Tandem RCM-Claisen Rearrangement-[2+2] cycloaddition of O,O'-(But-2-en-1,4-diyl)-bridged binaphthols

Article abstract of DOI:10.3390/molecules171214531

Attempted RCM of 2,2'-bis(allyloxy)-1,1'-binaphthyl resulted in a Claisen-type rearrangement of a postulated labile dioxacyclodecine proceeding at room temperature and followed by [2+2] cycloaddition. Structures of products were confirmed by X-ray crystallography. A mechanistic rationalisation based on relative stabilities of proposed intermediates and transition states is provided.

Full text of DOI:10.3390/molecules171214531

Molecules 2012, 17, 14531-14554; doi:10.3390/molecules171214531
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molecules
ISSN 1420-3049
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Article
Tandem RCM–Claisen Rearrangement–[2+2] Cycloaddition of
O,O'-(But-2-en-1,4-diyl)-bridged Binaphthols
Michael Abraham 1, Wolfgang Reischl 1, Karl A. Kirchner 2, Alexander Roller 3, Luis F. Veiros 4
and Michael Widhalm 1,*
1
Faculty of Chemistry, Institute of Organic Chemistry, University of Vienna, Währinger Straße 38,
A-1090 Wien, Austria; E-Mails: abraham350@gmail.com (M.A.);
wolfgang.reischl@univie.ac.at (W.R.)
2
Institute of Applied Synthetic Chemistry, Vienna University of Technology,
Getreidemarkt 9/163/AC, A-1060 Wien, Austria; E-Mail: karl.kirchner@tuwien.ac.at
3
Faculty of Chemistry, Institute of Inorganic Chemistry, University of Vienna, Währinger Straße 42,
A-1090 Wien, Austria; E-Mail: alexander.roller@univie.ac.at
4
Centro de Química Estrutural, Instituto Superior Técnico, Universidade Técnica de Lisboa,
1049-001 Lisboa, Portugal; E-Mail: veiros@ist.utl.pt
* Author to whom correspondence should be addressed; E-Mail: m.widhalm@univie.ac.at;
Tel.: +43-1-4277-52111; Fax: +43-1-4277-9521.
Received: 30 October 2012; in revised form: 29 November 2012 / Accepted: 3 December 2012 /
Published: 7 December 2012
Abstract: Attempted RCM of 2,2'-bis(allyloxy)-1,1'-binaphthyl resulted in a Claisen-type
rearrangement of a postulated labile dioxacyclodecine proceeding at room temperature and
followed by [2+2] cycloaddition. Structures of products were confirmed by X-ray
crystallography. A mechanistic rationalisation based on relative stabilities of proposed
intermediates and transition states is provided.
Keywords: DFT calculations; Grubbs II catalyst; cage compounds; spiro-compounds;
chiral macrocycle
1. Introduction
A sequence of reactions is designated as a tandem process if the reacting functional group(s) of each
step are formed or activated only in the preceding one and with no need of adding reagents for

Molecules 2012, 17
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individual steps. A further requirement is that all reactions proceed under the same conditions with no
mutual interference of by-products. Since advantages over conventional multistep synthesis by
avoiding work-up and purification of intermediates are obvious, such processes have found widespread
application [1–11]. With increasing complexity of target structures functional group tolerance and
stereoselectivity of transformations become crucial and are particularly challenging in the synthesis of
natural products and biologically active compounds. Consequently, the usefulness of tandem reactions
will also rely on a sufficient high degree of stereocontrol in each step. This requirement is often
fulfilled with rearrangements proceeding via cyclic transition states and with sigmatropic
rearrangements which represent stereospecific transformations. Typical examples are Cope and
Claisen rearrangements and variations like Claisen-Ireland, Claisen-Johnsen, Meerwein-Eschenmoser-
Claisen, thio- and aza-Claisen, and Carrol rearrangement [12–21]. A special situation arises when
atropisomeric biaryls are involved translating axial-chirality of the substrates into centro-chirality of
the products provided the reaction proceeds at a temperature where no racemisation of the biaryl takes
place. Particularly O,O'-disubstituted binaphthol derivatives have shown various rearrangements and
cyclisations ending up with configurationally stable polycyclic structures formed on cost of the
aromaticity of one of the benzene rings [22,23]. While most of published procedures require elevated
temperature to proceed, the present process takes place below 60 °C and affords a single rearranged
product in excellent yield. Such transformations offer a unique access to otherwise difficult to
synthesize centrochiral compounds, eventually useful as chiral building blocks [24]. The present paper
reports on a tandem sequence where up to three intramolecular transformations are involved producing
stereoselectively spiro- and finally chiral cage-compounds from simple binaphthyl precursors.
2. Results and Discussion
2.1. Synthesis and Rearrangements
In course of our attempts to synthesize macrocyclic chiral (di)olefins with incorporation of biaryl
units, eventually useful as chiral ligand in asymmetric catalysis, we investigated the RCM of
2,2'-bis(allyloxy)-1,1'-binaphthyl (2a), a versatile precursor previously applied in the synthesis of ring
systems [25–27]. While RCM of a homologue of 2a (4-butenyloxy instead allyloxy in positions 2 and 2′)
proceeded as expected, bridging positions 2 and 2′ of the binaphthol and yielding the
dioxacyclododecine product as a cis/trans mixture [28], compound 2a behaved completely different
(Scheme 1). Treatment with Grubbs II catalyst (DCM, reflux) resulted in the formation of a
C1 symmetrical species (35%) and a product with higher symmetry (59%). While in the latter case
ESI-MS gave a molecular peak of m/z 699.3 and correct HRMS for a dimeric structure 3a with
D2 symmetry, the former one gave the correct mass of m/z 338.2 for the desired product, but
disagreeing NMR spectra for structure 4a, with the spectroscopic data pointing rather to a rearranged
product 5a [29,30]. In order to increase the yield of the macrocycle we repeated the cyclisation at r.t.
with enantiopure precursor (R)-2a. Under these conditions 15% of starting material was recovered
after 10 h and only small amounts (4%) of 5a were formed. As the main product 70% of dimer 3a
([]D20 +110) was isolated (82% rel. to recovered starting material) thus confirming the relative biaryl
configurations in the racemic product to be (R)ax(R)ax/(S)ax(S)ax and absence of “meso-3a” with
(R)ax(S)ax configuration. The trans-geometry of double bonds was confirmed by macrocyclisation of

Molecules 2012, 17
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dibromide (R)-10 with (R)-1a yielding the same product obtained by RCM (Scheme 2). A crystal
structure of 3a was published [24].
Scheme 1. Rearrangement of 1,1'-binaphthyl derivatives with 2,2'-O-allyl fragments.
§
* See text. From 1a. Reagents and Conditions: a. reference [26] (2a); allylbromide, K2CO3,
acetone, reflux, 24 h (2b–d); b. Grubbs II (10%), DCM, r.t., 6–8 h; c. h, toluene (see text);
d. E-1,4-dibromobut-2-ene, Cs2CO3, acetone, reflux, 24 h.

