Exocyclic diastereotopic protons as a probe for conformational bias in eight-membered rings containing phosphorus and titanium

Article abstract of DOI:10.1080/10426507.2012.700349

The conformation in solution of eight-membered 12H-dibenzo[d,g][1,3,2]- dioxametallocin rings containing phosphorus and titanium, respectively, were studied by the NMR spectroscopy using ring substituents containing diastereotopic protons as a probe for conformational bias. The results of this study suggest that in addition to steric effects, an electronic effect due to donation of the lone pair of electrons on the ring oxygen atoms to the metal center influences the preferred conformation in solution.

Full text of DOI:10.1080/10426507.2012.700349

This article was downloaded by: [Pennsylvania State University]
On: 03 June 2013, At: 22:49
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Exocyclic Diastereotopic Protons as a
Probe for Conformational Bias in Eight-
Membered Rings Containing Phosphorus
and Titanium
Sai P. Shum a , Stephen D. Pastor b & David N. Rahni c
a Re-Synthesis Laboratory, BASF Corporation , Tarrytown , New York ,
USA
b Tzec Maun Observatory, Tzec Maun Foundation , Cloudcroft , New
Mexico , USA
c Department of Chemistry , Pace University , Pleasantville , New
York , USA
Accepted author version posted online: 22 Jun 2012.Published
online: 31 May 2013.
To cite this article: Sai P. Shum , Stephen D. Pastor & David N. Rahni (2013): Exocyclic Diastereotopic
Protons as a Probe for Conformational Bias in Eight-Membered Rings Containing Phosphorus and
Titanium, Phosphorus, Sulfur, and Silicon and the Related Elements, 188:5, 623-632
To link to this article: http://dx.doi.org/10.1080/10426507.2012.700349
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 188:623–632, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.700349
EXOCYCLIC DIASTEREOTOPIC PROTONS AS A PROBE
FOR CONFORMATIONAL BIAS IN EIGHT-MEMBERED
RINGS CONTAINING PHOSPHORUS AND TITANIUM
Sai P. Shum,1 Stephen D. Pastor,2 and David N. Rahni3
1Re-Synthesis Laboratory, BASF Corporation, Tarrytown, New York, USA
2Tzec Maun Observatory, Tzec Maun Foundation, Cloudcroft, New Mexico, USA
3Department of Chemistry, Pace University, Pleasantville, New York, USA
Abstract The conformation in solution of eight-membered 12H-dibenzo[d,g][1,3,2]-
dioxametallocin rings containing phosphorus and titanium, respectively, were studied by the
NMR spectroscopy using ring substituents containing diastereotopic protons as a probe for
conformational bias. The results of this study suggest that in addition to steric effects, an
electronic effect due to donation of the lone pair of electrons on the ring oxygen atoms to the
metal center influences the preferred conformation in solution.
Keywords Conformational analysis; 12H-dibenzo[d,g][1,3,2]dioxatitanocins; 12H-dibenzo
[d,g][1,3,2]dioxaphosphocin; diastereotopic protons
INTRODUCTION
The conformational analysis and elucidation of transannular intramolecular bond-
ing in certain medium-sized rings containing phosphorus, silicon, and germanium has
received considerable attention,1,2 stimulated in part by studies on the eight-membered
12H-dibenzo[d,g][1,3,2]dioxaphosphocin and corresponding silicon containing ring sys-
tem.3–6 In describing the conformation of the 12H-dibenzo[d,g][1,3,2]dioxametallocin ring
system, the commonly accepted nomenclature for the conformers of eight-membered rings
is used herein; namely the boat–chair (CS symmetry), boat–boat (CS symmetry), twist-boat
(C1 symmetry), boat (C1 symmetry), and twist (C2 symmetry), which are abbreviated BC,
BB, TB, B, and T, respectively (see Figure 1).7
The B conformation represents a highly distorted TB geometry halfway between the
C2 symmetric T and BB geometry.7c In eight-membered 12H-dibenzo[d,g][1,3,2]dioxa-
metallocins rings, the BC conformation is generally expected to be lowest in energy.1
In the solid state, X-ray crystallographic studies on the eight-membered 12H-dibenzo-
[d,g][1,3,6,2]dioxathiagermocin8,9 and 12H-dibenzo[d,g][1,3,6,2]dioxaselenagermocin10
revealed a boat–boat conformation with transannular bonding of sulfur and selenium, re-
spectively, to germanium. In solution, the NMR spectroscopic studies support a boat–boat
Received 13 January 2012; accepted 23 May 2012.
