 1.12 (s, 12 H) ppm. ¹³C NMR (125 MHz, CDCl₃):

δ = 167.1, 146.7, 143.4, 135, 133.7, 130.6, 130.4, 129.5, 129.2, 128.1,

128, 126.9, 83.7, 24.5 ppm. MS (EI, +): m/z (%) = 339.3 (17), 338.3

(81), 337.3 (29), 323.2 (12), 307.2 (11), 252.2 (22), 239.2 (28), 238.2

(14), 237.2 (18), 225.1 (13), 223.2 (18), 222.1 (46), 221.1 (20), 220.2

(24), 219.2 (22), 208.1 (15), 207.1 (100), 206.1 (26), 205.1 (14), 194.1

(41), 193.2 (49), 180.1 (13), 179.1 (55), 178.1 (43), 177.1 (14), 165.2

(13), 164.2 (33), 163.2 (18), 153.2 (14), 152.2 (43), 151.1 (16), 59.1

(12).

Regioisomers 29 and 31: To an oven-dried and argon-flushed

Schlenk tube was consecutively added 27 (236 mg, 897 μmol,

1.00 equiv.), potassium acetate (265 mg, 2.70 mmol, 3.01 equiv.),

bis(pinacolato)diboron

(251 mg,

987 μmol,

1.10 equiv.),

PdCl₂(dppf)·CH₂Cl₂(59.6, 8 mol-%), and anhydrous DMF (5 mL).

The mixture was degassed for 5 min and then heated to 100 °C for

1 h (the solution became dark). After cooling to room temperature,

tBME was added and the mixture was filtered through Celite, then

thoroughly washed with water and brine. After drying over

Na₂SO₄, the solvent was removed under reduced pressure. Column

chromatography (SiO₂; CH₂Cl₂/EtOAc, 20:1) gave a mixture of 29

and 31 (163 mg, 525 μmol, 59%) as a colorless oil. ¹H NMR

(400 MHz, CDCl₃, 25 °C): δ = 7.76–7.70 (m, 2 H), 7.48–7.42 (m, 2

H), 7.41–7.30 (m, 12 H), 4.77–4.73 (m, 4 H), 1.68–1.59 (m, 2 H),

1.20 (s, 24 H) ppm. ¹³C NMR (101 MHz, CDCl₃): δ = 148.4, 147.7,

143.9, 143.4, 143.3, 140.7, 135.3, 135.0, 130.6, 129.5, 129.4, 129.0,

128.5, 128.2, 128.1, 127.8, 127.3, 126.8, 125.9, 125.0, 84.2, 65.8,

65.6, 25.0 (2 C) ppm. MS (EI, +): m/z (%) = 311 (15), 310 (75), 309

(18), 224 (16), 211 (14), 210 (18), 209 (16), 195 (14), 195 (100), 193

(64), 192 (15), 165 (23).

Methyl

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1Ј-bi-

1

phenyl]-3-carboxylate (32): H NMR (600 MHz, CDCl₃, 25 °C): δ

= 8.04 (d, J_H,H= 1.7 Hz, 1 H), 7.98 (dd, J_H,H= 7.7, J_H,H

4

3

4

=

3

1.7 Hz, 1 H), 7.76 (d, J_H,H= 7.7 Hz, 1 H), 7.43–7.35 (m, 5 H),

3.92 (s, 3 H), 1.21 (s, 12 H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ

= 167, 147.5, 142.2, 134.4, 131.3, 129.7, 129.1, 128, 127.3, 127, 84.1,

52.2, 24.6 ppm. MS (EI, +): m/z (%) = 339.3 (13), 338.3 (59), 337.3

(15), 323.3 (18), 253.2 (10), 252.2 (46), 239.2 (24), 238.2 (18), 237.2

(39), 223.2 (18), 222.2 (100), 221.1 (27), 207.1 (46), 206.1 (10), 193.2

(16), 191.1 (21), 179.1 (30), 178.1 (25), 163.2 (14), 152.2 (27), 151.2

(11), 59.1 (11).

