Synthesis and structure of 4-R,5-R-[5-(hydroxy-diphenyl-methyl)-2, 2-dimethyl-[1,3] dioxolan-4-yl]-phenyl-methanone, a chiral ligand building block

Article abstract of DOI:10.1023/A:1024282114729

A triphenyl analog of taddol, 4-R,5-R-[5-(hydroxy-diphenyl-methyl)-2,2- dimethyl-[1,3]dioxolan-4-yl]-phenyl-methanone, has been synthesized and structurally characterized. This molecule could act as a chiral ligand building block in the creation of tuned taddol analogs. Structural analysis of the title compound reveals that the hydroxyl group is involved in an intramolecular hydrogen bond and does not take part in any intermolecular interaction. Crystal packing is influenced by C-H ... O hydrogen bonding and phenyl ... phenyl interactions. Crystal data: Triclinic, P1 (No. 1), a = 5.9343(4) A, b = 8.2367(17) A, c = 10.987(2) A, α = 88.290(6)°, β= 75.442(4)°, γ = 80.655(6)°, V = 512.86(15) A ³, Z = 1, D_calc = 1.258 mg/m₃. Final residual values were R₁ = 0.0407 for 3022 observed data (I > 2s(I) and wR₂ = 0.0941 for all 3524 unique data.

Full text of DOI:10.1023/A:1024282114729

C
Journal of Chemical Crystallography, Vol. 33, Nos. 5/6, June 2003 ( 2003)
Synthesis and structure of
4-R,5-R-[5-(hydroxy-diphenyl-methyl)-2,
2-dimethyl-[1,3]dioxolan-4-yl]-phenyl-methanone,
a chiral ligand building block
Lawrence C. Thompson,(1) Kyle S. Knight,(1) and William T. Pennington(2)
Received August 4, 2002
A triphenyl analog of taddol, 4-R,5-R-[5-(hydroxy-diphenyl-methyl)-2,2-dimethyl-
[1,3]dioxolan-4-yl]-phenyl-methanone, has been synthesized and structurally character-
ized. This molecule could act as a chiral ligand building block in the creation of tuned taddol
analogs. Structural analysis of the title compound reveals that the hydroxyl group is involved
in an intramolecular hydrogen bond and does not take part in any intermolecular interac-
---
tion. Crystal packing is influenced by C
H
O hydrogen bonding and phenyl phenyl
˚
˚
interactions. Crystal data: Triclinic, P1 (No. 1), a = 5.9343(4) A, b = 8.2367(17) A,
3
˚
˚
c = 10.987(2) A, = 88.290(6) , = 75.442(4) , = 80.655(6) , V = 512.86(15) A ,
Z = 1, Dcalc = 1.258 mg/m3. Final residual values were R1 = 0.0407 for 3022 observed
data (I > 2s(I)) and wR2 = 0.0941 for all 3524 unique data.
KEY WORDS: Taddol; chiral; ligand; precursor; triphenyl.
Introduction
Chiral diols based on the tetraaryl-1,3-
readily synthesized in enantiomerically pure form
using naturally available tartaric acid.
dioxolane-4,5-dimethanol structure, “taddol,” de-
veloped by Seebach and coworkers have been
remarkably useful as ligands in a wide vari-
ety of asymmetric reactions, including enantios-
elective alkylations, reductions and Diels-Alder
reactions,1 as well as in the formation of chiral
clathrate inclusion complexes.2 These compounds
have been particularly useful because they can be
Basic Taddol Structure
(1) Department of Chemistry, The University of Tennessee—
Chattanooga, Chattanooga, Tennessee 37403.
(2) Department of Chemistry, Clemson University, Clemson, South
Carolina.
To whom correspondence should be addressed. E-mail: kyle-
knight@utc.edu
The original taddol ligands were C2 symmet-
ric, a geometry that was thought to be valuable
in asymmetric catalysis because it made both
sites on the molecule yield the same enantiomeric
403
C
1074-1542/03/0600-0403/0 2003 Plenum Publishing Corporation