Address correspondence to Sai P. Shum, Re-Synthesis Laboratory, NC/I, BASF Corporation, Tarrytown,
New York 10591, USA; or Stephen D. Pastor, Tzec Maun Observatory, Tzec Maun Foundation, Cloudcroft, New
Mexico, USA. E-mail: sai.shum@basf.com; astro4d@yahoo.com
623

624
S. P. SHUM ET AL.
3
2
4
5
1
O
12
6
M
O 7
11
8
10
9
M
O
O
O
O
M
S
BB(C )
S
BC(C )
M
O
O
M
O
M
O
O
O
2
T(C )
1
TB(C )
1
B(C )
Figure 1 The Chemical Abstracts numbering system and conformations of the 12H-
dibenzo[d,g][1,3,2]dioxametallocin ring system. The TB conformation illustrated is one member of a
family of flexible TB forms.
conformation with transannular bonding of sulfur and selenium, respectively, to germa-
nium, but the absence of C(12) methylene protons make this conclusion more tentative.
2
The magnitude of the JHH geminal coupling constant for the C(12) methylene protons
was previously shown to be a powerful tool for determining the conformation of the
12H-dibenzo[d,g][1,3,2]dioxametallocin ring system in solution.5d,e,11,12 One approach to
mitigate the lack of C(12) methylene protons is to place substituents on the eight-membered
ring with potentially diastereotopic protons as a probe to determine if the ring is confor-
mationally biased in solution. Whether the protons will be observed to be diastereotopic
or not will be dependent upon both the symmetry of the ring conformation as well as the
presence or absence of processes that would lead to conformational averaging. In addi-
tion, substituents with potentially diastereotopic protons will provide an additional tool for
studying the conformation of eight-membered rings with C(12) methylene protons. This
will be shown to be the case for certain 12H-dibenzo[d,g][1,3,2]-dioxatitanocins for which
Floriani et al.12 suggested that the degree of nonequivalence (ꢀδ) of the C(12) methylene
protons was a powerful tool to monitor changes in the coordination sphere of titanium.
RESULTS AND DISCUSSION
12H-Dibenzo[d,g][1,3,2]dioxaphosphocins
A derivative of the 12H-dibenzo[d,g][1,3,2]dioxaphosphocin ring system with a sub-
stituent containing a diastereotopic proton probe was initially synthesized for comparison

DIASTEREOTOPIC PROTON PROBE
625
to the corresponding 12H-dibenzo[d,g][1,3,2]dioxatitanocin derivative. Reports from our
laboratory and others, notably Arbusov and Arshinova, have used both the degree on
nonequivalence observed for the C(12) methylene protons as well as the absolute magni-
tude of the corresponding geminal 2JHH coupling constant in the 1H NMR spectra of 12H-
dibenzo[d,g][1,3,2]dioxaphosphocin derivatives as a tool to determine the predominant
conformer(s) present in solution.11,13–17 The BB and BC conformations exhibit 2JHH gemi-
nal coupling constant in the range of −12 to −13 Hz, while the B conformation and family
of flexible TB conformations exhibit 2JHH geminal coupling constants in the range of −14
to −16 Hz. The 12H-dibenzo[d,g][1,3,2]dioxaphosphocin derivative provides a model of a
ring system that is known to be conformationally biased, albeit due to the asymmetry at phos-
phorus the C(12) methylene protons (or other potential exocyclic diastereotopic protons)
are inherently nonequivalent (cis/trans relationship to the lone-pair of electrons on phos-
phorus). The fact that in the 1H NMR spectra of 12H-dibenzo[d,g][1,3,2]dioxaphosphocin
derivatives the C(12) methylene protons usually display significant nonequivalence (ꢀδ
≈ 0.9 ppm) does not necessarily prove a comformationally biased ring system because of
this asymmetry at phosphorus, although at such distances the nonequivalence is expected
to be slight.18 However, numerous studies strongly support the contention that the 12H-
dibenzo[d,g][1,3,2]-dioxaphosphocin ring system is conformationally biased in solution.1,19
The methylenebisphenol 2 was prepared by the acid-catalyzed reaction of 1 with
paraformaldehyde in heptane solvent as a white crystalline solid (32% recrystallized).
The 6-methoxy-12H-dibenzo[d,g][1,3,2]dioxaphosphocin derivative 3 was prepared by
reaction of 2 sequentially with phosphorus(III) chloride followed by methyl alcohol using
triethylamine (TEA) as an acid acceptor (Scheme 1). The intermediate chloridite was
1
generated in situ and used without purification as described previously. (The 31P{ H}
chemical shift reported in Ref. 14b for the chloridite 2,4,8,10-tetrakis-(tert-butyl)-6-chloro-
12H-dibenzo[d,g][1,3,2]dioxaphosphocin is incorrect and should be 150.2 ppm.)14
1
In the H NMR spectrum of 3, the C(12) methylene protons are observed to be
nonequivalent. The upfield C(12)-methylene proton is observed as a doublet (2JHH
=
−13 Hz), whereas the downfield methylene proton is observed as a doublet of doublets
5
2
(2JHH = −13 Hz; JPH = 3 Hz). Both the magnitude of the JHH geminal coupling con-
5
stant and the observation of JPH long-range coupling to phosphorus are consistent with
a BC conformation. Following the procedure of Odorisio et al.,14b the tetra-tert-butyl-
12H-dibenzo[d,g][1,3,2]dioxaphosphocin derivative 4 was prepared [4: 1H NMR (CDCl3,
300.134 MHz): δ = 7.31 (d, 2H), 7.26 (d, 2H), 4.38 (dd, C(12)–H, 2JHCH = 12.5 Hz; 5JPH
3
2
= 2.5 Hz, 1H), 4.06 (d, POCH3, JHCOP = 8.5 Hz, 3H), 3.44 (d, JHCH = 12.5 Hz; 1H),
1.41 (s, 18H), 1.30 (s, 18H)]. The similar values of the geminal 2JHH and long-range 5JPH
coupling constants as well as the large degree of nonequivalence for the C(12)-methylene
protons (ꢀδ ≈ 0.9 ppm) for both 3 and 4 are consistent with a biased BC conformation for
both derivatives in solution.