Molecules 2012, 17
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Scheme 2. Synthesis of (R,R)-3a through macrocyclisation.
Reagents and Conditions: a. Methyl 4-bromocrotonate, K2CO3, 24 h, r.t.; b. DIBAL, DCM, −78 °C
 −20 °C, 12 h; c. PBr3, THF, −40 °C  r.t. overnight; d. (R)-1a, KOH, THF, 3 days, reflux.
It is interesting to note that the temperature plays a decisive role in the outcome of this reaction.
According to Piedra et al. the formation of dimers can be suppressed at elevated temperature (3 h,
120 °C, MW) and at higher dilution, while variation of the catalyst showed little influence. This
behaviour seems nearly unaffected from substituents in positions 6 or 7 of the naphthalene rings [24].
In contrast, when using substrates 2b–d with substituents in position 3 no dimeric species could be
detected (see below).
The rearrangement of an aryl-allylether undergoing a Claisen-type rearrangement is usually
formulated via a concerted or radical mechanism generating an aryloxy- and allyl radical in the latter
case (photo-Claisen rearrangement) [31]. As the most likely precursor for 5a we postulated labile
(E)-dioxacyclodecine 4a, which might smoothly traverse a chair-like transition state TS I to give spiro
compound 5a. The involvement of (labile) 4a with an E-double bond was supported since 5a was
obtained as the exclusive product when reacting 1a with E-1,4-dibromobut-2-ene (Cs2CO3, acetone,
20 h reflux, 94%) [32]. Mechanistic implications will be discussed below.
If 5a was irradiated with long wave-length UV light (>300 nm) in toluene for 3 h at ambient
temperature, a mixture of two rearranged products 6a (67%) and 7a (10%) was formed through
intramolecular [2+2] cycloaddition (6% of starting material was recovered). Inspection of a wire model
revealed that particularly for the formation of the predominating isomer 6a the required conformation
for a transition state like TS IIa can be easily adopted. While intramolecular [2+2] cycloadditions of
enones with olefins have been frequently observed [33,34], an analogous cyclisation of 1-allyl-
naphthalen-2(1H)-one was only reported in 1980 [35,36].
Similar treatment of 3,3′-diiodo substituted substrate 2b showed similar conversions and
corresponding products obtained, but displaying significantly different stability/reactivity. Thus, RCM
of 2b at r.t. in the dark yielded exclusively 5b (95%) without detectible amounts of dimerisation
product. If light was not rigorously excluded some rearranged product 6b (10%) was also detected. Its
structure was confirmed by crystal structure analysis (Figure 1). When a solution of 5b in toluene was
irradiated with visible light (60 W light bulb) for several hours, complete photoaddition took place
yielding a mixture of 6b and 7b (approx. 9:1). The isomers were separable by chromatography and
fully characterized by NMR and MS. The ease of accessing cyclobutanes 6b and 7b prompted us to
perform the sequence 2b  4b  5b  6b/7b in one pot. Conducting the RCM in toluene under
irradiation with visible light resulted in exclusive formation of 6b/7b (85:15, 89% total yield). For
comparative studies also bromo- as well as phenyl-substituted O-allyl precursors 2c and 2d,
respectively were investigated. Their behavior on treatment with Grubbs II catalyst was virtually the

Molecules 2012, 17
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same, yielding 5c and 5d in excellent yield (91% and 98%, respectively) and subsequent
photoisomerisation under UV irradiation gave 6c/7c (64%/10%) and 6d/7d (7%/39%), respectively.
Figure 1. Crystal structures of 5b (left), 6a (middle) and 6b (right). H-atoms and solvent
molecules omitted for clarity.
In view of intended use in asymmetric catalysis macrocyclic diolefin 3a was treated with
[RhCl(C2H4)2]2, [C3H5PdCl]2, and Pd2(dba)3 precursors which did not result in the formation of
complexes, instead Pd(PPh3)4 caused complete cleavage yielding a mixture of 5a (56%) and epi-5a
(20%). (Scheme 3) A tentative mechanistic interpretation is discussed in the Supporting Information.
Scheme 3. Pd(0) mediated cleavage of 3a and subsequent photoisomerisation of epi-5a.
Subsequent irradiation of epi-5a for 0.5 h afforded two products. The main product was expectedly
the corresponding epimer of 6a, epi-6a (36%) while no epi-7a could be detected. Instead
cyclobutanone 11 (25%) was formed. Both structures were confirmed by X-ray analysis (Figure 2).
Figure 2. Crystal structures of epi-5a (left), epi-6a (middle), and 11 (right). H-atoms and
solvent molecules omitted for clarity.

Molecules 2012, 17
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2.2. Calculations, Evidence for Existence of 4a, Its Geometry and Rearrangement to 5a
Geometries and energies of ground state structures as well as transition states were obtained using
program packages SPARTAN (B3LYP, MO6 and MP2) and GAUSSIAN09 (B3LYP) [37,38]. For
comparability reasons B3LYP data as determined in the absence of solvent and, where appropriate,
also in DCM (values in parenthesis) are collected in Table 1 and are discussed below.
Table 1. B3LYP (Ru: sdd, all other atoms: 6-31G**), MO6, and MP2 calculated free
a
energies of activation based on ground state and transition state energies for conversion
of 2a-pro-cis- and 2a-pro-trans-Ru, cis- and trans-Ru-Cycl, E- and Z-4a, and E-12.
Asterisks (*) denote results obtained with the corresponding biphenyl system.
G‡ b
B3LYP
1.0 (1.8)
2.2 (3.2)
17.2 (19.4)
7.7 (9.4)
26.4 (26.2)
32.3 (33.0)
3.9 (6.2)
8.3 (9.7)
8.6 (9.8)
39.1
MO6
MP2
2a-pro-trans-Ru*  trans-Ru-Cycl*
2a-pro-cis-Ru*  cis-Ru-Cycl*
trans-Ru-Cycl*  E-4a-Ru*
cis-Ru-Cycl*  Z-4a-Ru*
E-4a  5a
27.3
32.2
8.3
21.0
26.9
6.0
Z-4a  5a
E-12  E-4a
E-12  5a
E-12  epi-5a
E-12  E-13
E-12  14
E-12  epi-14
E-4a  epi-5a
10.6
10.4
40.0
13.5
14.4
41.4
8.2
7.8
35.2
13.6
16.2
39.2
7.3
7.1
39.1
a For details see Supporting Information; b kcal/mol in vacuo and DCM (in parentheses).
To trace the transformation from 2a into 5a under metathesis conditions several possibilities had to
be taken into account as outlined in Scheme 4 and energy profiles of alternative reaction paths were
determined. Our calculations are based on the established mechanism of the olefin metathesis
cyclisation with Grubbs II catalyst [39–41] and are carried out on a corresponding biphenyl skeleton
which is expected to be a realistic model for the transformation 2a  4a. Calculations on olefin
metathesis reaction with ethylene and Grubbs II catalyst supported a dissociative path with trans-
coordination of the olefin as a barrierless step [42]. Applied to our system an olefin-Ru-carbene,
2a-Ru, is postulated which coordinates the pending olefin with either re- or si-side to form (transient)
intermediates in the configuration determining step from which 2,3-cis- or 2,3-trans-substituted
metalla-cyclobutanes are obtained. Cycloreversion leads to Ru-olefin complexes of 4a and after
dissociation Z- and E-4a could undergo Claisen rearrangement to 5a. A direct transformation of a
Ru-cycle into 5a without traversing 4a would proceed via an anti-aromatic transition state (8
electrons) and seems highly unfavourable.
It was found that the metallacycle with trans geometry is more stable (G0 = 3.3 kcal/mol), but less
reactive [G‡ = 17.2 kcal/mol versus 7.7 kcal/mol, (19.4 kcal/mol versus 9.4 kcal/mol)] yielding E-4a-
Ru in a slightly more endergonic reaction (Figure 3, top and middle).

Molecules 2012, 17
Scheme 4. Formation of 5a from 2a and postulated intermediates of RCM.
14537
Ru
O
O
2a
2a-Ru
Ru
Ru
O
O
O
O
2a-pro-trans-Ru
2a-pro-cis-Ru
H
H
Ru
Ru
O
O
H
O
O
H
cis-Ru-Cycl
trans-Ru-Cycl
O
O
O
O
O
O
Ru
Ru
Z-4a-Ru
E-4a-Ru
5a
Ru
Ru
O
O
O
O
Z-4a
E-4a
Figure 3. Energy profile (B3LYP, single point energies in DCM in parenthesis) for the
formation of E and Z-olefin-carben-Ru complexes formed in course of a RCM with Grubbs
II catalyst. Calculations were performed on a simplified system using the corresponding
biphenyl species.

Molecules 2012, 17
14538
Figure 3. Cont.
The subsequent (presumably) barrierless dissociation delivers E- and Z-olefins. Although ground
state energies of E- and Z-4a are very similar (G0 < 0.2 kcal/mol), the barriers for the Claisen
rearrangement (Figure 3, bottom) differ significantly from each other with 26.2 kcal/mol (from E-4a)
and 33.0 kcal/mol (from Z-4a) and moreover, both are markedly higher than all barriers between
intermediates of the preceding RCM. Accordingly, these intermediates are in equilibrium and the
Claisen rearrangement is rate determining proceeding exclusively via E-4a with the equilibrium on the
product side (G0 = 1.2 kcal/mol, 0.8 kcal/mol in DCM). It should be pointed out that the
overall reaction proceeds under Curtin–Hammett conditions and as a consequence the formation of
5a via E-4a and Z-4a depends only on energy differences of corresponding transition states
G‡ = 5.7 kcal/mol (5.6 kcal).

