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

Article abstract of DOI:10.1002/hlca.201200147

TADDOL (=α,α,α′,α′-Tetraaryl-1,3- dioxolane-4,5-dimethanol) and the corresponding dichloride are converted to TADDAMINs (=(4S,5S)-2,2,N,N′-tetramethyl-α,α,α′, α′-tetraphenyl-1,3-dioxolan-4,5-dimethanamines) (Scheme 2) and ureas, 12-15, and to TADDOP derivatives with seven-membered O-P-O ester rings (Schemes 3 and 4). Cl/P-Replacement via the Michaelis-Arbuzov reaction (Scheme 7) on mono- and dichlorides, derived from TADDOL, are described. It was not possible to obtain phosphines with the P-atom attached to the benzhydrylic C-atom of the TADDOL skeleton (Schemes 6 and 7). The X-ray crystal structures (Figs. 1 and 2) of ten of the more than 30 new TADDOL derivatives are discussed. Full experimental details are presented. Copyright

Full text of DOI:10.1002/hlca.201200147

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Preparation and Characterization of New C2- and C1-Symmetric Nitrogen,
Oxygen, Phosphorous, and Sulfur Derivatives and Analogs of TADDOL
Part II
TADDAMIN-Derived and Phosphorous-Containing Compounds
by Arkadius Pichota1), Volker Gramlich2), Hans-Ulrich Bichsel3), Thomas Styner3), Thomas Knçpfel3),
Ralf Wꢀnsch4), Tobias Hintermann4), W. Bernd Schweizer, 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)
TADDOL (¼a,a,a’,a’-Tetraaryl-1,3-dioxolane-4,5-dimethanol) and the corresponding dichloride
are converted to TADDAMINs (¼(4S,5S)-2,2,N,N’-tetramethyl-a,a,a’,a’-tetraphenyl-1,3-dioxolan-4,5-
dimethanamines) (Scheme 2) and ureas, 12 – 15, and to TADDOP derivatives with seven-membered
OꢀPꢀO ester rings (Schemes 3 and 4). Cl/P-Replacement via the MichaelisꢀArbuzov reaction
(Scheme 7) on mono- and dichlorides, derived from TADDOL, are described. It was not possible to
obtain phosphines with the P-atom attached to the benzhydrylic C-atom of the TADDOL skeleton
(Schemes 6 and 7). The X-ray crystal structures (Figs. 1 and 2) of ten of the more than 30 new TADDOL
derivatives are discussed. Full experimental details are presented.
1. Introduction. – As discussed in the previous paper [1a] of this series5) of
publications on TADDOL (¼a,a,a’,a’-tetraaryl-1,3-dioxolane-4,5-dimethanol) deriv-
atives [1], the modification of the OH groups (HO ! RꢀO, RꢀOSOx, RꢀOPOx) and
their substitution by other heteroatoms (S, N, and P) in TADDOLs lead to a plethora
of chiral compounds for possible new applications in organic synthesis. The previous
report [1a] was focused on (mainly C1-symmetrical) S-containing derivatives, and in the
present report the preparation of hitherto unpublished (mainly C2-symmetrical) N- and
P-containing compounds derived from the parent TADDOL (1) is described. The
methods used for the transformations are likely to be applicable to TADDOLs with
geminal diaryl groups other than Ph and with substituents R other than Me at C(2) of
the dioxolane ring. The key intermediate en route to C1-symmetrical derivatives was the
monochloride 2, which is formed selectively under the conditions of the Appel reaction
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.
Part of the Diplomarbeit (Master Thesis) of H.-U. B. (1997/1998), T. S. (1999/2000) and T. K. (2000)
ETH Zꢀrich.
Postdoctoral Fellows 1996/1997 (R. W.) and 2000 (T. H.) ETH Zꢀrich.
Part I: ꢂCompounds Containing One or Two Sulfur Substituents and Use in Cu-Catalyzed
Enantioselective Conjugate Additions to Cyclic Enonesꢃ ( p. 1239 of this issue); Part III: ꢂSome New
Chiral Brønsted Acids for Organocatalysis and pKa Values in MeOꢀ(CH2)2ꢀOH/H2O – A Surveyꢃ
(p. 1303 of this issue).
2
3
4
5
)
)
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢀrich

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[1a][2][3]. The key intermediates for preparing C2-symmetrical derivatives are the
TADDOL (1) [4] itself or the dichloro derivation 3 [2][3] (Scheme 1). For the three
compounds 1 – 3, large-scale preparations have been described.
Scheme 1. Preparation of the Chloro Alcohol 2 and of the Dichloro Derivative 3 from TADDOL 1
[1a][2][3]
2. TADDAMIN Derivatives. – The diamines 4 and 5 were prepared6) by heating in
an autoclave the dichloro derivative 3 with NH3 [5] or with MeNH2, in the presence of
NH4Cl. Mixtures of the desired diamine and the trans-fused bicycles 6 and 7 are
formed; the ratio depends on the reaction conditions (temperature, pressure, presence
of excess NH4Cl, see Scheme 2 and Exper. Part); due to the strain of the trans-fused
dioxa-aza-bicyclo[3.3.0]octane skeleton, there is partial hydrolysis of the acetonide
group7) during chromatography on silica gel, with formation of the pyrrolidine-diol 8
(from 7; cf. the O- and S-analogs 9)7). Under optimized conditions, the ratios of mono-
to bicyclic product are such that 60 – 65% of the TADDAMINs (¼(4S,5S)-2,2,N,N’-
tetramethyl-a,a,a’,a’-tetraphenyl-1,3-dioxolane-4,5-dimethanamine)8) 4 and 5 can be
isolated after chromatography of the crude product mixtures. Treatment of the dichloro
compound with tenfold excess of PhNH2 gave the N-Ph-substituted TADDAMIN 10
(Scheme 2).
In unsuccessful attempts to generate a chiral, TADDAMIN-derived carbene A –
and transition metal complexes thereof [9] – from an orthoformic acid derivative of
type B [10], or from a thiourea such as 11 (R=H) [11], we have also prepared the ureas
12a, 13, and the thiourea 12b, as well as the compounds 14 and 15 obtained by
benzylation at the S-atom; with rac-2-phenylethyl bromide, the two diastereoisomers
(R)-15 and (S)-15 were formed in a 1:1 ratio, and one of them was isolated in pure
crystalline form (see X-ray analysis in Sect. 5). The N-Ph-substituted TADDAMIN
10 could not be converted to a urea under various conditions. Finally, the TADDAMIN
6
)
For the azido and thiocyanato route to the diamines 4 and 5, see [2][3]. For a conversion of 4 to 5,
see also Footnote 8.
This has also been observed with the corresponding tetrahydrothiophene derivative [2] (cf. [6][7]).
7
8
)
)
The doubly lithiated TADDAMIN
5 was used to generate achiral Li-enolates (cf. of
cyclohexanone), which, by way of coordination with the mono-lithio-TADDAMIN, reacted with
electrophiles (aldehydes, nitro-olefines) to give chiral products of high diastereoisomer and
enantiomer purity [8]; compound 5 was prepared for this investigation through the bis-formamide
(R ¼ CHO instead of Me in 5) and LiAlH4 reduction.

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Scheme 2. Preparation of the TADDAMINs 4 – 8 and 10 from the Dichloro Derivative 3 and NH3,
MeNH2, or PhHN2. Optimization of the yields of diamines 4 and 5 by carrying out the reaction in the
presence of excess NH4Cl; no solvent was used. The heterocyclic diols 8 and 9 are formed by hydrolysis of
the corresponding highly strained bicycles.
4 and pyridine-2,6-dicarbaldehyde were condensed (TsOH, molecular sieve (MS), in
boiling toluene) to give the macrocycle 16 (67%), the crystals of which turned out to be
one of the very few examples of an organic zeolite [12].
3. Phosphorous-Containing TADDOL Derivatives. – Since our first report on
TADDOP derivatives of type C and D, and their use in enantioselective transition
metal-catalyzed reactions [2][3][13], the compounds of type C have made a

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remarkable career in many laboratories. This is demonstrated by the list of contents9) in
a recent 32-page review article by Lam [14]10)11). Such TADDOP derivatives have,
however, not only been employed in transition metal catalysis but also as stoichiometric
reagents, for instance, for the preparation of b-amino phosphonates [20], or as kind of
organocatalysts for a sophisticated cross benzoin reaction [21] (with type C, R3 ¼ OH).
Not surprisingly, all the phosphoramidites 17, which we had prepared in the mid-
1990s, have, with one exception, 17d, now been described in the literature by other
groups (see references in Scheme 3)12). Compounds 17 have a tendency to hydro-
lyze13) to phosphite 19, which could be prepared from TADDOL and PCl3 with
aqueous workup in 81% yield14). Reactions of the intermediate TADDOP chloride
with bulky amines (cf. 2,2,6,6-tetramethylpiperidin-4-one ethylene ketal, Ph2NH,
phenothiazine) did not lead to the corresponding compounds 17; in one case, we
isolated ca. 10% of the rather unstable compound 20 (with a P,P bond) from a reaction
mixture15). Oxidation of the phosphoramidites 17 to the stable phosphoroxyamidites
18a – 18f (Scheme 3) was carried out with H2O2 (avoiding acidic conditions as with m-
chloroperbenzoic acid).
9
)
Hydrosilylations, hydroborations and diborations, hydrogenations, conjugate additions, allylic
substitutions, nucleophilic allylations, cycloadditions, miscellaneous reactions [14].
For a comparison of TADDOP ligands with corresponding biaryl and BINOL derivatives in Rh-
catalyzed multicomponent cycloadditions, see [15].
10
)
11
12
)
)
In some more or less randomly chosen papers published in 2011, the use of such phosphonites [16],
phosphoramidites [17][18], and phosphites [19] is described for Pt-, Pd-, and Cu-catalyzed
enantioselective diborations, direct arylations, conjugate allylations, ꢂdiastereodivergent deracemi-
zationꢃ, and 1,4-additions of Grignard reagents, respectively.
In the Exper. Part, we only present data differing from those published elsewhere; 17g is
commercially available; for 17, R2N ¼ pyrrolidin-1-yl, there is an Org. Synth. procedure in
preparation [22a]. For some spirocyclic phosphites and phosphonites, see [22b].
In the chromatographic purification (SiO2) of the phosphoramidites 17, we added some Et3N to
prevent this acid-catalyzed hydrolysis (see Exper. Part).
For previous preparations and an X-ray crystal structure of 19, see [20] [21]. Although compounds
of type 19 react as P-nucleophiles (RO)2PIIIOH, most of their crystal structures show a short P,O
bond (ca. 1.45 ꢄ) typical of a phosphate (RO)2PV(O)H (search in the Cambridge Crystallographic
Data Base).
There is an AB system of signals in the 31P-NMR spectrum at d 158 (PIII) and 13.5 ppm (PV). For full
characterization of 20, see Exper. Part.
13
14
)
)
15
)