Consistent with this interpretation, both pairs of potentially diastereotopic methyl
group protons exocyclic to the ring (the 1,1-dimethyl-group protons of the four 1,1,3,3-
tetramethylbutyl substituents located at the 2,4,8,10-positions of the ring, see Figure 1
for Chem. Abstracts numbering system) were observed to be nonequivalent. Four singlet
resonances are observed at 1.47 ppm, 1.42 ppm, 1.35 ppm, and 1.34 ppm that integrated
to six protons each, which were assigned to the four pairs of diastereotopic methyl-group
protons. Additionally, one pair of diastereotopic methylene-group protons is observed to
2
display significant nonequivalence (ꢀδ = 0.4 ppm, JHH = −15 Hz), whereas the other
1
pair is accidentally equivalent. The observed H NMR spectrum of 3 is fully consistent

626
S. P. SHUM ET AL.
OH
OH
OH
(CH2=O)n
HCl
1
2
O
P
1) PCl3, Et3N, Toluene
OMe
O
2) CH3OH, Et3N, Toluene
3
R
R
O
M
O
L1
L2
R
R
R= t-butyl ; M = P; L1 = OMe; L2 = lone pair
R= 1,1,3,3-tetramethylbutyl ; M = Ti; L1 = L2 = Cl
R= t-butyl ; M = Ti; L1 = L2 = Cl
4
5
6
7
R= t-butyl ; M = Ti; L1 = L2 = Me
Scheme 1
with a biased CS symmetric BC conformation in solution as suggested by the values of (1)
the geminal 2JHH and long-range 5JPH coupling constants, (2) the large degree of nonequiv-
alence for the C(12)-methylene protons, and (3) the observation of diastereotopic methyl
and methylene protons in the 1,1,3,3-tetramethylbutyl substituent used as an exocyclic
diastereotopic-proton probe.

DIASTEREOTOPIC PROTON PROBE
627
Of historical note, the observation of long-range 5JPH phosphorus to proton coupling
was originally suggested by us to be the result of a biased BB conformation in solution where
the geminal C(12)-methylene protons and phosphorus atom are in close proximity.14b Exten-
sive spectroscopic, solid-state crystallographic, and computational work in our laboratory
and others on 12H-dibenzo[d,g][1,3,2]dioxaphosphocins containing a trivalent phosphorus
atom strongly support a biased BC in solution.1,11,13–17,19 This conclusion is also supported
by work on related 12H-dibenzo[d,g][1,3,2]dioxametallocin ring systems in which the BC is
found to be lowest energy conformation. In certain 12H-dibenzo-[d,g][1,3,2]dioxasilocins,
in which steric interactions destabilize the BC conformation, the TB conformation is found
in solution (computational results suggested that the BB conformation was a transition state
or transient intermediate during the rapid equilibration of TB conformers).
12H-Dibenzo[d,g][1,3,2]dioxatitanocins
Floriani et al.12 suggested that the degree on nonequivalence (ꢀδ) of the C(12)
methylene protons in 12H-dibenzo[d,g][1,3,2]dioxatitanocins that had two chlorine sub-
stituents on titanium was a tool to monitor changes in the coordination sphere of tita-
nium. In this case, rapid ring inversion would lead to equivalence of the C(12) methy-
lene protons in the 12H-dibenzo[d,g][1,3,2]dioxatitanocin ring due to the conformational
exchange of the proton magnetic environments as observed for certain substituted 12H-
dibenzo-[d,g][1,3,2]dioxasilocins (the C(12) methylene protons are rendered homotopic
due to the presence of a C2 axis of symmetry through the C(12) carbon atom and tita-
nium atom in a time-averaged planar transition state.),5e which suggests that the 12H-
dibenzo[d,g][1,3,2]dioxa-titanocins studied by Floriani et al. are conformationally biased
in solution. Understanding the conformation of 12H-dibenzo[d,g][1,3,2]dioxatitanocins in
solution may lead to a better understanding of the polymerization efficiencies, molecular-
weights obtained, and observed stereoregulation obtained when using these ring systems
as polymerization catalysts.20, 21
The 12H-dibenzo[d,g][1,3,2]dioxatitanocin 5 was prepared as a red crystalline solid
1
(22% recrystallized) by the reaction of 2 with titanium(IV) chloride. In the H NMR
spectrum of 5 two doublet resonances are observed at 3.68 ppm and 4.14 ppm that were
assigned to two nonequivalent C-12 methylene protons (ꢀδ = 0.46 ppm). The nonequiv-
alence of the methylene protons along with the observation of two equivalent pairs of
1,1,3,3-tetramethylbutyl substituents in 5 requires the presence of a σ plane of symmetry
that passes through the C-12 carbon atom and the titanium atom. The presence of twisted
nonplanar structures such as the B or family of flexible TB conformations that rapidly pass
on the NMR time scale through the required σ plane of symmetry (e.g., the BB conforma-
tion, as either a transition state or intermediate) cannot be excluded. Indeed, the geminal
2
two-bond coupling constant JHH of the C-12 methylene protons of 5 is −14.8 Hz, and
larger than expected for a BC conformer. The magnitude of the observed coupling constant
observed for 5 is consistent with equilibrating B or TB conformations in solution.