(2Ј-Bromo-[1,1Ј-biphenyl]-3-yl)methanol (27): In an oven-dried and

argon-flushed Schlenk tube, 3-(hydroxymethyl)phenylboronic acid

(23; 400 mg, 2.63 mmol, 1.00 equiv.), 1-bromo-2-iodobenzene (21;

410 μL, 3.16 mmol, 1.20 equiv.), Cs₂CO₃(2.65 g, 8.04 mmol,

3.05 equiv.), and Pd(PPh₃)₄(60.1 mg, 2 mol-%) were added consec-

utively and suspended in THF (8 mL) and EtOH (2 mL) before 2-Iodo-5-methoxy-1,1Ј-biphenyl (33): To an oven-dried and argon-

degassing for 15 min. The suspension was then heated to 60 °C for

4 h. The reaction mixture was cooled to room temperature, tBME

was added, and the suspension was filtered through Celite. The

flushed Schlenk tube was consecutively added potassium carbonate

(1.19 g, 8.55 mmol, 3.0 equiv.) and phenylboronic acid (348.7 mg,

2.86 mmol, 1.00 equiv.) and vacuum applied for 5 min. Compound

orange solution was washed twice with aq. HCl (1 m), water and 4 (1.00 g, 3.20 mmol, 1.12 equiv. as a solution in 5 mL anhydrous

brine, dried with Na₂SO₄, before removing the solvent under re-

duced pressure. The residual oil was passed through a plug of silica

(eluent: EtOAc/cyclohexane, 1:2), the solvent was removed under

reduced pressure, and the orange oil was purified by column

toluene) was added along with anhydrous toluene (23 mL) and an-

hydrous EtOH (7 mL), and the solution was degassed for 15 min

before adding Pd(PPh₃)₂Cl₂(61.6 mg, 3 mol-%) and heating to

80 °C for 21 h. After cooling to room temperature, EtOAc was

chromatography (SiO₂; EtOAc/cyclohexane, 1:4) to give 27 added and the brown suspension was filtered. The solution was

1

(492 mg, 1.97 mmol, 71%) as an orange oil. H NMR (400 MHz, then adsorbed on Celite and subjected to column chromatography

CDCl₃, 25 °C): δ = 7.69–7.65 (m, 1 H), 7.47–7.30 (m, 6 H), 7.21

(SiO₂; EtOAc/pentane, 1:100 to 1:20) giving 33 (700 mg, 814 μmol,

(ddd, ³J_H,H= 8.0, 6.9, ⁴J_H,H= 2.2 Hz, 1 H), 4.76 (d, ³J_H,H= 5.9 Hz, 93%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ =

3

4

2 H), 1.72 (t, J_H,H= 5.9 Hz, 1 H) ppm. ¹³C NMR (101 MHz,

7.52 (d, J_H,H= 8.8 Hz, 1 H), 7.46–7.31 (m, 5 H), 6.87 (d, J_H,H=

3

4

CDCl₃): δ = 142.8, 141.8, 141.1, 133.5, 131.7, 129.2, 129.2, 128.6,

3.1 Hz, 1 H), 6.76 (dd, J_H,H= 8.8, J_H,H= 3.1 Hz, 1 H), 3.78 (s,

128.4, 127.8, 126.6, 123.0, 65.7 ppm. MS (EI, +): m/z (%) = 264 3 H) ppm. ¹³C NMR (101 MHz, CDCl₃, 25 °C): δ = 158.9, 143.5,

(97), 262 (100), 183 (42), 165 (100), 154 (84), 152 (79), 107 (9), 76

(9).

141.24, 133.8, 129.4, 128.1, 127.8, 116.8, 114.8, 113.2, 55.6 ppm.

MS (EI, +): m/z (%) = 264.9 (14), 263.9 (99), 262.9 (16), 261.9

Eur. J. Org. Chem. 0000, 0–0

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M. Mayor et al.

FULL PAPER

(100), 220.9 (29), 218.9 (30), 168.0 (27), 153.1 (14), 152.0 (25), 140.1

(43), 139.0 (80), 63.0 (14).

0.87 (s, 9 H), 0.01 (s, 6 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ

= 147.1, 141.9, 140.8, 139.8, 139.2, 138.2, 131.5, 130.4, 129.7 (2 C),

129.6 (2 C), 129.4, 128.5, 128.4, 128.3 (2 C), 127.9, 127.8, 127.6,

127.5, 127.0, 126.8, 126.1, 125.5, 122.2, 30.0, 18.4, 0.1 ppm. MS

(EI, +): m/z (%) = 439.1 (35), 438.0 (100), 408.0 (12), 364.0 (27),

318.0 (29), 317.1 (19), 315.1 (14), 302.0 (15), 75.0 (59).