Molecules 2012, 17
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This is also in agreement with the course of the base catalyzed reaction of 1a with E-1,4-dibromo-
but-2-ene at elevated temperature. The first step obviously forms the (mono)anion E-12 through
O-allylation of 1a (Scheme 5). Formally this intermediate can undergo four intramolecular
nucleophilic substitutions (i)–(iv) with attack of either phenolate or carbanion at either C1 or C3 of the
allyl moiety (SN or SN' reaction).
Scheme 5. Hypothetic reaction paths (i)–(iv) of anion E-12.
Since all steps yielding neutral intermediates/products from a charged species E-12 concomitant
with precipitation of KBr, these will proceed under kinetic control and are virtually irreversible. Under
the applied conditions E/Z isomerisation of 12 can be ruled out, but the flexibility of the key
intermediate E-12 resulted in a Boltzmann distribution of conformations with several local minima [43].
The lowest transition state with 3.9 kcal/mol (6.2 kcal/mol) was found for path (i) yielding E-4a. For
all other processes significantly higher barriers were obtained with 7.3 kcal/mol and 7.1 kcal/mol for (ii),
8.3 kcal/mol (9.7 kcal/mol) and 8.6 kcal/mol (9.8 kcal/mol) for (iv), and even more pronounced for
(iii) with 39.1 kcal/mol. This clearly points to a two-step process with E-4a as an intermediate as
depicted in Figure 4 [44]. Energies obtained with MP2 and MO6 show similar trends.
Transformations of 5a–d into 6a–d and 7a–d, as well as the formation of 11 from epi-5a, are
triggered by light and exited states are obviously involved. Due to their sufficient energy content
various diradical structures may be readily derived therefrom and have to be considered as feasible
intermediates [45–47]. A detailed investigation for better understanding of these processes is presently
under way and will be published in near future.

Molecules 2012, 17
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Figure 4. Energy profile (B3LYP) for the formation of 5a from E-12 under vacuum and in
DCM (values in parenthesis).
8.3
(9.7)
3.9
(6.2)
4.4
3.5)
(
12
E-
0.00
26.4
(26.2)
E-4a
G0 -0.8
5a
3. Experimental
3.1. General
Melting points: Kofler melting point apparatus, uncorrected. NMR: recorded at 400.27 MHz (1H)
and 100.66 MHz (13C), respectively on a Bruker AVIII400 spectrometer. Chemical shifts  are
reported in ppm; for 1H rel. to (residuals non-deuterated) solvent signals (chloroform-d: 7.24, toluene-d8:
2.08 ppm), for 13C to CDCl3 at 77.00 ppm, or CD3C6D5 at 21.40 ppm, respectively. Coupling patterns
are designated as s(inglet), d(oublet), t(riplet), q(uartet), m(ultiplet), p(seudo), and br(oad).

Molecules 2012, 17
14541
13C{1H}-NMR spectra are recorded in a J-modulated mode; signals are assigned as C, CH2, and CH3;
undesignated signals refer to CH-resonances. MS: ESI or EI (ESI-Qq ao TOF mass spectrometer,
Bruker, 70 eV).
For photo rearrangements a mercury medium pressure lamp doped with FeI2 (Heraeus TQ718-Z4,
700 W) was used operating at >300 nm in ice cooled Pyrex glass vessels.
Hexane fraction (PE), dichloromethane (DCM), and ethyl acetate (EtOAc) were distilled, absolute
THF from sodium benzophenone ketyl, toluene from LiAlH4, DCM and acetonitrile from CaH2;
DIBAL was used as a 1.0 molar solution in toluene. All the other chemicals were analytical grade and
used without further purification. Column chromatography was performed on SiO2, 40-63 µm.
Reported procedures have been followed to obtain 3,3′-disubstituted 2,2′-dihydroxy-1,1′-binaphthyl
precursors 1b–d [48–52] and diallyloxy compound 2a [26].
3.2. Syntheses and Rearrangements
3.2.1. Typical Procedure: 2,2'-Bis(allyloxy)-3,3'-diiodo-1,1'-binaphthyl (2b)
To a degassed solution of 2,2′-dihydroxy-3,3′-diiodo-1,1′-binaphthyl (1b, 269 mg, 0.5 mM) in
acetone (50 mL) was added allylbromide (242 mg, 2.0 mM, 173 µL), pulverised K2CO3 (208 mg,
1.5 mM) and the mixture was refluxed for 24 h. The solids were filtered off and washed with DCM.
After removal of solvents the product was purified by chromatography (DCM/PE, 25:75) to give 273 mg
1
(91%) of 2b; mp: 143–146 °C (DCM/PE). H-NMR (CDCl3) : 8.50 (s, 2H), 7.77 (dm, J = 8.3 Hz,
2H), 7.39 (ddd, J = 8.1, 6.9, 1.2 Hz, 2H), 7.25 (ddd, J = 8.3, 6.7, 1.3 Hz, 2H), 7.08 (dm, J = 8.6 Hz,
2H), 5.52 (ddpt, J = 17.1, 10.5, 5.6 Hz, 2H), 4.81 (m, 4H), 4.29 (ddpt, J = 11.9, 5.7, 1.4 Hz, 2H), 3.93
13
(ddpt, J = 11.9, 5.6, 1.4 Hz, 2H) ppm. C-NMR (CDCl3) : 153.90 (C), 139.74, 133.84 (C), 133.08,
132.15 (C), 127.03, 126.94, 125.88, 125.64 (C), 125.62, 117.28 (CH2), 92.70 (C), 74.42 (CH2) ppm.
HRMS (ESI): calcd for C26H20I2O2 NH4: 635.9896, found: 635.9901.
2,2'-Bis(allyloxy)-3,3'-dibromo-1,1'-binaphthyl (2c). Yield: 89%; mp: 98–101 °C (DCM/PE). 1H-NMR
(CDCl3) : 8.23 (s, 2H), 7.80 (dm, J = 8.5 Hz, 2H), 7.40 (ddd, J = 8.1, 6.6, 1.1 Hz, 2H), 7.25 (ddd,
J = 8.4, 6.9, 1.3 Hz, 2H), 7.08 (dm, J = 8.6 Hz, 2H), 5.52 (ddpt, J = 17.0, 10.6, 5.6 Hz, 2H), 4.82 (m,
13
4H), 4.36 (ddpt, J = 11.9, 5.6, 1.4 Hz, 2H), 4.05 (ddpt, J = 11.9, 5.6, 1.3 Hz, 2H) ppm. C-NMR
(CDCl3) : 151.95 (C), 133.16, 133.10 (C), 132.81, 131.42 (C), 127.11, 126.89 (C), 126.81, 125.92,
125.83, 117.76 (C), 117.17 (CH2), 74.46 (CH2) ppm. HRMS (ESI): calcd for C26H20Br2O2Na:
544.9728, found: 544.9732.
1
2,2'-Bis(allyloxy)-3,3'-diphenyl-1,1'-binaphthyl (2d). Yield: 90%; foam. H-NMR (CDCl3) : 7.94 (s,
2H), 7.89 (br d, J = 8.2 Hz, 2H), 7.73 (m, 4H), 7.33–7.46 (m, 8H), 7.24 (m, 4H), 5.27 (ddpt, J = 17.2,
10.4, 5.5 Hz, 2H), 4.64 (dm, J = 10.3 Hz, 2H), 4.54 (dpq, J = 17.1, 1.8 Hz, 2H), 3.94 (ddpt, J = 12.1,
13
5.4, 1.4 Hz, 2H), 3.70 (ddpt, J = 12.2, 5.6, 1.4 Hz, 2H) ppm. C-NMR (CDCl3) (One CH signal not
detected) : 153.30 (C), 139.03 (C), 135.42 (C), 133.81, 133.67 (C), 130.77 (C), 130.25, 129.48,
128.23, 127.99, 127.25, 126.28 (C), 126.17, 125.98, 124.92, 116.17 (CH2), 73.73 (CH2) ppm. HRMS
(ESI): calcd for C38H30O2Na: 541.2143, found: 541.2147.