404
Thompson, Knight, and Pennington
selectivity. Seebach has shown that selectivity can
actually be improved by breaking the symmetry
in the backbone of the ligand by moving to a less
symmetric structure that could adopt a more favor-
able conformation for catalysis. Recent studies of
chiral ligand systems have pointed out the value
of slight steric modifications in a chiral ligand to
tune it to a particular substrate.3
An approach to tuning the ligand system
would be by modification or replacement of
the aryl groups. This type of system could
be accessed from intermediates in which ad-
dition of the aryl groups was incomplete. By
synthesizing and isolating an intermediate con-
taining only three aryl groups, a precursor
could be made for systematic modification of
the ligand system. Toward this goal, a triph-
enyl analog to taddol, 4-R,5-R- [5-(hydroxy-
diphenyl-methyl)-2,2-dimethyl-[1,3] dioxolan-4-
yl]-phenyl-methanone, was synthesized. This
molecule could act as a chiral ligand building
block in the creation of tuned taddol analogs.
acid. The solution was refluxed for 7 h during
which time a methanol-toluene azeotrope was
slowly removed by distillation. The solution was
quenched with 0.5 g of NaHCO3. The product
was concentrated on a rotary and distilled under
vacuum to yield 80.9 g (329 mmol, 64.2%) yield
of the acetal. A 10 g (40.1 mmol) portion of this
product was then dissolved 50 mL diethyl ether.
To this solution was added 128 mL phenylmagne-
sium bromide (1.0 M in diethyl ether) slowly via
an addition funnel. The reactants were stirred for
3 h and then quenched with a saturated NH4Cl so-
lution. Two products, 1 and the tetrarylated com-
pound, were separated via recrystallization from
methanol to yield 5.65 g (16.0 mmol, 40%) of
the desired crystalline product as white needles.
m.p. 186–188 C. [ ]D = 21.0 (c = 7.76, ace-
1
tone). H NMR: (300 MHz): 7–8 (m, 15 aro-
maticH):5.96(d, j = 6Hz, 1C2HO):5.24(d, j =
6 Hz, 1C2HO): 0.6 (s, 3H): 0.5 (s, 3H). 13C APT
NMR (300 MHz) 197.145 [C(O)(CH5)2]:
145.581 [C(C)(OH)(CH5)2], 142.743, 135.822,
133.621, 129.409, 128.559, 128.385, 127.687,
127.535, 127.406, 126.131 (phenyl): 112.517
[C(O)2(CH3)2]: 80.971, 76.964 [C(C)(H)(O)]:
27.259, 26.364 (CH3).
X-ray crystallography
Intensity data for 1 was measured at 20
1 C with graphite-monochromated Mo K radia-
˚
tion ( = 0.71073 A) on a Rigaku AFC78 diffrac-
tometer with a Mercury CCD area detector. The
data were collected to a maximum 2 value of
53.3 in 0.5 oscillations (in ω) with two 15.0-s
exposures (to identify detector anomalies). The
data were corrected for Lorentz and polarization
effects, and an absorption correction4 was applied
to the data. The structure was solved by direct
methods and refined by using full-matrix least-
squares techniques (on F2). All non-hydrogen
atoms were refined anisotropically; hydrogen
atoms were refined isotropically. Data process-
ing was performed with Crystal Clear,5 and struc-
ture solution, refinement and the calculation of
1
Experimental
Synthesis of 4-R,5-R-[5-(hydroxy-diphenyl-
methyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-
phenyl-methanone (1)
A 105 g (512 mmol) portion of diethyl
tartrate and a 64 g (615 mmol) portion of
dimethoxypropane were added to 50 mL of
toluene containing 0.5 g of p-toluene sulfonic