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Scheme 3. Preparation of Phosphoramidites 17, Phoshoroxyamidites 18, and of the Phosphite 19, and
Isolation of the PV/PIII Derivative 20 from TADDOL, PCl3, R2NH, and H2O2
Phosphonic and phosphoric acid derivatives of TADDOL have also been prepared
by reaction of the Li2-dialkoxide with RPOCl2 (R ¼ alkyl or Cl). As outlined in
Scheme 4, the resulting primary products 21 and 23 can be used to prepare the
phosphono-acetate 22 and the methyl ester 24, the Na salt 25, as well as the anhydride
26 of the phosphoric acid derivative. Obviously, these PV compounds were prepared for
testing stereoselective olefinations (cf. 21 and 22) or phosphorylations (cf. 26), which
were, however, hitherto not seriously investigated16).
We also tried to prepare P-derivatives of the TADDAMIN 10 (Scheme 5), which
was first treated with 2 equiv. of BuLi and then with a chloro- or dichlorophosphine.
From the ꢂmessyꢃ product mixtures, the three compounds, 27 – 29, could be isolated in
pure form. Of the desired type of products with an NꢀP bond, only the methyl
diazaphosphite 27 was found. The Ph2PCl attacked the lithiated aniline moiety in the
para-position to give the phosphine 28 and the diphosphine 29. The crystal structure of
compound 27 is shown in Sect. 5.
16
)
The retirement of the corresponding author D. S., at the end of 2002 was accompanied by a
dramatic reduction in the group size and by the necessity to decide which one of the research areas
could be continued on small scale. The decision was made in favor of the investigation of peptides
consisting of homologated proteinogenic amino acid residues [28].

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Scheme 4. TADDOP-PV Derivatives 21 – 26 Prepared by Reaction of TADDOL with Phosphorylating
Reagents and Subsequent Conversions. The yields shown are those of purified, mostly recrystallized
materials (see Exper. Part).
a) 2.2 equiv. of BuLi. b) RPOCl2. c) POCl3. d) 21a, 4 equiv. of BuLi, then 4 equiv. of NCꢀCO2Me, e)
MeONa. f) NaOH/THF/H2O. g) 1 equiv. of 23/THF.
4. Results of Attempts to Replace the TADDOL OH Group(s) by R2P Groups. –
The successful application of DIOP (¼(ꢀ)-2,2-dimethyl-4,5-bis[(diphenylphosphino)-
methyl-1,3-dioxolone)-type ligands E in transition-metal chemistry [29] and the
numerous uses of TADDOLs as ligands for Lewis-acidic metal centers [30] suggest that
a C2-symmetrical diphosphine E (cf. R1 ¼ R2 ¼ R4 ¼ Ph, R3 ¼ Me, ꢂTADDDPꢃ) or a C1-
symmetrical monophosphine F with a R2P, and an amino or an alkoxy group might be
excellent chiral ligands. Thus, we have undertaken an intensive investigation towards
the preparation of phosphines of types E and F.
As outlined in Scheme 6, various starting materials G, reagents, and conditions were
employed to test the possibility of forming C,P bonds either by nucleophilic (CꢀX þ
HPR2 or metalꢀPR2) or by electrophilic (Cꢀmetal þ XPR2) phosphinylation. In no
case were we able to isolate a P-containing product, derived from TADDOL, from any
of the reactions mixtures. What we did isolate were products of elimination: the dienes

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Scheme 5. Reactions of the TADDAMIN 10 with a Chloro- and Dichlorophosphine Derivative. Besides
the isolated and characterized products 27 – 29 many non-identified compounds were present in the
crude reaction mixtures; from the reaction with Ph2PCl, 30% of starting material 10 was recovered.
3017) and 32 [34], and the – optically active18) – epoxide 31 (Scheme 6); the butadiene
could either have been formed by double elimination or by deoxygenation of the
epoxide 31, which, in turn, could have arisen from a process indicated in H (Scheme 6).
Thus, the structural instability inherent to the TADDOL skeleton has reared its ugly
head19)20)!
We than studied introductions of P substituents in the TADDOL scaffold by
MichaelisꢀArbuzov reactions [37], by using the dichloro compound 3, the sulfate 34,
and the chloro methoxy derivative 35 [1a], and the phosphites (MeO)3P, (MeO)2P-
Ph,or MeOPPh2 (Scheme 7). The cyclic sulfate 34 was included in this investigation,
because heterocyclic compounds of this type are known to undergo O,P-substitution
with P-nucleophiles [38]. Compound 34 was prepared from the readily available sulfite
33 [3] by oxidation with NaIO4 [39] (see also the crystal structure in Sect. 5). The
reactions of the di- and monochloro derivatives 3 and 35, respectively, with excess
methyl phosphites required high temperatures and long reaction times to occur (1208/
12 h). With the dichloride, cyclic phosphonate 36 and phosphinate 37 are formed in
modest yields; a single diastereoisomer, 36, and two diastereoisomers, (RP)-37 and
(SP)-37 (in a ratio of 3 :2), were isolated as products from the reaction with (MeO)3P
and with (MeO)2PPh, respectively. The configurations of the isomers 37 was assigned
by an X-ray crystal-structure analysis of the (SP)-isomer (see Sect. 5). The reaction of
17
)
Yellow powder, isolated from the reaction of G (X ¼ Y¼ Br) þ G (X ¼ Br, Y¼ OH) (ratio 2:1) with
PH3 pyridine in DMF in an autoclave; yield ca. 20%. Compound 30 has been isolated and
characterized before from 3 by heating at 808 for 5 d in DMF [2].
18
19
20
)
)
)
The racemic form of 31 has been described before [35].
See also cationic rearrangements observed with the TADDOL carrying methoxyphenyl groups [36].
There might be a chance to prepare TADDDP derivatives by radical processes, the intermediates of
which have a lower tendency to undergo rearrangements and/or eliminations.

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Scheme 6. Phosphine Derivatives E and F with Structures Similar to That of TADDOL, and Attempted
Reactions of F, Cl, Br, and Triflate Derivatives of TADDOL with Various PIII Reagents. The dibromo
derivative G (X ¼ Y¼ Br) is rather unstable and could not be isolated in pure form (from 1 þ SOBr2/
Et3N); it was used in a mixture with the monobromo derivative G (X ¼ Br, Y¼ OH). For the elimination
products 30 – 32, see Footnotes 17 and 18, and Exper. Part. In H, a generalized mechanistic picture is
proposed for the formation of the tetraphenyl-butadiene monoepoxide 31. A related double elimination
of X and RO would lead to tetraphenyl-butadiene 32, which could, however, also have been formed from
31, by the known deoxygenation of epoxides with phosphines [31]. Solutions of LiPH2 [32] and LiPEt2
[33] in Et2O were prepared according to literature procedures.
(MeO)3P with the cyclic sulfate took place at lower temperature (808)21), which might
be the reason why the monocyclic hydroxy phoshonate 38, and not the bicyclic
compound 36, was isolated. Monocyclic products 39 and 40 were also accessible from
the chloro methoxy derivative 35 (vide infra for the crystal structures of 38 and 39).
21
)
... it better had, because the sulfate 34 starts decomposing above ca. 958!

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Scheme 7. Preparation of the Sulfate 34 and Cl/P- and SO2O/P Replacements by the MichaelisꢀArbuzov
Reaction to Form PV Analogs 36 – 40 of TADDOL with a Benzhydrylic CꢀP Bond. Attempted
deoxygenation to a phosphine leads to dephosphinylation.
Thus, we finally had replaced a TADDOL OH group by a P-containing substituent
in the compounds 36 – 40! To obtain a monodentate phosphine ligand of type F (vide
supra; Scheme 6), we had, however, to remove an O- from the P-atom. This turned out
to be impossible in all our experiments carried out with the methoxy phosphine oxide
40, and employing almost 20 different reagents and conditions22). According to 31P-
NMR analyses, there were no P-containing compounds in the product mixtures. The
only compound, which was sometimes obtained in good yields, was the product 41 of
reductive removal of the P-atom. Thus, the weak benzhydrylic bond of the TADDOL-
type skeleton has prevented success, again20).
5. X-Ray Crystal Structures. – The structures of ten of the compounds described in
the previous sections are shown in Figs. 1 (TADDAMIN derivatives) and 2 (P-
containing compounds). Besides three monocyclic derivatives (10 in Fig. 1, and 38, 39,
22
)
These include silanes, disilanes, LiAlH4, LiAlH4/CeCl3, DIBAL-H, Cp2ZrClH, BH3, BH3/AlMe3,
Raney Ni/H2.