Molecules 2012, 17
14542
3.2.2. (15E,33E)-14,17,32,35-Tetrahydrotetranaphtho[2,1-b:1',2'-d:2'',1''-l:1''',2''' n][1,6,11,16]tetraoxa-
cycloicosine (3a) and 2-Vinyl-2,3-dihydro-2'H-spiro[benzo[f]chromene-1,1'-naphthalen]-2'-one (5a)
Diallylether 2a (37 mg, 0.1 mM) was dissolved in DCM (7 mL) and Grubbs II catalyst (8.5 mg,
10 mol%) in DCM (3 mL) was added under Ar at 40 °C during 6 h using a syringe pump. After removal
of solvent the products were separated by chromatography (EtOAc/PE, 10:90  30:70) to give 12 mg
(35%) of 5a followed by 20 mg (59%) of 3a (If the reaction was performed at r.t (10 h) 3a and 5a were
isolated in 70% and 4%, respectively). Spectroscopic date are in agreement with reference [24].
(15E,33E)-14,17,32,35-Tetrahydrotetranaphtho[2,1-b:1',2'-d:2'',1''-l:1''',2'''][1,6,11,16]tetraoxa-
cycloicosine (3a). White solid; 1H-NMR (CDCl3) : 7.92 (d, J = 8.2 Hz, 4H), 7.80 (d, J = 9.0 Hz, 4H),
7.36 (ddd, J = 7.8, 6.9, 0.8 Hz, 4H), 7.22 (ddd, J = 8.0, 6.7, 1.2 Hz, 4H), 7.12 (d, J = 8.8 Hz, 4H), 7.09
13
(d, J = 8.2 Hz, 4H), 5.54 (m, 4H), 4.39 (m, 8H) ppm. C-NMR (CDCl3) : 153.72 (C), 134.07 (C),
129.05, 129.02 (C), 127.87, 127.84, 126.15, 125.37, 123.37, 119.76 (C), 114.81, 68.42 (CH2) ppm.
HRMS (ESI): calcd for C48H36O4Na: 699.2511, found: 699.2508.
2-Vinyl-2,3-dihydro-2'H-spiro[benzo[f]chromene-1,1'-naphthalen]-2'-one (5a). White solid; mp:
213–216 °C (EtOAc/PE). 1H-NMR (CDCl3) : 7.71 (d, J = 8.9 Hz, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.63
(d, J = 9.8 Hz, 1H), 7.41 (dd, J = 7.7, 1.2 Hz, 1H), 7.24 (ptd, J = 7.5, 1.2 Hz, 1H), 7.20 (d, J = 8.9 Hz,
1H), 7.13 (m, 2H), 7.01 (ddd, J = 8.5, 7.5, 1.4 Hz, 1H), 6.80 (d, J = 7.9 Hz, 1H), 6.65 (d, J = 8.4 Hz,
1H), 6.37 (d, J = 9.7 Hz, 1H), 5.52 (ddd, J = 17.0, 10.3, 8.8 Hz, 1H), 4.94 (dd, J = 10.3, 1.1 Hz, 1H),
4.66 (dpt, J = 17.0, 1.1 Hz, 1H), 4.56 (pt, J = 10.9 Hz, 1H), 4.12 (dd, J = 10.9, 3.4 Hz, 1H), 2.99 (m,
13
1H) ppm. C-NMR (CDCl3) : 201.46 (C), 154.99 (C), 147.66 (C), 145.38, 131.71 (C), 131.20 (br),
130.66, 130.41 (C), 130.24 (C), 129.89, 129.06, 128.57, 127.61, 126.95, 126.40, 126.31, 123.84,
123.00, 119.06, 118.49 (C), 115.79 (C), 63.05 (CH2), 56.96 (C), 54.44 ppm. HRMS (ESI): calcd for
C24H19O2: 339.1385, found: 339.1381. (R,R)-5a was obtained similarly from (R)-2a; mp: 140–143 °C
(DCM/PE), []D20 +457 (c 1.51, toluene).
3.2.3. One Step Preparation of 5a from 1a
A degassed mixture of binaphthol 1a (286 mg, 1 mmol) and Cs2CO3 (977 mg, 3 mmol) in dry
acetone (20 mL) was heated to reflux and 1,4-dibromo-2-butene (214 mg, 1 mmol) in acetone (50 mL)
was added over 30 min. After reflux overnight the solids were separated, washed with DCM and the
filtrate evaporated. The residue was dissolved is DCM/water (30 mL/30 mL) and the aqueous phase
separated and extracted with DCM (10 mL). The organic phases were dried and the residue subjected
to chromatography (EtOAc/PE 10:90) to give 318 mg (94%) of 5a.
3.2.4. Photoisomerisation of 5a
A solution of 5a (252 mg, 0.746 mM) in toluene (10 mL) was irradiated (>300 nm) at 15–20 °C for
3 h. After removal of the solvent the mixture was subjected to chromatography (EtOAc/PE, 15:85) to
yield 26 mg (10%) of 7a and 168 mg (67%) of 6a; 16 mg (6%) of starting material were recovered.

Molecules 2012, 17
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(1R,10cR)-1,2,2a,2b,3,14b-Hexahydro-1,10c-methanobenzo[f]cyclobuta[3,4]naphtho[2,1-c]chromen-
1
15-one (6a). Mp: 164–165 °C (EtOAc/PE). H-NMR (CDCl3) : 7.79 (dm, J = 8.3 Hz, 1H), 7.78 (d,
J = 8.9 Hz, 1H), 7.30 (m, 2H), 7.16-7.24 (m, 3H), 7.18 (d, J = 8.9 Hz, 1H), 6.97 (m, 1H), 6.51 (br d,
J = 7.9 Hz, 1H), 4.41 (dd, J = 10.8, 3.5 Hz, 1H), 4.09 (br m, 1H), 4.08 (dd, J = 11.8, 11.1 Hz, 1H),
3.09 (dpt, J = 7.2, 5.0 Hz, 1H), 2.95 (dpt, J = 10.9, 5.7 Hz, 1H), 2.71 (m, 1H), 2.31 (m, 1H), 1.97 (d,
J = 10.5 Hz, 1H) ppm. 13C-NMR (CDCl3) (one C(quart.) not detected) : 208.92 (C), 155.10 (C),
141.74 (C), 136.64 (C), 133.58 (C), 130.21, 129.96 (C), 128.83, 128.38, 126.76, 126.69, 125.81,
125.34, 124.55, 123.22, 119.41, 112.10 (C), 66.49 (CH2), 48.19, 45.77, 44.73, 37.44, 32.46 (CH2)
ppm. HRMS (EI, 40 °C): calcd for C24H18O2: 338.1307, found: 338.1299.
(6R,11bR)-4a,5,6,7-Tetrahydro-4H-5,7:6,11b-dimethanobenzo[3,4]cyclohepta[1,2-c]benzo[f]chromen-
1
16-one (7a). Mp: 248–249 °C (EtOAc/PE). H-NMR (CDCl3) : 7.75 (2 × d, J ~ 8 Hz, 2H), 7.24 (m,
1H), 7.17 (d, J = 8.8 Hz, 1H), 7.11–7.17 (m, 2H), 7.04–7.17 (m, 2H), 6.85 (ddd, J = 8.8, 6.7, 2.0 Hz,
1H), 6.32 (dd, J = 7.5, 1.0 Hz, 1H), 4.23 (dd, J = 10.8, 4.8 Hz, 1H), 3.99 (m, 1H), 3.37 (dd, J = 13.0,
11.0 Hz, 1H), 3.28 (ddd, J = 7.4, 5.8, 0.8 Hz, 1H), 3.11 (ddd, J = 11.0, 8.4, 7.8 Hz, 1H), 2.92 (ddd,
J = 12.9, 4.8, 0.7 Hz, 1H), 2.49 (m, 1H), 1.78 (dm, J = 11.0 Hz, 1H) ppm. 13C-NMR (CDCl3) : 213.22
(C), 155.45 (C), 142.28 (C), 139.87 (C), 133.18 (C), 130.34 (C), 129.94, 128.85, 128.26, 127.69,
127.01, 126.77, 126.26, 124.52, 123.21, 118.89, 111.77 (C), 66.87 (CH2), 57.11 (C), 50.55, 44.53,
42.09, 37.17 (CH2), 32.37 ppm. HRMS (ESI): calcd for C24H18O2: 338.1307, found: 338.1301.
3.2.5. Photoisomerisation of epi-5a
A solution of epi-5a (18 mg in toluene-d8, 0.7 mL) was irradiated in a NMR tube for 0.5 h
1
(300 nm). H-NMR showed complete conversion and the mixture was separated by chromatography
(EtOAc/PE, 15:85) to give 11 (4 mg) and epi-6a (6 mg).
(2aR,2bS)-1,2,2a,2b,3,14b-Hexahydro-1,10c-methanobenzo[f]cyclobuta[3,4]naphtho[2,1-c]chromen-
1
15-one (epi-6a). Yield: 36%, mp: 230–234 °C (EtOAc/PE). H-NMR (CDCl3) : 7.78 (dd, J = 8.0,
1.3 Hz, 1H), 7.77 (d, J = 8.9 Hz, 1H), 7.36 (dm, J = 8.5 Hz, 1H), 7.31 (m, 1H), 7.28 (m, 1H), 7.25 (m,
1H), 7.23 (m, 1H), 7.10 (d, J = 8.8 Hz, 1H), 7.06 (ptd, J = 7.7, 1.6 Hz, 1H), 6.69 (dm, J = 7.8 Hz, 1H),
3.96 (dd, J = 10.4, 3.2 Hz, 1H), 3.94 (dd, J = 5.3, 5.0 Hz, 1H), 3.39 (dd, J = 12.0, 10.1 Hz, 1H), 2.99
(ddd, J = 7.0, 5.4, 4.7 Hz, 1H), 2.82 (ddd, J = 9.4, 6.9, 5.4 Hz, 1H), 2.77 (dd, J = 11.9, 3.0 Hz, 1H),
2.60 (pq, J = 5.3 Hz, 1H), 1.78 (d, J = 9.4 Hz, 1H) ppm. 13C-NMR (CDCl3) : 207.74 (C), 153.44 (C),
138.63 (C), 136.10 (C), 132.73 (C), 130.30, 129.40, 129.37 (C), 128.08, 127.90, 127.38, 127.35,
124.64, 124.56, 123.13, 119.07, 112.49 (C), 64.92 (CH2), 59.02 (C), 48.40, 46.01, 43.75, 40.49 (CH2),
38.48 ppm. HRMS (ESI): calcd for C24H18O2K: 377.0933, found: 377.0948.
(8aS)-8a,9,13b,14-Tetrahydro-9,14-methanobenzo[f]cyclobuta[3,4]naphtho[2,3-c]chromen-15(8H)-one
(11). Yield: 25%, mp: 245–248 °C, (EtOAc/PE). 1H-NMR (CDCl3) : 7.78 (br d, J = 8.0 Hz, 1H), 7.63
(br d, J = 8.5 Hz, 1H), 7.62 (br d, J = 8.8 Hz, 1H), 7.52 (ddd, J = 8.5, 6.9, 1.5 Hz, 1H), 7.37 (ddd,
J = 8.0, 6.9, 1.1 Hz, 1H), 7.28 (m, 1H), 7.17–7.25 (m, 3H), 6.92 (d, J = 8.8 Hz, 1H), 4.69 (d, J = 5.7 Hz,
1H), 4.00 (dd, J = 10.9, 4.2 Hz, 1H), 3.40 (br dd, J = 8.2, 5.7 Hz, 1H), 3.31 (ptd, J = 4.0, 1.0 Hz, 1H),
2.91 (br dpt, J = 12.0, 4.0 Hz, 1H), 2.71 (dd, J = 12.9, 4.2 Hz, 1H), 2.59 (dd, J = 11.9, 10.9 Hz, 1H),

