Preparation and characterization of new C2- and C 1-symmetric nitrogen, oxygen, phosphorous, and sulfur derivatives and analogs of TADDOL. part i

Article abstract of DOI:10.1002/hlca.201200146

The chloro alcohols 4-6 derived from TADDOLs (=α,α, α′,α′-tetraaryl-1,3-dioxolan-4,5-dimethanols) are used to prepare corresponding sulfanyl alcohols, ethers, and amines (Scheme 1 and Table 1). The dithiol analog of TADDOL and derivatives thereof, 45-49,

Full text of DOI:10.1002/hlca.201200146

Helvetica Chimica Acta – Vol. 95 (2012)
1239
Preparation and Characterization of New C2- and C1-Symmetric Nitrogen,
Oxygen, Phosphorous, and Sulfur Derivatives and Analogs of TADDOL1)
Part I
Compounds Containing One or Two Sulfur-Containing Substituents and Use in Cu-
Catalyzed Enantioselective Conjugate Additions to Cyclic Enones
by Arkadius Pichota2), Volker Gramlich3), Albert K. Beck, and Dieter Seebach*
Laboratorium fꢀr Organische Chemie, Departement fꢀr Chemie und Angewandte Biowissenschaften,
ETH-Zꢀrich, Hçnggerberg HCI, Wolfgang-Pauli-Strasse 10, CH-8093 Zꢀrich
(phone: þ 41-44-632-2990; fax: þ 41-44-632-1144; e-mail: seebach@org.chem.ethz.ch)
The chloro alcohols 4 – 6 derived from TADDOLs (¼a,a,a’,a’-tetraaryl-1,3-dioxolan-4,5-dimetha-
nols) are used to prepare corresponding sulfanyl alcohols, ethers, and amines (Scheme 1 and Table 1).
The dithiol analog of TADDOL and derivatives thereof, 45 – 49, were also synthesized. The crystal
structures of 16 representatives of this series of compounds are reported (Figs. 1 – 3 and Scheme 2). The
thiols were employed in Cu-catalyzed enantioselective conjugate additions of Grignard reagents to cyclic
enones, with cycloheptenone giving the best results (er up to 94 :6). The enantioselectivity reverses from
Si-addition with the sulfanyl alcohol to Re-addition with the alkoxy or dimethylamino thiols (Table 4).
CuI-Thiolates, 50 – 53, could be isolated in up to 84% yield (Scheme 2) and were shown to have
tetranuclear structures in the gas phase (by ESI-MS), in solution (CH2Cl2, THF; by vapor-pressure
osmometry and by NMR pulsed-gradient diffusion measurements; Table 5), and in the solid state (X-ray
crystal structures in Scheme 2). The Cu complex 50 of the sulfanyl alcohol is stable in air and in the
presence of weak aqueous acid, and it is a highly active catalyst (0.5 mol-%) for the 1,4-additions, leading
to the same enantio- and regioselectivities observed with the in situ generated catalyst (6.5 mol-%;
Scheme 3). Since the reaction mixtures contain additional metal salts (MgX2, LiX) it is not possible at
this stage, to propose a mechanistic model for the conjugate additions.
1. Introduction. – Since the first preparation in 1982 of the parent TADDOL A,
Arl ¼ Ph, R ¼ Me, by one of us (A. K. B), and its use as bis(alkoxide) ligand in
enantioselective organotitanium reagents [2], this skeleton has experienced numerous
applications for inducing chirality in the most general sense. In addition, the
conformational fixing effect of diarylmethanol groups (cf. the ThorpeꢀIngold effect)
and the steric effect of the diastereotopic geminal aryl groups in chiral molecules were
1
)
)
)
Partially mentioned in preliminary communications [1].
Part of the Ph.D. Thesis of A. P., ETH Dissertation No. 14015 (2000).
Laboratorium fꢀr Kristallographie, Sonnegstrasse 5, ETH Zꢀrich, CH-8092 Zꢀrich.
2
3
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢀrich

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Helvetica Chimica Acta – Vol. 95 (2012)
subsequently exploited for the same purpose4). The structural diversity of TADDOL
and its derivatives A is huge: the aryl (or heteroaryl) groups can be varied widely, the
substituents R on the dioxolane ring may be H, alkyl, or aryl, yea, the heterocyclic ring
may be opend as in B [7]. This is due to the simplicity of preparing these compounds:
(R,R)- or (S,S)-tartrates are converted to acetals or ketals by treatment with aldehydes
or ketones, followed by reaction with an excess of aryl Grignard reagent. The diversity
is further enhanced by modification (OH ! OR) or substitution (OH ! X) of one or
both TADDOL OH group(s) to give C1- or C2-symmetrical analogs of type C, which
can be used for stoichiometric (cf. C, X ¼ OH, Y¼ OOH, TADOOH [8]) or catalytic
[1a,c] enantioselective transformations, which would not be possible with the
TADDOLs themselves. For details, we refer to two comprehensive articles5) [9] and
a number of reviews addressing various aspects6) of the use of TADDOLs [10 – 19].
4
)
Cf. the diaryl-prolinol-derived organocatalysts i [3] and oxaborolidines ii [4], and the diaryl-
imidazolidinone (DIOZ) iii [5], to name only a few. See also ꢂThe ꢀMagicꢁ Diarylhydroxymethyl
Groupꢃ (M. Braun [6a]), ꢂThe gem-Diaryl Effect in Enantioselective Synthesisꢃ (D. S. and A. K. B.
[6b]), and the discussion in Sect. D of [6c].
5
6
)
ꢂTADDOLs, their derivatives, and TADDOL analogs: versatile chiral auxiliariesꢃ [9a]; ꢂUse of
TADDOLs and Their Derivatives in Asymmetric Synthesisꢃ [9b]; ꢀTADDOLate Ligandsꢃ [9c].
ꢂTartrate-Derived Ligands for Enantioselctive LiAlH4 Reduction of Ketones – A Comparison of
TADDOLs and BINOLsꢃ [10a,b]; ꢂTADDOLs – from enantioselective catalysis to dendritic
crosslinkers to cholesteric liquid crystalsꢃ [10c]; ꢂTADDOL and its derivatives – our dream of
universal chiral auxiliariesꢃ [11]; ꢂDeveloping catalytic enantioselective fluorinationꢃ [12a]; ꢂDevel-
opment of the titanium-TADDOLate-catalyzed asymmetric fluorination of b-ketoestersꢃ [12b]; ꢂCp
Titanium TADDOLateꢃ [13]; ꢂCatalytic asymmetric organozinc additions to carbonyl compoundsꢃ
[14]; ꢂPreparation of Polymer-Supported Ligands and Metal Complexes for Use in Catalysisꢃ [15];
ꢂRecent progress in chiral Brønsted acid catalysisꢃ [16]; ꢂCrown ethers, TADDOL, Nobin and
Metal(salen) compexes as chiral phase-transfer catalysts for asymmetric synthesisꢃ [17]; ꢂNoncovalent
organocatalysis based on hydrogen bondingꢃ [18]; ꢂTADDOL-Derived Phosphonites, Phosphites,
and Phosphoramidites in Asymmetric Catalysisꢃ [19].
)

Helvetica Chimica Acta – Vol. 95 (2012)
1241
In the present series of three papers7) [20], we describe the preparation of hitherto
unpublished or non-characterized TADDOL derivatives (mainly of the parent
structure A), in which OH groups are replaced by N- or S-containing substituents;
we also present crystal structures, an application for enantioselective conjugate
addition, and the determination of pKa values of TADDOL derivatives.
2. Preparation of the S- and N-Derivatives. – The conversions leading from
TADDOLs to these derivatives are outlined in Scheme 1, and the results were compiled
in Table 1. The central starting materials for mono-substitutions on TADDOL
skeletons are chloro-hydroxy compouds such as those from the parent TADDOL 1
[21a], the naphthalen-2-yl-TADDOL 3 [21a,b] and the hexaphenyl analog 2 [21c,d].
One of the OH groups can be replaced with Cl by the Appel reaction (PPh3/CCl4/
pyridine [22]), which stops at the stage of mono-substitution8)9); the yields drop from
those obtained with the parent TADDOL (i.e., 1 ! 4), when the procedure is applied
to the naphthalen-2-yl (i.e., 3 ! 6) and the hexaphenyl derivative (i.e., 2 ! 5), and
complex mixtures were obtained with the TADDOLs carrying naphthalen-1-yl or 4-
tolyl groups.
With the mono-chloro compounds 4 – 6 available, we have prepared other C1-
symmetrical TADDOL derivatives, 7 – 17, by nucleophilic replacement of the Cl-atom.
Thus, treatment with excess thiourea, followed by hydrolysis under basic conditions,
yields the sulfanyl derivatives 7 and 8, reaction with NH3, MeNH2, or Me2NH10)11)
provides the amino alcohols 9 – 12, and with alcohols or phenols (in the presence of
Et3N), the alkoxy and aryloxy alcohols 13 – 17 are formed12).
The OH-group of the amino, alkoxy and aryloxy alcohols 9 – 17 could be replaced
by nucleophilic substitutions via the corresponding Cl-derivatives, which are formed by
7
)
a) Part II: ꢂTADDAMIN-Derived and Phosphorous-Containing Compoundsꢃ (p. 1273 of this HCA
issue); b) Part III: ꢂSome New Chiral Brønsted Acids for Organocatalysis and pKa Values in
MeOꢀ(CH2)2ꢀOH/H2O – A Surveyꢃ (p. 1303 of this HCA issue).
8
9
)
)
.....even when excess reagent was employed.
Considering that this reaction is expected to occur via an Sn1 mechanism, and that the intermediate
cation could undergo rearrangements (Scheme 4 in [9a] and [23]), the 90% yield of crude product 4
is remarkable. For previous reports on 4, see [24].
The yields of this reaction and its selectivity (with respect to the tetrahydrofuran by-product iv)
could be greatly improved by using DMF as solvent and carrying out the reaction at lower
temperatures than previously reported [24b]. For preparation of TADDAMINs (¼(4S,5S)-2,2,N,N’-
tetramethyl-a,a,a’,a’-tetraphenyl-1,3-dioxolan-4,5-diamines) via azido-derivatives see [24a].
10
)
11
12
)
)
For FriedelꢀCrafts-type reactions with anilines (leading to trityl-substituted dioxolanes), see [1b].
Interestingly, the phenoxy group in 17 acts as a leaving group under mild conditions: when dissolved
in MeOH, 17 is converted to 13 under acid catalysis.

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 1. Preparation of Sulfur-Containing Derivatives 7, 8, 19, 21, and 31 – 40 from TADDOLs 1 – 3
a) 2 equiv. PPh3, 10 equiv. CCl4, CH2Cl2, r.t. b) 1. 20 – 30 equiv. SC(NH2)2, DMF, r.t.; 2. NaOH. c) HNR2,
autoclave, 50 – 808. d) MeOH Reflux or ROH 508, 1 – 1.5 equiv. Et3N. e) 5 equiv. 4-tBuꢀC6H4OH, 2 equiv.
Et3N, CH2Cl2, r.t. f) Me3SiCl (TMSCl), Et3N, CH2Cl2, r.t. g) (CF3SO2)2O or (CF3CO)2O, Et3N, CH2Cl2,
ꢀ 788 ! r.t. h) Bu4NF (TBAF), THF, r.t. i) SOCl2, CH2Cl2. k) SOCl2, Et3N, CH2Cl2. l) BuLi, ꢀ 788 !
r.t., SOCl2, THF. m) 5 equiv. SOCl2, 10 equiv. LiCl, THF, reflux. n) MeI, K2CO3, MeCN, CH2Cl2.

Helvetica Chimica Acta – Vol. 95 (2012)
1243
Table 1. Preparation of Monothiols 7, 8, and 31 – 38 Obtained from Monohydroxy TADDOLs 1 – 3, 10,
13 – 17, 21, and 22 via Replacement of Cl of the Corresponding Monochloro Compounds 4 – 6 and 23 – 30
with Thiourea
R
Arl
X
OH Derivative Cl Derivative (yield [%]) SH Derivative (yield [%])
Me Ph
Ph Ph
Me Naphthalen-2-yl OH
OH
OH
1
2
3
4 (76)
5 (56)
6 (64)
7 (75)
8 (63)
–
Me Ph
Me Ph
Me Naphthalen-2-yl MeO
Me Ph
Me Ph
Me Ph
Me Ph
Me Ph
Me2N
MeO
10
13
14
15
16
23 (98)
31 (79)
32 (66)
33 (47)
34 (74)
35 (65)
36 (43)
37 (74)
38 (75)
24 (quant.)
25 (97)a)
26 (75)
27 (quant.)
28 (quant.)
29 (81)
iPrO
BnO
4-tBuꢀC6H4O 17
CF3SO2NH 21
CF3CONH 22
30 (quant.)
a
1
) Conversion (determined by H-NMR).
the previously reported treatment with SOCl2 [24a] (!23 – 30); even the dimethyl-
amino- (23) and the 4-(tert-Butyl)-phenoxy chloro derivative (28) could be prepared by
this procedure. These Cl compounds were mainly used to prepare the thiols 31 – 38
(Scheme 1 and Table 1) by reaction with excess thiourea in DMF at room temperature,
followed by alkaline hydrolysis (Table 1 – 3). From the amino alcohol 9, the reaction
sequence (SOCl2; SC(NH2)2; NaOH) led to the amidine 41. Thioethers were prepared
by S-methylation (31 ! 39, 37 ! 40), or by Cl/SR substitution (23 ! 42), and the
seven-membered cyclic O,S-acetals 43 and 44 were formed as single diastereoisomers
from the sulfanyl alcohol 7 and acetaldehyde or benzaldehyde. The 2,2,2-trifluoro-
acetamides, 20 and 22, and the corresponding trifluoromethanesulfanoamides, 19 and
21 [24b], were obtained via the silyloxy derivative 18 [24b].

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Helvetica Chimica Acta – Vol. 95 (2012)
Table 2. Selected Physical Data of the Sulfanyl Derivatives of TADDOLs
Sulfanyl-TADDOL
X
M.p. [8]
[a]Dr:t: (c in CHCl3)
d(H) [ppm] of SH
7
8
OH
OH
Me2N
MeO
MeO
iPrO
BnO
4-tBuꢀC6H4O
CF3SO2NH
CF3CONH
SH
128 – 129
118 – 119
162 – 163b)
182 – 183
160 – 161
177 – 179
93 – 96
105 – 108
185 – 190
159 – 161
148 – 149
ꢀ 36.2 (1.0)
þ 148.8 (1.0)
ꢀ 90.9 (1.0)c)
þ 6.1 (1.2)
2.34 or 2.35a)
1.54 or 1.65a)
9.51
4.07
3.92
5.45
4.60
2.27
2.27d)
2.05e)
2.03
31
32
33
34
35
36
37
38
45
þ 63.0 (1.1)
ꢀ 43.2 (1.1)
ꢀ 60.0 (0.95)
ꢀ 64.5 (1.0)
ꢀ 59.7 (1.6)
ꢀ 97.4 (1.14)
ꢀ 32.4 (1.5)
c
a) Either SH or OH. b) Taken from [24b]. ) [24b]: [a]rD:t: ¼ ꢀ54.1 (c ¼ 0.98, AcOEt). d) d 8.75 ppm for
NH. e) d 8.66 ppm for NH.
Table 3. Selected NMR Data of the Sulfanyl Derivatives of TADDOLs
Sulfanyl-TADDOL
d(H)
d(C)
CH3ꢀC(2)
HꢀC(4,5)
C(4,5)
Arl2CꢀX
Arl2CꢀS
7
8
0.86
1.05
4.97
5.56
4.48
5.14
5.75
4.99
82.2
84.1
76.5a)
80.6
81.1
81.3
81.0
83.2
82.6
82.4
83.9
83.2
85.7
83.9a)
82.7
83.1
82.8
83.1
83.4
82.7
82.9
78.1
79.8
73.8a)
84.2
84.2
85.3
85.0
87.2
70.1
67.0
–
60.6
60.8
–
–
31
32
33
34
35
36
37
38
45c)
0.60
0.95
1.07
0.86
0.97
0.98
0.81
0.71
0.98
1.14
1.10
1.29
0.92
1.02
1.06
1.08
0.90
4.69b)
59.7
60.7
57.8
57.9
58.8
58.0
58.0
60.1
4.94
4.41
4.46
4.57
4.33
4.80
5.29
5.09
4.58
4.58
4.75
4.70
4.90
c
a) Taken from [24b]. b) HꢀC(4) and HꢀC(5) are isochronous. ) HꢀC(4), HꢀC(5), as well as CH3ꢀC(2)
and C(4,5) are isochronous.

Helvetica Chimica Acta – Vol. 95 (2012)
1245
The isolation of the dithiol 45 was a problem; in previous attempts [24][25] the
dichloro TADDOL derivative was treated with thiourea, NaSH, Na2S, or LiS13) under
various conditions to give mixtures of the dithiol 45, the 1,2-dithiane 46, and the
thiolane 47; the dithiol was readily oxidized to the disulfide14) in air, and the three
compounds could not be separated by chromatography. By carrying out the reaction
with thiourea in degassed DMF under an Ar atmosphere, a 9 :1 mixture of dithiol and
dithiane was isolated in 67% yield; a flash chromatography (10 l of pentane for a
200 mg sample!) led to further enrichment and eventually to crystalline dithiol 45, the
X-ray crystal structure of which could be determined (vide infra, Sect. 3). Subsequent
reaction of the dithiol 45 was actually performed with the material containing ca. 10%
of the dithiane 46 as an impurity. In this way, we prepared the Sn derivative 48 (50%)15
)
and the PdII complex 49 (79%), from which the dithiane could be readily separated.
3. X-Ray Crystal Structures. – The typical TADDOL structure is documented by
well over 150 X-ray analyses: a propeller-type C2-symmetric arrangement of the
diarylmethanol units, in which the quasi-axial aryl groups are in a type of edge-on, the
quasi-equatorial ones in a type of face-on conformation with respect to the C2 axis (see
D and E), with OꢀCꢀCꢀX and OꢀCꢀCꢀY dihedral angles around the exocyclic CꢀC
bond of ca. 1808 (antiperiplanar heteroatoms!; see G), and with a H-bridge between
the more acidic XH group on one of the two geminal diaryl-substituted C-atoms to a H-
bond acceptor on the other one (see F) [6c][9]. Those characteristic features are
confirmed in the crystal structures (deposited with the Cambridge Crystallographic
Data Centre (CCDC)) of the monohydroxy compounds (Fig. 1) and of the sulfanyl
derivatives (Fig. 2); the former ones contain OH ··· OR, or OH ··· N¼CHꢀNMe2, the
latter ones SH ··· SH, SH ··· OR, SH ··· NR2 or CF3SO2NH ··· SH H-bonds. The
13
)
In an unsuccessful attempt to prepare the bis[sulfonic acid] derived from 45, the dithioacetate v and,
upon its oxidation with performic acid, the monocyclic sulfoxide and sulfone vi were isolated [26].
14
15
)
)
All attempts to open the cyclic disulfide 46, reductively, back to the dithiol have been unsuccessful
in our laboratory.
Attempted proto- and bromo-destannylations (Ph/H; Ph/Br) to acess chiral SnH and SnBr
derivatives did not succeed: the SnꢀS rather than the SnꢀPh bond was cleaved by HCl and Br2.