Triphenyl analog of taddol, a chiral ligand building block
405
Table 2. Atomic Coordinates (104) and equivalent Isotropic
Table 1. Crystal Data for 1
Compound 1
3
2
˚
Displacement Coefficients (10 A ) for 1
Compound
CCDC no.
a
201733
x
y
z
U
eq
Color/shape
Colorless/prism
0.096 0.192 0.312
C25H24O4
Dimensions, mm
Chemical formula
Formula weight, g mol
O(1)
O(2)
O(3)
O(4)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
1485(3)
6063(3)
5474(3)
8546(5)
3375(4)
5623(4)
5336(5)
6664(5)
9289(6)
5614(7)
7170(5)
7190(4)
5521(5)
5568(6)
7265(6)
8933(6)
8901(5)
3595(4)
1564(5)
1633(6)
3756(6)
5793(5)
5718(5)
2699(4)
4042(4)
3426(5)
1450(5)
135(5)
4027(2)
2429(2)
3397(2)
6282(3)
4617(3)
4191(3)
4838(3)
2033(3)
1811(6)
523(4)
5884(3)
6474(3)
6177(3)
6804(4)
7736(4)
8027(4)
7395(3)
3851(3)
3913(3)
3253(4)
2524(4)
2454(4)
3124(3)
6487(3)
7356(3)
9036(3)
9871(3)
9026(3)
7335(3)
6011(2)
5151(2)
3290(2)
3896(2)
6368(2)
5309(2)
4016(2)
3848(2)
3320(4)
3690(4)
3360(2)
2070(2)
1451(2)
251(3)
51(1)
58(1)
56(1)
102(1)
42(1)
43(1)
47(1)
53(1)
82(1)
75(1)
54(1)
48(1)
58(1)
73(1)
75(1)
71(1)
59(1)
42(1)
55(1)
67(1)
67(1)
62(1)
52(1)
41(1)
50(1)
58(1)
58(1)
59(1)
50(1)
1
388.44
Crystal system, space group
Unit cell dimensions,
reflections used
Triclinic, P1 (No. 1)
2903 (all with I > 5 (I))
˚
a = 5.9343(4) A
˚
b = 8.2367(17) A
˚
c = 10.987(2) A
= 88.290(6)
= 75.442(4)
= 80.655(6)
512.86(15)
1
3
˚
Volume, A
C(9)
Z
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
Density (calculated), mg/m3
Absorption coefficient, mm
Trans. range
1.258
0.084, 0.72–1.00
308(3)
285(3)
1
,
1473(3)
7635(2)
8598(2)
9765(3)
9983(3)
9036(3)
7869(2)
6534(2)
7064(2)
7255(3)
6945(3)
6387(3)
6183(2)
Extinction coefficient
0.081(9)
Scan type, frame width (time/frame)
range, deg
Reflections measured
ω, 0.5 frames (15 s)
2.51–26.65
4917
Independent reflections, R
Observed reflections, [I > 2 (I)]
3524, 0.022
3022
merge
S
R1
wR2
1.13
0.0407 (0.0523)
0.0900 (0.0941)
a
b
P
P
a R1
=
kFo| |Fck/ |Fo|forobserveddata(I > 2 (I));num-
ber in parentheses is for all data.
bwR2 = { [w(Fo2 Fc2)2]/ [w(Fo2)2]}1/2 for observed data (I >
2 (I)); number in parentheses is for all data.
752(4)
P
P
aEquivalent isotropic U defined as one third of the trace of the or-
thogonalized U tensor.
ij
derived results were performed with SHELXTL-
Plus.6 Neutral atom scattering factors were those
of Cromer and Waber,7 and the real and imaginary
anomalous dispersion corrections were those of
Cromer.8 Relevant crystallographic data is given
in Table 1 and atomic coordinates are given in
Table 2.
Grignard reagent allowed for maximization of the
yield.
Bond distances and angles for 1 are listed
in Table 3. Figure 1 is a thermal ellipsoid plot
showing the molecular structure of 1 with thermal
ellipsoidsrepresentedatthe50%probabilitylevel.
Crystal packing down the a-axis is illustrated in
Fig. 2.
Results and discussion
The bonding distances and angles for 1 are all
within expected ranges for a hydrocarbon struc-
ture. The five-membered heterocyclic ring has an
envelope conformation, with the four-atom seg-
Compound 1 was synthesized from diethyl
tartrate by acetonide protection of the diol, fol-
lowed by the slow addition of 3.2 equiv. of phenyl-
magnesium bromide in diethyl ether. The tetraary-
lated species was also isolated; however, careful
control of the amount and rate of addition of the
--- --- ---
ment (O2 C2 C3 O3) planar (rms deviation
˚
of 0.018(4) A) and one atom (C4) displaced by
˚
0.425(4) A from the plane. The phenyl rings are all