In the 1H NMR spectrum of 5 two singlet resonances are observed at 1.42 ppm and
1.50 ppm that were assigned to one equivalent pair of diastereotopic methyl group protons
(the geminal dimethyl groups of the 1,1,3,3-tetramethylbutyl substituents in the 4,8-ring
positions are expected to display the largest nonequivalence). Similarly, the diastereotopic
methylene protons of the equivalent pair of 1,1,3,3-tetramethyl-butyl substituents are ob-
served as an AB quartet at 2.04 ppm. The other pair of diastereotopic methyl group protons

628
S. P. SHUM ET AL.
and methylene protons of the other pair of 1,1,3,3-tetramethylbutyl substituents are observed
to be accidentally equivalent. The observation of diastereotopic methyl and methylene pro-
tons in the exocyclic 1,1,3,3-tetramethylbutyl substituents along with the magnitude of the
C-12 geminal coupling constant and the degree of nonequivalence of the C-12 methylene
protons (ꢀδ) of 5 strongly suggest a conformationally biased system of equilibrating TB
or B conformations in solution.
Floriani reported that the solid-state conformation of 6 and 7 are flattened BB struc-
tures. (The two Caromatic–O–Ti–O torsion angles for 6 and 7 are small and for 7 near zero, C.
Floriani Personal Communication. In this case, the designation of a conformation as either
BC or BB could be misleading. The observed torsion angles of 6 are consistent with a BB
structure slightly twisted (a TB structure), whereas for 7 are an ideal BB conformation.
Due to the near zero Caromatic–O–Ti–O torsion angles reported for 7 (+0.3◦ and −0.3◦,
respectively), however, the solid-state conformation of 7 could be described as either a
flattened BC or BB given the reported estimated standard deviation of 1.23◦). The flat-
tening of the ring was suggested to be due to rehybridization of the oxygen atoms toward
sp hybridization with increased electron donation from the oxygen ligands to titanium.
The increased electron donation from oxygen to titanium is consistent with the very short
O–Ti bond lengths indicative of an O–Ti bond order greater than 2.12a However, the use
of solid-state conformational data to assign the conformation in solution must be exercised
with caution. Lattice energy and the resultant crystal-packing effects in the solid-state can
render the solid-state conformation different from the solution conformations.5e,7e
Indeed, the reported magnitude of the C-12 geminal methylene coupling constant
2
of 6 and 7 (2JHH = −14.4 Hz and JHH = −14.2 Hz, respectively) as well as the degree
of nonequivalence of the C-12 methylene protons (ꢀδ = 0.34 ppm and ꢀδ = 0.17 ppm,
respectively) is similar to 5 (2JHH = −14.8 Hz, ꢀδ = 0.46 ppm; the methyl substituents
1
bonded to Ti are nonequivalent in the H NMR of 7, see Ref. 12a), and is not consistent
with a flattened BB structure in solution. The magnitudes of 2JHH and ꢀδ for 6 and 7 are
consistent with a conformationally biased system of equilibrating TB or B conformations
in solution.
The results of this study support the suggestion by Floriani that the differences in ꢀδ
of the C-12 methylene protons in 12H-dibenzo[d,g][1,3,2]dioxatitanocin derivatives with
a change in coordination at titanium is due to conformational changes in solution.12a,22
Although, the solution conformation of 6 and 7 are not flattened BB conformations, the
possibility that the B and TB conformations are distorted due to the electron donation
of the oxygen ligands of the bisphenol to the titanium atom merits further consideration.
The coordination sphere around titanium would determine the electron density around the
titanium atom as well as the electron acceptor properties of the titanium orbitals bonded to
the oxygen ligands of the bisphenol. Increased Ti–O bonding would be expected to flatten
the ring system (the oxygen atom approaching sp hybridization) with a resultant change
in the stability of a particular conformation. The C-12 geminal methylene proton coupling
constant (2JHH = −14.2 Hz) of the previously reported 6-phenyl-substituted 12H-dibenzo-
[d,g][1,3,2]dioxaborocin14a,b is consistent with a TB conformation in solution rather than
the expected BC, which may be the result of electron donation from the oxygen ligands to
boron.