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Helvetica Chimica Acta – Vol. 95 (2012)
Fig. 1. X-Ray crystal structures of the five monohydroxy derivatives 11, 13, 15, 16, and 41 with the CCDC
(Cambridge Crystallographic Data Centre) codes. The OH bonds have a H-bonding interaction with an O
or N H-bond acceptor in seven-membered-ring arrangement. All exocyclic C,C bonds carry the
heteroatoms in a stereoelectronically less favorable antiperiplanar (ap) conformation.
structures of the thiolane derivative 47, with a trans-fused bicyclo[3.3.0]octane skeleton,
of the Sn compound 48, containing an almost perfectly planar five-membered ring, and
of the chloro dimethylamino derivative 23 are shown in Fig. 3. The crystals of 23 have
an unusually large unit cell (19 ꢁ 11 ꢁ 41 ꢄ)16) containing three independent mole-
cules, one of which has the rare structure with a heteroatom (see H), rather than a
benzene ring (see G) above the dioxolane ring, and thus with the stereoelectronically
16
)
This is typical of TADDOL crystals not containing host molecules with H-bond-acceptor properties
(see Sect. D in [6c]), see also TADDOL clathrates for enantiomer separation [21a][27] and
ꢂdestillative resolutionꢃ [28].

Helvetica Chimica Acta – Vol. 95 (2012)
1247
more favorable gauche-conformation of the exocyclic C,C bond (synclinal (sc)
OꢀCꢀCꢀCl dihedral angle)17
)
18).
4. Enantioselective Conjugate Addition of Grignard Reagents to Cyclic Enones
Catalyzed by TADDOL-Derived Thiolato-cuprates. – After the discovery by Gilman
et al. [29], that organocopper compounds and Li-cuprates add to a,b-unsaturated
carbonyl compounds in a 1,4-, rather than a 1,2-fashion (typical of Mg and Li
derivatives), Kharash and Tawney [30] found that Grignard reagents, such as MeMgBr,
can be induced to conjugatively add to cyclohexenone by the presence of catalytic
amounts of CuCl. The first enantioselective variant of this 1,4-addition was reported by
Lippard and co-workers [31]. In the past 20 years, numerous investigations about this
useful reaction have been carried out with excellent regio-, diastereo-, and enantio-
selectivities; herein, we can only refer to selected review articles [32]. The chiral
ligands used to complex the catalytically active Cu species vary widely, with sulfanes
prevailing in the early phases [32f][33][34]. The employment of Zn rather than Mg
reagents for Cu-catalyzed Michael additions can give superior results [32a,c,f].
17
)
Other examples are the fluoro hydroxy (C; R ¼ Me, Arl ¼ Ph, X ¼ F, Y ¼ OH [18], CCDC-118716),
the diazido (C; R ¼ Me, Arl ¼ Ph, X ¼ Y¼ N3 [24b], CCDC-NIBZIH), and the dichloro derivative
(C; R ¼ Me, Arl ¼ Ph, X ¼ Y¼ Cl [24b], CCDC-NICBUW), as well as the TADDOL A, R ¼ Me,
Arl ¼ 2-MeOꢀC6H4 ([23], CCDC-POPJIN) and the hexaphenyl analog A, R ¼ Arl ¼ Ph ([21c],
CCDC-VUSLEA; [23], CCDC-POPJOT). In these cases, the stereoelectronic gauche-effect (F, Cl,
N3 case) or steric repulsion (Ph6 case) is structure determining – in the absence of H-bonding
between the substituents of the dioxolane ring.
We have recently determined the crystal structure of the difluoro compound (C; R ¼ Me, Arl ¼ Ph,
X ¼ Y¼ F [1b], CCDC-858090; space group P1) which also has one of the F-atoms above the
dioxolane ring.
18
)

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Helvetica Chimica Acta – Vol. 95 (2012)
Fig. 2. X-Ray crystal structures of the five sulfanyl derivatives 31, 32, 36, 37, and 45 with the CCDC codes.
There are H-bonds between the SH groups and a heteroatom S, O, or N, in seven-membered H-bonded
rings. In 37, the CF3SO2NH H-atom acts as the H-bond donor. The heteroatoms on all exocyclic C,C
bonds are antiperiplanar to each other, i.e., not in the stereoelectronically more favorable gauche-
conformation.
We herein briefly present the results of an investigation, carried out more than ten
years ago2), in which we tested the TADDOL-derived thiols in Cu-catalyzed 1,4-
additions of Grignard reagents to cyclic enones (five- to eight-membered rings);
furthermore, we discuss some mechanistic investigations, and describe the isolation and
crystal structures of Cu complexes of some of these thiols.
First experiments were carried out by G. Jaeschke [1c][25] and L. Audergon [1c] in
our group. The mode of preparing the reaction mixture turned out to be very critical,
and there were severe reproducibility problems until we had optimized the procedure:
for a 1-mmol batch, a suspension of the thiol (0.065 mmol) and CuCl (0.05 mmol) in
10 ml of THF was treated at ꢀ 758 with 0.08 mmol of BuLi (for the sulfanyl alcohols 7
and 8, twice this amount was added), which led to a solution after 20 min at 08;

Helvetica Chimica Acta – Vol. 95 (2012)
1249
Fig. 3. X-Ray crystal structures of the bicyclic derivatives 47 and 48, and of the chloro dimethylamino
compound 23, of which three conformations were found in the unit cell of the crystal. Two of the
conformations have the familiar propeller-type structure (23a and a very similar form, 23a’, not shown
here); in the third one, 23b, the chloro(diphenyl)methyl group is rotated by 1208 to put the Cl-atom into a
gauche-arrangement with the neighboring dioxolane O-atom.
following the addition of the cycloalkenone (1.0 mmol) at ꢀ 758, the Grignard reagent
was added within 70 – 80 min with a syringe pump; it was very important that the
reaction was carried out on an Ar line19) and not with an Ar balloon. The results
obtained are compiled in Table 4. The following observations are noteworthy: i) The
yields of 3-substituted cycloalkanones are generally in the range of 50 – 80%. ii) The
enantioselectivities reach er values of up to 94 :6 (Entry 16 in Table 4). iii) The thiol 33
with naphthalen-2-yl groups is not superior to the Ph derivative20) (Entries 9/10 and 30/
31); the thiol 8 with six Ph groups is inferior (Entries 27/28). iv) The dimethylamino
thiol 31 and the methoxy thiol 32 give similar results (cf. Entries 8/9, 25/26, 29/30). v)
Replacement of MeO with other RO groups in the thiol causes no improvement
(Entries 9, 11 – 13) or, rather, a decrease (Entries 30, 32 – 34 in Table 4) of the
enantioselectivities. vi) Of the five-, six-, seven-, and eight-membered cycloalkenones,
cycloheptenone generally reacts with highest enantioselectivities, and this is why we
19
)
Heating the flask before use with a heatgun under high vacuum, and using super-dry and O2-free Ar
gas, the conversions were poor, there was more 1,2-adduct formation, and the enantioselectivities
dropped when we compared in-parallel Ar-line and Ar-balloon procedures! This comparison was
carried out with the aminothiol 31.
In many applications of TADDOL derivatives, the naphthalenyl-TADDOL gives higher
enantioselectivities than the parent phenyl compound.
20
)

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Table 4. Enantioselective Conjugate Addition of Grignard Reagents to Cycloalkenones Catalyzed by CuI
TADDOL-thiolates Derived from 7, 8, and 31 – 36. The absolute configurations of the products were
assigned a) by comparison of the optical-rotation data with those reported in the literature, b) by
comparison of the retention times (GC on chiral stationary phase; see Exper. Part) of major and minor
isomer by analogy, or c) by NMR analysis of the (R,R)-1,2-diphenylethylenediamine derivatives [35].
Entry
n
R
Thiol
Yield [%]
er
Sense of optical rotation
and absolute configuration
1
2
3
4
5
6
7
8
9
5
5
6
6
6
6
6
6
6
6
6
6
6
6
6
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
8
8
Bu
Bu
Me
Me
iPr
iPr
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Ph
Ph
Me
Me
Me
Et
7
31
7
32
7
30
50
60
76
78
58
77
77
76
65
86
84
84
n.d.a)
n.d.a)
51
58
76
67
69
59
74
76
53
65
56
87
88
77
79
75
40 : 60
70 : 30
20 : 80
80 : 20
25 : 75
69 : 31
18 : 82
89 : 11
85 : 15
85 : 15
85 : 15
84 : 16
73 : 27
40 : 60
54 : 46
6 : 94
89 : 11
89 : 11
17: 83
76 : 24
80 : 20
10 : 90
90 : 10
19 : 81
75 : 25
71 : 29
8 : 92
n.d.
n.d.
(S)
(R)
(S)
(R)
(ꢀ)-(S)
(þ)-(R)
(þ)-(R)
(þ)-(R)
(þ)-(R)
(þ)-(R)
(þ)-(R)
(S)
32
7
31
32
33
34
35
36
7
32
7
31
32
7
31
32
7
31
7
31
32
7
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
(R)
(ꢀ)-(S)
(þ)-(R)
(þ)-(R)
(S)
(R)
(R)
Et
Et
Pr
Pr
(ꢀ)-(S)
(þ)-(R)
(ꢀ)-(S)
(þ)-(R)
(þ)-(R)
(ꢀ)-(S)
(ꢀ)-(S)
(þ)-(R)
(þ)-(R)
(þ)-(R)
(þ)-(R)
(þ)-(R)
(þ)-(R)
(þ)
iPr
iPr
iPr
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
8
21 : 79
90 : 10
92.5 : 7.5
91 : 9
85 : 15
88 : 12
82.5 : 17.5
20 : 80
76 : 24
31
32
33
34
35
36
7
> 90b)
> 90b)
> 90b)
81
31
78
(ꢀ)
a) Incomplete conversion and formation of side-products. b) Conversion (GC).

Helvetica Chimica Acta – Vol. 95 (2012)
1251
Fig. 4. Positive nonlinear effect (NLE) for the Cu-catalyzed 1,4-addition of BuMgCl to cycloheptenone
using ligand 7 (a) and ligand 32 (b). The reactions were carried out under the conditions specified in
Table 4 and in the accompanying text.
conducted most experiments (Entries 16 – 34) with this enone. vii) Variation of the
Grignard reagent gives rise to similar results for MeMgBr, PrMgBr, and BuMgCl (cf.
Entries 17/23/29), while EtMgBr (Entries 19 – 21), iPrMgBr (Entries 5, 6, 24 – 26), and
PhMgCl (Entries 14/15) undergo additions with poor selectivities. viii) We were
surprised to see an almost complete reversal of selectivity when going from the
dimethylamino or methoxy thiol to the sulfanyl alcohol (Entries 1/2; 3/4; 5/6; 7/8, 9; 14/
15; 16/17, 18; 19/20, 21; 22/23; 24/25, 26; 27/29 – 34; 35/36; and the 4,4-dimethylcyclo-
hexenone shown on top of Table 4). ix) Considering the fact that thiolato-Cu
complexes may have tri- [36] or tetranuclear [37] structures, we were not surprised to
find that there is a (positive) non-linear effect (NLE [32h][36][38]) of enantiose-
lectivities in the addition of BuMgCl to cycloheptenone with the alkoxy-thiolato ligand
(from 7) and with the methoxy-thiolato ligand (from 32; Fig. 4). x) The results obtained
with other a,b-unsaturated carbonyl compounds, such as alkylidene malonates and
cinnamoyl derivatives, indicate that the TADDOL-derived thiol ligands give rise to
high enantioselectivities in this reaction only with cyclic enones (cf. similar differences
between open-chain and cyclic Michael acceptors with other thiol ligands [32h][34]).
5. Structural Investigations of the Cu Complexes. – For isolation of the
corresponding Cu complex, we treated the sulfanyl alkohol 7 with 1 equiv. CuCl and
1.1 – 1.5 equiv. Et3N in MeOH under reflux or in CH2Cl2 at room temperature. Under
both sets of conditions, the complex 50 was formed, which could be purified by flash
chromatography, and which is stable in air and under weakly acidic aqueous conditions.

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Helvetica Chimica Acta – Vol. 95 (2012)
Similarly, the Cu complexes 51 – 53 and the Ag complex 54 were obtained21). Complex
50 was also formed from Cu(OAc)2 and 7 in MeOH22). In an attempt to prepare an
analogous complex of the dimethylamino thiol 31 (with excess CuCl in MeOH), we
isolated the peculiar disulfide salt 55 (see the crystal structure in Scheme 2). The
tetranuclear structure of the complexes 50 – 54 was established by X-ray crystal-
structure analysis, by ESI-mass spectrometry, by vapor-pressure osmometry, and/or by
NMR diffusion spectroscopy1).
In the crystal, the complex 50 has a structure with a C2-symmetry axis23) through
two of the Cu-atoms. The four Cu-atoms form a plane, above and below which the S-
atoms are located alternatively, to form an eight-membered (Cu-S)4 ring. The Cu-atoms
are coordinatively unsaturated (no interaction with the HO groups!). According to the
osmometry measurements, all complexes 50 – 52 and 54 are tetranuclear in CH2Cl2, and
this is in line with the ESI mass spectra showing [M þ K]þ peaks for the tetramers (see
Table 5 and Exper. Part). van Koten and co-workers have reported that their Cu-
Table 5. Molecular-Weight Determination of the Cuprates 50 – 52 and of 54 by Osmometry and
Electrospray-Ionization Mass Spectrometry
Cuprate complexes
Mr calc.
Osmometry (CH2Cl2) found
2195.8
ESI-MS [M þ K]þ found
2219
2717
2275
2398
50
51
52
54
2180.7
2677.9
2236.8
2358.0
2211.7
2329.6
thiolate complex is trinuclear in the non-polar solvent toluene and mononuclear in
coordinating solvents such as THF [36a – c]. Since all our conjugate Grignard additions
were carried out in THF (Table 4), we have determined the structures of the complexes
50 and 52, as well as of the in situ generated complex from dimethylamino thiol 31 by
1H-NMR pulsed-gradient diffusion measurements24) in (D8)THF at 208. All three
complexes turned out to be tetranuclear in this solvent, and even when we added excess
tBuNC there was no deaggregation. Thus, the tetranuclear structures of the Cu
complexes of TADDOL-derived thiols are very stable. NOE Measurements of the
three complexes ꢂgarnishedꢃ with tBuNC show distinct differences between the OH/SH
21
)
)
)
The alkoxy-thiolate complexes 52 and 53 are less stable than 50, and the corresponding benzyloxy
derivative could not be isolated at all.
With CuII-acetate, a 2:1 reaction must have taken place, in which CuII was reduced to CuI by the
thiol 7, probably with disulfide formation (cf. 55).
22
23
Actually, two crystals grown from different solvent mixtures were analyzed. One has the space
group C2221 (with an approximate C2 axis), the other has the space group P21212 (with a
crystallographic C2 axis; CCDC-CUPQEJ). For a ꢂnon-crystallographerꢃ, the differences between
the two dimorphic structures are minor.
This method was first applied for the determination of aggregation of transition-metal complexes
(in independent investigations) by the groups of Pregosin [1a] and Brintzinger [39]. For details of
the measurements with our thiolato-Cu complexes, we refer to [1a] and the ETH Dissertation
No. 14323 of M. Valentini (2001).
24
)

Helvetica Chimica Acta – Vol. 95 (2012)
1253
Scheme 2. Preparation of TADDOL-Derived Thiolato-Cu and -Ag Complexes 50 – 54, a Bis-Ammonium
Dichloro Cuprate Salt, 55, Derived from the Amino Thiol 31, and X-Ray Crystal Structures of 50 and 55
derivative on the one hand, and the MeO/SH and Me2N/SH derivatives on the other
t
hand, including cross-peaks between the Bu H-atoms and H-atoms of the ligands
[1a]2). We herein refrain from discussing details of the NMR spectra, which may not be
relevant to the mechanism of the conjugate addition of Grignard reagents (Table 4 and
Scheme 3). The fact is that the TADDOL-derived CuI-thiolato complexes are present
as tetranuclear species in the gas phase (cf. MS), in solution (cf. NMR), and in the solid
state (cf. X-ray).

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 3. Conjugate Addition of BuMgCl to Cycloheptenone, with 0.5 mol-% of the Pure Cu Complex
50 as Catalyst. The yield of the product of 1,2-addition is < 5%. The enantioselectivities with
cyclohexenone and cyclooctenone are 82 :18 and 80 :20 (cf. Entries 7, 27, and 35 in Table 4), respectively.
For a comparison with the in situ procedure (Table 4), note that 0.5 mol-% of the tetranuclear complex
corresponds to 2 mol-% of the monomer.
The complex 50 derived from the sulfanyl alcohol 7 turned out to be a highly active
catalyst for conjugate additions to cycloalkenones, and its use is very simple: rather
than treating a mixture of CuCl and 7 with BuLi (ca. 6 mol-% each), then adding the
enone, and finally the Grignard reagent (within 70 – 80 min; Table 4), the enone and
the complex 50 (0.5 mol-%) are dissolved in THF, and the Mg compound is added
(within 30 min; Scheme 3). The enantioselectivities with the six-, seven-, and eight-
membered cyclic enones are identical within experimental error for the two procedures.
In contrast, use of the isolated Cu complexes 52 and 53, prepared from the methoxy and
isopropoxy thiols 32 and 34 (Scheme 2), gave much poorer results according to the new
procedure (up to 40% 1,2-adduct and low enantioselectivities in the range of 2 :1 with
cycloheptenone; cf. Entries 30 and 32 of Table 4)25).
We are unable to discuss possible mechanistic models for these reactions, which
would be compatible with the observed results: in the original procedure (Table 4),
there are LiX derivatives involved, and in both procedures there is an increasing
amount of Mg salts with proceeding addition of the Grignard reagent. The LiO or
XMgO groups, which must be present when the sulfanyl alcohol 7 is employed, may
become ligands at the Cu center, which, in turn, could lead to deaggregation. On the
other hand, the poor selectivities observed with the isolated MeO- and iPrO-substituted
tetranuclear Cu complexes 52 and 53, as compared to the in situ procedure, might be
considered as a hint as to a less highly aggregated catalytic species in the presence of Li
ions with the two alkoxy ligands, and also with the Me2N-substituted ligand (cf. Table 4,
Entry 30), which all give rise to preferred formation of the (R)-enantiomers, while the
sulfanyl-alcohol-derived ligand leads to the (S)-3-alkylcycloalkanones.
We gratefully acknowledge the contributions of the co-workers of the services of the Laboratorium
fꢂr Organische Chemie: Prof. Dr. B. Jaun, B. Brandenberg, P. Zumbrunnen (NMR); Dr. W. Amrein, H. U.
Hediger, R. Hꢃfliger, O. Greter (MS), M. Schneider, D. Manser (elementary analyses, molecular
25
)
The Ag complex 54 gave a racemic product with cycloheptenone; Ag derivatives generally do not
add to a,b-unsaturated carbonyl compounds in a 1,4-fashion.