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Fig. 1. X-Ray crystal structures of TADDAMIN derivatives 10, 12a, 12b, and (R)-15
in Fig. 2), there are seven bicyclic ones, one [4.3.0] skeleton (37 in Fig. 2) and six [5.3.0]
skeletons (12a, 12b, and 15 in Fig. 1, and 23, 27, and 34 in Fig. 2). In all but one structure,
the characteristic TADDOL-type features are observed, with quasi-axial and quasi-
equatorial Ph groups on the CPh2 centers and antiperiplanar OꢀCꢀCꢀX conformations
around the exocyclic CꢀC bonds. Only in the methoxy-phosphonate 39 (in Fig. 2), the
P(O)(OMe)2 group occupies the ꢂaxialꢃ position, with a gauche-relationship between
the dioxolane O- and the P-atom (sterically and stereoelectronically favorable). In the
other two monocyclic structures, the hydroxy-phosphonate 38 (Fig. 2) and the N,N’-
diphenyl-TADDAMIN 10 (Fig. 1), there are H-bonds between the OH group and the
P(O) O-atom in the first case, and between the anilino-NH group and the aniline N-
atom in the second case23). In the structures 12a and 12b (Fig. 1), there is a deviation of
the urea moieties from coplanarity, while, in the seven-membered ring of the 2-
phenylethylsulfanyl-diazepin 15, five ring atoms, more or less accurately, share a plane.
The other three seven-membered rings, containing the sequences of atoms NꢀPꢀN
23
)
For a discussion of the delicate interplay between H-bonding, steric, and stereoelectronic effects
that govern the conformation around the exocyclic dioxolane CꢀC bond in TADDOLs and their
analogs, see [1a].

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Fig. 2. X-Ray crystal structures of the P-containing compounds 23, 27, and 37 – 39, and of the sulfate 34
(27), OꢀPꢀO (23) and OꢀSꢀO (34) (Fig. 2), are strongly folded, and the oxa-phospha-
cyclohexane ring in (SP)-37 exhibits a chair conformation with an axial P(O) O-atom
and two axial Ph substituents (Fig. 2). In a metal complex of 27, the two neighboring N-
Ph groups (one quasi-axial, the other quasi-equatorial) will provide a strongly
asymmetric environment; thus it would be worthwhile to improve the yield of the
reaction of TADDAMIN 10 with phosphinylating reagents.

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Of the ꢂformallyꢃ C2-symmetrical TADDOL-derived compounds with bicy-
clo[3.3.0]octane, bicyclo[4.3.0]nonane, and bicyclo[5.3.0]decane skeletons (Fig. 3,
top), described in the present series of papers [1] or in previous publications by us
and others, essentially none has a geometrically exact C2-structure in the crystal. Not
only do different conformations around the C,Ph bonds lead to deviations from C2-
symmetry but also the conformations, i.e., the folding of the rings, especially of the
seven-membered rings (Fig. 3, bottom). On the other hand, the NMR spectra of these
compounds are compatible with C2-symmetry: there are, for instance, single signals for
the Me H-atoms and for the bridgehead CH H-atoms in the 1H-NMR spectra. Thus, at
least on the NMR time scale, there is C2-symmetry at ambient temperatures24).
We gratefully acknowledge the contributions of the co-workers of the services of the Laboratorium
fꢀr Organische Chemie: Prof. Dr. B. Jaun, B. Brandenberg, and P. Zumbrunnen (NMR), Dr. W. Amrein,
H. U. Hediger, R. Hꢁfliger, and O. Greter (MS), M. Schneider, and D. Manser (elementary analyses,
molecular weights). We also acknowledge the generous financial support by ETH Zꢀrich 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. TADDOL and TADDOL derivatives were prepared according to literature procedures:
TADDOL (1) [4], dichloride 3 [2][3], sulfite 33 [3], and chloride 35 [1a]. All other reagents were used as
received from Fluka or Aldrich. All indicated reaction temp. were monitored with an internal
thermometer (Ebro-TTX-690 digital thermometer). Autoclaves used for reactions under high pressure:
80 (home-made, ETH Zꢀrich), 240, and 450 ml (Autoclave Engineers); the pressure was monitored with
a Haenni-ED-510 apparatus (Piezoresitiver Druckmessumformer). 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 integrators and Macherey-Nagel FS-Hydrodex b-PM
cap. column (50 m ꢁ 0.25 mm i.d.) for enantiomer separations. M.p.: Bꢀchi-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 MHz, 13C: 75, and 19F: 282 MHz) or Gemini 200 (1H: 200, and 13C: 50 MHz); chemical shifts (d) in
ppm downfield from TMS (d 0.0) 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-
24
)
This is also true of the monocyclic compounds i with an intramolecular H-bond.

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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-
Fig. 3. Different types of C2-symmetrical bicyclic TADDOL derivatives and analogs (top) and view along
the ꢂformalꢃ C2 axes in some of the corresponding crystal structures (bottom). For the crystal structures
with bicyclo[3.3.0] and -[5.3.0] skeletons, see the present paper and [1][3]; for the crystal structure of the
cyclic disulfide with bicyclo[4.3.0] skeleton, see [2].

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dihydroxybenzoic acid matrix). Elemental analyses were performed by the Microanalytical Laboratory
of the Laboratorium fꢀr Organische Chemie, ETH Zꢀrich.
2. General Procedures. Preparation of the TADDAMINs 4 and 5, and the Pyrrols 6 and 7. General
Procedure 1 (GP 1). Dichloro compound 3, NH4Cl (12.74 g, 240 mmol, 30 equiv.), and NH3 (condensed
at ꢀ 788) or MeNH2 (25 ml, 0.8 mol) were placed in an autoclave, the mixture was heated to 1008
(30 bar) and stirred for 2 d. The autoclave was cooled to r.t., and the excess NH3 or MeNH2 was vented.
The crude product was dissolved in CH2Cl2/H2O, and the aq. phase was neutralized with 1n HCl soln. The
org. phase was washed with sat. aq. NaHCO3 soln., H2O, and sat. aq. NaCl soln., and dried (MgSO4). The
solvent was removed under reduced pressure, and the residue was purified.
Preparation of Urea-TADDOL Derivatives 12 and 13. General Procedure 2 (GP 2). Caution: The
following reactions should be carried out in a well-ventilated hood because of the toxicity of phosgene and
thiophosgene. In analogy to [40], a soln. of the appropriate TADDAMIN derivative (1 equiv.) in toluene
(ca. 0.1m) was treated with Et3N (2 – 3 equiv.) and cooled to 08. Phosgene (COCl2; 1 equiv.; 20% soln. in
toluene) or thiophosgene (1 equiv.; neat) was added, and the mixture was stirred at 08 for 1.5 h. The
mixture was warmed to r.t., washed quickly with H2O, and the org. layer was separated and dried
(MgSO4). The solvent was removed under reduced pressure, and the residue was purified as indicated.
Preparation of Isothiourea-TADDOL Derivatives 14 and 15. General Procedure 3 (GP 3). To a soln.
of thiourea derivative 12b (1 equiv.) in DMF (0.08m) was added the appropriate alkyl bromide (1.0 –
1.3 equiv.) at r.t. After stirring for 7 h – 7 d, sat. aq. NaHCO3 soln. was added, the org. layer was
separated, and the aq. layer was extracted with CH2Cl2. The combined org. layers were washed with H2O
(3ꢁ), dried (MgSO4), and the solvent was removed under reduced pressure. The residue was purified as
indicated.
Preparation of TADDOL-Derived Phosphoramidites 17a – 17h. General Procedure 4 (GP 4). To a
soln. of TADDOL 1 (1 equiv.) in CH2Cl2 (40 ml) was added Et3N (2 equiv.) at ꢀ 508. After stirring for
5 min, PCl3 (1 equiv.) was added dropwise over 15 min, which led to the formation of a white precipitate.
The mixture was slowly warmed to ꢀ 208 (ca. 100 min), and then cooled to ꢀ 508 again. Et3N (1 equiv.)
and the appropriate amine (1 equiv.) were added consecutively, and the mixture was slowly warmed to
r.t. After stirring at ambient temp. for further 12 h, sat. aq. NaCl soln. (50 ml) and sat. aq. NaHCO3 soln.
(5 ml) were added, the org. layer was separated, and the aq. layer was extracted with Et2O (2ꢁ). The
combined org. layers were dried (MgSO4), and then the solvent was removed under reduced pressure.
The crude product was purified as indicated.
Preparation of TADDOL-Derived Phosphoroxy Amidites 18a – 18f. General Procedure 5 (GP 5). To
a soln. of the appropriate phosphoramidite 17 (1 equiv.) in Et2O (10 ml) was added 30% aq. H2O2 soln.
(5 – 11 equiv.) ar r.t. The mixture was stirred for 12 h at ambient temp., and then sat. aq. NaCl soln.
(10 ml) was added. The org. layer was separated, and the aq. layer was extracted with Et2O (20 ml). The
combined org. layers were dried (Na2SO4), and the solvent was removed under reduced pressure. The
crude product was purified by FC (3 – 4 drops of Et3N added to 100 ml of solvent).
Preparation of P-Containing TADDOL Derivatives 36 – 40 by MichaelisꢀArbuzov Reaction. General
Procedure 6 (GP 6). To a soln. of the appropriate TADDOL chloride or sulfate (1 equiv.) in DMF (0.1 –
4.5m) was added the indicated P compound (5 – 50 equiv.), and the mixture was stirred for 24 h at 80 –
1208. After cooling to r.t., the solvent was removed under reduced pressure (cooling trap!), and the
residue was purified by FC.
3. Preparation of the TADDAMINs 4 – 8, and 10. (4S,5S)-2,2-Dimethyl-a,a,a’,a’-tetraphenyl-1,3-
dioxolane-4,5-dimethanamine (4) and (3aS,6aS)-Tetrahydro-2,2-dimethyl-4,4,6,6-tetraphenyl-4H-1,3-di-
oxolo[4,5-c]pyrrole (6). According to GP 1, 3 (5.00 g, 9.95 mmol) and NH4Cl (15.94 g, 300 mmol,
30 equiv.) were placed in an autoclave (250 ml) under Ar. After cooling to ꢀ 788, 44 g of NH3 were
condensed in, and the mixture was heated to 1008 (30 bar) and stirred for 2 d. The autoclave was cooled
to r.t., and the excess NH3 was vented. The crude product was dissolved in CH2Cl2/H2O, and the aq. phase
was neutralized with 1n HCl soln. The org. phase was washed with sat. aq. NaHCO3 soln., H2O, and sat.
aq. NaCl soln, and dried (MgSO4). The residue (4/6 2 :1 by 1H-NMR) was dissolved in Et2O, whereby 4
(1.25g, 34%) precipitated as a colorless powder. The mother liquor was purified by FC (SiO2 (100 g);
Et2O) to afford another crop of 4 (1.59 g, 34%). Total yield: 2.84 g (61%). [a]rD:t: ¼ ꢀ43.1 (c ¼ 0.98,