Methyl 5Ј-Methoxy-[1,1Ј:2Ј,1ЈЈ:3ЈЈ,1ЈЈЈ-quaterphenyl]-2ЈЈЈ-carboxyl-

ate (34): To an oven-dried and argon-flushed Schlenk tube was

added potassium phosphate (66.8 mg, 315 μmol, 3.00 equiv.) and

vacuum applied for 5 min. Compound 33 (28.1 mg, 107 μmol,

1.00 equiv. as a solution in 0.5 mL dioxane) and 14 (34.0 mg,

105 μmol, 1.00 equiv. as a solution in 0.5 mL dioxane) were added

along with dioxane (600 μL) and water (400 μL). The solution was

degassed for 15 min before adding Pd(PPh₃)₂Cl₂(2.50 mg, 3 mol-

%) and heating to 80 °C for 4 h. After cooling to room temperature,

EtOAc and water were added, the organic phase was washed with

water (2ϫ) and brine (1ϫ). After drying over Na₂SO₄, the solvent

was removed under reduced pressure. Column chromatography

(SiO₂; EtOAc/cyclohexane, 1:4) gave 34 (41.8 mg, 109 μmol, 51%)

as a highly viscous, colorless oil. ¹H NMR (400 MHz, CDCl₃,

25 °C): δ = 7.79–7.75 (m, 1 H), 7.46–7.33 (m, 3 H), 7.25–7.23 (m,

3 H), 7.21–7.17 (m, 3 H), 7.11–7.05 (m, 3 H), 7.02–6.95 (m, 3 H),

3.88 (s, 3 H), 3.63 (s, 3 H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ

= 169.2, 158.9, 142.3, 141.8, 141.7, 141.6, 141.1, 140.9, 140.8, 131.6,

131.1, 130.8, 130.1, 129.9, 129.7, 128.7, 128.0, 127.5, 127.1, 126.6,

126.3, 115.9, 113.1, 55.4, 51.9 ppm. MS (EI, +): m/z (%) = 395.0

(31), 394.1 (100), 362.1 (16), 361.1 (13), 335.1 (15), 334.1 (11), 333.1

(13), 331.1 (11), 319.1 (12), 303.0 (11), 302.0 (17), 291.1 (18), 290.0

(13), 289.0 (27), 151.0 (13), 144.7 (22), 138.1 (14).

Methyl 5Ј-Nitro-[1,1Ј:2Ј,1ЈЈ:3ЈЈ,1ЈЈЈ-quaterphenyl]-2ЈЈЈ-carboxylate

(39): To an oven-dried and argon-flushed Schlenk tube was added

potassium phosphate (313 mg, 1.47 mmol, 3.20 equiv.) and vacuum

applied for 5 min. Compound 37 (131 mg, 470 μmol, 1.02 equiv. as

a

solution in 3.2 mL dioxane) and 14 (150 mg, 461 μmol,

1.00 equiv. as a solution in 1.0 mL dioxane) were added along with

dioxane (2.3 mL) and water (1.6 mL) and the solution was degassed

for 15 min before adding Pd(PPh₃)₂Cl₂(10.4 mg, 3 mol-%) and

heating to 80 °C for 3 h. After cooling to room temperature, EtOAc

and water were added and the organic phase was washed with

water (2ϫ) and brine (1ϫ). After drying over Na₂SO₄, the solvent

was removed under reduced pressure. Column chromatography

(SiO₂; EtOAc/cyclohexane, 1:8) gave 39 (153 mg, 372 μmol, 81%)

as a highly viscous, colorless oil. ¹H NMR (400 MHz, CDCl₃,

25 °C): δ = 8.32 (d, ⁴J_H,H= 2.2 Hz, 1 H), 8.31–8.21 (m, 1 H), 7.94–

3

7.74 (m, 2 H), 7.71–7.51 (m, 2 H), 7.44 (dddd, J_H,H= 11.0, 7.4,

4

5.7, J_H,H= 1.6 Hz, 2 H), 7.37–7.27 (m, 3 H), 7.25–7.10 (m, 4 H),

7.06–6.92 (m, 1 H), 3.67 (s, 3 H) ppm. MS (EI, +): m/z (%) = 410.1

(25), 409.1 (89), 378.0 (25), 377.0 (61), 376.1 (23), 360.1 (15), 350.1

(32), 349.1 (26), 348.1 (19), 332.1 (18), 331.1 (43), 330.1 (26), 329.1

(14), 313.1 (11), 304.1 (20), 303.1 (52), 302.1 (100), 301.1 (29), 300.1

(39), 289.1 (16), 276.1 (16), 226.0 (10), 165.6 (11), 152.1 (20), 151.1

(47), 150.1 (37), 144.6 (21), 143.7 (10), 138.1 (25).