Helvetica Chimica Acta – Vol. 95 (2012)
1255
weights); and Dr. W. B. Schweizer, M. Solar (X-ray, see Footnote 18). We also acknowledge the generous
financial support by ETH Zꢂrich and Novartis AG, Basel.
Experimental Part
1. General. Abbreviations: FC, flash chromatography; h.v., high vacuum, 0.01 – 0.1 Torr. THF was
freshly distilled over K before use. Et3N was distilled over CaH2. CH2Cl2 was used in puriss. quality.
Solvents for workup and chromatography: pentane and hexane were distilled over P4O10 or Sikkon (anh.
CaSO4; Fluka), AcOEt over Sikkon, Et2O over KOH/FeSO4, and CH2Cl2 over P4O10. PCl3 was distilled
before use. All indicated reaction temp. were monitored with an internal thermometer (Ebro-TTX-690
digital thermometer). Autoclave used for reactions under high pressure: 80 ml (home-made, ETH
Zꢀrich); the pressure was monitored with a Haenni-ED-510 apparatus (Piezoresistiver Druckmessum-
former). TLC: Macherey-Nagel Alugram SIL G/UV254 or Merck 60 F254 silica gel plates; detection by
UV254 nm light or I2 or by dipping in/spraying with phosphomolybdic acid soln. (phosphomolybdic acid
(25 g), Ce(SO4)2 · 4 H2O (10 g), H2SO4 (60 ml), H2O (940 ml)), followed by heating. FC: Fluka silica gel
60 (0.040 – 0.063 mm), at ca. 0.3 bar. GC: Carlo Erba Fractovap 4160 with Carlo Erba DP 700 CE. M.p.:
Bꢂchi-510 apparatus; uncorrected. Optical rotations: Perkin-Elmer 241 polarimeter (10-cm, 1-ml cell), at
r.t. IR spectra: Perkin-Elmer 1620 FT-IR spectrometer, in cmꢀ1. NMR Spectra: Bruker AMX-500 (1H:
500 and 13C: 125 MHz), AMX-400 (1H: 400 and 13C: 100 MHz), Varian Gemini-300 (1H: 300, 13C: 75, and
19F: 282 MHz), Mercury-300 (1H: 300, 13C: 75, 19F: 282 MHz), or Gemini-200 (1H: 200 and 13C: 50 MHz);
chemical shifts (d) in ppm downfield from TMS (d 0.0 ppm) as internal standard; J values in Hz. MS: VG
Tribrid (EI; 70 eV), VG ZAB-2 SEQ (FAB; 3-nitrobenzyl alcohol matrix), IonSpec Ultima (FT-ICR-
MALDI; 4.7 T; 2,5-dihydroxybenzoic acid matrix), Bruker REFLEX (TOF-MALDI; N2 laser), or
Finnigan MAT TSQ 7000 (ESI) spectrometer; in m/z (% of basic peak). HR-MS: IonSpec Ultima (FT-
ICR-MALDI; 4.7 T; 2,5-dihydroxybenzoic acid matrix). Elemental analyses were performed by the
Microanalytical Laboratory of the Laboratorium fꢀr Organische Chemie, ETH Zꢀrich.
2. General Procedures. Preparation of Monochloro TADDOL Derivatives by Apple Reaction.
General Procedure 1 (GP 1). To a soln. of the appropriate TADDOL derivative (1 equiv.) in CH2Cl2
(0.3 – 0.65m), Ph3P (2 equiv.), pyridine (2 – 6 equiv.), and CCl4 (10 equiv.) were added at r.t. After stirring
for 2 – 5 d at ambient temp., the solvent was removed under reduced pressure, and the crude product was
purified as indicated.
Preparation of Monochloro TADDOL Derivatives with SOCl2. General Procedure 2 (GP 2). To a
soln. of the appropriate mono-ether (1 equiv.) in CH2Cl2 (0.1 – 0.3m), Et3N (1.3 – 1.5 equiv.) and SOCl2
(1.2 – 1.3 equiv.) were added. The mixture was stirred at reflux for 1.5 h where upon the color of the
mixture changed from yellow to black. After cooling to r.t., the mixture was carefully poured into sat. aq.
NaHCO3 soln. and stirred for 5 min. The org. layer was separated, and the aq. layer was extracted with
CH2Cl2 (2ꢁ). The combined org. layers were washed with H2O, sat. NaCl soln., and dried (Na2SO4). The
solvent was removed under reduced pressure, and the crude product was used without further
purification.
Preparation of Monochloro TADDOL Derivatives with SOCl2 in the Presence of LiCl. General
Procedure 3 (GP 3). The appropriate mono-ether (1 equiv.) and LiCl (10 equiv.) were dissolved (some
LiCl may remain undissolved) in THF (0.1m), SOCl2 (3 – 5 equiv.) was added, and the mixture was
refluxed for 6 h (TLC control) where upon a colorless precipitate (LiCl) was formed, which partially
disappeared by cooling to r.t. The mixture was then carefully poured into sat. aq. NaHCO3 soln. and
stirred for 5 min. Et2O was added, the org. layer was separated, and the aq. layer was extracted with Et2O
(2ꢁ). The combined org. layers were washed with sat. aq. NaCl soln. and dried (Na2SO4). The solvent
was removed under reduced pressure, and the crude product was used either without further purification
or purified as indicated.
Preparation of TADDOL Monoether Derivatives. General Procedure 4 (GP 4). The appropriate
monochloro TADDOL derivative (1 equiv.) was suspended in the appropriate alcohol (0.1 – 0.2 m), Et3N
(1.2 equiv.) was added, and the mixture was heated. After cooling to r.t., the suspension was filtered, and
the residue was purified as indicated.

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Helvetica Chimica Acta – Vol. 95 (2012)
Preparation of TADDOL Monothiol Derivatives. General Procedure 5 (GP 5). The appropriate
monochloro TADDOL derivative was dissolved in DMF (0.1 – 0.3m), thiourea (20 – 30 equiv.) was
added, and the mixture was stirred at r.t. for 3 d. NaOH soln. (1 or 2n) and Et2O (ca. 20 ml) were added,
and the mixture was stirred for 1 h. The org. layer was separated, and the aq. layer was extracted with
Et2O (3 ꢁ 25 ml). The combined org. layers were washed with H2O (2 ꢁ 25 ml) and sat. aq. NaCl soln.
(15 ml), and dried (Na2SO4). The solvent was removed under reduced pressure, and the residue was
purified by FC.
Methylation of Thiols. General Procedure 6 (GP 6). The appropriate thiol (1 equiv.) was dissolved in
MeCN/CH2Cl2 (0.08 m) and treated with K2CO3 (1 or 2 equiv.). The mixture was cooled to ꢀ 108, treated
with MeI (1 equiv.), and stirred at r.t. until completion (TLC control). The mixture was washed with H2O
(2ꢁ) and sat. NaCl soln., and the org. phase was dried (Na2SO4). The solvent was removed under
reduced pressure, and the residue was purified by FC.
Preparation of S,O-Acetals. General Procedure 7 (GP 7). A soln. of 7 (1 equiv.) in CH2Cl2 (0.12m)
was cooled to ꢀ 258, and the appropriate aldehyde (1 or 6 equiv.) was added. The mixture was stirred for
30 min, BF3 · Et2O (1 equiv.) was added, and stirring was continued for 45 min at ꢀ 258 and then for
30 min at 08. A 5% Na2CO3 soln. was added, the mixture was stirred for 15 min, and the phases were
separated. The aq. phase was extracted with CH2Cl2, and the combined org. layers were washed with H2O
and sat. NaCl soln., and dried (Na2SO4). The solvent was removed under reduced pressure, and the
residue was purified by FC.
3. Preparation of Monochloro TADDOLs 4, ent-4, 24, ent-24, 25 – 30. (4R,5R)- and (4S,5S)-5-
[(Chloro)(diphenyl)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-methanol (4 and ent-4, resp.).
Compound 4. A soln. of TADDOL 1 (10.0 g, 21.4 mmol) in CH2Cl2 (38 ml) was treated with Ph3P (11.3 g,
43.0 mmol), pyridine (3.5 ml, 43.0 mmol), and CCl4 (4.5 ml, 47.0 mmol) according to GP 1 for 3 d. The
soln. was concentrated under reduced pressure to ca. 20 ml, and the residue was purified by flash
filtration (pentane/Et2O 8 :2; 350 g of SiO2). The filtrate was concentrated under reduced pressure to ca.
30 – 40 ml. Colorless crystals were formed upon standing for 6 h, which were isolated and identified as 4
(7.80 g, 76%). M.p. 133 – 1358 ([24b]: 135 – 1378). [a]rD:t: ¼ ꢀ17.8 (c ¼ 1.0, CHCl3) ([24b]: ꢀ 18.1 (c ¼ 0.4,
CHCl3)). 1H-NMR (300 MHz, CDCl3): 0.91 (s, Me); 1.07 (s, Me); 1.82 (s, OH); 5.12 (d, J ¼ 5.9, CH); 5.35
(d, J ¼ 5.9, CH); 7.15 – 7.42 (m, 20 arom. H). The anal. data matched those of [24b].
Compound ent-4. A soln. of TADDOL ent-1 (5.0 g, 10.7 mmol) in CH2Cl2 (20 ml) was treated with
Ph3P (5.60 g, 21.4 mmol), pyridine (1.7 ml, 21.4 mmol), and CCl4 (2.5 ml, 25 mmol) according to GP 1.
Purification by FC afforded ent-4 (3.05 g, 60 %). [a]rD:t: ¼ þ17.5 (c ¼ 1.3, CHCl3).
(4R,5R)-5-[(Chloro)(diphenyl)methyl]-a,a,2,2-tetraphenyl-1,3-dioxolane-4-methanol (5). A soln. of
2 (7.70 g, 13.0 mmol) in CH2Cl2 (20 ml) was treated with Ph3P (6.80 g, 26.0 mmol), CCl4 (13.0 ml,
134 mmol), and pyridine (2.1 ml, 26.0 mmol) according to GP 1 for 5 d. FC (2ꢁ) (1. pentane/Et2O 9 :1;
80 g of SiO2; 2. pentane/Et2O 95 :5; 80 g of SiO2) and crystallization from pentane/Et2O (95 :5; 40 ml)
yielded 5 (4.45 g, 56%). Colorless solid. M.p. 165 – 1668. [a]rD:t: ¼ þ118.9 (c ¼ 1.04, CHCl3). IR (CHCl3):
3539m, 3089w, 3062w, 3007w, 1948w, 1892w, 1810w, 1599w, 1492m, 1449s, 1324w, 1165w, 1107s, 1064m,
1029m, 960w, 640m, 617w. 1H-NMR (400 MHz, CDCl3): 1.61 (s, OH); 5.57 (d, J ¼ 3.4, CH); 5.80 (d, J ¼
3.4, CH); 6.94 – 7.38 (m, 28 arom. H); 7.45 – 7.52 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 77.23,
79.96 (C); 82.98, 85.51 (CH); 112.60 (C); 124.73, 125.04, 126.34, 126.59, 126.76, 126.82, 126.97, 127.05,
127.24, 127.43, 127.57, 127.84, 127.88, 127.97, 128.11, 128.70, 129.61 (CH); 141.24, 142.18, 143.72, 144.08,
145.66, 146.49 (C). FAB-MS: 425 (11, [M ꢀ 184]þ), 391 (9, [M ꢀ 218]þ), 361 (100, [M ꢀ 248]þ), 183 (58),
179 (27), 167 (41) 105 (37). Anal. calc. for C41H33ClO3 (609.16): C 80.84, H 5.46, Cl 5.82; found: C 80.70,
H 5.65, Cl 5.90.
(4R,5R)-5-{(Chloro)[di(naphthalen-2-yl)]methyl}-2,2-dimethyl-a,a-di(naphthalen-2-yl)-1,3-dioxo-
lane-4-methanol (6). A soln. of 3 (6.10 g, 9.15 mmol) in CH2Cl2 (30 ml) was treated with Ph3P (4.80 g,
18.30 mmol), pyridine (5.0 ml, 62 mmol), and CCl4 (9.0 ml, 93.0 mmol) according to GP 1 for 2 d. FC
(pentane/Et2O 8 :2 ! 1:1; 80 g of SiO2) yielded 6 (4.00 g, 64%), which was used without further
1
purification (caution: very prone to hydrolysis on silica gel). Solid foam. H-NMR (300 MHz, CDCl3):
1.34 (s, Me); 1.38 (s, Me); 5.60 (d, J ¼ 5.3, CH); 5.76 (d, J ¼ 5.3, CH); 6.75 – 6.90 (m, 4 arom. H); 7.36 – 7.53
(m, 12 arom. H); 7.64 – 7.90 (m, 8 arom. H); 8.00 – 8.05 (m, 2 arom. H); 8.16 – 8.18 (m, 2 arom. H).

Helvetica Chimica Acta – Vol. 95 (2012)
1257
(4R,5R)- and (4S,5S)-4-[(Chloro)(diphenyl)methyl]-5-[(methoxy)(diphenyl)methyl]-2,2-dimethyl-
1,3-dioxolane (24 and ent-24, resp.). A soln. of 13 (2.50 g, 5.20 mmol) in CH2Cl2 (25 ml) was treated with
Et3N (1.10 ml, 7.80 mmol) and SOCl2 (0.50 ml, 6.87 mmol) according to GP 2. Workup yielded 24 (2.78 g,
quant.) as a brown solid foam, which was used without further purification. For anal. purposes, a sample
was purified by FC (pentane/Et2O). Colorless foam. M.p. 115 – 1178. [a]rD:t: ¼ þ50.9 (c ¼ 1.07, CHCl3). IR
(CHCl3): 3059w, 3007m, 2936w, 2827w, 1598w, 1492m, 1445m, 1380m, 1370m, 1318w, 1166m, 1093s,
1034w, 980w, 893m, 865m. 1H-NMR (300 MHz, CDCl3): 0.97 (s, Me); 1.29 (s, Me); 2.30 (s, MeO); 4.85 (d,
J ¼ 6.6, CH); 5.16 (d, J ¼ 6.9, CH); 7.18 – 7.50 (m, 20 arom. H). 13C-NMR (75 MHz, CDCl3): 27.69, 27.80,
51.71 (Me); 79.52 (C); 80.83, 82.50 (CH); 83.80, 109.87 (C); 126.93, 127.10, 127.30, 127.41, 127.44, 127.52,
127.59, 128.79, 129.47, 130.02, 130.63 (CH); 139.32, 140.87, 144.01, 144.80 (C). FAB-MS: 431 (4, [M ꢀ
MeO ꢀ Cl ꢀ 1]þ), 318 (32), 237 (70), 197 (100), 167 (49), 136 (38), 105 (65).
Compound ent-24: A soln. of ent-13 (0.70 g, 1.50 mmol) in CH2Cl2 (10 ml) was treated with Et3N
(0.31 ml, 2.25 mmol) and SOCl2 (0.14 ml, 1.90 mmol) according to GP 2. Workup yielded ent-24 (745 mg,
99%), which was used without further purification.
(4R,5R)-4-{(Chloro)[di(naphthalen-2-yl)]methyl}-5-{(methoxy)[di(naphthalen-2-yl]methyl}-2,2-di-
methyl-1,3-dioxolane (25). A soln. of 14 (2.10 g, 3.10 mmol) in CH2Cl2 (25 ml) was treated with Et3N
(0.64 ml, 4.60 mmol) and SOCl2 (0.30 ml, 4.13 mmol) according to GP 2. Workup yielded 25 (2.10 g,
97%) as a beige solid foam, which was used without further purification. 1H-NMR (300 MHz, CDCl3):
1.14 (s, Me); 1.46 (s, Me); 2.12 (s, MeO); 5.10 (d, J ¼ 6.5, CH); 5.48 (d, J ¼ 6.8, CH); 7.27 – 7.31 (m, 2 arom.
H); 7.39 – 7.93 (m, 24 arom. H); 8.06 (d, J ¼ 1.9, 1 arom. H); 8.20 (d, J ¼ 1.9, 1 arom. H). 13C-NMR
(75 MHz, CDCl3): 27.82, 28.05, 51.99 (Me); 81.42, 82.78 (CH); 83.92, 109.86 (C); 125.87, 125.97, 126.05,
126.12, 126.20, 126.28, 126.34, 126.76, 127.23, 127.28, 127.39, 127.51, 128.06, 128.54, 128.70, 128.79, 129.17,
129.20 (CH); 132.34, 132.44, 132.62, 132.76, 137.25, 138.18, 140.32 (C).
(4R,5R)-4-[(Chloro)(diphenyl)methyl]-2,2-dimethyl-5-[(1-methylethoxy)(diphenyl)methyl]-1,3-di-
oxolane (26). A soln. of 15 (2.90 g, 5.70 mmol) in CH2Cl2 (50 ml) was treated with Et3N (1.20 ml,
8.55 mmol) and SOCl2 (0.58 ml, 8.00 mmol) according to GP 2. Workup yielded a mixture (3.15 g) of 26
1
(73%) and 15 (27%; according to H-NMR) as a brown solid foam, which was used without further
purification. 1H-NMR (300 MHz): 0.31 (d, J ¼ 5.8, Me); 0.95 (2s, 2 Me); 1.06 (d, J ¼ 5.9, Me); 3.50 – 3.58
(m, CH); 4.71 (d, J ¼ 6.8, CH); 4.84 (d, J ¼ 6.8, CH); 7.20 – 7.41 (m, 16 arom. H); 7.61 – 7.66 (m, 4 arom.
H). 13C-NMR (75 MHz): 23.38, 24.11, 27.25, 27.56 (Me); 66.82 (CH); 76.16 (C); 81.72, 81.79 (CH); 84.79,
108.68 (C); 126.67, 126.93, 127.09, 127.30, 127.38, 127.54, 127.59, 128.61, 130.29, 130.76, 131.05 (CH);
140.21, 141.59, 141.75, 145.92 (C).
(4R,5R)-4-[(Chloro)(diphenyl)methyl]-5-[(diphenyl)(phenylmethoxy)methyl]-2,2-dimethyl-1,3-di-
oxolane (27). A soln. of 16 (3.00 g, 5.40 mmol) in CH2Cl2 (25 ml) was treated with Et3N (1.05 ml,
7.60 mmol) and SOCl2 (0.47 ml, 6.40 mmol) according to GP 2. Workup yielded 27 (3.08 g, 99%) as a
brown solid foam, which was used without further purification. 1H-NMR (300 MHz): 0.99 (s, Me); 1.08 (s,
2
2
Me); 3.97 (d, J ¼ 11.8, 1 H, CH2); 4.09 (d, J ¼ 11.8, 1 H, CH2); 4.78 (d, J ¼ 7.2, CH); 4.97 (d, J ¼ 7.2,
CH); 6.94 – 7.41 (m, 21 arom. H); 7.45 – 7.54 (m, 2 arom. H); 7.55 – 7.65 (m, 2 arom. H). 13C-NMR
(75 MHz): 27.14, 27.65 (Me); 66.13 (CH2); 75.93 (C); 80.88, 82.00 (CH); 84.56, 108.57 (C); 126.77, 126.98,
127.09, 127.30, 127.38, 127.46, 127.52, 127.80, 128.24, 129.84, 130.36 (CH); 139.09, 139.95, 141.70, 141.78,
145.39 (C).
(4R,5R)-4-[(Chloro)(diphenyl)methyl]-5-{[4-(1,1-dimethylethyl)phenoxy](diphenyl)methyl}-2,2-di-
methyl-1,3-dioxolane (28). A soln. of 17 (2.25 g, 3.75 mmol) in THF (50 ml) was cooled to ꢀ 758, and
BuLi (2.70 ml, 4.30 mmol; 1.6m soln. in hexane) was added dropwise over 5 min. After warming to 08, the
mixture was stirred for 30 min at this temp. Then, SOCl2 (0.31 ml, 4.30 mmol) was added dropwise over
10 min, the mixture was allowed to warm to r.t. and refluxed for 2 h (TLC control is not possible due to
complete hydrolysis of 28 on the silica plate). Workup according to GP 2 yielded 28 (2.50 g, quant.) as a
yellow solid, which was used without further purification. 1H-NMR (300 MHz): 0.99 (s, Me); 1.10 (s, Me)
1.15 (s, tBu); 4.89 (d, J ¼ 6.9, CH); 4.93 (d, J ¼ 6.9, CH); 6.37 – 6.44 (m, 2 arom. H); 6.85 – 6.92 (m, 2 arom.
H); 7.04 – 7.22 (m, 6 arom. H); 7.27 – 7.39 (m, 10 arom. H); 7.56 – 7.63 (m, 2 arom. H); 7.64 – 7.70 (m, 2
arom. H). 13C-NMR (75 MHz): 27.27, 27.62, 31.39 (Me); 33.85, 76.30 (C); 82.10, 83.71 (CH); 86.47, 109.15
(C); 119.92, 124.74, 126.90, 127.12, 127.32, 127.38, 127.51, 127.58, 128.30, 129.65, 130.42, 130.65 (CH);
138.66, 140.41, 141.72, 143.35, 145.28, 153.04 (C). ESI-MS (pos.): 1248 (22, [2 M þ 16]þ), 667 (28, [M ꢀ