Helvetica Chimica Acta – Vol. 95 (2012)
1287
CHCl3) ([3]: [a]Dr:t: ¼ ꢀ42.96 (c ¼ 0.68, CHCl3). The anal. data matched those reported in [2][3][5]. For
anal. data of 6, see below and [3].
(4S,5S)-N4,N5,2,2-Tetramethyl-a,a,a’,a’-tetraphenyl-1,3-dioxolane-4,5-dimethanamine
(5),
(3aS,6aS)-Tetrahydro-2,2,5-trimethyl-4,4,6,6-tetraphenyl-4H-1,3-dioxolo[4,5-c]pyrrole (7), and (3S,4S)-
1-Methyl-2,2,5,5-tetraphenylpyrrolidine-3,4-diol (8). According to GP 1, 3 (4.00 g, 7.96 mmol), NH4Cl
(12.74 g, 240 mmol), and MeNH2 (25 ml, 0.8 mol) were placed in an autoclave (80 ml), the mixture was
heated to 1008 (30 bar) and stirred for 2 d. The autoclave was cooled to r.t., and the excess MeNH2 was
vented. The crude product was dissolved in CH2Cl2/H2O, and the aq. phase was neutralized with 1n HCl
soln. The org. phase was washed with sat. aq. NaHCO3 soln., H2O, and sat. aq. NaCl soln, and dried
(MgSO4). The solvent was removed under reduced pressure, and the residue was purified by FC (2ꢁ) (1.
pentane/CH2Cl2 5 :7; 100 g of SiO2; 2. toluene/AcOEt 9 :1; 150 g of SiO2) to afford 5 (2.80 g, 62%), 7
(0.30 g, 8%), and 8 (0.23 g, 7%).
Data of 5. M.p. 197 – 2008 ([2]: M.p. 200 – 2038). The anal. data matched those of [2][3].
Data of 7. White foam. Rf (pentane/CH2Cl2 5 :7) 0.65. [a]rD:t: ¼ ꢀ95.2 (c ¼ 1.09, CHCl3). IR (CHCl3):
1
3692w, 3087w, 3058m, 3007s, 2936m, 2803w, 1953w, 1813w, 1599m, 1493m, 1444s, 1383s, 958s. H-NMR
(400 MHz, CDCl3): 1.22 (s, 2 Me); 2.40 (s, NMe); 4.82 (s, 2 CH); 7.13 – 7.16 (m, 4 arom. H); 7.22 – 7.32 (m,
16 arom. H). 13C-NMR (100 MHz, CDCl3): 26.7, 31.53 (Me); 70.09 (C); 81.73 (CH); 118.65 (C); 126.56,
127.08, 127.31, 127.93, 129.25, 129.47 (CH); 142.21, 142.82 (C). EI-MS: 461 (7, Mþ), 384 (83), 362 (30),
346 (37), 207 (53), 196 (100), 194 (90), 179 (77), 167 (53), 118 (67). Anal. calc. for C32H31NO2 (461.61): C
83.26, H 6.77, N 3.03; found: C 83.09, H 6.99, N 2.91.
Data of 8. M.p. 192 – 1958. Rf (toluene/AcOEt 9 :1) 0.85. [a]rD:t: ¼ ꢀ52.4 (c ¼ 0.94, CHCl3). IR
(CHCl3): 3555m, 3059m, 3007s, 2807w, 1962w, 1897w, 1815w, 1757w, 1598w, 1490s, 1443s, 1401m. 1H-NMR
(400 MHz, CDCl3): 1.55 – 1.64 (m, 2 OH); 2.30 (s, Me); 4.65 – 4.71 (m, 2 CH); 7.08 – 7.11 (m, 4 arom. H);
7.25 – 7.39 (m, 16 arom. H). 13C-NMR (100 MHz, CDCl3): 30.10 (Me); 73.38 (C); 76.36 (CH); 127.21,
127.40, 127.60, 127.91, 129.89, 129.97 (CH); 142.91, 142.58 (C). FAB-MS: 421 (23, Mþ), 420 (27), 419 (36),
360 (19), 345 (17), 344 (42), 343 (100), 209 (12), 208 (12), 197 (13), 196 (43), 195 (16), 179 (14), 167 (43),
165 (17), 148 (34), 117 (30).
(3aS,6aS)-Tetrahydro-2,2-dimethyl-4,4,6,6-tetraphenyl-4H-1,3-dioxolo[4,5-c]pyrrole (6). According
to GP 1, 3 (15.0 g, 33.5 mmol) was placed in an autoclave (450 ml) and dissolved in THF (200 ml). The
autoclave was cooled to ꢀ 508, NH3 (65.0 g, 3.80 mol) was condensed in. The mixture was heated to 1008
(39 bar) and stirred for 80 h. After cooling to r.t., excess NH3 was vented, and the crude product was
dissolved in CH2Cl2 (400 ml). After addition of H2O (200 ml), the aq. phase was neutralized with 1n HCl
soln. For better phase separation, sat. aq. NaCl soln. (100 ml) and CCl4 (300 ml) were added. The org.
phase was washed with H2O (2 ꢁ 400 ml) and sat. aq. NaCl soln. (250 ml), and dried (MgSO4). The
solvent was removed under reduced pressure to afford crude 6 (12.5 g, 83%). For further purification, a
sample (5.00 g) was purified by FC (SiO2 (800 g); pentane/Et2O 35 :1) and subsequent trituration with
pentane (15 ml; 30 min under reflux and 1 h at r.t.) to yield anal. pure 6 (3.00 g). Colorless solid. M.p.
140 – 1418 ([3]: M.p. 140 – 1418). [a]Dr:t: ¼ ꢀ230.9 (c ¼ 1.01, CHCl3) ([3]: [a]Dr:t: ¼ ꢀ222.6 (c ¼ 0.5, CHCl3)).
The anal. data matched those of [3].
(4S,5S)-2,2-Dimethyl-N4,N5,a,a,a’,a’-hexaphenyl-1,3-dioxolane-4,5-dimethanamine (10). A soln. of
3 (5.55 g, 11.02 mmol) in CH2Cl2 (11 ml) was treated with PhNH2 (10.0 ml, 109.6 mmol), and the mixture
was stirred at r.t. for 16 h. The brown soln. was washed with H2O, dried (MgSO4), and the solvent was
removed under reduced pressure. The crude product was purified by FC (SiO2 (200 g); CH2Cl2), and
subsequent trituration with Et2O under reflux afforded 10 (4.81 g, 71%). Colorless crystals. M.p. 239 –
2408. Rf (CH2Cl2) 0.75. [a]rD:t: ¼ ꢀ73.2 (c ¼ 1.00, CHCl3). IR (CHCl3): 3286m, 3061m, 3007m, 2935w,
1
1953w, 1828w, 1601s, 1496s, 1447m, 1372m, 1083m, 1064m, 891m. H-NMR (400 MHz, CDCl3): 0.91 (s,
2 Me); 4.28 (s, 2 CH); 5.94 (s, 2 NH); 6.27 (d, J ¼ 7.7, 4 arom. H); 6.53 (t, J ¼ 2.6, 2 arom. H); 6.81 – 6.84
(m, 4 arom. H); 7.07 – 7.15 (m, 6 arom. H); 7.32 – 7.34 (m, 4 arom. H); 7.42 – 7.48 (m, 6 arom. H); 7.78 – 7.80
(m, 4 arom. H). 13C-NMR (100 MHz, CDCl3): 26.7 (Me); 67.13 (C); 84.65 (CH); 107.48 (C); 116.84,
118.23, 126.65, 127.61, 127.81, 128.28, 128.74, 130.78 (CH); 139.04, 142.46, 145.02 (C). FAB-MS: 618 (8,
[M þ 2]þ), 617 (18, [M þ 1]þ), 466 (6), 447 (10), 446 (25), 432 (35), 432 (100), 388 (8), 373 (9), 345 (11),
259 (11), 258 (33), 179 (8). Anal. calc. for C43H40N2O2 (616.81): C 83.73, H 6.54, N 4.54; found: C 83.69, H
6.65, N 4.50.