2-Bromo-5-nitro-1,1Ј-biphenyl (37): To an oven-dried and argon-

flushed Schlenk tube was consecutively added potassium carbonate

(513 mg, 3.67 mmol, 3.00 equiv.),

6

(449 mg, 1.37 mmol,

1.12 equiv.), and phenylboronic acid (149 mg, 1.22 mmol,

1.00 equiv.) before vacuum was applied for 5 min. Anhydrous tolu-

ene (10 mL) and anhydrous EtOH (2.5 mL) were added and the

solution was degassed for 15 min before adding Pd(PPh₃)₂Cl₂

(26.0 mg, 3 mol-%) and heating to 80 °C for 18 h. After cooling to

room temperature, EtOAc was added and the brown suspension

was filtered. The residual oil was adsorbed on Celite and subjected

to column chromatography (SiO₂; EtOAc/pentane, 1:20) to give 37

(232 mg, 833 μmol, 68%). ¹H NMR (400 MHz, CDCl₃, 25 °C): δ

Methyl 5Ј-Amino-[1,1Ј:2Ј,1ЈЈ:3ЈЈ,1ЈЈЈ-quaterphenyl]-2ЈЈЈ-carboxylate

(41): A solution of 39 (41.5 mg, 101 μmol, 1.00 equiv.) and SnCl₂

(98.0 mg, 507 μmol, 5.00 equiv.) in EtOAc (4 mL) was heated to

reflux for 6 h. After cooling to room temperature, EtOAc and satd.

aq. NaHCO₃were added, the organic phase was washed with water

(1ϫ) and brine (1ϫ). After drying over Na₂SO₄, the solvent was

removed under reduced pressure. Column chromatography (SiO₂;

EtOAc/cyclohexane, 1:2) gave 41 (19.4 mg, 51.1 μmol, Ͻ50%) as a

colorless oil. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.78–7.74

(m, 1 H), 7.43 (td, ³J_H,H= 7.6, ⁴J_H,H= 1.4 Hz, 1 H), 7.35 (td, ³J_H,H

4

3

4

= 8.20 (d, J_H,H= 2.7 Hz, 1 H), 8.06 (dd, J_H,H= 8.8, J_H,H

=

3

2.7 Hz, 1 H), 7.86 (d, J_H,H= 8.8 Hz, 1 H), 7.52–7.44 (m, 3 H),

7.44–7.39 (m, 2 H) ppm. ¹³C NMR (63 MHz, CDCl₃): δ = 144.3,

139.2, 134.4, 130.4, 129.4, 128.9, 128.6, 126.0, 123.4 ppm. MS (EI,

+): m/z (%) = 278.9 (41), 276.9 (41), 153.1 (13), 152.1 (100), 151.1

(28), 150.1 (14), 76.0 (14).

4

= 7.6, J_H,H= 1.4 Hz, 1 H), 7.30–7.21 (m, 4 H), 7.19–7.15 (m, 3

4

H), 7.08 (td, J_H,H= 1.8, 0.6 Hz, 1 H), 7.07–7.02 (m, 2 H), 7.02–

6.97 (m, 1 H), 6.78–6.73 (m, 2 H), 3.79 (s, 2 H), 3.63 (s, 3 H) ppm.