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Helvetica Chimica Acta – Vol. 95 (2012)
Cl ꢀ 1 þ 2 MeOH þ Na]þ), 651 (32, [M ꢀ Cl ꢀ 1 þ MeOH þ K]þ), 635 (70, [M ꢀ Cl ꢀ 1 þ MeOH þ
Na]þ), 616 (28, Mþ), 391 (100).
N-({(4S,5R)-5-[(Chloro)(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}diphenylmethyl)-1,1,1-
trifluoromethanesulfonamide (29). A soln. of 21 (4.80 g, 8.00 mmol) in THF (95 ml) was treated with
LiCl (3.39 g, 80.0 mmol) and SOCl2 (3.00 ml, 41.2 mmol) according to GP 3. Trituration of the crude
product with hexane (30 ml) under reflux for 30 min yielded 29 (4.00 g, 81%). For anal. purposes, a
sample was triturated with Et2O. Colorless solid. M.p. 193 – 1948 (dec.). [a]rD:t: ¼ ꢀ47.5 (c ¼ 0.45, CHCl3).
IR (CHCl3): 3240m, 3067w, 3008w, 2916w, 1496w, 1445m, 1373s, 1177m, 1138m, 1082m, 1054m, 1029w,
931w, 893w, 833w, 600s. 1H-NMR (400 MHz, CDCl3): 1.00 (s, Me); 1.04 (s, Me); 4.61 (d, J ¼ 7.3, CH); 4.75
(d, J ¼ 7.3, CH); 6.81 (br. s, NH); 7.16 – 7.21 (m, 1 arom. H); 7.23 – 7.46 (m, 15 arom. H); 7.55 – 7.63 (m, 4
arom. H). 13C-NMR (100 MHz, CDCl3): 26.89, 27.15 (Me); 70.65, 76.92 (C); 81.73, 82.50 (CH); 109.01,
1
118.82 (q, J(C,F) ¼ 322, CF3) (C); 127.07, 127.52, 127.71, 128.07, 128.30, 128.49, 128.54, 128.60, 130.00,
130.12, 130.90 (CH); 137.36, 137.61, 139.14, 143.97 (C). 19F-NMR (282 MHz, CDCl3): ꢀ 76.91. ESI-MS
(pos.): 671 (17, [M þ MeOH þ Na þ 1]þ), 666 (24, [M þ MeOH þ NH4 þ 1]þ), 638 (16, [M þ Na]þ), 634
(48, [M þ NH4 þ 1]þ), 629 (29, [M þ 14]þ), 602 (15, [M ꢀ Cl ꢀ 1 þ Na]þ), 580 (9, [M ꢀ Cl]þ), 512 (76,
[M ꢀ Cl ꢀ CF3 þ 1]þ), 508 (100, [M ꢀ 107]þ). ESI-MS (neg.): 614 (100, [M ꢀ 1]ꢀ). Anal. calc. for
C32H29ClF3NO4S (616.10): C 62.38, H 4.74, Cl 5.75, N 2.27; found: C 62.26, H 4.83, Cl 6.00, N 2.21.
N-({(4S,5R)-5-[(Chloro)(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}diphenylmethyl)-2,2,2-
trifluoroacetamide (30). A soln. of 22 (2.20 g, 3.92 mmol) in THF (50 ml) was teated with LiCl (1.60 g,
37.7 mmol) and SOCl2 (1.20 ml, 16.5 mmol) according to GP 3. Workup yielded 30 (2.56 g, quant.) as a
beige solid foam, which was used without further purification. M.p. 150 – 1528 (dec.). [a]rD:t: ¼ ꢀ112.6 (c ¼
1.05, CHCl3). IR (CHCl3): 3360w, 3063w, 3007w, 2938w, 1739s, 1538m, 1520m, 1496m, 1445m, 1382m,
1372m, 1326w, 1176s, 1070m, 896w, 855w. 1H-NMR (300 MHz, CDCl3): 0.74 (s, Me); 0.82 (s, Me); 4.97 (d,
J ¼ 6.8, CH); 5.11 (d, J ¼ 6.8, CH); 7.22 – 7.45 (m, 18 arom. H); 7.51 – 7.55 (m, 2 arom. H); 7.75 (br. s,
NH). 13C-NMR (75 MHz, CDCl3): 26.88, 27.16 (Me); 67.10, 75.67 (C); 80.72, 81.74 (CH); 109.97, 115.75
1
(q, J(C,F) ¼ 290, CF3) (C); 127.52, 127.55, 127.62, 127.78, 128.03, 128.07, 128.30, 128.35, 128.53, 129.51,
129.68, 130.82 (CH); 137.57, 139.30, 140.82, 145.47, 155.33 (q, 2J(CF) ¼ 37, CO) (C). 19F-NMR (282 MHz,
CDCl3): ꢀ 75.72. ESI-MS (pos.): 680 (16, [M þ 101]þ), 639 (46, [M þ 60]þ), 635 (42, [M þ MeOH þ
Na þ 1]þ), 618 (16, [M þ K]þ), 602 (100, [M þ Na]þ), 598 (67, [M ꢀ Cl ꢀ 1 þ Na þ MeOH]þ), 593 (25,
[M ꢀ Cl ꢀ 1 þ NH4 þ MeOH]þ), 566 (29, [M ꢀ Cl ꢀ 1 þ Na]þ), 544 (66, [M ꢀ Cl]þ), 431 (22, [M ꢀ
148]þ). ESI-MS (neg.): 614 (50, [M þ Cl]ꢀ), 578 (100, [M ꢀ 1]ꢀ), 560 (22, [M ꢀ 19]ꢀ), 542 (26, [M ꢀ
37]ꢀ).
4. Preparation of the TADDOL Mono-ethers 13, ent-13, 14 – 17. (4R,5R)- and (4S,5S)-5-
[(Methoxy)(diphenyl)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-methanol (13 and ent-13,
resp.). Compound 13. Monochloride 4 (3.86 g, 7.96 mmol) in MeOH (60 ml) was treated with Et3N
(1.20 ml, 8.61 mmol) according to GP 4 under reflux for 1.5 h. Filtration yielded anal. pure 13 (3.16 g,
83%). Colorless solid. M.p. 165 – 1668 ([24b]: 169.8 – 170.48). [a]rD:t: ¼ ꢀ30.1 (c ¼ 1.35, CHCl3) ([24b]:
[a]Dr:t: ¼ ꢀ27.0 (c ¼ 1.00, CHCl3)). IR (CHCl3): 3321br., 3059m, 2941m, 1957w, 1817w, 1600w, 1495s, 1447s,
1
1381m, 1372m, 1168s, 1087s,1048s, 882s, 641m. H-NMR (300 MHz, CDCl3): 0.93 (s, Me); 1.03 (s, Me);
2.97 (s, MeO); 4.25 (d, J ¼ 8.1, CH); 4.59 (d, J ¼ 8.1, CH); 6.35 (s, OH); 7.20 – 7.50 (m, 18 arom. H); 7.62 –
7.65 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 26.85, 27.06, 52.41 (Me); 77.24 (C); 79.30, 81.51 (CH);
84.75, 108.87 (C); 126.91, 127.07, 127.20, 127.64, 127.70, 127.88, 128.40, 128.66, 129.98 (CH); 137.11, 138.86,
143.85, 146.43 (C). MALDI-FT-ICR-MS: 503.2 (72, [M þ Na]þ), 413.2 (20, [M ꢀ MeO ꢀ OCMe2 ꢀ 1 þ
Na]þ), 273.0 (100). HR-MS: 503.2191 ([M þ Na]þ, C32H32NaO4; calc. 503.2193 (ꢀ0.4 ppm)). Anal. calc.
for C32H32O4 (480.60): C 79.97, H 6.71; found: C 79.94, H 6.63.
Compound ent-13. Monochloride ent-4 (0.95 g, 1.96 mmol) in MeOH (15 ml) was treated with Et3N
(0.30 ml, 2.15 mmol) according to GP 4 to yield ent-13 (0.79 g, 84%). [a]rD:t: ¼ þ25.0 (c ¼ 1.15, CHCl3).
(4R,5R)-5-{(Methoxy)[di(naphthalen-2-yl]methyl}-2,2-dimethyl-a,a-di(naphthalen-2-yl)-1,3-dioxo-
lane-4-methanol (14). The crude monochloride 6 (4.00 g, 5.84 mmol) in MeOH (60 ml) was treated
(without Et3N) according to GP 5 under reflux for 3 h and subsequent stirred at r.t. overnight. The
residue was purified by FC (SiO2 (200 g); pentane/Et2O 95 :5) to yield 14 (2.23 g, 57%). Colorless solid.
M.p. 155 – 1568. Rf (hexane/AcOEt 8 :2) 0.40. [a]rD:t: ¼ ꢀ52.8 (c ¼ 1.15, CHCl3). IR (CHCl3): 3318br.,
3061s, 2940w, 1951w, 1631w, 1599m, 1505s, 1381s, 1372s, 1273m, 1168s, 1086s, 952w. 1H-NMR (400 MHz,

Helvetica Chimica Acta – Vol. 95 (2012)
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CDCl3): 0.99 (s, Me); 1.14 (s, Me); 3.07 (s, MeO); 4.52 (d, J ¼ 8.2, CH); 4.90 (d, J ¼ 8.2, CH); 6.67 (s,
OH); 7.28 – 7.94 (m, 26 arom. H); 8.12 (s, 1 arom. H); 8.33 (s, 1 arom. H). 13C-NMR (100 MHz, CDCl3):
27.03, 27.27, 53.03 (Me); 77.59 (C); 79.65, 82.27 (CH); 85.02, 109.20 (C); 125.52, 125.73, 125.86, 125.92,
126.06, 126.11, 126.18, 126.33, 126.39, 126.59, 126.67, 126.78, 126.92, 127.17, 127.31, 127.36, 127.47, 127.49,
127.53, 127.55, 127.84, 127.98, 128.53, 128.60, 128.69, 128.70, 128.85, 130.03 (CH); 132.44, 132.52, 132.53,
132.68, 132.80, 132.81, 132.85, 132.99, 135.47, 136.31, 141.64, 143.40 (C). ESI-MS (pos.): 735 (34, [M þ
MeOH þ Na]þ), 719 (17, [M þ K]þ), 703 (100, [M þ Na]þ). ESI-MS (neg.): 680 (60, Mꢀ), 679 (100,
[M ꢀ 1]ꢀ). Anal. calc. for C48H40O4 (680.84): C 84.68, H 5.92; found: C 84.70, H 6.19.
(4R,5R)-2,2-Dimethyl-5-[(1-methylethoxy)(diphenyl)methyl]-a,a-diphenyl-1,3-dioxolane-4-metha-
nol (15). Monochloride 4 (4.00 g, 8.25 mmol) in iPrOH (40 ml) was treated with Et3N (1.72 ml,
12.35 mmol) according to GP 5 at 508 for 15 h. To remove NH4Cl, the residue was dissolved in CH2Cl2
and washed with H2O. The org. layer was separated and dried (Na2SO4), and the solvent was removed
under reduced pressure to yield 15 (3.08 g, 73%). Colorless solid. M.p. 203 – 2058. Rf (hexane/AcOEt
95 :5) 0.42. [a]Dr:t: ¼ ꢀ16.3 (c ¼ 1.0, CHCl3). IR (CHCl3): 3310s (br.), 3059w, 3007s, 2934w, 1600w, 1495m,
1446s, 1382m, 1372s, 1332w, 1170m, 1130w, 1110m, 1082s, 1050s, 1033s, 1016s, 918w, 885m, 835w. 1H-NMR
(400 MHz): 0.45 (d, J ¼ 5.9, Me); 0.89 (s, Me); 1.05 (s, Me); 1.39 (d, J ¼ 6.2, Me); 3.73 – 3.82 (m, CH);
4.25 (d, J ¼ 8.2, CH); 4.54 (d, J ¼ 8.2, CH); 6.61 (s, OH); 7.17 – 7.39 (m, 16 arom. H); 7.52 – 7.55 (m, 2
arom. H); 7.64 – 7.67 (m, 2 arom. H). 13C-NMR (100 MHz): 23.32, 24.26, 26.77, 27.10 (Me); 68.71 (CH);
77.34 (C); 79.95, 81.27 (CH); 85.40, 108.60 (C); 126.88, 126.94, 127.67, 127.76, 127.80, 127.86, 128.48, 128.87,
130.41, 130.47 (CH); 138.68, 139.77, 143.84, 146.37 (C). ESI-MS (pos.): 1055 (35, [2 M þ K]þ), 1039 (40,
[2 M þ Na]þ), 1034 (100, [2 M þ NH4]þ), 563 (29, [M þ MeOH þ Na]þ), 554 (12, [M þ 46]þ), 547 (35,
i
[M þ K]þ), 531 (43, [M þ Na]þ), 526 (56, [M þ NH4]þ), 522 (13, [M þ 14]þ), 449 (74, [M ꢀ PrO]þ),
i
391 (90, [M ꢀ PrO ꢀ Me2CO]þ). Anal. calc. for C34H36O4 (508.66): C 80.28, H 7.13; found: C 80.42, H
7.15.
(4R,5R)-5-[(Diphenyl)(phenylmethoxy)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-metha-
nol (16). Monochloride 4 (4.00 g, 8.25 mmol) in BnOH (40 ml) was treated with Et3N (1.72 ml,
12.35 mmol) according to GP 5 at 508 for 12 h. The residue was purified by FC (SiO2 (60 g); pentane/
Et2O) to yield 16 (3.50 g, 76%). Colorless solid. M.p. 211 – 2138. Rf (hexane/AcOEt 9 :1) 0.48. [a]Dr:t:
¼
ꢀ26.1 (c ¼ 1.1; CHCl3). IR (CHCl3): 3370s, 3091w, 3061m, 3007s, 2934w, 1600w, 1495s, 1447s, 1381m,
1
1372s, 1332m, 1169s, 1082s, 1056s, 1020s, 920w, 881m, 643m. H-NMR (400 MHz): 0.95 (s, Me); 1.14 (s,
Me); 3.79 (d, 2J ¼ 10.5, 1 H, CH2); 4.16 (d, J ¼ 8.3, CH); 4.30 (d, 2J ¼ 10.5, 1 H, CH2); 4.56 (d, J ¼ 8.3,
CH); 5.84 (s, OH); 7.10 – 7.25 (m, 7 arom. H); 7.27 – 7.37 (m, 11 arom. H); 7.38 – 7.50 (m, 5 arom. H);
7.60 – 7.64 (m, 2 arom. H). 13C-NMR (100 MHz): 26.74, 27.13 (Me); 67.16 (CH2); 76.92 (C); 79.95, 82.09
(CH); 85.30, 108.41 (C); 126.88, 126.92, 127.04, 127.31, 127.63, 127.71, 127.79, 127.97, 128.27, 128.48, 128.55,
128.59, 130.02, 130.05 (CH); 136.49, 137.31, 139.41, 143.47, 145.89 (C). ESI-MS (pos.): 616 (10, [M þ
60]þ), 602 (13, [M þ 46]þ), 595 (28, [M þ K]þ), 579 (24, [M þ Na]þ), 574 (100, [M þ NH4]þ), 449
(14, [M ꢀ BnO]þ), 391 (17, [M ꢀ BnO ꢀ Me2CO]þ). Anal. calc. for C38H36O4 (556.70): C 81.99, H 6.52;
found: C 81.92, H 6.50.
(4R,5R)-5-{[4-(1,1-Dimethylethyl)phenoxy](diphenyl)methyl}-2,2-dimethyl-a,a-diphenyl-1,3-dioxo-
lane-4-methanol (17). To a soln. of 4 (2.00 g, 4.10 mmol) in CH2Cl2 (40 ml) was added Et3N (1.14 ml,
8.20 mmol) and 4-(tert-butyl)phenol (3.08 g, 20.5 mmol) at r.t. After stirring for 3 d at ambient temp., the
mixture was washed with 2n NaOH soln. The org. layer was separated, and the aq. layer was extracted
with CH2Cl2. The combined org. layers were washed with H2O and sat. NaCl soln., and dried (Na2SO4).
The solvent was removed under reduced pressure, and the crude product was purified by FC (pentane/
Et2O 97:3; 80 g SiO2). Subsequent trituration with pentane afforded 17 (1.37 g, 56%). Colorless solid.
M.p. 148 – 1498 ([1b]: 154 – 1558). [a]rD:t: ¼ ꢀ54.2 (c ¼ 0.88, CHCl3) ([1b]: [a]rD:t: ¼ ꢀ50.5 (c ¼ 0.65,
1
t
CHCl3)). H-NMR (300 MHz, CDCl3): 0.98 (s, Me); 1.09 (s, Me); 1.15 (s, Bu); 4.40 (d, J ¼ 8.1, CH);
4.77 (d, J ¼ 8.1, CH); 5.92 (s, OH); 6.48 – 6.54 (m, 2 arom. H); 6.89 – 6.96 (m, 2 arom. H); 7.02 – 7.12 (m, 3
arom. H); 7.13 – 7.26 (m, 5 arom. H); 7.30 – 7.47 (m, 8 arom. H); 7.69 – 7.77 (m, 4 arom. H). ESI-MS (pos.):
1236 (8, [2 M þ K þ 1]þ), 1215 (44, [2 M þ NH4 þ 1]þ], 653 (18, [M þ MeOH þ Na]þ), 637 (32, [M þ
K]þ), 621 (58, [M þ Na]þ), 616 (100, [M þ NH4]þ). ESI-MS (neg.): 657 (100, [M þ AcO]ꢀ), 633 (74,
[M þ Cl]ꢀ), 597 (64, [M ꢀ 1]ꢀ). The anal. data matched those of [1b].