Although we have previously used steric effects primarily to explain the ob-
served solution conformation in certain eight-membered 12H-dibenzo[d,g][1,3,2]dioxa-
metallocins,5e–f systems where electron donation from the oxygen ligands of the bisphenol
to an electron acceptor may result in a solution conformation that is different from the

DIASTEREOTOPIC PROTON PROBE
629
expected low energy BC conformer.23,24 This may particularly be the case with the 12H-
dibenzo[d,g][1,3,2]dioxametallocin ring system because in the case of the silicon ring
system the pseudoequatorial preference for a substituent on the C-12 carbon atom or the
silicon atom is greater than the energy between the BC and TB conformations.5e A similar
electronic perturbation may lead to an energetic preference of the TB conformation over
the normally preferred BC conformer.
EXPERIMENTAL
All melting points (mp) were determined in open capillary tubes and were uncor-
1
1
1
rected. The H NMR (300.134 MHz), 13C{ H} NMR, and 31P{ H} NMR spectra were
obtained with a Bruker 300 FT NMR spectrometer (Bruker BioSpin GmbH, Rheinstetten,
Germany). All 31P{ H} chemical shift values are reported in ppm relative to 85% phos-
1
phoric acid (external), where a positive sign is downfield from the standard. Significant
1H NMR spectral data are tabulated in the following order: multiplicity (m, multiplet; s,
singlet; d, doublet; t, triplet; dd, doublet of doublets), atom assignments, coupling constant
in Hertz, and number of protons. Reagents were purchased from commercial laboratory
supply houses and solvents were dried prior to use. Reactions were carried out under a dry
atmosphere of argon.
2,2ꢀ-Methylenebis[4,6-di(1,1,3,3-tetramethylbutyl)phenol] (2)
To a stirred mixture of 4,6-di(1,1,3,3-tetramethylbutyl)phenol 1 (79.5 g, 250 mmol)
and paraformaldehyde (3.75 g, 125 mmol) in 60 mL of heptane was added 2 mL of concen-
trated hydrochloric acid. The reaction mixture was stirred for 5 h at ambient temperature.
The reaction mixture was heated at 50–60◦C for 5 h, and then the water of reaction was
removed at reflux temperature with a Dean–Stark trap. The volatiles were removed in vacuo
and the residue was recrystallized sequentially from hexane (300 mL) and then from methyl
alcohol (300 mL) to give 26.0 g (32%) of a white crystalline solid, mp 111.5◦C: IR (KBr
1
pellet): ν = 3590, 3410 (OH) cm−1; H NMR (CDCl3): δ = 7.20 (d, 2H), 7.11 (d. 2H),
5.59 (s, OH, 2H), 3.90 (s, C(12)–H, 2H), 1.85 (s, CH2, 4H), 1.70 (s, CH2, 4H), 1.40 (s,
C(CH3)2, 12H), 1.32 (s, C(CH3)2, 12H), 0.72 (s, C(CH3)3, 18H), 0.69 (s, C(CH3)3, 18H).
Anal. calcd. for C45H7602: C, 83.27; H, 11.80. Found: C, 83.21; H, 11.48%.
2,4,8,10-Tetrakis(1,1,3,3-tetramethylbutyl)-6-methoxy-12H-
dibenzo[d,g][1,3,2]di-oxaphosphocin (3)
To a solution of TEA (1.10 g, 10 mmol) in toluene (10 mL) at 0◦C was added dropwise
sequentially phosphorus(III) chloride (0.42 mL, 5 mmol) followed by a solution of 2 (3.24 g,
5 mmol) in toluene (20 mL). The reaction mixture was stirred at ambient temperature for
18 h. To the reaction mixture was added a solution of methyl alcohol (0.16 g, 5 mmol)
and TEA (0.51 g, 5 mmol) in toluene (10 mL). The reaction mixture was stirred 18 h at
ambient temperature, and then the resultant precipitate of TEA hydrochloride was removed
by filtration. The volatiles were removed in vacuo and the residue was triturated with ethyl
alcohol. The resultant solid was recrystallized from ethyl alcohol to give 2.59 g (73%) of a
white crystalline solid, mp 132–132.5◦C: IR (KBr pellet): ν = 1025 (POC aliphatic stretch)
1
1
cm−1
;
31P{ H} NMR (CDCl3): δ = 128.8; H NMR (CDCl3): δ = 7.25 (overlapping d,