Molecules 2012, 17
14544
13
1.88 (ddd, J = 12.9, 8.2, 1.1 Hz, 1H) ppm. C-NMR (CDCl3) : 211.87 (C), 154.15 (C), 139.89 (C),
132.38 (C), 132.25 (C), 130.30, 130.21 (C), 129.50, 127.81, 127.37, 127.35, 126.32, 124.50, 124.11,
123.37, 119.09, 110.41 (C), 66.06 (CH2), 64.40 (C), 54.20, 45.26, 37.60, 36.62 (CH2), 35.65 ppm. HRMS
(ESI): calcd for C24H18O2Na: 361.1204, found: 361.1194.
3.2.6. 3',5-Diiodo-2-vinyl-2,3-dihydro-2'H-spiro[benzo[f]chromene-1,1'-naphthalen]-2'-one (5b)
To a degassed solution of 2b (189 mg, 0.3 mM) in DCM (18 mL) was added Grubbs II catalyst
(15 mg, 5 mol%) dissolved in DCM (2 mL) over 10 h at r.t. in the dark using a syringe pump. Removal
of the solvent was followed by column chromatography (EtOAc/PE, 10:90; the column was wrapped
with aluminium foil) to give 172 mg (95%) of 5b.
3',5-Diiodo-2-vinyl-2,3-dihydro-2'H-spiro[benzo[f]chromene-1,1'-naphthalen]-2'-one
(5b).
Mp:
1
254–259 °C (EtOAc/PE). H-NMR (CDCl3) : 8.37 (s, 1H), 8.31 (s, 1H), 7.56 (dm, J = 8.1 Hz, 1H),
7.34 (dd, J = 7.7, 1.5 Hz, 1H), 7.24 (ptd, J = 7.5, 1.3 Hz, 1H), 7.15 (m, 1H), 7.13 (m, 1H), 7.02 (ddd,
J = 8.5, 6.9, 1.5 Hz, 1H), 6.72 (dm, J = 7.9 Hz, 1H), 6.51 (dm, J = 8.6 Hz, 1H), 5.38 (ddd, J = 17.0,
10.3, 8.8 Hz, 1H), 5.01 (ddd, J = 10.3, 1.3, 0.5 Hz, 1H), 4.68 (dpt, J = 17.0, 1.1 Hz, 1H), 4.53 (dd,
J = 11.0, 10.8 Hz, 1H), 4.20 (dd, J = 11.0, 3.4 Hz, 1H), 2.91 (m, 1H) ppm. 13C-NMR (CDCl3) : 54.43,
57.89 (C), 63.78 (CH2), 88.06 (C), 102.32 (C), 116.60 (C), 119.36 (CH2), 123.55, 123.82, 127.12,
127.40, 127.59, 127.68, 128.62, 130.23, 131.28, 131.36 (C), 131.42 (C), 131.54 (C), 140.10,147.29
(C), 152.24 (C), 154.40, 194.70 (C) ppm. HRMS (EI, 30 °C): calcd for C24H16I2O2: 589.9240, found:
589.9230.
3',5-Dibromo-2-vinyl-2,3-dihydro-2'H-spiro[benzo[f]chromene-1,1'-naphthalen]-2'-one (5c). Yield:
1
91%; pale yellow foam. H-NMR (CDCl3) : 8.08 (s, 1H), 8.05 (s, 1H), 7.59 (dm, J = 8.1 Hz, 1H),
7.37 (dd, J = 7.6, 1.4 Hz, 1H), 7.25 (ptd, J = 7.5, 1.3 Hz, 1H), 7.15 (m, 2H), 7.03 (ddd, J = 8.5, 6.9, 1.4
Hz, 1H), 6.72 (dm, J = 7.8 Hz, 1H), 6.54 (dm, J = 8.6 Hz, 1H), 5.42 (ddd, J = 17.0, 10.5, 8.9 Hz, 1H),
5.01 (dd, J = 10.4, 1.2 Hz, 1H), 4.69 (dpt, J = 17.0, 1.1 Hz, 1H), 4.56 (pt, J = 11.1 Hz, 1H), 4.23 (dd,
13
J = 11.1, 3.4 Hz, 1H), 2.99 (ddd, J = 11.7, 8.9, 3.5 Hz, 1H) ppm. C-NMR (CDCl3) : 193.67 (C),
151.05 (C), 146.93, 146.67 (C), 133.15, 131.13, 130.62 (C), 130.47 (C), 130.29 (C), 129.89, 128.84,
127.85, 127.56 (2 CH), 126.97, 124.04, 123.53, 122.70 (C), 119.60 (CH2), 117.37 (C), 113.25 (C),
63.57 (CH2), 58.72 (C), 54.34 ppm. HRMS (ESI): calcd for C24H16Br2O2Na: 516.9415, found:
516.9415.
3',5-Diphenyl-2-vinyl-2,3-dihydro-2'H-spiro[benzo[f]chromene-1,1'-naphthalen]-2'-one (5). Yield:
1
98%; pale yellow solid. H-NMR (CDCl3) : 7.73 (2 × s, 2H), 7.69 (m, 1H), 7.68 (m, 2H), 7.54 (m,
2H), 7.44–7.50 (m, 3H), 7.31-7.41 (m, 4H), 7.27 (ptd, J = 7.5, 1.3 Hz, 1H), 7.15 (m, 2H), 7.02 (ddd,
J = 8.5, 6.9, 1.5 Hz, 1H), 6.88 (dm, J = 7.7 Hz, 1H), 6.78 (dm, J = 8.6 Hz, 1H), 5.60 (ddd, J = 17.1,
10.4, 8.8 Hz, 1H), 4.96 (ddd, J = 10.3, 1.4, 0.5 Hz, 1H), 4.71 (dm, J = 17.1 Hz, 1H), 4,54 (dd, J = 10.2,
13
10.0 Hz, 1H), 4.13 (dd, J = 10.8, 3.3 Hz, 1H), 3.05 (ddd, J = 9.9, 8.9, 3.3 Hz, 1H) ppm. C-NMR
(CDCl3) : 199.83 (C), 152.82 (C), 147.56 (C), 142.90, 138.45 (C), 136.47 (C), 135.51 (C), 131.92
(C), 131.56, 131.36 (C), 130.71 (C), 130.59, 130.33, 129.94, 129.88 (C), 129.35, 128.90, 128.73,