406
Thompson, Knight, and Pennington
˚
---
O1
O2 = 2.762(3) A; O1 H1
O2 =
119(3) ) and is not directly involved in any
intermolecular interactions. Reasonably strong
---
C H
O hydrogen bonding from a phenyl
---
C H to the methanone oxygen atom links
molecules related0 by translation along the
O40 =
˚
a-axis (H24
3.306(3) A; C25 H24
O4 = 2.43(3) A; C25
O40 = 147(2) ).
˚
---
Packing of the resulting chains is dominated
by phenyl
phenyl interactions with centroid–
centroid distances ranging from 4.715(3) to
˚
5.102(3) A and dihedral angles of 44.71(9) to
89.44(9) (see Fig. 2).
Fig. 1. Molecularstructureof1. Thermalellipsoidsareshown
The structural data can be used to predict the
geometry of the product of nucleophilic attack at
the ketone. Based on this structure, the most im-
portant geometric feature around the ketone is the
dioxolane ring, which should be conformation-
ally rigidified by the presence of the intramolec-
ular hydrogen bond. This ring should hinder the
approach of a nucleophile to the Si face of the car-
bonyl, and thereby promoting selective attack at
the Re face. The hydrogen-bonding would suggest
that a monometallated intermediate (with a main
at the 50% probability level.
˚
planar (maximum deviation of 0.016(2) A). The
molecule is reported with the expected absolute
configuration based on the starting material, and
the refined Flack parameter of 0.1(11) confirms
the assignment.
Surprisingly, the strongest hydrogen-
---
bonding donor (O1 H1) interacts in an
˚
intramolecular fashion (H1
O2 = 2.27(4) A;
˚
Table 3. Important Bond Distances (A) and Angles (deg) for 1
Distances
---
---
O(2) C(4)
O(1) C(1)
1.435(3)
1.440(3)
1.434(3)
1.531(3)
1.538(3)
1.523(3)
1.511(4)
1.420(3)
1.430(3)
1.209(3)
1.532(3)
1.542(3)
1.502(4)
1.482(3)
---
O(2) C(2)
---
O(3) C(3)
---
---
O(4) C(7)
O(3) C(4)
---
C(1) C(20)
---
C(1) C(2)
---
---
C(2) C(3)
C(1) C(14)
---
C(3) C(7)
---
C(4) C(5)
---
---
C(7) C(8)
C(4) C(6)
Angles
---
---
---
---
C(4) O(2) C(2)
109.18(17)
107.25(18)
110.13(16)
109.11(17)
107.06(17)
113.25(18)
104.99(18)
104.77(19)
111.8(2)
108.2(2)
120.0(2)
119.3(2)
118.7(2)
C(3) O(3) C(4)
107.77(18)
108.40(18)
108.47(17)
113.29(18)
103.94(17)
111.1(2)
114.2(2)
110.7(3)
107.8(2)
113.1(3)
--- ---
--- ---
O(1) C(1) C(20)
--- ---
O(1) C(1) C(2)
--- ---
C(20) C(1) C(2)
--- ---
O(1) C(1) C(14)
--- ---
C(20) C(1) C(14)
--- ---
C(2) C(1) C(14)
--- ---
O(2) C(2) C(1)
--- ---
O(2) C(2) C(3)
--- ---
C(1) C(2) C(3)
--- ---
O(3) C(3) C(7)
--- ---
O(3) C(3) C(2)
--- ---
C(7) C(3) C(2)
--- ---
O(2) C(4) O(3)
--- ---
O(2) C(4) C(5)
--- ---
O(3) C(4) C(5)
--- ---
O(2) C(4) C(6)
--- ---
O(3) C(4) C(6)
--- ---
C(5) C(4) C(6)
--- ---
O(4) C(7) C(8)
--- ---
O(4) C(7) C(3)
--- ---
120.7(2)
118.8(2)
122.5(2)
C(8) C(7) C(3)
--- ---
C(13) C(8) C(9)
--- ---
C(13) C(8) C(7)
--- ---
C(9) C(8) C(7)
--- ---
C(19) C(14) C(1) 123.56(19)
C(15) C(14) C(1)
118.1(2)

Triphenyl analog of taddol, a chiral ligand building block
407
has been used to predict the selectivity of nucle-
ophilic attack at the ketone. In future work, we
hope to examine this selectivity and test these
new compounds as ligands for enantioselective
catalysis.
Acknowledgments
We thank Research Corporation and the Univer-
sity of Tennessee at Chattanooga for support of this
work. Financial support of the National Science Foun-
dation for purchase of the CCD-based X-ray system
at Clemson University (CHE-9808165) is gratefully
acknowledged.
Fig. 2. Crystal packing viewed down the a-axis.
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A triphenyl analog of taddol, 4-R,5-R-
[5-(hydroxy-diphenyl-methyl)-2,2-dimethyl-[1,3]
dioxolan-4-yl]-phenyl-methanone, has been syn-
thesized and structurally characterized. Structure
analysis of the title compound reveals that the
hydroxyl group is involved in an intramolecular
hydrogen bond and does not take part in any
intermolecular interaction. The structural data
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