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Helvetica Chimica Acta – Vol. 95 (2012)
5. Preparation of the TADDAMIN 11. (4R,5S)-5-[(Dimethylamino)(diphenyl)methyl]-a,a,2,2-
tetraphenyl-1,3-dioxolane-4-methanol (11). Monochloride 4 (2.40 g, 4.00 mmol) and Me2NH (ca. 35 g,
776 mmol) were placed in an autoclave (80 ml) and heated at 808 for 3 d (4.5 bar). After cooling to r.t.,
excess Me2NH was vented, and the crude product was dissolved in CH2Cl2. The soln. was washed with 1n
NaOH soln. and sat. NaCl soln., and dried (Na2SO4). The solvent was removed under reduced pressure,
and the residue was purified by FC (SiO2 (80 g); pentane/Et2O) to yield 11 (337 mg, 14%). Colorless
solid foam. For anal. purposes, 11 was recrystallized from EtOH. Colorless crystals. M.p. 225 – 2278.
[a]Dr:t: ¼ þ108.8 (c ¼ 1.10, CHCl3). IR (CHCl3): 3062m, 3007s, 2950w, 2798w, 1599w, 1492m, 1448s, 1349w,
1096s, 1048w, 1031s, 1004w, 988w, 944w, 905w, 642m. 1H-NMR (400 MHz, CDCl3): 1.48 (s, MeN); 2.25 (s,
MeN); 4.23 (d, J ¼ 8.7, CH); 5.18 (d, J ¼ 8.7, CH); 6.41 – 6.55 (m, 1 arom. H); 6.57 – 6.63 (m, 2 arom. H);
6.70 – 7.00 (m, 6 arom. H); 7.11 – 7.54 (m, 16 arom. H); 7.58 – 7.68 (m, 1 arom. H); 7.83 – 7.90 (m, 2 arom.
H); 7.95 – 8.06 (m, 1 arom. H); 8.71 (s, OH). 13C-NMR (100 MHz, CDCl3): 40.45, 41.19 (Me); 73.45, 74.97
(C); 78.10, 86.15 (CH); 108.09 (C); 125.20, 125.62, 126.58, 126.75, 126.77, 126.95, 126.99, 127.20, 127.40,
127.59, 127.62, 127.78, 128.06, 128.16, 129.48, 130.75, 131.21, 134.42 (CH); 135.67, 136.80, 142.75, 143.82,
144.01, 146.62 (C). FAB-MS: 1236 (6, [2 M þ 1]þ), 618 (65, [M þ 1]þ), 540 (6), 391 (17), 381 (15), 361
(71), 307 (14), 210 (100), 183 (23), 167 (42). Anal. calc. for C43H39NO3 (617.79): C 83.60, H 6.36, N 2.27;
found: C 83.58, H 6.49, N 2.27.
6. Preparation of the Trifluoroacetamides 20 and 22. N-[((4S,5R)-5-{(Diphenyl)[(trimethylsilyl)oxy]-
methyl}-2,2-dimethyl-1,3-dioxolan-4-yl)(diphenyl)methyl]-2,2,2-trifluoroacetamide (20). According to
[24b], amino alcohol 9 (6.00 g, 12.89 mmol) was TMS-protected to afford 18 (7.0 g, quant.). To a soln.
of 18 in CH2Cl2 (100 ml) at ꢀ 758 was added dropwise over 30 min (temp. ꢂꢀ 708) a soln. of (CF3CO)2O
(2.77 ml, 19.95 mmol) in CH2Cl2 (15 ml). The mixture was stirred for 15 min at ꢀ 758, then a soln. of Et3N
(1.80 ml, 12.90 mmol) in CH2Cl2 (8 ml) was added dropwise over 30 min (temp. ꢂꢀ 708). After warming
up slowly to r.t. and stirring overnight at ambient temp., the mixture was washed with H2O. The org. layer
was separated, washed with sat. NaCl soln., and dried (Na2SO4). The solvent was removed under reduced
pressure to afford 20 (7.95 g, 97% from 9). Colorless solid. M.p. 145 – 1488 (dec.). [a]rD:t: ¼ ꢀ41.9 (c ¼ 1.04,
CHCl3). IR (CHCl3): 3338w, 3064w, 2992w, 1731s, 1533m, 1496m, 1446m, 1372w, 1254m, 1177s, 1080m,
1
1053m, 893m, 866m, 846m. H-NMR (400 MHz, CDCl3): ꢀ 0.26 (s, Me3Si); 1.10 (s, Me); 1.25 (s, Me);
4.14 (d, J ¼ 8.2, CH); 4.38 (d, J ¼ 8.2, CH); 7.03 – 7.10 (m, 4 arom. H); 7.15 – 7.28 (m, 6 arom. H); 7.42 –
7.49 (m, 6 arom. H); 7.63 – 7.72 (m, 4 arom. H); 8.04 (br. s, NH). 13C-NMR (100 MHz, CDCl3): 2.18, 26.75,
1
26.99 (Me); 66.18 (C); 81.48 (CH); 81.68 (C); 83.17 (CH); 107.05, 115.63 (q, J(C,F) ¼ 289, CF3) (C);
127.13, 127.33, 127.48, 127.75, 127.94, 127.99, 128.05, 128.55, 129.34, 130.63 (CH); 135.93, 141.02, 142.11,
2
142.29, 155.49 (q, J(C,F) ¼ 37, CO) (C). 19F-NMR (282 MHz, CDCl3): ꢀ 74.39. MALDI-FT-ICR-MS:
656.2 (25, [M þ Na]þ), 566.2 (10), 486.3 (5), 431.2 (5), 395.1 (10), 301.1 (100), 273.0 (62), 255.1 (44).
HR-MS: 656.2419 ([M þ Na]þ, C36H38F3NNaO4Si; calc. 656.2414 (þ0.76 ppm)).
2,2,2-Trifluoro-N-[{(4S,5R)-5-[(hydroxy)(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}(diphe-
nyl)methyl]acetamide (22). To a soln. of 20 (7.26 g, 11.45 mmol) in THF (60 ml) was added (Bu)4NF ·
3 H2O (5.40 g, 17.20 mmol) at r.t. After stirring for 30 min (TLC control) at ambient temp., Et2O
(30 ml) was added, and the mixture was washed with 1n HCl soln. The org. layer was separated, and the
aq. layer was extracted with Et2O (2ꢁ). The combined org. layers were washed with H2O and sat. NaCl
soln., and dried (Na2SO4). The solvent was removed under reduced pressure, and the crude product was
purified by FC (pentane/Et2O 8 :2; 150 g SiO2). Subsequent trituration with hexane under reflux for 2 h
yielded 22 (5.75 g, 89%). Colorless solid. M.p. 196 – 1998. [a]rD:t: ¼ ꢀ103.1 (c ¼ 1.07, CHCl3). IR (CHCl3):
3584w, 3254m, 3065m, 2994w, 2936w, 1957w, 1892w, 1735s, 1572m, 1496m, 1447m, 1382m, 1372m, 1337w,
1322w, 1177s, 1163s, 1098m, 1030m, 885m, 637w. 1H-NMR (400 MHz, CDCl3): 0.60 (s, Me); 1.03 (s, Me);
2.90 (s, OH); 4.35 (d, J ¼ 7.6, CH); 4.88 (d, J ¼ 7.6, CH); 7.22 – 7.50 (m, 20 arom. H); 9.85 (br. s, NH).
13C-NMR (100 MHz, CDCl3): 26.80, 27.27 (Me); 65.78, 79.20 (C); 79.88, 81.82 (CH); 110.15, 116.09 (q,
1J(C,F) ¼ 290, CF3) (C); 127.35, 127.37, 127.46, 127.50, 127.57, 127.95, 128.02, 128.46, 128.74, 129.08, 129.15,
129.72 (CH); 135.40, 140.72, 141.12, 145.88, 155.32 (q, 2J(C,F) ¼ 36, CO) (C). 19F-NMR (282 MHz,
CDCl3): ꢀ 75.44. ESI-MS (pos.): 616 (6, [M þ MeOH þ Na]þ), 600 (32, [M þ K]þ), 584 (33, [M þ
Na]þ), 579 (100, [M þ NH4]þ), 544 (18, [M ꢀ OH]þ), 431 (18, [M ꢀ OH ꢀ NHCOCF3 ꢀ 1]þ). ESI-MS
(neg.): 560 (100, [M ꢀ 1]ꢀ). Anal. calc. for C33H30F3NO4 (561.60): C 70.58, H 5.38, N 2.49; found: C 70.40,
H 5.56, N 2.47.

Helvetica Chimica Acta – Vol. 95 (2012)
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7. Preparation of the TADDOL-Derived thiols 7, ent-7, 8, 31, 32, ent-32, 33 – 38 and 45. (4R,5R)- and
(4S,5S)-5-[(Diphenyl)(sulfanyl)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-methanol (7 and ent-
7, resp.). Compound 726). Monochloride 4 (7.00 g, 14.40 mmol) was treated with thiourea (22.0 g,
290 mmol) in DMF (45 ml) according to GP 5. FC (SiO2 (450 g); hexane/AcOEt 98 :2 ! 95 :5) and
subsequent trituration with boiling pentane (20 ml) for 1 h yielded 7 (4.50 g). After partially removing
the solvent from the mother liquor, further 7 (750 mg) were obtained. Total yield: 5.25 g (75%).
Colorless powder. M.p. 128 – 1298 ([40a]: 120 – 1218). Rf (hexane/AcOEt 98 :2) 0.29. [a]rD:t: ¼ ꢀ36.2 (c ¼
1.0, CHCl3) ([40a]: [a]rD:t: ¼ ꢀ31.8 (c ¼ 1, CHCl3)). IR (CHCl3): 3566m, 3365w, 3061m, 3008s, 2936w,
2561w, 1954w, 1892w, 1599w, 1494s, 1446s, 1380s, 1370s, 1165s, 1064s, 1036m, 1016m, 972w, 886m.
1H-NMR (300 MHz, CDCl3): 0.86 (s, Me); 1.05 (s, Me); 2.34, 2.35 (2s, OH, SH); 4.97 (d, J ¼ 6.7, CH); 5.14
(d, J ¼ 6.7, CH); 7.18 – 7.49 (m, 20 arom. H). 13C-NMR (75 MHz, CDCl3): 27.69, 27.80 (Me); 60.58, 78.12
(C); 82.16, 83.18 (CH); 110.83 (C); 127.02, 127.10, 127.13, 127.25, 127.35, 127.49, 127.60, 127.93, 128.02,
128.66, 130.18 (CH); 143.51, 144.67, 146.32, 146.61 (C). ESI-MS (pos.): 537 (6, [M þ MeOH þ Na]þ), 521
(7, [M þ K]þ), 505 (12, [M þ Na]þ), 500 (100, [M þ NH4]þ). ESI-MS (neg.): 481 (100, [M ꢀ 1]ꢀ), 423
(6, [M ꢀ 58]ꢀ). Anal. calc for C31H30O3S (482.64): C 77.15, H 6.26, S 6.64; found: C 77.25, H 6.28, S 6.58.
The NMR data matched those of [40a].
Compound ent-7. Compound ent-4 (2.0 g, 4.1 mmol) was treated with thiourea (6.3 g, 82 mmol) in
DMF (20 ml) according to GP 5. FC (250 g of SiO2) and tritutarion with pentane (15 ml) yielded ent-7
(1.25 g, 63%). [a]rD:t: ¼ þ36.7 (c ¼ 1.0, CHCl3).
(4R,5R)-5-[(Diphenyl)(sulfanyl)methyl]-a,a,2,2-tetraphenyl-1,3-dioxolane-4-methanol (8). Mono-
chloride 5 (3.00 g, 4.90 mmol) was treated with thiourea (9.4 g, 123 mmol) in DMF (35 ml) according to
GP 5. FC (SiO2 (200 g); pentane/Et2O 95 :5) yielded 8 (1.9 g, 63%). For anal. purposes, a sample was
recrystallized (pentane, ꢀ 208). Colorless solid. M.p. 118 – 1198. Rf (hexane/dioxane 9 :1) 0.27. [a]Dr:t:
¼
þ148.8 (c ¼ 1.0, CHCl3). IR (CHCl3): 3542s, 3062m, 3007m, 2582w, 1949w, 1889w, 1810w, 1598w,
1492s, 1449s, 1323w, 1103s, 1062s, 1028s, 962m, 942m, 639m. 1H-NMR (400 MHz, CDCl3): 1.54, 1.66 (2s,
OH, SH); 5.56 (d, J ¼ 3.7, CH); 5.76 (d, J ¼ 3.7, CH); 6.95 – 7.46 (m, 30 arom. H). 13C-NMR (100 MHz,
CDCl3): 60.82, 79.82 (C); 84.13, 85.71 (CH); 112.15 (C); 124.80, 125.10, 126.48, 126.52, 126.65, 126.72,
127.03, 127.10, 127.75, 127.85, 127.88, 127.96, 128.11, 128.67, 129.58 (CH); 142.62, 144.42, 144.65, 144.92,
145.61, 146.33 (C). MALDI-FT-ICR-MS: 629.2 (100, [M þ Na]þ), 413.2 (24, [M ꢀ SH ꢀ Ph2CO ꢀ 1 þ
Na]þ), 273.0 (35). HR-MS: 629.2104 ([M þ Na]þ, C41H34NaO3S; calc. 629.2121 (ꢀ2.70 ppm)). Anal.
calc. for C41H34O3S (606.78): C 81.16, H 5.65, S 5.28; found: C 81.28, H 5.91, S 5.13.
(4R,5S)-5-[(Dimethylamino)(diphenyl)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-metha-
nethiol (31). Monochloride 23 (1.87 g, 3.65 mmol) was treated with thiourea (8.4 g, 111 mmol) in DMF
(30 ml) according to GP 5. FC (SiO2 (80 g); pentane/Et2O 8 :2) yielded 31 (1.56 g, 84%). For anal.
purposes, a sample was recrystallized (pentane). Colorless crystals. [a]rD:t: ¼ ꢀ90.9 (c ¼ 1.0, CHCl3), ꢀ
60.9 (c ¼ 1.0, AcOEt) ([24b]: ꢀ 54.1 (c ¼ 0.98, AcOEt)). 1H-NMR (300 MHz, CDCl3): 0.60 (s, Me);
1.14 (s, Me); 1.70 (s, MeN); 2.20 (s, NMe); 4.48 (d, J ¼ 8.1, CH); 4.99 (d, J ¼ 8.1, CH); 6.85 – 7.39 (m, 16
arom. H); 7.50 – 7.57 (m, 1 arom. H); 8.10 – 8.14 (m, 2 arom. H); 8.21 – 8.26 (m, 1 arom. H); 9.51 (br. s,
SH). The anal. data match those of [24b].
(4R,5R)- and (4S,5S)-5-[(Methoxy)(diphenyl)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-
methanethiol (32 and ent-32). Compound 32. Monochloride 24 (4.00 g, 8.02 mmol) was treated with
thiourea (6.0 g, 79 mmol) in DMF (35 ml) according to GP 5. FC (hexane/AcOEt 95 :5; 200 g SiO2)
yielded 32 (2.65 g, 66%). For anal. purposes, a sample was recrystallized (pentane/CH2Cl2). Colorless
powder. M.p. 182 – 1838. Rf (hexane/AcOEt 95 :5) 0.39. [a]rD:t: ¼ þ6.5 (c ¼ 1.0, CHCl3). IR (CHCl3):
3059m, 2990s, 2937m, 2831w, 2512m, 1958w, 1599m, 1493s, 1445s, 1380s, 1370s, 1318m, 1177s, 1081s, 1033s,
1020m, 893s, 867m. 1H-NMR (500 MHz, CDCl3): 0.95 (s, Me); 1.10 (s, Me); 2.62 (s, MeO); 4.07 (s, SH);
4.69 (s, 2 CH); 7.11 – 7.31 (m, 13 arom. H); 7.35 – 7.40 (m, 3 arom. H); 7.45 – 7.49 (m, 2 arom. H); 7.64 – 7.66
(m, 2 arom. H). 13C-NMR (125 MHz, CDCl3): 27.37, 27.50, 51.81 (Me); 59.68 (C); 80.57, 82.68 (CH);
84.18, 108.07 (C); 126.39, 126.72, 126.91, 126.98, 127.43, 127.54, 127.68, 128.62, 129.87, 130.60, 130.88 (CH);
26
)
The sulfanyl alcohol 7 has first been prepared in 30% yield by treatment of 1 with Lawesson
reagent, and the preparation of the corresponding O,S-acetal of CH2O (cf. 43 and 44) was described
in the same report [40a].