MS (EI, +): m/z (%) = 380.0 (30), 379.0 (100), 330.0 (10), 319.0

(17), 318.1 (15), 302.0 (11), 158.7 (14), 152.1 (11).

tert-Butyldimethyl{[5Ј-nitro-(1,1Ј:2Ј,1ЈЈ:3ЈЈ,1ЈЈЈ-quaterphenyl)-2ЈЈЈ-yl]-

methoxy}silane (38): To an oven-dried and argon-flushed Schlenk

tube was added potassium phosphate (178 mg, 841 μmol,

3.00 equiv.) and vacuum applied for 5 min. Compound 37 (79.5 mg,

286 μmol, 1.02 equiv. as a solution in 1.8 mL dioxane) and 19

(115 mg, 280 μmol, 1.00 equiv. as a solution in 1 mL dioxane) were

added along with dioxane (0.4 mL) and water (0.8 mL). The solu-

tion was degassed for 15 min before adding Pd(PPh₃)₂Cl₂(5.9 mg,

3 mol-%) and heating to 80 °C for 5.5 h. After cooling to room

temperature, EtOAc and water were added and the organic phase

was washed with water (2ϫ) and brine (1ϫ). After drying over

Na₂SO₄, the solvent was removed under reduced pressure. Column

chromatography (SiO₂; EtOAc/cyclohexane, 1:50) gave 38 (117 mg,

235 μmol, 84%) as a highly viscous, colorless oil. ¹H NMR

(500 MHz, CDCl₃, 25 °C): δ = 8.34–8.29 (m, 1 H), 8.28–8.23 (m, 1

H), 7.67–7.59 (m, 1 H), 7.55–7.51 (m, 1 H), 7.48–7.40 (m, 1 H),

7.38–7.33 (m, 1 H), 7.30–7.28 (m, 1 H), 7.28–7.25 (m, 4 H), 7.25–

7.22 (m, 1 H), 7.20–7.16 (m, 1 H), 7.16–7.13 (m, 1 H), 7.13–7.11

1-{[6-Bromo-(1,1Ј-biphenyl)-3-yl]diazenyl}pyrrolidine (44): To an

oven-dried and argon-flushed Schlenk tube was consecutively

added potassium carbonate (733 mg, 5.25 mmol, 3.00 equiv.), 8

(745 mg, 1.96 mmol, 1.12 equiv.), and phenylboronic acid (213 mg,

1.75 mmol, 1.00 equiv.) then vacuum was applied for 5 min. An-

hydrous toluene (14 mL) and anhydrous EtOH (14 mL) were added

and the solution was degassed for 15 min before adding Pd(PPh₃)

₂Cl₂(37.2 mg, 3 mol-%) and heating to 80 °C for 23 h. After cool-

ing to room temperature, EtOAc was added and the brown suspen-

sion was filtered and adsorbed on Celite. Column chromatography

(SiO₂; CH₂Cl₂/toluene, 1:100) gave 44 (356 mg, 1.08 mmol, 62%)

1

as a brown solid. H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.58 (d,

³J_H,H= 8.5 Hz, 1 H), 7.46–7.34 (m, 5 H), 7.28–7.24 (m, 2 H), 3.77

3

(s, 4 H), 2.10 (d, J_H,H= 5.7 Hz, 2 H), 2.00 (d, J_H,H= 5.7 Hz, 2

H) ppm. MS (EI, +): m/z (%) = 331.0 (4), 329.0 (4), 232.9 (18),

230.9 (18), 153.1 (16), 152.1 (100), 151.1 (16).

2-Bromo-5-iodo-1,1Ј-biphenyl (46):^[23]In

a pressure tube, 44

(m, 1 H), 6.91 (dd, ³J_H,H= 7.6, ⁴J_H,H= 1.4 Hz, 1 H), 4.49 (s, 2 H), (345 mg, 1.04 mmol, 1.00 equiv.) was heated to reflux at 120 °C in

14

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Pathways to a Helical Hexaphenyl “Geländer” Molecule

MeI (1 mL) overnight. The solvent was removed under reduced

pressure and the remaining residue was dissolved in EtOAc. Water

was added and the organic phase was washed with NaHCO₃(2ϫ)

and brine (1ϫ). After drying over Na₂SO₄, the solvent was re-

moved under reduced pressure, adsorbed on Celite and subjected

107 μmol, 1.00 equiv. as a solution in 0.5 mL dioxane) and 14

(19.7 mg, 60.7 μmol, 1.02 equiv. as a solution in 0.5 mL dioxane)

were added along with dioxane (0.6 mL) and water (0.4 mL). The

solution was degassed for 15 min before adding Pd(PPh₃)₂Cl₂

(1.30 mg, 3 mol-%) and heating to 80 °C for 4 h. After cooling to

room temperature, EtOAc and water were added, and the organic

to column chromatography (SiO₂; CH₂Cl₂/toluene, 1:100) to give

1

46 (309 mg, 861 μmol, 83%). H NMR (400 MHz, CDCl₃, 25 °C): phase was washed with water (2ϫ) and brine (1ϫ). After drying

4

3

4

δ = 7.66 (d, J_H,H= 2.2 Hz, 1 H), 7.50 (dd, J_H,H= 8.4, J_H,H

=

over Na₂SO₄, the solvent was removed under reduced pressure.