Molecules 2012, 17
14545
128.20, 128.14, 128.01, 127.51, 127.26, 127.12, 126.30, 123.82, 123.39, 118.32 (C), 116.69 (C), 63.16
(CH2), 57.79 (C), 54.13 ppm. HRMS (ESI): calcd for C36H26O2Na: 513.1830, found: 513.1847.
3.2.7. Photoisomerisation of 5b (Typical Procedure)
A sample containing ca.15 mg of 5b in toluene-d8 in a NMR tube was irradiated for a total of 10 h
(60 W, light bulb) after which 1H-NMR indicated absence of 5b and formation of 6b and 7b (ca. 9:1),
separable by chromatography (EtOAc/PE, 10:90).
(1R,10cR)-1,5-Diiodo-1,2,2a,2b,3,14b-hexahydro-1,10c-methanobenzo[f]cyclobuta[3,4]naphtho[2,1-
c]chromen-15-one (6b). Yield: 75%; mp: 248–249 °C (EtOAc/PE). 1H-NMR (CDCl3) : 8.35 (s, 1H),
7.64 (dm, J = 8.0 Hz, 1H), 7.32 (dd, J = 7.4, 1.4 Hz, 1H), 7.26 (ddd, J = 8.0, 6.8, 1.2 Hz, 1H), 7.21
(ptd, J = 7.4, 1.2 Hz, 1H), 7.17 (ddd, J = 8.3, 6.8, 1.5 Hz, 1H), 6.98 (m, 2H), 6.38 (br d, J = 7.9 Hz,
1H), 4.46 (br d, J = 6.8 Hz, 1H), 4.45 (dd, J = 11.0, 3.5 Hz, 1H), 3.97 (dd, J = 11.8, 11.1 Hz, 1H), 3.11
(m, 1H), 2.95 (ddd, J = 10.8, 7.1, 1.4 Hz, 1H), 2.46 (d, J = 10.7 Hz, 1H), 2.26 (m, 1H) ppm. 13C-NMR
(CDCl3) : 201.23 (C), 152.37 (C), 140.48, 139.98 (C), 133.56 (C), 133.10 (C), 131.23 (C), 128.58,
127.79, 127.57, 127.40, 126.48, 125.88, 125.46, 124.14, 112.46 (C), 87.90 (C), 65.72 (CH2), 58.16
(C), 56.58, 44.10, 43.33 (CH2), 39.88, 35.86 (C) ppm. HRMS (EI, 30 °C): calcd for C24H16I2O2:
589.9240, found: 589.9231.
(6R,11bR)-2,6-Diiodo-4a,5,6,7-tetrahydro-4H-5,7:6,11b-dimethanobenzo[3,4]cyclohepta[1,2-
c]benzo[f]chromen-16-one (7b). Yield: 12%, mp: 151–152 °C (EtOAc/PE). 1H-NMR (CDCl3) : 8.37
(s, 1H), 7.65 (dm, J = 8.1 Hz, 1H), 7.26 (ddd, J = 8.0, 6.8, 1.1 Hz, 1H), 7.17 (ptd, J = 7.5, 1.2 Hz, 1H),
7.08 (m, 1H), 7.07 (m, 1H), 6.96 (dm, J = 8.8 Hz, 1H), 6.87 (m, 1H), 6.29 (dd, J = 8.0, 1.2 Hz, 1H),
4.36 (dd, J = 11.2, 4.9 Hz, 1H), 4.16 (ddd, J = 8.5, 4.9, 0.9 Hz, 1H), 3.17 (dpt, J = 11.1, 8.1 Hz, 1H),
3.45 (dd, J = 13.0, 11.1 Hz, 1H), 3.06 (ddd, J = 13.0, 4.8, 0.6 Hz, 1H), 2.57 (ddm, J = 7.8, 4.8 Hz, 1H),
13
1.73 (dm, J = 11.1 Hz, 1H) ppm. C-NMR (CDCl3) : 205.34 (C), 152.83 (C), 140.54 (C), 140.21,
138.76 (C), 132.85 (C), 131.65 (C), 128.88, 128.28, 127.27, 127.15, 127.03, 126.37, 125.17, 124.13,
112.34 (C), 87.37 (C), 67.42 (CH2), 58.20, 54.34 (C), 51.19, 44.44, 36.82 (C), 35.72 (CH2) ppm.
HRMS (ESI): calcd for C24H16I2O2Na: 612.9137, found: 612.9135.
(1R,10cR)-1,5-Dibromo-1,2,2a,2b,3,14b-hexahydro-1,10c-methanobenzo[f]cyclobuta[3,4]naphtho[2,1-
c]chromen-15-one (6c). Yield: 64%, crystalline precipitate, mp: 324–328 °C (EtOAc/PE, dec.).
1H-NMR (CDCl3) : 8.14 (s, 1H), 7.72 (dm, J = 8.2 Hz, 1H), 7.39 (dd, J = 7.4, 1.3 Hz, 1H), 7.33 (ddd,
J = 8.0, 6.8, 1.0 Hz, 1H), 7.27 (ptd, J = 7.6, 1.3 Hz, 1H), 7.22 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.07 (dm,
J = 8.8 Hz, 1H), 7.03 (ptd, J = 7.5, 1.4 Hz, 1H), 6.44 (br d, J = 7.8 Hz, 1H), 4.55 (dd, J = 11.0, 3.4 Hz,
1H), 4.40 (d, J = 6.9 Hz, 1H), 4.03 (dd, J = 11.9, 11.1 Hz, 1H), 3.20 (m, 1H), 2.97 (ddd, J = 10.8, 7.2,
1.5 Hz, 1H), 2.49 (d, J = 10.8 Hz, 1H), 2.31 (dm, J = 12.1 Hz, 1H) ppm. 13C-NMR (CDCl3) : 200.42
(C), 150.97 (C), 139.77 (C), 133.58, 133.40 (C), 132.42 (C), 130.15 (C), 128.67, 127.84, 127.64,
127.54, 126.55, 125.91, 125.26, 124.39, 113.28 (C), 113.22 (C), 65.71 (CH2), 58.80 (C), 57.38 (C),
54.93, 44.27, 41.55 (CH2), 35.85 ppm. HRMS (ESI): calcd for C24H16Br2NaO2: 516.9415, found:
516.9425.