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Helvetica Chimica Acta – Vol. 95 (2012)
138.26, 140.47, 144.91, 146.23 (C). FAB-MS: 495 (9, [M ꢀ 1]þ), 463 (43, [M ꢀ SH]þ), 447 (21, [M ꢀ SH ꢀ
Me ꢀ 1]þ), 431 (96, [M ꢀ SH ꢀ MeO ꢀ 1]þ), 407 (35, [M ꢀ MeO ꢀ Me2CO]þ), 389 (28), 373 (25), 237
(91, [M ꢀ MeO ꢀ OCHCPh2SH]þ), 197 (100), 179 (70). Anal. calc. for C32H32O3S (496.67): C 77.39, H
6.49, S 6.46; found: C 77.28, H 6.31, S 6.34.
Compound ent-32. Compound ent-24 (745 mg, 1.50 mmol) was treated with thiourea (1.1 g,
15 mmol) in DMF (10 ml) according to GP 5. FC (80 g SiO2) yielded ent-32 (490 mg, 67%). [a]rD:t: ¼ ꢀ6.1
(c ¼ 1.0, CHCl3).
(4R,5R)-5-{(Methoxy)[di(naphthalen-2-yl]methyl}-2,2-dimethyl-a,a-di(naphthalen-2-yl)-1,3-dioxo-
lane-4-methanethiol (33). Monochloride 25 (2.10 g, 3.00 mmol) was treated with thiourea (12.0 g,
158 mmol) in DMF (30 ml) according to GP 5. FC (2 ꢁ ; 1. SiO2 (70 g); pentane/Et2O 95 :5; 2. SiO2
(210 g); hexane/toluene 1:1) yielded 33 (0.95 g, 47%). For anal. purposes, a sample was purified by
further FC (SiO2 (10 g); pentane/Et2O 95 :5). Colorless solid. M.p. 160 – 1618. Rf (pentane/Et2O 95 :5)
0.25. [a]rD:t: ¼ þ63.0 (c ¼ 1.1, CHCl3). IR (CHCl3): 3060s, 2958s, 2935m, 2512w, 1950w, 1922w, 1631w,
1599m, 1504s, 1463w, 1433w, 1380s, 1370s, 1274m, 1170s, 1126s, 1084s, 1064s, 1019w, 951w, 891s, 860s.
1H-NMR (400 MHz, CDCl3): 1.07 (s, Me); 1.29 (s, Me); 2.41 (s, MeO); 3.92 (s, SH); 4.94 (d, J ¼ 7.5, CH);
5.09 (d, J ¼ 7.5); 7.24 – 7.30 (m, 2 arom. H); 7.37 – 7.58 (m, 8 arom. H); 7.63 – 7.83 (m, 15 arom. H); 7.85 –
7.94 (m, 2 arom. H); 8.20 (s, 1 arom. H). 13C-NMR (100 MHz, CDCl3): 27.57, 27.73, 52.17 (Me); 60.67 (C);
81.04, 83.05 (CH); 84.16, 108.29 (C); 125.83, 125.90, 125.97, 126.07, 126.14, 126.23, 126.35, 126.63, 126.84,
127.15, 127.23, 127.27, 127.28, 127.33, 127.35, 127.53, 127.65, 128.35, 128.42, 128.59, 128.63, 128.67, 129.40,
129.44, 129.51 (CH); 132.18, 132.22, 132.41, 132.44, 132.46, 132.67, 132.80, 132.82, 136.63, 138.03, 142.47,
143.12 (C). ESI-MS (pos.): 751 (42, [M þ MeOH þ Na]þ), 735 (22, [M þ K]þ), 719 (100, [M þ Na]þ).
ESI-MS (neg.): 696 (56, Mꢀ), 695 (100, [M ꢀ 1]ꢀ). Anal. calc. for C48H40O3S (696.91): C 82.73, H 5.78, S
4.60; found: C 82.62, H 5.86, S 4.57.
(4R,5R)-2,2-Dimethyl-5-[(1-methylethoxy)(diphenyl)methyl]-a,a-diphenyl-1,3-dioxolane-4-metha-
nethiol (34). A ca. 7:3 mixture (3.10 g) of 26 (2.24 g, 4.25 mmol) and 15 was treated with thiourea (9.0 g,
118 mmol) in DMF (38 ml) according to GP 5. FC (SiO2 (100 g); pentane/Et2O 97:3) and subsequent
trituration with MeOH (8 ml) for 30 min yielded 33 (1.65 g, 74%). Colorless solid. M.p. 177 – 1798. Rf
(pentane/Et2O 9 :1) 0.69. [a]rD:t: ¼ ꢀ43.2 (c ¼ 1.1, CHCl3). IR (CHCl3): 3059m, 2987m, 2935m, 2508m,
1599w, 1492m, 1444s, 1381s, 1370s, 1316w, 1177s, 1113m, 1074s, 1060s, 1038s, 1019s, 919w, 898m, 870w,
832w, 651w, 633w. 1H-NMR (400 MHz): 0.43 (d, J ¼ 5.9, Me); 0.86 (s, Me); 0.92 (s, Me); 1.29 (d, J ¼ 6.2,
Me); 3.59 – 3.69 (m, CH); 4.41 (d, J ¼ 7.7, CH); 4.58 (d, J ¼ 7.7, CH); 5.45 (s, SH); 7.12 – 7.30 (m, 10 arom.
H); 7.32 – 7.43 (m, 6 arom. H); 7.65 – 7.70 (m, 2 arom. H); 7.72 – 7.77 (m, 2 arom. H). 13C-NMR
(100 MHz): 23.66, 24.38, 27.07, 27.19 (Me); 57.84 (C); 68.32, 81.33, 82.75 (CH); 85.34, 107.37 (C); 126.33,
126.64, 126.74, 126.98, 127.44, 127.52, 127.56, 127.84, 128.43, 130.39, 130.89, 131.97 (CH); 139.11, 141.06,
142.62, 147.08 (C). ESI-MS (pos.): 579 (98, [M þ MeOH þ Na]þ), 563 (74, [M þ K]þ), 547 (100, [M þ
Na]þ). ESI-MS (neg.): 523 (88, [M ꢀ 1]ꢀ), 265 (100), 255 (74). Anal. calc. for C34H36O3S (524.72): C
77.83, H 6.91, S 6.11; found: C 77.71, H 7.01, S 6.10.
(4R,5R)-5-[(Diphenyl)(phenylmethoxy)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-metha-
nethiol (35). Monochloride 27 (3.05 g, 5.30 mmol) was treated with thiourea (8.1 g, 106 mmol) in DMF
(32 ml) according to GP 5. FC (SiO2 (80 g); pentane/Et2O 95 :5) yielded 35 (2.52 g, 83%). Colorless
solid foam. Subsequent trituration with MeOH yielded 35 (1.98 g, 65%). Colorless solid. M.p. 93 – 968. Rf
(pentane/Et2O 95 :5) 0.50. [a]rD:t: ¼ ꢀ60.0 (c ¼ 0.95, CHCl3). IR (CHCl3): 3062m, 3008s, 2932w, 2880w,
2527m, 1597w, 1494s, 1445s, 1380m, 1371m, 1318w, 1171m, 1065s, 1023s, 922m, 900m, 866w, 656w, 628w.
2
2
1H-NMR (400 MHz): 0.97 (s, Me); 1.02 (s, Me); 3.80 (d, J ¼ 10.7, 1 H, CH2); 4.21 (d, J ¼ 10.7, 1 H,
CH2); 4.46 (d, J ¼ 7.8, CH); 4.58 (d, J ¼ 7.8, CH); 4.60 (s, SH); 7.05 – 7.14 (m, 5 arom. H); 7.20 – 7.33 (m,
13 arom. H); 7.35 – 7.48 (m, 3 arom. H); 7.55 – 7.61 (m, 2 arom. H); 7.67 – 7.73 (m, 2 arom. H). 13C-NMR
(100 MHz): 27.09, 27.17 (Me); 57.91 (C); 66.88 (CH2); 80.95, 83.10 (CH); 84.99, 107.35 (C); 126.31, 126.74,
126.99, 127.07, 127.44, 127.64, 127.67, 127.82, 127.85, 128.29, 128.35, 128.45, 129.81, 130.58, 131.57 (CH);
137.61, 137.88, 140.78, 142.66, 146.69 (C). ESI-MS (pos.): 627 (15, [M þ MeOH þ Na]þ), 611 (86, [M þ
K]þ), 595 (78, [M þ Na]þ), 590 (100, [M þ NH4]þ). ESI-MS (neg.): 571 (100, [M ꢀ 1]ꢀ). Anal. calc. for
C38H36O3S (572.77): C 79.69, H 6.33, S 5.60; found: C 79.65, H 6.27, S 5.48.
(4R,5R)-5-{[4-(1,1-Dimethylethyl)phenoxy](diphenyl)methyl}-2,2-dimethyl-a,a-diphenyl-1,3-dioxo-
lane-4-methanethiol (36). Monochloride 28 (2.40 g, 3.75 mmol) was treated with thiourea (5.7 g,

Helvetica Chimica Acta – Vol. 95 (2012)
1263
75 mmol) in DMF (50 ml) according to GP 5. FC (pentane/Et2O 98 :2; 250 g SiO2) yielded 36 (980 mg,
43%). Colorless powder. M.p. 105 – 1088. Rf (pentane/Et2O 9 :1) 0.72. [a]rD:t: ¼ ꢀ64.5 (c ¼ 1.0, CHCl3). IR
(CHCl3): 3061w, 3007m, 2984m, 2554w, 1604w, 1508s, 1445m, 1380m, 1370m, 1177s, 1062m, 1033w, 1015m,
924w, 896m. 1H-NMR (400 MHz): 0.98 (s, Me); 1.06 (s, Me); 1.16 (s, tBu); 3.93 (s, SH); 4.57 (d, J ¼ 7.65,
CH); 4.75 (d, J ¼ 7.65, CH); 6.48 – 6.51 (m, 2 arom. H); 6.89 – 6.96 (m, 2 arom. H); 7.04 – 7.24 (m, 10
arom. H); 7.31 – 7.47 (m, 6 arom. H); 7.74 – 7.84 (m, 4 arom. H). 13C-NMR (100 MHz): 27.15, 27.21, 31.36
(Me); 33.94, 58.83 (C); 83.15, 83.40 (CH); 87.25, 107.65 (C); 120.60, 125.01, 126.36, 126.90, 126.95, 127.08,
127.32, 127.47, 127.53, 127.70, 128.41, 129.72, 130.80, 131.36 (CH); 137.94, 139.87, 143.04, 144.36, 147.04,
152.37 (C). ESI-MS (pos.): 669 (46, [M þ MeOH þ Na]þ), 653 (44, [M þ K]þ), 637 (100, [M þ Na]þ).
ESI-MS (neg.): 613 (100, [M ꢀ 1]ꢀ). Anal. calc. for C41H42O3S (614.85): C 80.09, H 6.88, S 5.22; found: C
80.08, H 7.03, S 5.31.
N-[{(4S,5R)-5-[(Diphenyl)(sulfanyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}(diphenyl)methyl]-
1,1,1-trifluoromethanesulfonamide (37). A soln. of 29 (3.90 g, 6.30 mmol) in CH2Cl2 (8 ml) was treated
with thiourea (12.0 g, 158 mmol) in DMF (60 ml) according to GP 5. After purification by FC (SiO2
(60 g); pentane/Et2O 9 :1), the resulting solid foam was dissolved in CH2Cl2 and precipitated with
hexane. Further trituration with hexane under reflux yielded 37 (2.90 g, 74%). Colorless solid. M.p. 185 –
1908 (dec.). Rf (hexane/AcOEt 8 :2) 0.42. [a]rD:t: ¼ ꢀ59.7 (c ¼ 1.16, CHCl3). IR (CHCl3): 3274m, 3064m,
2886m, 2825w, 1598w, 1496m, 1445m, 1373s, 1177m, 1139m, 1080m, 1055m, 1033m, 897w, 858w, 600s.
1H-NMR (400 MHz, CDCl3): 0.81 (s, Me); 1.08 (s, Me); 2.27 (s, SH); 4.33 (d, J ¼ 7.5, CH); 4.70 (d, J ¼
7.5, CH); 7.10 – 7.31 (m, 10 arom. H); 7.37 – 7.50 (m, 8 arom. H); 7.67 – 7.70 (m, 2 arom. H); 8.75 (br. s,
NH). 13C-NMR (100 MHz, CDCl3): 26.78, 27.19 (Me); 57.98, 70.06 (C); 82.59, 82.68 (CH); 108.36, 118.96
1
(q, J(C,F) ¼ 322, CF3) (C); 126.96, 127.14, 127.67, 127.72, 128.15, 128.17, 128.54, 129.82, 130.51, 130.88
(CH); 137.96, 138.12, 139.78, 147.99 (C). 19F-NMR (282 MHz, CDCl3): ꢀ 76.80. ESI-MS (pos.): 668 (17,
[M þ MeOH þ Na]þ), 658 (16, [M þ 45]þ), 652 (5, [M þ K]þ), 636 (100, [M þ Na]þ), 631 (16, [M þ
NH4]þ). ESI-MS (neg.): 612 (100, [M ꢀ 1]ꢀ). Anal. calc. for C32H30F3NO4S2 (613.72): C 62.63, H 4.93,
N 2.28, S 10.45; found: C 62.40, H 5.05, N 2.20, S 10.49.
N-[{(4S,5R)-5-[(Diphenyl)(sulfanyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}(diphenyl)methyl]-
2,2,2-trifluoroacetamide (38). A soln. of crude 30 (2.56 g, ca. 3.90 mmol) in CH2Cl2 (5 ml) was treated
with thiourea (7.4 g, 97 mmol) in DMF (20 ml) according to GP 5. FC (pentane/Et2O 95 :5; 120 g SiO2)
yielded 38 (1.70 g, 75% from 22). Colorless foam. Trituration with hexane (35 ml) yielded anal. pure 38
(1.28 g, 56% from 22). Colorless solid. M.p. 159 – 1618. [a]rD:t: ¼ ꢀ97.4 (c ¼ 1.14, CHCl3). IR (CHCl3):
3399w, 3230w, 3062w, 2936w, 1736s, 1540m, 1496m, 1444m, 1381m, 1372w, 1327w, 1177s, 1060m, 897w,
865w, 657w. 1H-NMR (400 MHz, CDCl3): 0.71 (s, Me); 0.90 (s, Me); 2.05 (s, SH); 4.80 (d, J ¼ 7.1, CH ) ;
4.90 (d, J ¼ 7.1, CH); 7.13 – 7.51 (m, 20 arom. H); 8.66 (br. s, NH). 13C-NMR (100 MHz, CDCl3): 26.92,
27.23 (Me); 57.96, 66.94 (C); 82.39, 82.87 (CH); 109.21, 115.80 (q, 1J(C,F) ¼ 290, CF3) (C); 127.45, 127.52,
127.65, 127.85, 127.88, 127.92, 128.00, 128.35, 129.37, 129.61, 130.72 (CH); 136.75, 139.84, 140.78, 148.10,
155.11 (q, 2J(CF) ¼ 37, CO) (C). 19F-NMR (282 MHz, CDCl3): ꢀ 75.19. MALDI-FT-ICR-MS: 600.2
(100, [M þ Na]þ), 566.2 (10), 487.2 (4), 431.2 (7), 301.1 (11), 200.1 (10). Anal. calc. for C33H30F3NO3S
(577.67): C 68.61, H 5.23, N 2.42, S 5.55; found: C 68.71, H 5.34, N 2.42, S 5.45.
(4R,5R)-2,2-Dimethyl-a,a,a’,a’-tetraphenyl-1,3-dioxolane-4,5-dimethanethiol (45). A soln. of di-
chloro-TADDOL [24] (3.00 g, 5.96 mmol) in DMF (30 ml, degassed by three freeze-thaw cycles) was
treated with thiourea (15.0 g, 197 mmol) according to GP 5. Purification by FC (SiO2 (80 g); pentane/
Et2O 95 :5 ! 9 :1) yielded a 9 :1 mixture (1H-NMR) 45/46 (total yield: 2.00 g, 67%). A sample (600 mg)
was purified by FC (SiO2 (80 g); pentane (10 l) ! pentane/Et2O 95 :5) to yield pure (> 96% according to
1H-NMR) 45 (250 mg). For anal. purposes, a sample was recrystallized from pentane. Colorless solid.
M.p. 148.5 – 149.58. Rf (pentane; 10 runs) 0.30 (46: 0.49). [a]rD:t: ¼ ꢀ32.4 (c ¼ 1.5, CHCl3). IR (CHCl3):
3061m, 3008s, 2936w, 2569w, 1597w, 1493s, 1444s, 1380m, 1370m, 1162m, 1084m, 1055s, 1038m . 1H-NMR
(300 MHz, CDCl3): 0.98 (s, 2 Me); 2.03 (s, 2 SH); 5.29 (s, 2 CH); 7.14 – 7.37 (m, 16 arom. H); 7.48 – 7.52
(m, 4 arom. H). 13C-NMR (75 MHz, CDCl3): 28.01 (Me); 60.11 (C); 83.92 (CH); 110.50 (C); 126.97,
127.09, 127.54, 127.99, 129.27, 130.48 (CH); 145.16, 146.97 (C). ESI-MS (neg.): 497.2 (100, [M ꢀ 1]ꢀ).
Anal. calc. for C31H30O2S2 (498.71): C 74.66, H 6.06, S 12.86; found: C 74.69, H 6.17, S 12.71. A 6 :4
mixture 45/46 has already been reported in the literature [24b].