2.2 Hz, 1 H), 7.46–7.42 (m, 1 H), 7.42–7.35 (m, 5 H) ppm. ¹³C Column chromatography (SiO₂; CH₂Cl₂/toluene, 1:100) gave 52

NMR (101 MHz, CDCl₃, 25 °C): δ = 144.9, 140.1, 139.9, 137.8, (30.7 mg, 53.4 μmol, 90%) as a highly viscous, colorless oil. ¹H

134.9, 129.4, 128.3, 128.3, 122.8, 92.5 ppm. MS (EI, +): m/z (%) =

359.9 (57), 357.8 (59), 153.1 (13), 152.1 (100), 151.1 (28), 150.1 (16),

126.1 (11), 76.1 (26), 75.1 (13), 74.0 (11), 63.0 (11).

NMR (400 MHz, CDCl₃, 25 °C): δ = 8.02 (dd, ⁴J_H,H= 1.9, 0.9 Hz,

3

4

1 H), 7.98–7.93 (m, 1 H), 7.77 (dd, J_H,H= 7.7, J_H,H= 1.4 Hz, 1

H), 7.58–7.53 (m, 1 H), 7.50–7.39 (m, 4 H), 7.38–7.31 (m, 4 H),

3

4

7.19 (tdd, J_H,H= 8.9, J_H,H= 3.8, 1.6 Hz, 6 H), 7.10–7.06 (m, 3

3

4

2-(6-Bromo-[1,1Ј-biphenyl]-3-yl)-5,5-dimethyl-1,3,2-dioxaborinane

(48): In an oven-dried and argon-flushed Schlenk tube, isoprop-

ylmagnesium chloride lithium chloride complex solution (700 μL,

909 μmol, 1.10 equiv.) was added to a degassed solution of 46

(297 mg, 826 μmol, 1.00 equiv.) in THF (6 mL) at –40 °C before

stirring for 3 h. After GC–MS analysis revealed full conversion, a

solution of triisopropyl borate (230 μL, 992 μmol, 1.20 equiv.) in

THF (1 mL) was added and the mixture was stirred at –40 °C for

1 h and subsequently warmed to room temperature before stirring

for another 2 h. After adding 2,2-dimethyl-1,3-propanediol

(109 mg, 1.03 mmol, 1.25 equiv.), the reaction was stirred for 13 h.

CH₂Cl₂and saturated aq. NH₄Cl were added and the organic layer

was washed with water and brine. After drying over Na₂SO₄, the

solvent was removed under reduced pressure. Column chromatog-

raphy (SiO₂; CH₂Cl₂/toluene, 1:100) gave 48 (90.5 mg, 262 μmol,

32%) as a brown oil. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.75

H), 6.94 (dd, J_H,H= 7.6, J_H,H= 1.3 Hz, 1 H), 6.92–6.88 (m, 2

H), 3.88 (s, 3 H), 3.62 (s, 3 H) ppm. ¹³C NMR (101 MHz, CDCl₃):

δ = 169.1, 167.0, 142.2, 142.0, 141.4, 140.9, 140.8, 140.1, 139.9,

139.6, 138.5, 134.7, 132.4, 131.1, 130.9, 130.8, 130.7, 130.5, 130.5,

130.3, 130.2, 129.9, 129.9, 129.7, 129.0, 128.8, 128.6, 128.2, 128.0,

128.0, 127.9, 127.8, 127.8, 127.4, 127.1, 126.6, 126.4, 52.1, 51.9,

29.7 ppm. MS (EI, +): m/z (%) = 576.1 (10), 575.1 (44), 574.1 (100),

511.1 (11), 482.1 (14), 481.1 (12), 454.0 (12), 450.0 (11), 219.3 (12).

Acknowledgments

The authors acknowledge financial support by the Swiss National

Science Foundation (SNF).