630
S. P. SHUM ET AL.
4H), 4.28 (dd, C(12)–H, 5JPH = 3 Hz, 2JHH = −13 Hz, 1H), 4.06 (d, OCH3, 3JPH = 8 Hz,
3H), 3.41 (d, C(12)–H, 2JHH = −13 Hz, 1H), 2.15 (d, downfield half of AB quartet, 2JHH
2
= −15 Hz, 2H), 1.75 (d, upfield half of AB quartet, JHH = −15 Hz, 2H), 1.72 (s, CH2,
4H), 1.47 (s, CH3, 6H), 1.42 (s, CH3, 6H), 1.35 (s, CH3, 6H), 1.34 (s, CH3, 6H), 0.75
1
(s, C(CH3)3, 18H), 0.69 (s, C(CH3)3, 18H); 13C{ H} NMR (CDCl3): δ = 1.46 (d, JPC
=
6.5 Hz), 1.45 (s), 1.40 (d, JPC = 3.6 Hz), 135.4 (d, JPC = 2.7 Hz), 1.25 (s), 1.24 (s), 57.0
(s), 53.4 (d, JCP = 2.7 Hz), 49.9 (d, JPC = 2.9 Hz), 39.4 (s), 38.4 (s), 35.8 (s), 32.8 (s), 32.7
(s), 32.5 (s), 32.4 (s), 32.0 (s), 31.9 (s), 31.8 (s), 31.5 (s). Anal. calcd. for C46H77PO3: C,
77.92; H, 10.95. Found: C, 78.01; H, 10.89%.
2,4,8,10-Tetrakis(1,1,3,3-tetramethylbutyl)-6,6-dichloro-12H-
dibenzo[d,g][1,3,2]di-oxatitanocin (5)
To a solution of 2 (2.73 g, 3 mmol) in toluene (10 mL) was added titanium(IV)
chloride (0.33 mL, 3 mmol), and the resultant reaction mixture was stirred for 18 h at
ambient temperature. The volatiles were removed in vacuo and the residue was purified
1
by recrystallization from hexane to give 0.5 g (22%) of a red crystalline solid; H NMR
(CDCl3) δ 7.26 (d, 2 H), 7.14 (d, 2 H), 4.14 (d, C(12)–H, 2JHH = −14.8 Hz, 1 H), 3.68 (d,
C(12)–H, 2JHH = −14.8 Hz, 1 H), 2.04 (AB q, CH2, 4 H), 1.68 (s, CH2, 4 H), 1.50 (s, CH3,
6 H), 1.42 (s, CH3, 6 H), 1.34 (s, C(CH3)2, 12 H), 0.68 (s, C(CH3)3, 36 H). The accidental
equivalence of the tert-butyl protons is removed in benzene-d6 (60 MHz). Anal. calcd for
C45H74Cl2O2Ti: C, 70.57; H, 9.74. Found: C, 70.80; H, 9.72.
REFERENCES
1. Quin, L. D. In: R. S. Glass (Ed.), Conformational Analysis of Medium-Sized Heterocycles; VCH:
Weinheim, 1988.
2. Holmes, R. R.; Prakasha, T. K.; Pastor, S. D. In: L. D. Quin, J. G. Verkade (Eds.), Phosphorus-31
NMR Spectral Properties in Compound Characterization and Structural Analysis; VCH: New
York, 1994; pp. 27–39.
3. (a) Buisman, G. J. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Tetrahedron: Asymmetry 1993,
4, 1625–1634; (b) van Leeuwen, P. W. N. M.; Buisman, G. J. H.; van Rooy, A.; Kamer, P. C.
J. Recl. Trav. Chim. Pays-Bas. 1994, 113, 61–62; (c) Jongsma, T.; Fossen, M.; Challa, G.; van
Leeuwen, P. W. N. M. J. Mol. Catal. 1993, 83, 17–35; (d) van Rooy, A.; Orij, E. N.; Kramer,
P. C. J.; van Leeuwen, P. W. N. M. Organometallics 1995, 14, 34–43; (e) Buisman, G. J. H.;
Martin, M. E.; Vos, E. J.; Klootwijk, A.; Kramer, P. C. J.; van Leeuwen, P. W. N. M. Tetrahedron:
Asymmetry 1995, 6, 719–738; (f) Buisman, G. J. H.; van der Veen, L. A.; Klootwijk, A.; de
Lange, W. G. J.; Kramer, P. C. J.; van Leeuwen, P. W. N. M.; Vogt, D. Organometallics 1997, 16,
2929–2939; (g) van der Veen, L. A.; Keeven, P. H.; Shoemaker, G. C.; Reek, J. N. H.; Kramer,
P. C. J.; van Leeuwen, P. W. N. M.; Lutz, M.; Spek, A. L. Organometallics 2000, 19, 872–883.
4. (a) Holmes, R. R.; Dieters, J. A. Inorg. Chem. 1994, 33, 3235–3238; (b) Holmes, R. R. Acc.
Chem. Res. 1998, 31, 535–542; (c) Sherlock, D. J.; Chandrasekaran, A.; Prakasha, T. K.;
Day, R. O.; Holmes, R. R. Inorg. Chem. 1998, 37, 93–101; (d) Chandrasekaran, A.; Sood,
P.; Holmes, R. R. Inorg. Chem. 1998, 37, 459–466; (e) Sood, P.; Chandrasekaran, A.; Day, R. O.;
Holmes, R. R. Inorg. Chem. 1998, 37, 3747–3752; (f) Sood, P.; Chandrasekaran, A.; Day, R. O.;
Holmes, R. R. Inorg. Chem. 1998, 37, 6329–6336; (h) Timosheva, N. V.; Chandrasekaran, A.;
Holmes, R. R. Phosphorus Sulfur Silicon Relat. Elem. 2006, 181, 1957–1970.