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Helvetica Chimica Acta – Vol. 95 (2012)
4. Preparation of the TADDAMIN derivatives 12 – 16 and 27 – 29. (3aS,8aS)-Hexahydro-2,2-
dimethyl-4,4,8,8-tetraphenyl-6H-1,3-dioxolo[4,5-e][1,3]diazepin-6-one (12a). A soln. of 4 (2.10 g,
4.50 mmol) in toluene (60 ml) was treated with Et3N (1.26 ml, 9.0 mmol) and phosgene (2.33 ml,
4.50 mmol; 20% soln. in toluene) according to GP 2. The crude product was dissolved in Et2O, and 12a
(0.37 g) was precipitated by addition of pentane as a colorless solid. The solvent of the mother liquor was
removed, and the residue was purified by FC (SiO2 (180 g); pentane/Et2O 1:2) to afford further 12a
(1.07 g). White foam. Total yield 1.44 g (64%). M.p. 224 – 2258. Rf (pentane/Et2O 1:2) 0.32. [a]Dr:t:
¼
ꢀ100.6 (c ¼ 1.03, CHCl3). IR (CHCl3): 3394m, 3076w, 3007m, 2912w, 1953w, 1897w, 1810w, 1759w,
1
1598w, 1446s, 1493m, 1405s, 600w. H-NMR (400 MHz, CDCl3): 1.25 (s, 2 Me); 4.54 (s, 2 CH); 5.16 (s,
2 NH); 7.12 – 7.15 (m, 4 arom. H); 7.22 – 7.26 (m, 6 arom. H); 7.35 – 7.40 (m, 6 arom. H); 7.59 – 6.22 (m, 4
arom. H). 13C-NMR (100 MHz, CDCl3): 26.90 (Me); 65.94 (C); 79.14 (CH); 109.89 (C); 127.52, 127.72,
127.80, 128.05, 128.40, 128.59, 129.03 (CH); 140.83, 144.51, 160.20 (C). EI-MS: 490 (5, Mþ), 390 (20), 237
(10), 207 (10), 182 (100). Anal. calc. for C32H30N2O3 (490.61): C 78.34, H 6.16, N 5.71; found: C 77.89, H
6.38, N 5.57.
(3aS,8aS)-Hexahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-6H-1,3-dioxolo[4,5-e][1,3]diazepine-6-thione
(12b). A soln. of 4 (3.00 g, 6.46 mmol) in toluene (50 ml) was treated with Et3N (2.70 ml, 19.40 mmol)
and thiophosgene (CSCl2; 0.50 ml, 6.52 mmol) according to GP 2. The crude product was triturated with
Et2O for 15 min to afford 12b (1.03 g). After removing the solvent from the filtrate, the residue was
triturated with Et2O to afford further 12b (0.40 g). Purification of the mother liquor by FC (SiO2; Et2O)
afforded further 12b (1.00 g). Total yield: 2.43 g (74%). Beige powder. M.p. > 3108. Rf (pentane/Et2O
2 :3) 0.66. [a]Dr:t: ¼ ꢀ218.7 (c ¼ 0.98, CHCl3). IR (CHCl3): 3387w, 3059w, 2990m, 2046m, 1811w, 1734w,
1657w, 1599m, 1525m, 1612s, 1494s, 1446s, 1428m, 1381m, 1104s, 875m. 1H-NMR (400 MHz, CDCl3): 1.20
(s, 2 Me); 4.59 (s, 2 CH); 6.85 (s, 2 NH); 7.12 – 7.15 (m, 4 arom. H); 7.25 – 7.29 (m, 6 arom. H); 7.39 – 7.43
(m, 6 arom. H); 7.60 – 7.63 (m, 4 arom. H). 13C-NMR (100 MHz, CDCl3): 26.89 (Me); 70.53 (C); 77.91
(CH); 110.84 (C); 127.65, 127.98, 128.11, 128.52, 128.80, 129.29 (CH); 139.56, 143.32, 185.87 (C). FAB-
MS: 1013 (22, [2 M þ 1]þ), 507 (100, [M þ 1]þ), 237 (30), 179 (75). Anal. calc. for C32H30N2O2S (506.67):
C 75.86, H 5.97, N 5.53, S 6.33; found: C 75.90, H 6.51, N 5.58, S 6.35.
(3aS,8aS)-Hexahydro-2,2,5,7-tetramethyl-4,4,8,8-tetraphenyl-6H-1,3-dioxolo[4,5-e][1,3]diazepin-6-
one (13). A soln. of 5 (95 mg, 0.19 mmol) in toluene (2.5 ml) was treated with Et3N (26 ml, 9.0 mmol)
and COCl2 (100 ml, 0.19 mmol; 20% soln. in toluene) according to GP 2. The crude product was purified
by FC (SiO2 (40 g); pentane/Et2O 1:2) to afford 13 (73 mg, 73%). White solid foam. Drying at 1008 in
h.v. for 3 h afforded 13. Colorless solid. M.p. 162 – 1638. Rf (pentane/Et2O 2 :3) 0.66. [a]rD:t: ¼ ꢀ136.4 (c ¼
0.94, CHCl3). IR (CHCl3): 3671w, 3061m, 3007s, 2936m, 2635w, 2461w, 2256w, 1957w, 1750s, 1612s, 1493s,
1446s, 1337s, 600w. 1H-NMR (400 MHz, CDCl3): 0.94 (s, 2 Me); 2.46 (s, 2 NMe); 5.33 (s, 2 CH); 7.25 – 7.38
(m, 20 arom. H). 13C-NMR (100 MHz, CDCl3): 26.75, 37.54 (Me); 71.99 (C); 80.82 (CH); 111.74 (C);
127.19, 127.33, 127.76, 128.13, 128.68, 130.54 (CH); 140.28, 141.96, 164.84 (C). FAB-MS: 1037 (19, [2 M þ
1]þ), 519 (100, [M þ 1]þ ), 460 (30), 418 (17), 265 (25), 179 (48). Anal. calc. for C34H34N2O3 (518.66): C
78.74, H 6.61, N 5.40; found: C 78.58, H 6.81, N 5.38.
(3aS,8aS)-3a,5,8,8a-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-6-[(phenylmethyl)sulfanyl]-4H-1,3-
dioxolo[4,5-e][1,3]diazepine (14). A soln. of 12b (830 mg, 1.64 mmol) in DMF (20 ml) was treated with
BnBr (0.25 ml, 2.1 mmol) according to GP 3 for 7 h. Purification by FC (SiO2 (40 g); pentane/Et2O 5 :1)
afforded 14 (850 mg, 87%). White foam. For anal. purposes, a sample was crystallized from pentane/Et2O
by slow evaporation of the solvent. M.p. 202 – 2048. Rf (pentane/Et2O 1:1) 0.84. [a]rD:t: ¼ ꢀ142.5 (c ¼ 1.03,
CHCl3). IR (CHCl3): 3385w, 3062w, 3008m, 1667s, 1600w, 1494s, 1445s, 1372m, 1096s, 1032w, 881m.
1H-NMR (400 MHz, CDCl3): 0.89 (s, Me); 1.05 (s, Me), 4.12 (d, J ¼ 13.7, CH2); 4.28 (d, J ¼ 13.7, CH2);
4.58 (d, J ¼ 9.05, CH); 4.71 (s, NH); 4.76 (d, J ¼ 9.05, CH); 7.16 – 7.30 (m, 21 arom. H); 7.35 – 7.38 (m, 2
arom. H); 7.50 – 7.52 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 26.8, 27.0 (Me); 36.9 (CH2); 68.1, 71.4
(C); 77.8, 78.5 (CH); 110.5 (C); 126.3, 126.6, 126.8, 126.9, 127.42, 127.44, 127.5, 127.6, 127.8, 128.4, 128.5,
128.6, 129.0, 129.7, 130.2 (CH); 138.6, 140.9, 142.0, 145.2, 146.5, 148.8 (C). HR-MS: 597.2573 ([M þ H]þ,
C39H37N2O2Sþ; calc. 597.2576 (ꢀ0.33 ppm)). MALDI-FT-ICR-MS: 597.3 (100, [M þ H]þ), 546.3 (32).
Anal. calc. for C39H36N2O2S (596.79): C 78.49, H 6.08, N 4.69, S 5.37; found: C 78.60, H 6.37, N 4.75, S 5.44.
(3aS,8aS)-3a,5,8,8a-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-6-{[(1R)- and (1S)-1-phenylethyl]-
sulfanyl}-4H-1,3-dioxolo[4,5-e][1,3]diazepine ((R)-15 and (S)-15, resp.). A soln. of 12b (2.0 g, 3.9 mmol)