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Helvetica Chimica Acta – Vol. 95 (2012)
8. Preparation of Thioether 39, Trifluoromethanesulfonamide 40, Formamidine 41, Oxathiepines 43
and 44, Thiophene 47, Sn Complex 48, and Pd Complex 49. (4S,5R)-N,N,2,2-Tetramethyl-5-[(methyl-
sulfanyl)(diphenyl)methyl]-a,a-diphenyl-1,3-dioxolane-4-methanamine (39). A soln. of 31 (100 mg,
0.20 mmol) in MeCN/CH2Cl2 2 :1 (3 ml) was treated with K2CO3 (28 mg, 0.20 mmol) and MeI (14 ml,
0.22 mmol) according to GP 6 at r.t. After stirring overnight, purification by FC (SiO2 (15 g); pentane/
Et2O 96 :4) yielded 39 (90 mg, 85%). Colorless solid foam. M.p. 148 – 1548. Rf (hexane/AcOEt 8 :2) 0.52.
[a]Dr:t: ¼ ꢀ40.8 (c ¼ 1.3, CHCl3). IR (CHCl3): 3089w, 3058w, 2935w, 2867w, 2831w, 2788w, 1597w, 1491m,
1
1443m, 1379w, 1359w, 1173m, 1054m, 1034m, 1011w, 928w, 886w. H-NMR (400 MHz, CDCl3): 0.49 (s,
Me); 1.04 (s, Me); 1.52 (s, Me); 1.75 (br. s, Me); 1.95 (br. s, Me); 4.77 (br. s, CH); 5.02 (br. s, CH); 6.70 –
7.60 (m, 17 arom. H); 7.85 – 7.90 (m, 2 arom. H); 7.95 – 8.25 (br. s, 1 arom. H). 13C-NMR (100 MHz,
CDCl3): 14.75, 26.63, 27.50, 41.28 (br.) (Me); 62.68, 74.18 (C); 77.45, 83.58 (CH); 106.87 (C); 125.85,
126.04, 126.84, 127.00, 127.19, 127.23, 129.28, 131.94 (CH); 137.57, 139.48, 144.61 (C). ESI-MS (pos.): 546
(4, [M þ Na]þ], 524 (100, [M þ 1]þ), 479 (18, [M ꢀ Me2N]þ), 431 (27, [M ꢀ Me2N ꢀ MeS ꢀ 1]þ). Anal.
calc. for C34H37NO2S (523.74): C 77.97, H 7.12, N 2.67, S 6.12; found: C 77.91, H 7.30, N 2.59, S 6.12.
N-[{(4S,5R)-2,2-Dimethyl-5-[(methylsulfanyl)(diphenyl)methyl]-1,3-dioxolan-4-yl}(diphenyl)meth-
yl]-1,1,1-trifluoromethanesulfonamide (40). A soln. of 37 (250 mg, 0.41 mmol) in MeCN/CH2Cl2 3 :2
(5 ml) was treated with K2CO3 (113 mg, 0.82 mmol) and MeI (26 ml, 0.42 mmol) according to GP 6 at r.t.
After stirring for 7 h, purification by FC (SiO2 (20 g); pentane/Et2O 95 :5) yielded 40 (226 mg, 87%).
Colorless solid. M.p. 181 – 1838. Rf (hexane/AcOEt 8 :2) 0.50. [a]rD:t: ¼ ꢀ107.6 (c ¼ 1.23, CHCl3). IR
(CHCl3): 3008m, 2871m, 2801m, 1598w, 1496m, 1444m, 1373s, 1177m, 1139m, 1081m, 1057m, 1032m,
966w, 938w, 896w, 853w, 600s. 1H-NMR (400 MHz, CDCl3): 0.61 (s, Me); 1.09 (s, Me); 1.58 (s, Me); 4.25
(d, J ¼ 7.4, CH); 4.77 (d, J ¼ 7.4, CH); 7.14 – 7.29 (m, 10 arom. H); 7.37 – 7.50 (m, 8 arom. H); 7.72 – 7.77
(m, 2 arom. H); 10.11 (br. s, NH). 13C-NMR (100 MHz, CDCl3): 13.37, 26.78, 27.41 (Me); 59.67, 69.50
(C); 78.70, 82.55 (CH); 108.41, 119.08 (q, 1J(C,F) ¼ 322, CF3) (C); 126.82, 126.98, 127.50, 127.54, 128.06,
128.09, 128.40, 129.80, 130.65 (CH); 138.53, 138.60, 140.24, 142.80 (C). 19F-NMR (282 MHz, CDCl3):
ꢀ 76.93. ESI-MS (pos.): 663 (8, [M þ K]þ), 650 (14, [M þ Na]þ), 645 (100, [M þ NH4]þ). ESI-MS
(neg.): 626 (100, [M ꢀ 1]ꢀ). Anal. calc. for C33H32F3NO4S2 (627.75): C 63.14, H 5.14, N 2.23, S 10.22;
found: C 63.24, H 5.15, N 2.19, S 10.16.
N’-[{(4S,5R)-5-[(Hydroxy)(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}(diphenyl)methyl]-
N,N-dimethylmethanimidamide (41). A soln. of 9 (1.40 g, 3.01 mmol) in CH2Cl2 (20 ml) was treated with
Et3N (0.40 ml, 2.86 mmol) and SOCl2 (0.40 ml, 5.50 mmol) according to GP 2. The residue was dissolved
in DMF (50 ml) and treated with thiourea (19.0 g, 250 mmol) according to GP 5. Purification by FC
(SiO2 (80 g); pentane/Et2O 9 :1 ! Et2O) yielded 41 (310 mg, 20%). Colorless crystals. M.p. 212 – 2158. Rf
(hexane/AcOEt 4 :1) 0.04. [a]rD:t: ¼ ꢀ27.0 (c ¼ 1.2, CHCl3). IR (CHCl3): 3056w, 3007m, 1637s, 1493m,
1
1444m, 1380m, 1370m, 1077m, 1050m, 901w, 886w. H-NMR (400 MHz, CDCl3): 1.05 (s, Me); 1.06 (s,
Me); 2.74 (br. s, MeN); 3.18 (br. s, MeN); 4.23 (d, J ¼ 8.4, CH); 4.37 (d, J ¼ 8.4, CH); 6.42 (s, OH); 7.02 –
7.06 (m, 2 arom. H); 7.11 – 7.34 (m, 14 arom. H); 7.59 – 7.64 (m, 4 arom. H); 9.46 (s, NCH). 13C-NMR
(100 MHz, CDCl3): 27.09, 27.12, 35.52 (br.), 40.96 (br.) (Me); 69.74, 76.88 (C); 81.83, 82.06 (CH); 107.88
(C); 126.46, 126.56, 126.65, 126.88, 126.91, 127.64, 127.78, 127.80, 129.12, 129.72, 130.56 (CH); 143.02,
144.14, 144.90, 147.48 (C); 156.26 (CH). FAB-MS: 1041.4 (16.5, [2 M þ H]þ), 521.2 (100, [M þ H]þ),
443.1 (8.8), 338.1 (8.1), 237.1 (61.2), 179.1 (27.5), 167.1 (23.2), 104.9 (19.6). Anal. calc. for C34H36N2O3
(520.67): C 78.43, H 6.97, N 5.38; found: C 78.41, H 6.78, N 5.45.
(3aR,8aR)-Tetrahydro-2,2,6-trimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3]oxathiepin (43). A
soln. of 7 (718 mg, 1.49 mmol) in CH2Cl2 (12 ml) was treated with MeCHO (0.50 ml, 8.85 mmol) and
BF3 · Et2O (0.20 ml, 1.60 mmol) according to GP 7. FC (SiO2 (80 g); hexane/AcOEt 9 :1) yielded 43
(623 mg, 82%). Colorless solid. M.p. 255 – 2578. Rf (hexane/AcOEt 9 :1) 0.50. [a]rD:t: ¼ ꢀ125.5 (c ¼ 1.1,
CHCl3). IR (CHCl3): 3062m, 3007s, 2931m, 1950br., 1900br., 1810br., 1711s, 1598m, 1492s, 1445s, 1382m,
1373s, 1248s, 1164s, 1074s, 1035s, 1001s, 967m, 924m, 896m, 877m, 857m, 832w, 658w, 635m, 615w, 607w.
1H-NMR (400 MHz, CDCl3): 0.10 (s, Me); 1.50 (d, J ¼ 7.2, MeCH); 1.52 (s, Me); 4.71 (d, J ¼ 8.6, CH);
5.11 (q, J ¼ 6.3, MeCH); 5.50 (d, J ¼ 8.6, CH); 7.12 – 7.29 (m, 10 arom. H); 7.32 – 7.38 (m, 4 arom. H);
7.40 – 7.42 (m, 2 arom. H); 7.49 – 7.51 (m, 2 arom. H); 7.59 – 7.61 (m, 2 arom. H). 13C-NMR (100 MHz,
CDCl3): 23.67, 24.55, 27.89 (Me); 60.31 (C); 73.74, 80.64 (CH); 83.02 (C); 83.16 (CH); 109.16 (C); 126.39,
127.07, 127.16, 127.19, 127.42, 127.65, 127.79, 127.84, 128.23, 128.77, 128.80, 132.49 (CH); 140.81, 141.54,

Helvetica Chimica Acta – Vol. 95 (2012)
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145.97, 149.60 (C). ESI-MS (pos.): 563 (8, [M þ MeOH þ Na]þ), 547 (35, [M þ K]þ), 526 (100, [M þ
NH4]þ). Anal. calc. for C33H32O3S (508.21): C 77.92, H 6.34, S 6.30; found: C 77.86, H 6.32, S 6.39.
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,6,8,8-pentaphenyl-1,3-dioxolo[4,5-e][1,3]oxathiepin (44). A
soln. of 7 (519 mg, 1.08 mmol) in CH2Cl2 (10 ml) was treated with PhCHO (0.11 ml, 1.08 mmol) and
BF3 · Et2O (0.14 ml, 1.08 mmol) according to GP 7. Purification by FC (2ꢁ) (SiO2 (50 g); hexane/AcOEt
95 :5) yielded 44 (324 mg, 53%). Colorless solid. M.p. 208 – 2108. Rf (hexane/AcOEt 9 :1) 0.40. [a]Dr:t:
¼
ꢀ300.2 (c ¼ 0.5, CHCl3). IR (CHCl3): 3065m, 3007m, 2934m, 1963br., 1800br., 1598m, 1493s, 1446s,
1392m, 1371m, 1316w, 1164s, 1067s, 1032s, 988m, 928s, 886m, 845m, 816w, 654w, 648w, 620m, 609w.
1H-NMR (400 MHz, CDCl3): 0.38 (s, Me); 1.16 (s, Me); 4.65 (d, J ¼ 8.1, CH); 5.81 (d, J ¼ 8.1, CH); 6.03 (s,
PhCH); 7.13 – 7.39 (m, 19 arom. H); 7.50 – 7.53 (m, 4 arom. H); 7.73 – 7.93 (m, 2 arom. H). 13C-NMR
(100 MHz, CDCl3): 25.55, 27.59 (Me); 62.87 (C); 80.32, 81.02, 82.38 (CH); 84.01 (C); 111.14 (C); 126.09,
127.12, 127.19, 127.24, 127.37, 127.56, 127.67, 127.84, 128.08, 128.28, 128.33, 128.38, 129.49, 131.48 (CH);
139.01, 140.88, 141.71, 144.01, 144.65 (C). ESI-MS (pos.): 630 (22, [M þ 60]þ), 616 (18, [M þ 46]þ), 588
(100, [M þ NH4]þ), 571 (12, [M þ 1]þ). Anal. calc. for C33H32O3S (570.75): C 79.97, H 6.00, S 5.62;
found: C 79.91, H 6.23, S 5.60.
(3aR,6aR)-Tetrahydro-2,2-dimethyl-4,4,6,6-tetraphenylthieno[3,4-d]-1,3-dioxole (47). In analogy to
[40b], to a soln. of hexamethyldisilathiane (0.27 ml, 1.30 mmol) in THF (10 ml) was added MeLi (1.60 ml,
2.55 mmol; 1.6m soln. in hexane), and the mixture was refluxed for 2 h. A soln. of dichloro-TADDOL
[24] (621 mg, 1.23 mmol) in THF (5 ml) was added, and the purple mixture was stirred under reflux for
44 h. After cooling to r.t., H2O (10 ml), Et2O (10 ml), and sat. NaCl soln. (10 ml) were added, the phases
were separated, and the aq. phase was extracted with Et2O (3 ꢁ 10 ml). The combined org. layers were
washed with H2O (10 ml) and sat. NaCl soln., and dried (Na2SO4). The solvent was removed under
reduced pressure, and the residue was purified by FC (SiO2 (70 g); hexane/AcOEt 9 :1) to yield 47
(334 mg, 58%). Beige solid foam. M.p. 174 – 1768 ([24a]: 1798). Rf (hexane/AcOEt 9 :1) 0.60. [a]Dr:t:
¼
ꢀ389.8 (c ¼ 0.5, CHCl3) ([24a]: [a]rD:t: ¼ ꢀ428.3 (c ¼ 1, CHCl3)). 1H-NMR (300 MHz): 1.20 (s, 6 H,
Me); 4.97 (s, 2 H, CH); 7.18 – 7.34 (m, 16 arom. H); 7.58 – 7.61 (m, 4 arom. H). The anal. data matched
those of [24a].
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,6,6,8,8-hexaphenyl[1,3,2]dithiastannepino[5,6-d]-1,3-diox-
ole (48). A 9 :1 mixture 45/46 (1.20 g, 2.40 mmol), dissolved in CH2Cl2 (20 ml), was treated with Ph2SnCl2
(830 mg, 2.40 mmol) and Et3N (0.70 ml, 5.02 mmol). The mixture was stirred for 12 h at r.t., washed with
0.5n NaOH soln. (10 ml), and the aq. phase was extracted with CH2Cl2. The combined org. layers were
dried (Na2SO4), and the solvent was removed under reduced pressure. The residue was dissolved in a
small amount of CCl4 and purified by FC (SiO2 (80 g); pentane/Et2O 95 :5; Rf (48) < Rf (45/46)).
Caution: 48 is prone to hydrolysis on SiO2. Trituration with MeOH under reflux for 5 min yielded 48
(950 mg, 51%). Colorless powder. M.p. 179 – 1808. Rf (hexane/AcOEt 8 :2) 0.50. [a]rD:t: ¼ ꢀ333.0 (c ¼ 1.95,
CHCl3). IR (CHCl3): 3056m, 3007s, 2938w, 1951w, 1896w, 1813w, 1597w, 1578w, 1492s, 1443s, 1431s, 1380s,
1370m, 1332w, 1071s, 1060s, 1045s, 1021w, 996m, 870w, 842m, 835m, 644w. 1H-NMR (400 MHz, CDCl3):
0.60 (s, 2 Me); 6.05 (s, 2 CH); 7.07 – 7.34 (m, 22 arom. H); 7.53 – 7.57 (m, 8 arom. H). 13C-NMR (100 MHz,
CDCl3): 27.06 (Me); 64.32 (t, 2J(C,Sn) ¼ 8.9) (C); 85.34 (t, 2J(C,Sn) ¼ 5.7) (CH); 109.12, 111.61 (C);
126.52, 126.84, 126.98, 127.67, 128.71 (t, 3J(C,Sn) ¼ 33.8), 129.17, 129.84 (t, 2J(C,Sn) ¼ 7.2), 131.13, 135.88
(t, J(C,Sn) ¼ 24.5) (CH); 137.62, 145.00 (t, 1J(C,Sn) ¼ 12.4), 148.79 (C). 119Sn-NMR (149 MHz, CDCl3):
ꢀ 27.04. EI-MS: 532 (9), 500 (7), 383 (5), 351 (8), 265 (10), 237 (8), 229 (6), 211 (11), 207 (58), 198
(100), 179 (42). Anal. calc. for C43H38O2S2Sn (769.61): C 67.11, H 4.98, S 8.33; found: C 67.10, H 4.98, S
8.10.
[(4R,5R)-2,2-Dimethyl-a,a,a’,a’-tetraphenyl-1,3-dioxolane-4,5-dimethanethiolato(2ꢀ)-kS4,kS5]{1,1’-
(1,2-ethanediyl)bis[1,1-diphenylphosphine-kP]}palladium (49).
A 9 :1 mixture 45/46 (500 mg,
1.00 mmol), dissolved in CH2Cl2 (10 ml), was treated with [Pd(dppe)Cl2] (518 mg, 0.90 mmol) and
Et3N (250 ml, 1.80 mmol). The mixture was stirred for 15 min at r.t., during which the color of the
suspension changed from yellow to orange-red. After filtration the solvent was removed under reduced
pressure to ca. 2 – 3 ml, and, after FC (SiO2 (15 g); CH2Cl2; Rf (49) < Rf (45/46)), 49 (672 mg, 79%) was
isolated. For anal. purposes, a sample of 49 was recrystallized (CH2Cl2). Orange-yellow crystals. M.p.
150 – 1608 (dec.). Rf (CH2Cl2) 0.41. [a]rD:t: n.d. (0% transmission). IR (CHCl3): 3054m, 3006s, 2933w,
1595w, 1486s, 1436s, 1412w, 1378w, 1368w, 1308w, 1175w, 1103s, 1044s, 999w, 877m. 1H-NMR (400 MHz,