5. (a) Clarke, F. H.; Fuhrer, H.; Meier, H.; Pastor, S. D.; Rist, G.; Shum, S. P. Helv. Chim. Acta
1993, 76, 1476–1480; (b) Pastor, S. D.; Spivack, J. D.; Rodebaugh, R. K.; Bini, D. J. Org.

DIASTEREOTOPIC PROTON PROBE
631
Chem. 1984, 49, 1297–1300; (c) Pastor, S. D.; Rogers, J. S.; NabiRahni, M. A.; Stevens, E. D.
Inorg. Chem. 1996, 35, 2157–2161; (d) Pastor, S. D.; Smith, A. R.; Rihs, G. Phosphorus Sulfur
Silicon Relat. Elem. 1996, 115, 169–177; (e) Burke, L. P.; DeBellis, A. D.; Fuhrer, H. Meier, H.;
Pastor, S. D.; Rihs, G.; Rist, G.; Rodebaugh, R. K.; Shum, S. P. J. Am. Chem. Soc. 1997, 119,
8313–8323; (f) Khoury, N.; Pastor, S. D.; Rahni, D.; Richardson, C. F.; Syed, N. A.; Shum, S.
P.; Chandrasekaran, A. Phosphorus Sulfur Silicon Relat. Elem. 2004, 179, 483–497.
6. (a) Wong, C. Y.; McDonald, R.; Cavell, R. G. Inorg. Chem. 1996, 35, 325–334; (b) Luo, H.;
McDonald, R.; Cavell, R. G. Angew. Chem. Int. Ed. 1998, 37, 1098–1099.
7. For discussions on the nomenclature of eight-membered rings see (a) Hendrickson, J. B. J. Am.
Chem. Soc. 1964, 86, 485–492; (b) Fraser, R. R.; Raza, M. A.; Renaud, R. N.; Layton, R. B.
Can. J. Chem. 1975, 53, 167–176; (c) Anet, F. A. L.; Yavari, I. J. Am. Chem. Soc. 1977, 99,
6986–6991; (d) Moore, J. A.; Anet, F. A. L. In: W. Lwowski (Ed.), Comprehensive Heterocyclic
Chemistry, Vol. 7; Pergamon Press: Oxford, 1984, pp. 653–707; (e) Arshinova, R. P.; Danilova,
O. I.; Arbusov, B. A. Phosphorus Sulfur Silicon Relat. Elem. 1987, 34, 1–14; (f) Arshinova, R.
P. Russ. Chem. Rev. 1988, 57, 1142–1161.
8. Pastor, S. D.; Huang, V.; NabiRahni, D. Phosphorus Sulfur Silicon Relat. Elem. 1988, 139,
87–96.
9. Pastor, S. D.; Huang, V.; NabiRahni, D.; Koch, S. A.; Hsu, H.-F. Inorg. Chem. 1997, 36,
5966–5968.
10. Thompson, T.; Pastor, S. D.; Rihs, G. Inorg. Chem. 1999, 38, 4163–4167.
11. (a) Arshinova, R. P. Phosphorus Sulfur Silicon Relat. Elem. 1992, 68, 155–191; (b) For theoretical
discussions on the hyperconjugative contribution to the magnitude to the geminal coupling
constant and the dependence on the geometry of the ring, see Barfield, M.; Grant, D. M. J. Am.
Chem. Soc. 1963, 85, 1899–1904; (c) Pople, J. A.; Bothner-By, A. A. J. Chem. Phys. 1965, 42,
1339–1349; (d) Barfield, M.; Sternhell, S. J. Am. Chem. Soc. 1972, 94, 1905–1913; (e) Barfield,
M.; Grant, D. M. J. Am. Chem. Soc. 1961, 83, 4726–4729.
12. (a) Floriani, C.; Corazza, F.; Lesueur, W.; Chiesi-Villa, A.; Guastini, C. Angew. Chem. Int. Ed.
Engl. 1989, 28, 66–67; (b) Corazza, F.; Floriani, C.; Chiesi-Villa, A.; Guastini, C. Inorg. Chem.
1991, 30, 145–148; (c) Lesueur, W.; Rogers, A. J.; Floriani, C.; Chiesi-Villa, A.; Rizzoli, C.
Inorg. Chem. 1998, 37, 44–49.
13. For a review see Arshinova, R. P.; Danilova, O. I.; Arbusov, B. A. Phosphorus Sulfur Silicon
Relat. Elem. 1987, 34, 1–14.