Helvetica Chimica Acta – Vol. 95 (2012)
1289
in DMF (50 ml) was treated with 1-phenylethyl bromide (0.54 ml, 4.0 mmol) according to GP 3 for 7 d.
Purification by FC (3 ꢁ ; 1. SiO2 (100 g); pentane/Et2O 15 :1; 2. SiO2 (160 g); toluene/hexane 1:1; 3. SiO2
(36 g); toluene/hexane 1:2) afforded diastereoisomerically enriched (R)-15 (350 mg) and (S)-15
(360 mg) besides a mixture of (R)-15/(S)-15 (450 mg, 19%) and starting material 12b (675 mg, 34%).
Recrystallization from Et2O afforded pure (R)-15 (320 mg, 13%). Colorless crystals. Similarly, (S)-15
(126 mg, 5%) was obtained by recrystallization from hexane. Colorless crystals. Total yield of 15: 37%.
Data of (R)-15. M.p. 231 – 2328. Rf (toluene) 0.71. [a]rD:t: ¼ ꢀ54.8 (c ¼ 1.06, CHCl3). IR (CHCl3):
3390m, 3064w, 3008m, 2926w, 1662s, 1600w, 1493s, 1474s, 1445s, 1372m, 1096s, 1029w, 960w, 880w.
1H-NMR (400 MHz, CDCl3): 0.89 (s, Me); 1.05 (s, Me); 1.52 (d, J ¼ 7.3, Me); 4.59 (d, J ¼ 9.1, CH); 4.66 (d,
J ¼ 9.0, CH); 4.66 (s, NH); 4.78 (q, J ¼ 7.3, CH); 6.98 – 7.01 (m, 2 arom. H); 7.09 – 7.46 (m, 19 arom. H);
7.49 – 7.51 (m, 4 arom. H). 13C-NMR (100 MHz, CDCl3) 22.5, 26.8, 27.0 (Me); 45.9 (CH); 67.8, 71.4 (C);
77.9, 78.5 (CH); 110.5 (C); 126.3, 126.4, 126.7, 127.0, 127.4, 127.45, 127.49, 127.51, 127.8, 128.42, 128.45,
128.6, 128.7, 130.1 (CH); 141.2, 141.7, 144.1, 145.3, 146.8, 148.9 (C, N2CS). HR-MS: 611.2728 ([M þ H]þ,
C40H39N2O2Sþ; calc. 611.2732 (ꢀ0.65 ppm)). MALDI-FT-ICR-MS: 611.3 (7, [M þ H]þ); 507.2 (79),
431.2 (19), 345.2 (42), 273.0 (100), 267.1 (29). Anal. calc. for C40H38N2O2S (610.82): C 78.66, H 6.27, N
4.59, S 5.25; found: C 78.73, H 6.48, N 4.45, S 5.24.
Data of (S)-15. M.p. 197 – 1988. Rf (toluene) 0.59. [a]rD:t: ¼ ꢀ264.7 (c ¼ 1.02, CHCl3). IR (CHCl3):
3386w, 3062w, 3007m, 1664s, 1600w, 1477s, 1445s, 1372m, 1172s, 1096s, 1028w, 960w, 880w. 1H-NMR
(400 MHz, CDCl3): 0.85 (s, Me); 1.00 (s, Me); 1.70 (d, J ¼ 7.1, Me); 4.52 (d, J ¼ 9.0, CH); 4.66 (q, J ¼ 7.1,
CH); 4.66 (s, NH); 4.79 (d, J ¼ 9.0, CH); 7.04 – 7.07 (m, 2 arom. H); 7.14 – 7.31(m, 21 arom. H); 7.49 – 7.52
(m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 22.4, 26.7, 27.0 (Me); 46.2 (CH); 68.2, 71.6 (C); 77.4, 78.2
(CH); 110.5 (C); 126.3, 126.6, 126.9, 127.3, 127.4, 127.5, 127.6; 127.7, 128.3, 128.56, 128.60, 129.7, 130.4
(CH); 140.8, 142.2, 143.3, 145.4, 146.2, 148.7 (C, N2CS). HR-MS: 611.2725 ([M þ H]þ, C40H39N2O2Sþ;
calc. 611.2732 (ꢀ1.1 ppm)). MALDI-FT-ICR-MS: 633.3 (8, [M þ Na]þ), 611.3 (9, [M þ H]þ); 507.2
(100), 431.2 (23), 345.2 (51), 267.1 (36). Anal. calc. for C40H38N2O2S (610.82): C 78.66, H 6.27, N 4.59, S
5.25; found: C 78.44, H 6.39, N 4.60, S 5.26.
(3aS,5E,12E,14aS,17aS,19E,26E,28aS)-3a,4,14,14a,17a,18,28,28a-Octahydro-2,2,16,16-tetramethyl-
4,4,14,14,18,18,28,28-octaphenyl-7,11:25,21-dinitrilo-1,3-dioxolo[4,5-c][1,3]dioxolo[4,5-p][1,6,14,19]tet-
raazacyclohexacosine (16). To a soln. of 4 (0.60 g, 1.3 mmol) in toluene (150 ml), in a 500-ml round-
bottomed flask, equipped with a condenser and 4-ꢄ molecular sieve (1 g) in the gas phase [41], was
added pyridine-2,6-dicarbaldehyde (0.174 g, 1.3 mmol) and TsOH · H2O (24 mg, 0.13 mmol). After 3 h
heating under reflux, the solvent was evaporated, and the residue was dried under h.v. Purification by FC
(alumina (75 g); pentane/Et2O) yielded 16 (0.47 g, 67%). Colorless solid. M.p. 304 – 3058. Rf (alumina,
pentane/Et2O 1:1) 0.8. [a]rD:t: ¼ ꢀ131.91 (c ¼ 1.08, CHCl3). IR (CHCl3): 3061m, 3007s, 2934w, 1642s,
1584w, 1566w, 1494s, 1445s, 1380m, 1334m, 1164m, 1071s, 1022m, 930m, 906m, 879m. 1H-NMR (400 MHz,
CDCl3): 0.21 (s, Me); 0.91 (s, Me); 4.81 (s, CH); 6.28 (s, CH); 7.01 – 7.22 (m, 8 arom. H); 7.18 (s, CHN);
7.32 – 7.51 (m, 11 arom. H); 7.63 – 7.67 (m, 4 arom. H); 8.17 (s, CHN). 13C-NMR (100 MHz, CDCl3): 26.3,
27.7 (Me); 75.7, 76.3 (C); 80.5, 80.8 (CH); 106.1, 114.0 (C); 120.9, 121.9, 126.4, 126.5, 126.9, 127.0, 127.1,
127.5, 127.8, 128.4, 128.8, 130.3, 131.3, 132.5, 136.5 (CH); 138.0, 141.6, 145.0, 145.9, 153.6, 155.3 (C); 156.9,
159.1 (CHN). MALDI-FT-ICR-MS: 1149.5 (100, [M þ Na]þ); 1127.2 (25, [M þ H]þ), 883.4 (65), 383.2
(91). Anal. calc. for C76H66N6O4 (1127.40): C 80.97, H 5.90, N 7.45; found: C 80.93, H 6.09, N 7.44.
(3aS,8aS)-Hexahydro-6-methoxy-2,2-dimethyl-4,4,5,7,8,8-hexaphenyl-4H-1,3-dioxolo[4,5-e][1,3,2]di-
azaphosphepine (27). To a soln. of 10 (1.54 g, 2.5 mmol) in THF (20 ml), BuLi (3.4 ml, 5.3 mmol) was
added dropwise at ꢀ 708. The soln. was warmed to ꢀ 108 (ca. 20 min), then cooled again to ꢀ 708, and
MeOPCl2 (0.27 ml, 0.28 mmol) was added. The dry ice was removed from the cooling bath, and the
mixture was warmed slowly to r.t. (ca. 3 h) and stirred for further 2 h at r.t. The solvent was removed
under reduced pressure, and the residue (dried under h.v.) was purified by FC (2 ꢁ ; 1. SiO2 (75 g);
hexane/Et2O 10 :1; 2. SiO2 (18 g); hexane/Et2O 20 :1) to afford 27 (150 mg, 9%). Colorless solid. M.p.
142 – 1438 (dec.). Rf (hexane/Et2O 10 :1) 0.5. [a]rD:t: ¼ ꢀ15.0 (c ¼ 0.78, CHCl3). IR (CHCl3): 3062m,
3003m, 2935m, 1595m, 1488s, 1445m, 1381m, 1170m, 1075s, 1022s, 948w, 911w, 891m. 1H-NMR (400 MHz,
CDCl3): 0.32 (s, Me); 0.51 (s, Me); 3.16 (d, 3J (H,P) ¼ 14.0, MeO); 5.89 (d, J ¼ 7.6, CH); 6.29 (d, J ¼ 7.6,
CH); 6.78 – 7.37 (m, 26 arom. H); 7.68 – 7.70 (m, 2 arom. H); 7.92 – 7.94 (m, 2 arom. H). 13C-NMR
(100 MHz, CDCl3): 26.7, 27.8, 54.6 (d, 2J (C,P) ¼ 36.1) (Me); 75.8 (d, 2J ¼ 7.5), 79.3 (d, 2J ¼ 11.4) (C); 81.1,