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Helvetica Chimica Acta – Vol. 95 (2012)
CDCl3): 0.82 (s, 2 Me); 2.04 – 2.24 (m, 2 H); 2.29 – 2.45 (m, 2 H); 5.70 (s, 2 CH); 6.89 – 6.97 (m, 6 arom.
H); 7.06 – 7.13 (m, 10 arom. H); 7.23 – 7.29 (m, 4 arom. H); 7.34 – 7.38 (m, 6 arom. H); 7.43 – 7.48 (m, 6
arom. H); 7.62 – 7.67 (m, 4 arom. H); 7.91 – 7.96 (m, 4 arom. H). 13C-NMR (100 MHz, CDCl3): 27.33 (dd,
1J(C,P) ¼ 2J(C,P) ¼ 22.5) (CH2); 62.84 (C); 85.31 (CH); 108.38 (C); 124.35, 125.31, 125.69, 126.46, 128.27,
128.32, 128.38, 128.80, 128.86, 128.93, 129.07, 129.29, 129.55, 129.77, 129.99, 130.22, 130.43, 130.71, 131.25,
132.93, 133.04, 133.09, 133.14, 134.30, 134.36, 134.42, 146.35, 152.54, 152.56 (C,P coupling!). 31P-NMR
(162 MHz, CDCl3): 48.13. ESI-MS (pos.): 1039 (60, [M þ K – 1]þ), 1023 (100, [M þ Na – 1]þ), 1001 (58,
Mþ), 569 (21), 537 (16). Anal. calc. for C57H52O2P2PdS2 (1001.54): C 68.36, H 5.23, S 6.40, P 6.19; found:
C 68.21, H 5.46, S 6.32, P 6.24.
9. Preparation of the Cu and Ag complexes 50 – 54. Tetrakis{m-(4R,5R)-5-[(Diphenyl)(sulfa-
nylꢀkS,kS)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-methanolato(1ꢀ)}tetracopper(I) (50). To
a stirred soln. of 7 (750 mg, 1.55 mmol) in CH2Cl2 (12 ml) at r.t. were added Et3N (325 ml, 2.33 mmol) and
CuCl (153 mg, 1.55 mmol). After 25 min, the heterogeneous mixture was concentrated to ca. 2 ml on a
rotovap, and the residue was purified by FC (SiO2 (10 g); pentane/Et2O 1:1). To the combined fractions
containing 50 was added hexane (10 ml), and subsequent concentration on a rotovap led to precipitation
of 50 (710 mg, 84%). Colorless solid. M.p. 192 – 1958 (dec.). Rf (hexane/AcOEt 8 :2) 0.45. [a]rD:t: ¼ ꢀ71.6
(c ¼ 1.04, CHCl3). IR (CHCl3): 3360s, 3058w, 3007m, 2936w, 1597w, 1493m, 1446m, 1380m, 1370m,
1169m, 1060s, 1033w, 901w, 882w. 1H-NMR (400 MHz): 0.60 (s, 2 Me); 0.68 (s, 2 Me); 0.82 (s, 2 Me); 1.32
(s, 2 Me); 4.20 (d, J ¼ 8.0, 2 CH); 4.42 (d, J ¼ 8.0, 2 CH); 4.47 (d, J ¼ 6.5, 2 CH); 4.79 (s, 2 OH); 5.35 (d,
J ¼ 6.5, 2 CH); 5.38 (s, 2 OH); 5.92 (br., 2 arom. H); 6.43 (br., 2 arom. H); 6.50 – 7.95 (m, 76 arom. H).
13C-NMR (100 MHz, CDCl3): 26.55, 27.17, 27.53 (Me); 60.95, 61.37, 77.19, 77.76 (C); 81.40, 82.79, 84.62
(CH); 107.35, 111.20 (C); 124.53, 126.31, 126.76, 127.06, 127.21, 127.39, 127.49, 127.64, 127.79, 127.94,
128.26, 128.41, 128.73, 129.01, 129.37, 130.98, 131.81, 133.84 (CH); 140.64, 142.36, 142.76, 143.48, 146.01,
148.67, 153.82, 154.15 (C). ESI-MS (pos.): 2219 (100, [M þ K]þ), 2204 (20, [M þ Na]þ). Anal. calc. for
C124H116O12S4Cu4 (2180.72): C 68.30, H 5.36, S 5.88; found: C 68.12, H 5.43, S 5.80.
Tetrakis{m-(4R,5R)-5-[(Diphenyl)(sulfanylꢀkS,kS)methyl]-a,a,2,2-tetraphenyl-1,3-dioxolane-4-
methanolato(1ꢀ)}tetracopper(I) (51). A stirred suspension of 8 (270 mg, 0.44 mmol) in MeOH (5 ml) at
r.t. was added Et3N (100 ml, 0.72 mmol). The mixture became a clear soln., which turned turbid again
after a few min. After addition of CuCl (44 mg, 0.44 mmol), the mixture was heated to reflux for ca.
10 min (TLC: Rf (hexane/AcOEt 4 :1) 0.16 (51), 0.51 (8)). Removal of the solvent to ca. 2 ml in a
rotovap, filtration, dissolution in CH2Cl2, and FC (SiO2 (6 g); pentane/Et2O 1:1) gave 51 (160 mg, 55%).
Colorless solid. M.p. 172 – 1748 (dec.). Rf (hexane/AcOEt 4 :1) 0.16. [a]rD:t: ¼ þ241.6 (c ¼ 1.05, CHCl3). IR
(CHCl3): 3691w, 3542m, 3353s, 3086w, 3061m, 3007m, 2958w, 2928w, 1952w, 1896w, 1810w, 1599m, 1492s,
1448s, 1317w, 1170m, 1096s, 1089s, 1058s, 1030s, 943m. 1H-NMR (400 MHz): 3.21 (br., 2 H); 4.24 (d, J ¼
8.1, 2 CH); 4.57 (d, J ¼ 8.1, 2 CH); 4.66 (d, J ¼ 5.2, 2 CH); 5.39 (d, J ¼ 5.2, 2 CH); 5.44 (s, 2 H); 5.54 (d,
J ¼ 3.8, 2 H); 6.12 – 6.25 (m, 2 arom. H); 6.24 (t, J ¼ 7.1, 2 arom H); 6.42 (d, J ¼ 8.3, 2 arom. H); 6.54 (br., 4
arom. H) 6.68 – 7.76 (m, 110 arom. H). 13C-NMR (100 MHz, CDCl3): 60.75, 61.11, 77.43, 78.64 (C); 83.44,
84.80, 85.41. 85.94 (CH); 108.48, 109.78 (C); 124.03, 124.81, 125.02, 125.05, 125.59, 126.21, 126.26, 126.42,
126.51, 126.68, 126.89, 127.04, 127.16, 127.38, 127.46, 127.60, 127.68, 127.78, 127.82, 127.90, 127.95, 128.07,
128.32, 128.49, 129.70, 129.93, 130.03, 1333.09 (CH); 139.60, 141.12, 141.60, 143.15, 143.72, 143.86, 144.55,
145.35, 145.69, 152.57, 154.67 (C). ESI-MS (pos.): 2717 (100, [M þ K]þ), 2701 (58, [M þ Na]þ).
Tetrakis{m-(4R,5R)-5-[(methoxy)(diphenyl)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxolane-4-
methanethiolatoꢀkS,kS(1ꢀ)}tetracopper(I) (52). To a soln. of 32 (180 mg, 0.36 mmol) in CH2Cl2 (8 ml)
at r.t. were added Et3N (90 ml, 0.65 mmol) and CuCl (36 mg, 0.36 mmol). After stirring for ca. 15 min
(TLC: Rf (hexane/AcOEt 4 :1) 0.58 (52), 0.72 (32)), evaporating to a volume of 2 ml, and FC (SiO2
(6 g); pentane/Et2O 4 :1), the product-containing fractions were combined. After adding MeOH (5 ml),
the solvent was evaporated to afford 52 (130 mg, 64%). Colorless solid. M.p. 144 – 1468 (dec.). Rf
(hexane/AcOEt 8 :2) 0.58. [a]rD:t: ¼ þ63.0 (c ¼ 1.0, CHCl3). IR (CHCl3): 3058m, 2987m, 2936m, 2900w,
2825w, 1597w, 1493m, 1444m, 1379m, 1369m, 1318w, 1177m, 1094s, 1080s, 1054s, 1032m, 892m. 1H-NMR
(400 MHz): 0.65 – 1.10 (br., 24 H); 2.98 (br., 2 MeO); 3.10 (br., 2 MeO); 4.25 (br., 4 CH); 4.63 (br.,
2 CH); 4.73 (br., 2 CH); 6.18 (br., 2 arom. H); 6.40 – 7.95 (m, 76 arom. H); 8.50 (br., 2 arom. H).
13C-NMR (100 MHz, CDCl3): 27.37, 51.72 (Me); 61.22 (C); 81.19, 82.46, 83.21, 84.17; 107.24 (C); 126.35,
127.09, 127.46, 129.51, 129.99, 131.24, 131.83. ESI-MS (pos.): 2275 (99, [M þ K]þ), 2259 (60, [M þ Na]þ,

Helvetica Chimica Acta – Vol. 95 (2012)
1267
1741 (100, [M ꢀ 106 þ 1]þ ). Anal. calc. for C128H124O12S4Cu4 (2236.83): C 68.73, H 5.59, S 5.73; found: C
68.62, H 5.77, S 5.58.
Tetrakis{m-(4R,5R)-2,2-dimethyl-5-[(1-methylethoxy)(diphenyl)methyl]-a,a-diphenyl-1,3-dioxo-
lane-4-methanethiolatoꢀkS,kS(1ꢀ)}tetracopper(I) (53). To a stirred soln. of 34 (411 mg, 0.78 mmol) in
CH2Cl2 (5 ml) at r.t. were added Et3N (163 ml, 1.17 mmol) and CuCl (77.5 mg, 0.78 mmol). After 25 min,
the mixture was concentrated to ca. 2 ml on a rotovap, followed by FC (SiO2 (8 g); pentane/Et2O 8 :2).
The residues of the product-containing fractions were subjected to further FC (2ꢁ) (pentane/Et2O 95 :5;
1. 12 g of SiO2, 2. 16 g of SiO2). The obtained product was triturated with MeOH to afford 53 (72 mg,
16%). Colorless solid. M.p. 142 – 1438 (dec.). Rf (pentane/Et2O 8 :2) 0.64. [a]rD:t: ¼ ꢀ20.0 (c ¼ 0.85,
CHCl3). ESI-MS (pos.): 2388 (38, [M þ K]þ), 2372 (15, [M þ Na]þ), 1825 (30, [M ꢀ 108 þ 1]þ, 1799 (43,
[M ꢀ 108 þ 1 ꢀ Cu þ K]þ, 1784 (36, [M ꢀ 108 þ 1 ꢀ Cu þ Na]þ, 1238 (100, [M ꢀ (2 ꢁ 108) þ 2 ꢀ Cu]þ).
Tetrakis{m-(4R,5R)-5-[(Diphenyl)(sulfanylꢀkS,kS)methyl]-2,2-dimethyl-a,a-diphenyl-1,3-dioxo-
lane-4-methanolato(1ꢀ)}tetrasilver(I) (54). A stirred suspension of 7 (500 mg, 1.04 mmol) in MeOH
(10 ml) at r.t. was converted to a clear soln. within 10 min by adding Et3N (160 ml, 1.14 mmol). Addition
of AcOAg (173 mg, 1.04 mmol) and heating at reflux for 15 min led to a grey precipitate (627 mg), which
was filtered off, dissolved in CH2Cl2 and subjected to FC (SiO2 (6 g); pentane/Et2O 1:1). To the
combined product fractions was added MeOH (ca. 6 ml), and concentration in a rotovap led to
precipitation of 54 (525 mg, 86%). Colorless solid. M.p. 195 – 1968 (dec.). [a]rD:t: ¼ ꢀ5.8 (c ¼ 1.0, CHCl3).
Rf (pentane/Et2O 1:2) 0.70. IR (CHCl3): 3328s, 3060m, 3008s, 2937w, 1599w, 1493m, 1446m, 1381m,
1371m, 1170s, 1058s, 900m, 882m, 852w, 658w. 1H-NMR (500 MHz): 0.81 (s, 2 Me); 0.87 (s, 2 Me); 1.05 (s,
2 Me); 1.38 (s, 2 Me); 4.06 (d, J ¼ 8.1, 2 CH); 4.37 (d, J ¼ 7.0, 2 CH); 4.45 (d, J ¼ 8.1, 2 CH); 5.14 (d, J ¼
7.0, 2 CH); 5.19 (s, 2 OH); 5.77 (s, 2 OH); 6.09 (br., 2 arom. H); 6.19 (br., 2 arom. H); 6.51 (br., 4 arom.
H); 6.97 (t, J ¼ 7.3, 2 arom. H); 7.03 – 7.41 (m, 42 arom. H); 7.45 – 7.70 (m, 20 arom. H); 7.87 (d, J ¼ 7.4, 4
arom. H); 8.01 (m, J ¼ 7.5, 4 arom. H). 13C-NMR (125 MHz): 26.58, 27.27, 27.46, 27.62 (CH3); 59.80, 59.98,
3
3
76.93, 77.57 (C); 81.51 (d, J(C,Ag) ¼ 11.1), 83.10, 83.75 (d, J(C,Ag) ¼ 8.0), 84.01 (CH); 107.37, 109.67
(C); 124.18, 126.20, 126.64, 126.78, 127.11, 127.42, 127.46, 127.54, 127.72, 127.75, 127.82, 128.14, 128.48,
128.74, 128.86, 129.49, 130.26, 131.51, 134.02 (CH); 140.87, 142.71, 142.98, 144.08, 146.07, 147.25, 156.22,
156.87 (C). ESI-MS (pos.): 2398 (12, [M þ K]þ), 2382 (12, [M þ Na]þ). Anal. calc. for C124H116Ag4O12S4
(2358.01): C 63.16, H 4.96, S 5.44. found: C 62.98, H 5.25, S 5.25.
10. Enantioselective CuI-Catalyzed Addition of Grignard Reagents to Cyclic Enones Using the Thiol
Ligands 7, 8, 31 – 36 and the Cu complexes 50 – 53. a) In situ Procedure. Under an Ar atmosphere, the thiol
ligand (0.065 mmol) and CuCl (0.05 mmol) are suspended in 10 ml of THF and combined at ꢀ 788 with
BuLi (0.08 mmol for 31 – 36, 0.16 mmol for 7 and 8). The stirred mixture is allowed to warm to 08,
whereupon a clear soln. is formed (ca. 20 min). After cooling back to ꢀ 788, 1.0 mmol enone is added,
and the RMgCl soln. (0.5m in THF) is introduced, within 70 – 80 min, using a syringe pump. After stirring
for another 30 – 45 min, a sat. NH4Cl soln. is added, and, after warming to r.t., the mixture is combined
with Et2O and H2O. The phases are separated, the aq. layer is extracted with Et2O (2ꢁ), and the
combined org. phases are washed with sat. NaCl and dried (Na2SO4). After careful evaporation of the
solvent under reduced pressure, the residue is purified by bulb-to-bulb distillation. For yields and
selectivities, see Table 4.
b) With the Isolated Cu Complex. The enone (1.0 mmol) and the Cu complex (0.5 mmol 50 – 53) are
dissolved in 10 ml of THF, and the soln. is combined (within 30 min) with the Grignard reagent at ꢀ 788
as described above.
c) Derivatization of the 3-Alkyl- and 3-Phenylcycloalkanones with (R,R)-1,2-Diphenylethylenedi-
amine for the er Determination. Following the procedure of Alexakis et al. [41], 0.2 mmol of the ketone in
2 ml of CH2Cl2 was combined with 2 equiv. of the enantiomerically pure diamine and a bead of 4-ꢄ
molecular sieve (MS). After stirring for 1 h at r.t., the MS was removed, the solvent was evaporated, and
the residue was dissolved in 0.6 ml of CDCl3. The signals of the diastereoisomeric aminals in the
13C-NMR spectra used for configurational assignments are specified in the procedures (vide infra).
d) er Determination by Other Methods. In one case, 3-butylcyclooctanone, the er was determined by
derivatization with (R,R)-butane-2,3-diol; in another case, 3-butyl-4,4-dimethylcyclohexanone, by
derivatization with (R,R)-pentane-2,4-diol in analogy to literature procedures [33][42][43]. For the

1268
Helvetica Chimica Acta – Vol. 95 (2012)
Table 6. Crystallographic Data for Compounds 11, 13, 15, 16, 31, 32, 36, 37, and 41
11
13
15
16
Formula
Formula weight [g/mol]
T [K]
Wavelength [ꢄ]
C43H39NO3
617.75
293(2)
0.71073
MoKa
C32H32O4
480.61
293(2)
0.71073
MoKa
C34H36O4
508.63
293(2)
1.54178
CuKa
C38H36O4
556.67
293(2)
1.54178
CuKa
Source
Crystal dimensions [mm]
0.3 ꢁ 0.2 ꢁ 0.1
monoclinic
P21
4.4 < q < 50.0
9.778(5)
17.473(2)
10.578(5)
90
0.4 ꢁ 0.3 ꢁ 0.2
orthorhombic
P212121
1.6 < q < 20.0
8.129(5)
16.011(9)
20.43(1)
90
0.3 ꢁ 0.1 ꢁ 0.1
orthorhombic
P212121
3.7 < q < 50.0
9.64(1)
15.23(2)
19.34(2)
90
0.3 ꢁ 0.2 ꢁ 0.2
orthorhombic
P212121
3.5 < q < 50.0
9.574(7)
16.79(1)
19.34(1)
90
Crystal system
Space group
q Range [8]
a [ꢄ]
b [ꢄ]
c [ꢄ]
a [8]
b [8]
106.00(4)
90
1737(2)
2
1.181
0.573
90
90
2659(3)
4
1.200
90
90
2838(5)
4
1.191
90
90
3109(4)
4
1.189
g [8]
V [ꢄ3]
Z
1calc [g cmꢀ3
]
m [mmꢀ1
]
0.078
0.606
0.599
Total reflections measured
Independent reflections
Reflections observed
No. of variables
Criterion
1855
1855
1803
425
I > 2s(I)
3.57
1463
1463
1105
330
I > 2s(I)
2.88
1694
1694
1416
344
I > 2s(I)
3.71
1849
1849
1752
380
I > 2s(I)
4.25
Final R [%]
wR2 [%]
9.37
6.18
10.43
10.91
Goodness-of-fit
D1 (max, min) [e ꢄꢀ3
CCDC No.
1.092
0.801
0.979
1.141
]
0.123, ꢀ 0.147
0.088, ꢀ 0.097
0.128, ꢀ 0.129
0.173, ꢀ 0.188
158335
158336
158337
158338
GC determination of er values, a b-DEX 120 (30 m ꢁ 0.25-mm inner diameter) column by Supelco was
used. Details are given with the product specifications, below.
1
3-Butylcyclopentanone. H-NMR (200 MHz, CDCl3): 0.87 – 0.97 (m, Me); 1.29 – 2.54 (m, 13 H).
(2R,3R)-7-Butyl-2,3-diphenyl-1,4-diazaspiro[4.4]nonane). 13C-NMR (50 MHz, CDCl3): 48.2 (3R)/
47.5 (3S); 41.1 (3R); 40.2 (3S) [41].
3-Butylcyclohexanone. [a]rD:t: ¼ þ12.8 (c ¼ 0.9, CHCl3), er(R/S) 89 :11 ([34]: [a]rD:t: ¼ þ9.4 (c ¼ 2.78,
CHCl3), er(R/S) 80 :20). 1H-NMR (300 MHz, CDCl3): 0.82 – 0.93 (m, Me); 1.22 – 1.40 (m, 7 H); 1.55 –
2.47 (m, 8 H). 13C-NMR (75 MHz, CDCl3): 13.87; 22.60; 25.20; 28.75; 31.23; 36.21; 38.97; 41.45; 48.18;
212.32.
(2R,3R)-7-Butyl-2,3-diphenyl-1,4-diazaspiro[4.5]decane. 13C-NMR (75 MHz, CDCl3): 46.9 (3S)/
46.1 (3R); 40.0 (3R); 38.8 (3S); 35.4 (3R); 34.5 (3S) [41].
3-Butyl-4,4-dimethylcyclohexanone. 1H-NMR (300 MHz, CDCl3): 0.89 (t, J ¼ 7.1, Me); 0.99 (s, Me);
1.03 (s, Me); 1.05 – 1.76 (m, 9 H); 1.99 – 2.09 (m, 1 H); 2.25 – 2.47 (m, 3 H). 13C-NMR (75 MHz, CDCl3):
13.99; 19.45; 22.74; 28.71; 29.70; 30.23; 32.83; 38.30; 40.49; 42.91; 46.76; 212.43. GC: p, 100 kPa; T, 1208,
tR1(3R) 28.8, tR2 (3S) 31.2 min.
rac-Ketal from 3-Butyl-4,4-dimethylcyclohexanone and (R,R)-Pentane-2,4-diol. 1H-NMR (200 MHz,
CDCl3): 0.76 (s, Me); 0.77 (s, Me); 0.85 – 0.93 (m, 16 H); 1.02 – 1.62 (m, 34 H); 1.79 – 2.08 (m, 4 H); 3.86 –
4.13 (m, 4 H).