[1] For selected examples, see: a) M. Banerjee, R. Shukla, R. Ra-

thore, J. Am. Chem. Soc. 2009, 131, 1780; b) A. C. Grimsdale,

K. Leok Chan, R. E. Martin, P. G. Jokisz, A. B. Holmes,

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[3] For selected examples, see: a) D. Vonlanthen, J. Rotzler, M.

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F. Jia, H.-S. Wu, Z. Chen, Y. Mo, Eur. J. Org. Chem. 2013,

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12824; d) D. M. Hudgins, C. W. Bauschlicher, L. J. Allaman-

dola, Astrophys. J. 2005, 632, 316–332.

4

3

(d, J_H,H= 1.6 Hz, 1 H), 7.65 (d, J = 8.0 Hz, 1 H), 7.59 (dd, J_H,H

4

= 8.0, J_H,H= 1.6 Hz, 1 H), 7.43–7.40 (m, 4 H), 7.40–7.33 (m, 1

H), 3.75 (s, 4 H), 1.02 (s, 6 H) ppm. ¹³C NMR (151 MHz, CDCl₃):

δ = 142.0, 141.5, 137.0, 134.2, 132.6, 129.7, 128.1, 127.6, 125.8,

72.6, 32.1, 22.1 ppm. MS (EI, +): m/z (%) = 346.9 (19), 346.0 (99),

345.0 (43), 344.0 (100), 343.0 (26), 260.9 (13), 259.9 (62), 258.9 (28),

257.9 (62), 256.9 (16), 179.0 (22), 178.0 (34), 177.1 (13), 152.1 (34),

151.1 (14), 56.1 (26), 55.1 (13).

Methyl 4ЈЈ-Bromo-[1,1Ј:2Ј,1ЈЈ:3ЈЈ,1ЈЈЈ-quaterphenyl]-3-carboxylate

(50): To an oven-dried and argon-flushed Schlenk tube was consec-

utively added potassium carbonate (547 mg, 547 μmol, 3.04 equiv.),

25 (69.5 mg, 201 μmol, 1.12 equiv.), and 48 (61.0 mg, 180 μmol,

1.00 equiv.) before vacuum was applied for 5 min. Anhydrous tolu-

ene (2 mL) and anhydrous EtOH (0.5 mL) were added and the

solution was degassed for 15 min before adding Pd(PPh₃)₂Cl₂

(3.7 mg, 3 mol-%) and heating to 80 °C for 5.5 d. After cooling to

room temperature, EtOAc was added, the brown suspension was

filtered and adsorbed on Celite. Twofold column chromatography

(SiO₂; CH₂Cl₂/toluene, 1:100) gave 50 (26.1 mg, 59.5 μmol, 33%)

[4] For an overview of functional helical structures, see: C.

Schmuck, Angew. Chem. Int. Ed. 2003, 42, 2448–2452; Angew.

Chem. 2003, 115, 2552.

[5] For selected examples, see: a) J. E. Field, G. Muller, J. P. Riehl,

D. Venkataraman, J. Am. Chem. Soc. 2003, 125, 11808; b) Y.

Morisaki, M. Gon, T. Sasamori, N. Tokitoh, Y. Chujo, J. Am.

Chem. Soc. 2014, 136, 3350; c) Y. Yang, R. Correa da Costa,

D. M. Smilgies, A. J. Campbell, M. J. Fuchter, Adv. Mater.

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M. Gantenbein, D. Vonlanthen, D. Häussinger, W. Klopper,

M. Mayor, Org. Biomol. Chem. 2013, 11, 110–118; e) D. Casar-

ini, L. Lunazzi, M. Mancinelli, A. Mazzanti, C. Rosini, J. Org.

Chem. 2007, 72, 7667–7676; f) H. Saito, T. Mori, Y. Origane,

T. Wada, Y. Inoue, Chirality 2008, 20, 278–281; g) T. Kudernac,

N. Ruangsupapichat, M. Parschau, B. Macia, N. Katsonis,

S. R. Harutyunyan, K. H. Ernst, B. L. Feringa, Nature 2011,

479, 208; h) N. Koumura, R. W. Zijlstra, R. A. van Delden, N.

Harada, B. L. Feringa, Nature 1999, 401, 152–155; i) C.

Scott Hartley, J. Org. Chem. 2011, 76, 9188–9191.