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82.7 (CH); 111.3 (C); 116.9, 118.3, 122.4, 125.61, 125.65, 126.2, 126.3, 126.61, 126.64, 126.71, 126.73,
126.76, 126.84, 127.38, 127.44, 127.6, 127.8, 128.0, 128.1, 128.3, 128.8, 129.4, 130.5, 130.8, 132.0, 132.7, 132.8,
133.9 (CH); 140.5, 140.6, 143.8, 145.7, 146.0, 146.8, 147.0, 147.3 (C). 31P-NMR (120 MHz, CDCl3): 136.7.
MALDI-FT-ICR-MS: 677.3 (100, [M þ H]þ); 431.2 (24), 345.2 (37), 273.0 (29). Anal. calc. for
C44H41N2O3P (676.79): C 78.09, H 6.11, N 4.14, P 4.58; found: C 77.92, H 6.34, N 3.98, P 4.61.
(4S,5S)-N4-[4-(Diphenylphosphino)phenyl]-2,2-dimethyl-N5,a,a,a’,a’-pentaphenyl-1,3-dioxolane-
4,5-dimethanamine (28) and (4S,5S)-N4,N5-Bis[4-(diphenylphosphino)phenyl]-2,2-dimethyl-a,a,a’,a’-
tetraphenyl-1,3-dioxolane-4,5-dimethanamine (29). To a soln. of 10 (0.2 g, 0.32 mmol) in THF (2.6 ml)
was added BuLi (0.5 ml, 0.75 mmol) at ꢀ 708. The soln. was warmed to 08, stirred for further 1 h, and
then PClPh2 (0.22 ml, 1.6 mmol) was added at 08. The red mixture was stirred for further 3 h at 08, and the
solvent was removed under reduced pressure. Purification of the residue by FC (SiO2 (25 g); pentane/
Et2O 15 :2) afforded, besides recovered 10 (50 mg, 25%), 28 (110 mg, 42%), and 29 (15 mg, 5%).
Data of 28. Rf (pentane/Et2O 5 :1) 0.25. [a]rD:t: ¼ ꢀ77.8 (c ¼ 0.93, CHCl3). IR (CHCl3): 3286m (br.),
3059m, 3007m, 2935w, 1597s, 1497s, 1447m, 1434m, 1391m, 1382m, 1324m, 1084m, 908m, 892m. 1H-NMR
(400 MHz, CDCl3): 0.88 (s, Me); 0.92 (s, Me); 4.32 (d, J ¼ 8.0, CH); 4.33 (d, J ¼ 8.0, CH); 5.67 (br. s, NH);
6.22 – 6.24 (m, 2 arom. H, NH); 6.27 – 6.30 (m, 2 arom. H); 6.57 (m, 1 arom. H); 6.77 – 6.86 (m, 4 arom.
H); 7.08 – 7.47 (m, 26 arom. H); 7.73 – 7.76 (m, 4 arom. H). 13C-NMR (75 MHz, CDCl3): 26.8, 26.9 (Me);
67.4, 67.5 (C); 84.5, 84.8 (CH); 107.8 (C); 117.1, 117.2, 117.5, 118.9, 126.95, 126.98, 127.9, 128.0, 128.1, 128.2,
128.4, 128.46, 128.52, 128.6, 129.1, 130.96, 131.01, 133.5, 133.8, 134.5, 134.8 (CH); 139.3, 139.6, 142.7, 145.2,
146.6 (C). 31P-NMR (162 MHz, CDCl3): ꢀ 6.45. HR-MS: 801.3607 ([M þ H]þ, C55H50N2O2Pþ; calc.
801.3609 (ꢀ0.25 ppm)). MALDI-FT-ICR-MS: 839.3 (15, [M þ K]þ), 801.4 (46, [M þ H]þ), 573.1 (47),
481.2 (38), 442.2 (100), 273.0 (95). Anal. calc. for C55H49N2O2Pþ (800.98): C 82.47, H 6.17, N 3.50, P 3.87;
found: C 82.30, H 6.37, N 3.54, P 3.70.
1
Data of 29. White solid foam. Rf (pentane/Et2O 5 :1) 0.14. H-NMR (300 MHz, CDCl3): 0.89 (s,
Me); 4.39 (s, CH); 6.02 (br. s, NH); 6.24 – 6.28 (m, 4 arom. H); 6.79 – 6.85 (m, 4 arom. H); 7.10 – 7.41 (m,
36 arom. H); 7.70.-7.73 (m, 4 arom. H). HR-MS: 985.4053 ([M þ H]þ, C67H59N2O2P2þ ; calc. 985.4052
(ꢀ0.10 ppm)). MALDI-FT-ICR-MS: 1039.4 (9), 985.4 (3, [M þ H]þ), 458.2 (57), 442.4 (97), 273.0
(100).
5. Preparation of the TADDOP Derivatives 17 – 26. 1-[(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-
tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphosphepin-6-yl]piperidine (17a). TADDOL (1; 1.50 g,
3.21 mmol) was treated with Et3N (0.90 ml, 6.42 mmol) and PCl3 (0.28 ml, 3.21 mmol), and then with
Et3N (0.45 ml, 3.21 mmol) and piperidine (0.32 ml, 3.21 mmol) according to GP 4. Washing the crude
product (1.79 g) with ice-cold Et2O (20 ml) afforded 17a (1.69 g, 91%). For anal. purposes, a sample was
purified by FC (hexane/CH2Cl2 1:3; 3 – 4 drops of Et3N added to 100 ml of solvent). Colorless powder.
M.p. 210 – 2128. [a]rD:t: ¼ ꢀ151.4 (c ¼ 1.13, CHCl3). IR (CHCl3): 3066w, 3008m, 2937m, 2853w, 1600w,
1494m, 1447m, 1382w, 1372m, 1164m, 1086w, 1047m, 1036s, 1018s, 951s, 879m, 822w, 640w. 1H-NMR
(300 MHz, CDCl3): 0.30 (s, Me), 1.33 (s, Me), 1.54 – 1.64 (m, 3 CH2), 3.17 – 3.23 (m, NCH2), 3.28 – 3.33
(m, NCH2), 4.79 (d, J ¼ 8.4, CH), 5.19 (dd, J(H,H) ¼ 8.4, J(H,P) ¼ 3.4, CH), 7.18 – 7.37 (m, 12 arom. H),
7.43 – 7.52 (m, 4 arom. H), 7.63 – 7.67 (m, 2 arom. H), 7.78 – 7.81 (m, 2 arom. H). 13C-NMR (75 MHz,
CDCl3): 25.10, 25.20, 26.90, 26.95, 27.48, 44.74, 45.00, 81.08, 81.58, 82.21, 82.47, 82.61, 82.66, 111.56, 125.39,
127.05, 127.18, 127.23, 127.30, 127.46, 127.56, 127.72, 128.11, 128.32, 128.87, 128.93, 129.13, 142.05, 142.42,
146.78, 147.29. 31P-NMR (122 MHz, CDCl3): 138.15. FAB-MS: 580 (1, Mþ), 384 (18), 326 (16), 238 (17),
237 (97), 236 (21), 208 (13), 207 (30), 180 (19), 179 (100). Anal. calc. for. C36H38NO4P (579.68): C 74.59,
H 6.61, N 2.42; found: C 74.63, H 6.60, N 2.12. Anal. data match those in [23].
4-[(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphosphe-
pin-6-yl]morpholine (17b). TADDOL (1; 1.50 g, 3.21 mmol) was treated with Et3N (0.90 ml, 6.42 mmol)
and PCl3 (0.28 ml, 3.21 mmol), and then with Et3N (0.45 ml, 3.21 mmol) and morpholine (0.28 ml,
3.21 mmol) according to GP 4. Washing the crude product (1.80 g) with ice-cold Et2O (20 ml) afforded
17b (1.47 g, 79%). For anal. purposes, a sample was recrystallized from hexane/CH2Cl2 (2 :1) at ꢀ 208.
Colorless powder. M.p. 209 – 2108 ([24]: M.p. 2308). [a]rD:t: ¼ ꢀ159.2 (c ¼ 1.00, CHCl3). IR (CHCl3):
3062w, 3007m, 2964w, 2903w, 2857w, 1600w, 1494m, 1447m, 1383m, 1372m, 1346w, 1297w, 1256m, 1165m,
1
1110s, 1081m, 1050s, 1038s, 1013m, 956s, 916m, 879s, 826m, 640w. H-NMR (300 MHz, CDCl3): 0.32 (s,
Me); 1.28 (s, Me); 3.18 – 3.24 (m, NCH2); 3.25 – 3.37 (m, NCH2); 3.68 – 3.72 (m, 2 OCH2); 4.82 (d, J ¼ 8.4,