14. (a) Pastor, S. D.; Spivack, J. D. J. Heterocycl. Chem. 1983, 20, 1311–1313; (b) Odorisio, P. A.;
Pastor, S. D.; Spivack, J. D.; Steinhuebel, L. P.; Rodebaugh, R. K. Phosphorus Sulfur Silicon
Relat. Elem. 1983, 15, 9–13; (c) Odorisio, P. A.; Pastor, S. D.; Spivack, J. D.; Phosphorus Sulfur
Silicon Relat. Elem. 1984, 19, 1–10; (d) Odorisio, P. A.; Pastor, S. D.; Spivack, J. D.; Bini,
D.; Rodebaugh, R. K. Phosphorus Sulfur Silicon Relat. Elem. 1984, 19, 285–293; (e) Pastor, S.
D.; Ng, K.; Rodebaugh, R. K.; Shimanskas, C. J. Sulfur Lett. 1985, 3, 29–37; (f) Pastor, S. D.;
Denney, D. Z. Phosphorus Sulfur Silicon Relat. Elem. 1987, 32, 105–111.
15. (a) Kolly, S.; Meier, H.-R.; Rihs, G.; Winkler, T. Helv. Chim. Acta 1988, 71, 1101–1107;
(b) Nietzshmann, E.; Jurkschat, K.; Baumeister, U.; Dargatz, M.; Hartung, H.; Tzschach, A.
Z. Anorg. Allg. Chem. 1989, 578, 99–109; (c) Hug, P.; Kolly, S.; Meier, H.-R.; Pitteloud, R.;
Poppinger, D.; Rihs, G.; Rist, G. Helv. Chim. Acta 1990, 73, 618–625.
16. For studies in analogous systems containing tetracoordinate phosphorus see (a) Rzepa, H. S.;
Sheppard, R. N. J. Chem. Res. (S) 1988, 102–103; (b) Goddard, J. D.; Payne, A. W.; Cook, N.;
Luss, H. R. J. Heterocycl. Chem. 1988, 25, 575–588; (c) Reddy, C. D.; Reddy, R. S. N.; Raju,
C. N.; El Masri, M.; Berlin, K. D.; Subramanian, S. Magn. Reson. Chem. 1991, 29, 1140–1146;
(d) For a 12H-dibenzo[d,g][1,3,2]dioxaphosphocin with a pentacoordinate phosphorus see
Abdou, W. M.; Denney, D. B.; Denney, D. Z.; Pastor, S. D. Phosphorus Sulfur Silicon Relat.
Elem. 1985, 22, 99–107.
17. (a) See also Ref. 7f.; (b) Arshinova, R. P.; Plyamovatyi, A. Ch.; Kadyrov, R. A.; Gnevashev, S.
G.; Arbuzov, B. A. Phosphorus Sulfur Silicon Relat. Elem. 1989, 41, 449–453.

632
S. P. SHUM ET AL.
18. Jennings, W. B. Chem. Rev. 1975, 75, 307–322.
19. For a review see Pastor, S. D. Trends Heterocycl. Chem. 1993, 3, 295.
20. (a) Van der Linden, A.; Schaverien, C. J.; Meijboom, N.; Ganter, C.; Orpen, A. G. J. Am. Chem.
Soc. 1995, 117, 3008–3021; (b) J. Froese, R. D.; Musaev, D. G.; Matsubara, T.; Morokuma,
K. J. Am. Chem. Soc. 1997, 119, 7190–7196; (c) Gielens, E. E. C. G.; Dijkstra, T. W.; Berno,
P.; Meetsma, A.; Hessen, B.; Teuben, J. H. J. Organomet. Chem. 1999, 591, 88–95; (d) Ouchi,
M.; Kamigaito, M.; Sawamoto, M. Macromolecules 1999, 32, 6407–6411; (e) Takeuchi, D.;
Nakamura, T.; Aida, T. Macromolecules, 2000, 33, 725–729
21. Takeuchi, D.; Aida, T.; Endo, T. Macromol. Chem. Phys. 2000, 201, 2267–2275.
22. (a) Pelter, A.; Smith, K. In: D. Barton, W. D. Ollis (Eds.), Comprehensive Organic Chemistry, Vol.
3; Pergamon Press: Oxford, 1979, p. 915; (b) Cotton, F. A.; Wilkinson, G. Advanced Inorganic
Chemistry, 5th Ed.; Wiley: New York, 1988, p. 162.
23. For other important related work, see (a) Okuda, J.; Fokken, S.; Kang, H.-C.; Massa, W. Chem.
Ber. 1995, 128, 221–227; (b) for observation of a flattened dioxatitanocin ring, see Toscano, P.
J.; Schermerhorn, E. J.; Barren, E.; Liu, S.; Zubieta, J. J. Coord. Chem. 1998, 43, 169–185.
24. Anomeric effects have been considered in dialkylamino-substitued12H-dibenzo-
[d,g][1,3,2]dioxaphosphocins, see Litvinov, I. A.; Kataeva, O. N.; Naumov, V. A.; Arshinova,
R. P.; Arbuzov, B. A. Izv. Akad. Nauk SSSR, Ser. Khim. (Engl. Transl.) 1987, 1839.
25. For a general discussion on the anomeric effect in conformational analysis, see Juaristi, E.
Stereochemistry & Conformational Analysis Wiley: New York, 1991, Chapter 17.