Molecules 2012, 17
14546
(6R,11bR)-2,6-dibromo-4a,5,6,7-tetrahydro-4H-5,7:6,11b-dimethanobenzo[3,4]cyclohepta[1,2-
c]benzo[f]chromen-16-one (7c). Yield: 10%, mp: 240–246 °C (EtOAc/PE), colorless prisms. 1H-NMR
(CDCl3) : 8.11 (s, 1H), 7.68 (br d, J = 8.3 Hz, 1H), 7.28 (m, 1H), 7.18 (ptd, J = 7.5, 1.5 Hz, 1H), 7.10
(br d, J = 7.4 Hz, 1H), 7.09 (m, 1H), 6.96 (d, J = 8.6 Hz, 1H), 6.88 (ptd, J = 7.6, 1.4 Hz, 1H), 6.27 (br d,
J = 8.0 Hz, 1H), 4.39 (dd, J = 11.1, 4.8 Hz, 1H), 4.16 (dd, J = 8.1, 5.1 Hz, 1H), 3.57 (dpt, J = 11.2,
8.2 Hz, 1H), 3.47 (dd, J = 12.9, 11.1 Hz, 1H), 3.01 (dd, J = 13.0, 4.9 Hz, 1H), 2.58 (dd, J = 7.8,
5.1 Hz, 1H), 1.81 (d, J = 11.2 Hz, 1H) ppm. 13C-NMR (CDCl3) : 203.99 (C), 151.50 (C), 140.24 (C),
138.69 (C), 133.27, 132.10 (C), 130.53 (C), 128.74, 128.38, 127.42, 127.09, 127.06, 126.49, 125.04,
124.37, 113.24 (C), 112.80 (C), 67.17 (CH2), 58.83 (C), 56.07, 55.87 (C), 50.01, 42.10, 35.68 (CH2)
ppm. HRMS (ESI): calcd for C24H16Br2NaO2: 518.9394, found: 518.9372.
(1R,10cR)-1,5-Diphenyl-1,2,2a,2b,3,14b-hexahydro-1,10c-methanobenzo[f]cyclobuta[3,4]naphtho[2,1-
1
c]chromen-15-one (6d). Yield: 7%, mp: 322–327 °C (EtOAc/PE), colorless prisms. H-NMR (CDCl3)
: 7.79 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.61 (m, 2H), 7.48 (dd, J = 7.5, 1.2 Hz, 1H), 7.44 (m, 2H),
7.36 (m, 1H), 7.21–7.33 (m, 5H), 7.11 (m, 2H), 7.10 (m, 1H), 7.07 (ptd, J = 7.7, 1.4 Hz, 1H), 7.00 (d,
J = 8.6 Hz, 1H), 6.61 (d, J = 7.8 Hz, 1H), 4.46 (dd, J = 11.1, 3.6 Hz, 1H), 4.24 (d, J = 6.2 Hz, 1H),
4.14 (dd, J = 11.6, 11.0 Hz, 1H), 3.00 (pq, J = 6.0 Hz, 1H), 2.81 (ddd, J = 10.3, 6.4, 1.7 Hz, 1H), 2.41
13
(m, 1H), 2.40 (d, J = 10.3 Hz, 1H) ppm. C-NMR (CDCl3) : 207.29 (C), 152.92 (C), 141.15 (C),
140.09 (C), 138.65 (C), 136.65 (C), 132.97 (C), 132.35 (C), 131.00, 129.86, 129.52 (C), 128.47,
128.40, 128.30, 127.96, 127.17, 127.14, 127.05, 127.02, 126.35, 126.07, 125.68, 124.69, 123.43,
112.72 (C), 65.44 (CH2), 58.76 (C), 57.88 (C), 49.80, 46.07, 36.89 (CH2), 34.08 ppm. HRMS (ESI):
calcd for C36H26NaO2: 513.1825, found: 513.1824.
(6R,11bR)-2,6-Diphenyl-4a,5,6,7-tetrahydro-4H-5,7:6,11b-dimethanobenzo[3,4]cyclohepta[1,2-c]benzo
1
[f]chromen-16-one (7d). Yield: 39%, oil. H-NMR (CDCl3) : 7.82 (s, 1H), 7.80 (br d, J = 8.3 Hz,
1H), 7.65 (m, 2H), 7.41–7.52 (m, 7H), 7.38 (m, 1H), 7.29 (m, 1H), 7.26 (m, 2H), 7.11 (m, 2H), 6.98
(m, 1H), 6.51 (d, J = 7.8 Hz, 1H), 4.39 (dd, J = 10.9, 4.9 Hz, 1H), 4.26 (dd, J = 8.4, 4.7 Hz, 1H), 3.54
(dd, J = 13.1, 10.9 Hz, 1H), 3.22 (dpt, J = 10.9, 8.3 Hz, 1H), 3.08 (dd, J = 12.9, 4.9 Hz, 1H), 2.82 (dd,
13
J = 7.9, 4.7 Hz, 1H), 1.90 (d, J = 10.9 Hz, 1H) ppm. C-NMR (CDCl3) : 211.38 (C), 153.10 (C),
142.06 (C), 139.75 (C), 138.48 (C), 136.54 (C), 132.67 (C), 131.86 (C), 130.76, 129.94 (C), 129.84,
129.01, 128.53, 128.19, 128.00, 127.87, 127.82, 127.20 (2 × CH), 126.69, 126.47, 124.37, 123.50,
112.62 (C), 66.82 (CH2), 58.87 (C), 53.90 (C), 51.00, 48.95, 38.67, 35.91 (CH2) ppm. HRMS (ESI):
calcd for C36H26NaO2: 513.1825, found: 513.1824.
3.2.8. Synthesis of 6b/7b from 2b (One Pot Procedure)
Grubbs II catalyst (12.6 mg, 0.015 mM) dissolved in toluene (1.5 mL) was slowly added during 6 h
to a stirred solution of 2b (145 mg, 0.235 mM) in toluene (14 mL) at r.t. During this time the reaction
mixture was irradiated using a desk lamp. Extractive work-up and chromatographic purification
afforded 103 mg (76%) of 6b and 17 mg (13%) of 7b.
(2E,2'E)-Dimethyl 4,4'-(R)-1,1'-binaphthyl-2,2'-diylbis(oxy)dibut-2-enoate [(R)-8]. (R)-2,2'-Dihydroxy-
1,1'-binaphthyl 1a (859 mg, 3 mM) was dissolved in acetonitrile (25 mL). After addition of methyl

Molecules 2012, 17
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4-bromocrotonate (1.61 g, 9 mM) and K2CO3 (1.26 g, 9 mM) the mixture was stirred at r.t. under Ar
for 24 h. Standard work-up with water/DCM and drying (MgSO4) was followed by column
20
chromatography (EtOAc/PE, 30:70) to yield 1.07 g (74%) of (R)-8; oil; []D +30.6 (c 1.00, CHCl3).
1H-NMR (CDCl3) : 7.94 (d, J = 9.0 Hz, 2H), 7.86 (br d, J = 8.2 Hz, 2H), 7.33 (ddd, J = 8.0, 6.5,
1.4 Hz, 2H), 7.32 (d, J = 9.0 Hz, 2H), 7.22 (ddd, J = 8.2, 6.7, 1.4 Hz, 2H), 7.14 (dm, J = 8.6 Hz, 2H),
6.81 (dpt, J = 15.7, 3.9 Hz, 2H), 5.63 (dpt, J = 15.8, 2.2 Hz, 2H), 4.66 (m, 4H), 3.63 (s, 6H) ppm.
13C-NMR (CDCl3) : 166.44 (C), 153.33 (C), 143.07, 134.02 (C), 129.62, 129.53 (C), 127.99, 126.56,
125.32, 123.94, 121.09, 120.17 (C), 115.01, 67.79 (CH2), 51.45 (CH3) ppm. HRMS (ESI): calcd for
C30H26O6Na: 505.1627, found: 505.1616.
(2E,2'E)-4,4'-(R)-1,1'-Binaphthyl-2,2'-diylbis(oxy)dibut-2-en-1-ol [(R)-9]. To a degassed solution of
(R)-8 (1.07 g, 2.22 mM) in abs. DCM (30 mL) was added at −78 °C DIBAL (1 mol solution in toluene,
8.9 mL, 8.9 mM) and the reaction was kept at −20 °C for 12 h after which time TLC (EtOAc, 100%)
indicated complete conversion. A saturated solution of potassium sodium tartrate (30 mL) and glycol
(0.5 mL) was added and the mixture was stirred at r.t. for 3 h. The organic phase was separated and the
aqueous phase was extracted with DCM (10 mL). The combined organic extracts were washed with
brine and dried (Na2SO4). After evaporation the crude product was purified by chromatography
(EtOAc / PE 50:50  100:0) to give 672 mg (71%) of (R)-9; white solid; mp: 38–40 °C; []D20 +65.2
1
(c 1.00, CHCl3). H-NMR (CDCl3) : 7.91 (d, J = 9.1 Hz, 2H), 7.84 (d, J = 8.1 Hz, 2H), 7.37 (d,
J = 9.1 Hz, 2H), 7.30 (ddd, J = 8.0, 6.7, 1.2 Hz, 2H), 7.19 (ddd, J = 8.4, 6.7, 1.3 Hz, 2H), 7.11 (br d,
J = 8.4 Hz, 2H), 5.55 (m, 4H), 4.50 (m, 4H), 3.90 (m, 4H), 1.73 (br s, 2H) ppm. 13C-NMR (CDCl3) :
153.93 (C), 134.13 (C), 131.61, 129.39 (C), 129.20, 127.86, 126.72, 126.23, 125.48, 123.68, 120.66
(C), 115.99, 69.25 (CH2), 62.71 (CH2) ppm. HRMS (ESI) calcd for C28H26O4Na: 449.1729, found:
449.1727.
(2E,2'E)-4,4'-(R)-1,1'-Binaphthyl-2,2'-diylbis(oxy)dibut-2-en-1-ylbromide [(R)-10]. To a solution of
(R)-9 (580 mg, 1.36 mM) in dry THF (15 mL) was dropwise added at −40 °C PBr3 (810 mg, 3.06 mM,
2.2 equiv, 284 µL) in THF (1 mL) and the mixture was slowly warmed up overnight. Sat. sodium
bicarbonate solution (5 mL) was added, followed by water (10 mL) and DCM (20 mL). The aqueous
layer was extracted with DCM (2 × 15 mL) and the combined extracts were washed with brine and
dried (MgSO4). After evaporation the crude bromide was purified by chromatography (DCM/PE,
20
1
30:70) to give 544 mg (72%) of (R)-10 as a colorless oil; []D +13.7 (c 1.00, THF). H-NMR
(CDCl3) : 7.94 (d, J = 9.0 Hz, 2H), 7.86 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 9.9 Hz, 2H), 7.32 (m, 2H),
13
7.22 (m, 2H), 7.14 (d, J = 8.4 Hz, 2H), 5.60 (m, 4H), 4.53 (m, 4H), 3.74 (m, 4H) ppm. C-NMR
(CDCl3) : 153.76 (C), 133.99 (C), 130.56, 129.42 (C), 129.35, 127.92 (2 × CH), 126.33, 125.43, 123.76,
120.44 (C), 117.71, 68.57 (CH2), 31.96 (CH2) ppm. HRMS (ESI) calcd for C28H2479Br81BrO2Na:
575.0023, found: 575.0045.
Macrocyclisation of (R)-10 with (R)-1. To a degassed solution of (R)-binaphthol 1 (57 mg, 0.2 mM) in
THF (7 mL) was added KOH (22 mg, 0.4 mM, 0.4 mL of a 1 N aqueous solution) and the mixture was
refluxed for 30 min. Dibromide (R)-10 (110 mg, 0.2 mM) dissolved in THF (3 mL) was added and the
reaction was refluxed for 3 d. Extractive work-up with DCM/water and chromatographic purification