1

as a colorless solid. H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.95

4

3

(tt, J_H,H= 3.3, 1.5 Hz, 2 H), 7.51 (d, J_H,H= 8.2 Hz, 1 H), 7.45

4

(d, J_H,H= 1.7 Hz, 4 H), 7.39–7.29 (m, 4 H), 7.29–7.22 (m, 1 H),

4

3

7.19–7.13 (m, 2 H), 7.07 (d, J_H,H= 2.3 Hz, 1 H), 6.98 (dd, J_H,H

= 8.2, J_H,H= 2.3 Hz, 1 H), 3.90 (s, 3 H) ppm. MS (EI, +): m/z

4

(%) = 444.9 (26), 444.0 (87), 443.0 (28), 441.9 (87), 332.1 (11), 331.1

(36), 305.0 (26), 304.1 (100), 303.1 (73), 302.0 (88), 301.1 (17), 300.1

(26), 289.0 (20), 276.0 (12), 226.0 (12), 152.0 (10), 151.0 (34), 150.1

(27), 144.6 (13), 138.1 (19).

[6] R. A. Pascal Jr., Chem. Rev. 2006, 106, 4809–4819.

[7] For an overview, see: M. Gingras, Chem. Soc. Rev. 2013, 42,

968–1095.

[8] K. Kawasumi, Q. Zhang, Y. Segawa, L. T. Scott, K. Itami, Nat.

Chem. 2013, 5, 739–744.

Dimethyl

3ЈЈ-Phenyl-[1,1Ј:2Ј,1ЈЈ:4ЈЈ,1ЈЈЈ:3ЈЈЈ,1ЈЈЈЈ-quinquephenyl]-

2ЈЈЈЈ,3-dicarboxylate (52): To an oven-dried and argon-flushed

Schlenk tube was added potassium phosphate (37.9 mg, 179 μmol,

3.00 equiv.) and vacuum applied for 5 min. Compound 50 (26.4 mg,

Eur. J. Org. Chem. 0000, 0–0

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Pages: 17

M. Mayor et al.

[9] a) K. Tsubaki, H. Tanaka, K. Takaishi, M. Miura, H. Mori- [17] a) S. O. Lawesson, Acta Chem. Scand. 1957, 11, 1075–1076; b)

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shi, M. Kawamoto, K. Tsubaki, Org. Lett. 2010, 12, 1832–

1835.

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[10] a) B. Kiupel, C. Niederalt, M. Nieger, S. Grimme, F. Vögtle,

Angew. Chem. Int. Ed. 1998, 37, 3031–3034; Angew. Chem.

1998, 110, 3206; b) M. Modjewski, S. V. Lindeman, R. Ra-

thore, Org. Lett. 2009, 11, 4656–4659. Geländer is the German

word for banister and was introduced by Fritz Vögtle for such

axially chiral systems.

[19] M. N. Eliseeva, L. T. Scott, J. Am. Chem. Soc. 2012, 134,

15169–15172.

[20] J. F. W. McOmie, M. L. Watts, D. E. West, Tetrahedron 1968,

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[21] R. Scholl, J. Mansfeld, Ber. Dtsch. Chem. Ges. 1910, 43, 1734–

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[14] T. Jensen, H. Pedersen, B. Bang-Andersen, R. Madsen, M.

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[23] Similar to: J. S. Moore, E. J. Weinstein, Z. Wu, Tetrahedron

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Jørgsen, Angew. Chem. 2008, 47, 888–890.

Received: October 9, 2014

Published Online: ᭿

16

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Date: 17-12-14 15:00:51

Pages: 17

Pathways to a Helical Hexaphenyl “Geländer” Molecule

Helical Structures

The synthesis of

a

helical, interlinked

M. Rickhaus, L. M. Bannwart, O. Unke,

H. Gsellinger, D. Häussinger,

M. Mayor* ..................................... 1–17

Geländer (banister) type hexaphenyl olig-

omer is symbolized in the figure as a maze;

this is a representation of both the often

convoluted synthetic possibilities as well as

the successful resolution of the maze to re-

ach the target structure.

Through the Maze: Cross-Coupling Path-

ways to a Helical Hexaphenyl “Geländer”

Molecule

Keywords: Helical structures / Cross-cou-

pling / Conformation analysis / Chirality /

Regioselectivity

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Article Doi

Through the maze: Cross-coupling pathways to a helical hexaphenyl "Gel?nder" molecule

DOI: 10.1002/ejoc.201403322

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