Molecules 2012, 17
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20
(EtOAc / PE, 20:80) yielded 95 mg (70%) of (R,R)-3a; mp: 159–160 °C (EtOAc/PE); []D +110
(c 0.42, CHCl3). Spectroscopic data fully agreed with the racemic compound.
Palladium mediated cleavage of (R,R)-3a. Macrocycle (R,R)-3a (80 mg, 0.12 mmol) and Pd(PPh3)4
(14 mg, 0.012 mmol) were heated in toluene (60 °C) for 48 h. The crude mixture was separated by
column chromatography (EtOAc/PE, 10:9020:80) to give a 44 mg fraction consisting of (R,R)-5a
(36 mg, 45%) and 6a (8 mg, 10%) followed by 19 mg (24%) of (R,S)-epi-5a; mp: 153–155 °C
(EtOAc/PE). 1H-NMR (CDCl3) : 7.70 (d, J = 9.3 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 9.9 Hz,
1H), 7.44 (dd, J = 7.5, 1.4 Hz, 1H), 7.29 (ptd, J = 7.3, 1.2 Hz, 1H), 7.18 (ptd, J = 7.7, 1.4 Hz, 1H), 7.17
(d, J = 9.1 Hz, 1H), 7.15 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 7.07 (br d, J = 7.6 Hz, 1H), 7.07 (ddd,
J = 8.4, 6.9, 1.4 Hz, 1H), 6.62 (dm, J = 8.5 Hz, 1H), 6.41 (d, J = 10.0 Hz, 1H), 5.00 (m, 2H), 4.94 (m,
1H), 4.24 (pt, J = 11.3 Hz, 1H), 4.07 (dd, J = 11.3, 4.0 Hz, 1H), 3.11 (m, 1H) ppm. 13C-NMR (CDCl3)
: 203.10 (C), 154.17 (C), 145.01, 143.65 (C), 131.54 (C), 131.00, 130.70 (C), 130.25 (C), 130.01,
129.60, 129.44 (2 × CH), 128.74, 127.48, 126.51, 126.46, 123.86, 123.11, 119.75 (CH2), 118.86,
115.35 (C), 64.09 (CH2), 57.18 (C), 51.34 ppm. HRMS (ESI): calcd for C24H18O2Na: 361.1207, found:
361.1204.
3.3. Crystallographic Structure Determination
X-ray diffraction measurements were performed on an X8 APEX II CCD diffractometer at 100 or
150 K. Single crystals were positioned at 50, 35, 35, 35, 45 and 35 mm from the detector and 1270,
1831, 2488, 1406, 1467 and 1278 frames were measured, each for 60, 10, 30, 5, 10 and 10 s over 1°
scan width for epi-5a, 5b, 6a, epi-6a, 6b and 11, respectively. The data were processed using SAINT
software [53]. Crystal data, data collection parameters, and structure refinement details are given in
Table 2. The structures were solved by direct methods and refined by full-matrix least-squares
techniques. Non-hydrogen atoms were refined with anisotropic displacement parameters. H atoms
were placed at calculated positions and refined as riding atoms in the subsequent least squares model
refinements. The isotropic thermal parameters were estimated to be 1.2 times the values of the
equivalent isotropic thermal parameters of the non-hydrogen atoms to which hydrogen atoms are
bonded. The following computer programs were used: structure solution, SHELXS-97 refinement,
SHELXL-97 [54] molecular diagrams, ORTEP [55] computer: Pentium IV. CCDC 907285−907290
contain the supplementary crystallographic data for this paper. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Molecules 2012, 17
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Table 2. Crystal data and details of data collection for epi-5a, 5b, 6a, epi-6a, 6b and 11.
Compound
formula
Fw
epi-5a
C24H18O2
338.38
5b
C24H16I2O2
590.17
6a
C24H18O2
338.38
epi-6a
C24H18O2
338.38
6b
11
C73.88H52.25I6O7.13 C24H18O2
1815.31
338.38
space group P21212
P-1
P212121
P21
C2/c
P212121
a [Å]
b [Å]
c [Å]
 [°]
 [°]
 [°]
40.275(2)
14.7521(9)
8.8731(5)
8.9274(6)
14.7039(14)
15.9680(16)
90.792(4)
105.289(3)
90.064(3)
2021.7(3)
4
9.3461(5)
10.0950(6)
18.2172(11)
11.9996(7)
9.7117(6)
15.2652(9)
28.1310(16)
11.8338(8)
37.359(2)
7.9726(2)
11.6491(4)
17.7858(6)
108.528(3)
95.219(6)
V [Å3]
Z
5271.9(5)
12
1718.77(17)
4
1686.75(17)
4
12385.1(13)
8
1651.84(9)
4
 [Å]

0.71073
0.70713
1.939
0.71073
1.308
0.71073
1.333
0.71073
1.947
0.71073
1.361
calcd [g cm−3] 1.279
T [K]
100(2)
0.080
0.0565
0.1402
1.054
100(2)
3.128
0.0628
0.1592
100(2)
0.082
0.0294
0.0781
1.034
150(2)
0.084
0.0431
0.1011
1.045
100(2)
3.068
0.0483
0.0960
1.083
150(2)
0.085
0.0384
0.1032
1.049
 [mm−1]
a
R1
b
wR2
GOFc
1.191
a R1 = ||Fo| − |Fc||/|Fo|. b wR2 = {[w(Fo2 − Fc2)2]/[w(Fo ) ]}1/2. c GOF = {[w(Fo2 − Fc2)2]/(n − p)}1/2, where n is the number of reflections and p is the total number of
2 2
parameters refined.

Molecules 2012, 17
14550
3.4. Calculations
All calculations were performed using software packages SPARTAN (B3LYP, MO6 and MP2) and
the Gaussian09 on the Phoenix Linux Cluster of the Vienna University of Technology [38]. The
geometry and energy of the ruthenium model compounds and the transition states were optimized at
the B3LYP level [56–58] with the Stuttgart/Dresden ECP (SDD) basis set to describe the electrons of
the ruthenium atom [59–61], and a standard 6-31g** basis set was employed for all other atoms [62–68].
All geometries were optimized without symmetry constraints. Frequency calculations were performed
to confirm the nature of the stationary points, yielding one imaginary frequency for the transition states
and none for the minima. Each transition state was further confirmed by following its vibrational mode
downhill on both sides and obtaining the minima presented on the energy profiles. All energies
reported are Gibbs free energies and thus contain zero-point, thermal, and entropy effects at 298 K and
1 atm pressure. The solvation energies were calculated on the geometries from B3LYP gas phase
optimizations via the polarizable continuum model (PCM) [69,70] with the radii and nonelectrostatic
terms based on Truhlar and co-workers’ solute electron density (SMD) solvation model [71] with
solvation parameters corresponding to CH2Cl2.
4. Conclusions
Summarising, we have developed an operationally simple one-pot procedure for transforming
O,O'-diallyl substituted axial chiral binaphthols into centro-chiral species through a RCM followed by
a Claisen-type rearrangement of reactive (E)-dioxacyclodecine intermediates 4a–d. This mechanistic
assumption was supported and rationalized by DFT calculations performed on E-4a, corresponding
precursors and hypothetical intermediates. Under irradiation further rearrangement took place yielding
strained cage compounds 6a–d and 7a–d through a formal [2+2] cycloaddition.
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Sample Availability: Samples of the compounds 3a and 5a are available from the authors.
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