Helvetica Chimica Acta – Vol. 95 (2012)
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CH); 5.19 (dd, J(H,H) ¼ 8.4, J(H,P) ¼ 3.4, CH); 7.19 – 7.40 (m, 12 arom. H); 7.46 – 7.49 (m, 2 arom. H);
7.56 (dd, J ¼ 7.8, J ¼ 1.9, 2 arom. H); 7.63 (d, J ¼ 7.2, 2 arom. H); 7.74 – 7.77 (m, 2 arom. H). 13C-NMR
(75 MHz, CDCl3): 25.35, 27.10, 27.45, 43.92, 44.24, 67.76, 67.89, 81.00, 81.38, 81.92, 82.27, 111.83, 127.06,
127.16, 127.32, 127.48, 127.63, 127.73, 128.05, 128.11, 128.62, 128.75, 128.84, 128.90, 141.60, 142.05, 142.78,
146.02, 146.36, 146.81. 31P-NMR (122 MHz, CDCl3): 138.13. FAB-MS: 1092 (9), 1064 (16), 1051 (12),
1049 (14), 1048 (23), 599 (16), 598 (32), 583 (42), 582 (100, Mþ), 580 (19), 431 (21). Anal. calc. for
C35H36NO5P (581.65): C 72.27, H 6.24, N 2.41; found: C 72.17, H 6.33, N 2.28. Anal. data match those in
[24].
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-N,N-bis(phenylmethyl)-1,3-dioxolo[4,5-
e][1,3,2]dioxaphosphepin-6-amine (17c). TADDOL (1; 2.82 g, 6.03 mmol) was treated with Et3N
(1.69 ml, 12.13 mmol) and PCl3 (0.53 ml, 6.07 mmol), and then with Et3N (0.84 ml, 6.06 mmol) and
Bn2NH (1.16 ml, 6.03 mmol) according to GP 4. Purification by FC (hexane/Et2O 3 :1; 3 – 4 drops of Et3N
added to 100 ml of solvent) afforded 17c (2.88 g, 69%). Colorless powder. M.p. 190 – 1928. [a]rD:t: ¼ ꢀ63.3
(c ¼ 0.98, CHCl3). IR (CHCl3): 3062w, 3007m, 2934w, 1952w, 1892w, 1812w, 1601w, 1494m, 1447s, 1383m,
1
1372w, 1290w, 1165m, 1086m, 1049s, 1039m, 999m, 975s, 918w, 878s, 826m, 640w. H-NMR (300 MHz,
CDCl3): 0.32 (s, Me); 1.33 (s, Me); 4.19 (dd, J(H,H) ¼ 10.0, J(H,P) ¼ 10.3, 2 CH2); 4.87 (d, J ¼ 8.4, CH);
5.34 (dd, J(H,H) ¼ 8.4, J(H,P) ¼ 3.4, CH); 7.21 – 7.48 (m, 16 arom. H); 7.70 – 7.73 (m, 2 arom. H); 7.86 –
7.89 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 25.33, 27.50, 47.88, 48.21, 81.69, 81.84, 81.97, 82.13, 82.42,
111.77, 127.04, 127.14, 127.20, 127.36, 127.46, 127.60, 127.72, 128.19, 128.32, 128.85, 129.03, 129.17, 129.34,
138.64, 141.78, 142.57, 146.52, 147.02. 31P-NMR (122 MHz, CDCl3): 139.19. FAB-MS: 691 (5, Mþ), 690
(9), 496 (20), 438 (27), 432 (18), 431 (53), 374 (11), 373 (12), 345 (18), 265 (11), 238 (20), 237 (100), 207
(15), 179 (81). Anal. calc. for. C45H42NO4P (691.81): C 78.13, H 6.12; N 2.02; found: C 78.23, H 6.33, N
1.94. NMR and MS data match those in [23].
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-N,N-diprop-2-en-1-yl-1,3-dioxolo[4,5-e][1,3,
2]dioxaphosphepin-6-amine (17d). TADDOL (1; 3.00 g, 6.42 mmol) was treated with Et3N (1.80 ml,
12.84 mmol) and PCl3 (0.56 ml, 6.42 mmol), and then with Et3N (0.90 ml, 6.42 mmol) and diallylamine
(0.79 ml, 6.42 mmol) according to GP 4. Purification by FC (hexane/Et2O 3 :1; 3 – 4 drops of Et3N added
to 100 ml of solvent) afforded 17d (2.63 g, 69%). Colorless powder. M.p. 118 – 1198. [a]rD:t: ¼ ꢀ123.3 (c ¼
1.05, CHCl3). IR (CHCl3): 3061m, 3008s, 1601w, 1494m, 1447m, 1384w, 1372w, 1166m, 1086m, 1050s,
1035s, 1018s, 945m, 882m. 1H-NMR (300 MHz, CDCl3): 0.28 (s, Me); 1.34 (s, Me); 3.44 – 3.88 (m,
2 NCH2); 4.77 (d, J ¼ 8.4, 1 H); 5.12 – 5.23 (m, 5 H); 5.74 – 5.89 (m, 2 H); 7.15 – 7.80 (m, 20 arom. H).
13C-NMR (75 MHz, CDCl3): 25.15; 27.50; 46.94; 47.21; 81.42; 81.77; 82.13; 82.40; 82.55; 111.57; 116.85;
127.10; 127.22; 127.36; 127.52; 127.59; 127.72; 128.12; 128.87; 128.93; 129.17; 136.32; 141.83; 142.44; 146.62;
147.18. 31P-NMR (122 MHz, CDCl3): 141.27. FAB-MS: 591 (12, Mþ), 431 (100), 373 (21), 345 (36), 237
(54), 179 (50). Anal. calc. for C37H38NO4P (591.69): C 75.11, H 6.47, N 2.37; found: C 75.39, H 6.52, N
2.15.
(3aR,8aR)-Tetrahydro-2,2-dimethyl-N,N-bis(1-methylethyl)-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-
e][1,3,2]dioxaphosphepin-6-amine (17e). TADDOL (1; 1.50 g, 3.21 mmol) was treated with Et3N
(0.90 ml, 6.42 mmol) and PCl3 (0.28 ml, 3.21 mmol), and then with Et3N (0.45 ml, 3.21 mmol) and iPr2NH
(0.46 ml, 3.21 mmol) according to GP 4. Purification of the crude product (1.85 g) by FC (hexane/Et2O
3 :1; 3 – 4 drops of Et3N added to 100 ml of solvent) afforded 17e (1.61 g, 88%). For anal. purposes, a
sample was recrystallized from hexane/Et2O (15 :1) at ꢀ 208. Colorless powder. M.p. 169 – 1708 ([25]:
M.p. 174 – 1758). [a]rD:t: ¼ ꢀ107.0 (c ¼ 1.15, CHCl3) ([25]: [a]rD:t: ¼ ꢀ83.4 (c ¼ 0.7, CH2Cl2)). IR (CHCl3):
3066w, 3008w, 2970m, 2933w, 2874w, 1493w, 1459w, 1448m, 1396w, 1382w, 1364w, 1163m, 1130w, 1103w,
1
1085m, 1051s, 1042s, 1032m, 1006m, 982s, 918w, 878m, 819w, 652w, 636w. H-NMR (300 MHz, CDCl3):
0.24 (s, Me); 1.20 (d, J ¼ 6.5, 2 Me); 1.25 (d, J ¼ 6.5, 2 Me); 1.44 (s, Me); 3.98 (sept., J ¼ 6.5,2 NCH); 4.62
(d, J ¼ 8.7, CH); 5.21 (dd, J(H,H) ¼ 8.7, J(H,P) ¼ 3.4, CH); 7.17 – 7.33 (m, 12 arom. H); 7.44 – 7.49 (m, 4
arom. H); 7.64 (d, J ¼ 7.80, 2 arom. H); 7.84 (d, J ¼ 8.1, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 24.05,
24.21, 24.27, 24.40, 25.09, 27.73, 44.11, 44.40, 80.74, 81.25, 82.30, 82.74, 83.06, 83.13, 111.00, 126.81, 126.93,
127.09, 127.16, 127.41, 127.48, 127.79, 128.71, 128.81, 129.13, 142.24, 142.99, 147.12, 147.67. 31P-NMR
(122 MHz, CDCl3): 141.04. FAB-MS: 1190 (11), 1189 (13), 777 (16), 747 (19), 733 (14), 718 (11), 634
(12), 618 (23), 612 (67), 608 (17), 597 (95), 596 (100, [M þ 1]þ), 594 (88), 580 (36), 537 (66), 431 (80),

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Helvetica Chimica Acta – Vol. 95 (2012)
400 (97), 341 (49), 236 (69). Anal. calc. for. C37H42NO4P (595.71): C 74.60, H 7.11, N 2.35; found: C 74.46,
H 7.25, N 2.18. NMR and MS data match those in [25].
(3aR,8aR)-N,N-Diethyltetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]diox-
aphosphepin-6-amine (17f). To a soln. of PCl3 (0.28 ml, 3.21 mmol) in toluene (5 ml) was added Et3N
(0.90 ml, 6.42 mmol) at ꢀ 608 under Ar, and then a soln. of TADDOL (1; 1.50 g, 3.21 mmol) in toluene
(15 ml) was added dropwise over 15 min. The mixture was stirred for further 45 min at ꢀ 608, then the
cooling bath was removed, and the mixture was allowed to warm slowly to r.t. which led to the formation
of a colorless precipitate. After cooling to ꢀ 408, Et3N (0.45 ml, 3.21 mmol) and Et2NH (0.33 ml,
3.21 mmol) were added consecutively. The mixture was warmed to r.t. and stirred for further 12 h at r.t.
Workup according to GP 4. Purification of the crude product (1.59 g) by FC (hexane/Et2O 3 :1; 3 – 4
drops of Et3N added to 100 ml of solvent) afforded 17f (1.01 g, 57%). Colorless powder. M.p. 159 – 1618.
IR (CHCl3): 3061w, 3007m, 2934w, 2870w, 1599w, 1494m, 1447s, 1382m, 1165m, 1086s, 1052s, 1028s, 1012s,
1
942m, 918w, 878s, 822w, 640w. H-NMR (300 MHz, CDCl3): 0.30 (s, Me); 1.18 (t, 2 Me); 1.36 (s, Me);
3.20 – 3.33 (m, 2 CH2); 4.78 (d, J ¼ 8.7, CH); 5.21 (dd, J(H,H) ¼ 8.7, J(H,P) ¼ 3.4, CH); 7.18 – 7.37 (m, 12
arom. H); 7.45 – 7.52 (m, 4 arom. H); 7.62 (d, J ¼ 6.9, 2 arom. H); 7.81 (d, J ¼ 6.9, 2 arom. H). 13C-NMR
(75 MHz, CDCl3): 15.12, 15.15, 25.13, 27.51, 38.68, 38.97, 81.14, 81.26, 81.45, 82.18, 82.45, 82.61, 82.66,
111.43, 127.01, 127.07, 127.17, 127.23, 127.30, 127.43, 127.54, 127.65, 127.91, 128.07, 128.20, 128.32, 128.85,
128.923, 129.16, 142.02, 142.62, 146.86, 147.39. 31P-NMR (122 MHz, CDCl3): 142.04. FAB-MS: 569 (5),
568 (12, Mþ), 432 (10), 431 (29), 373 (11), 372 (24), 345 (8), 314 (16), 265 (11), 238 (26), 237 (100), 207
(16), 179 (55).
(3aR,8aR)-Tetrahydro-N,N,2,2-tetramethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphos-
phepin-6-amine (17g). TADDOL (1; 1.50 g, 3.21 mmol) was treated with Et3N (0.90 ml, 6.42 mmol) and
PCl3 (0.28 ml, 3.21 mmol), and then with Et3N (0.88 ml, 6.30 mmol), and a suspension of Me2NH · HCl
(0.36 g, 4.41 mmol) in CH2Cl2 (5 ml) according to GP 4. Purification of the crude product (1.62 g) by FC
(hexane/CH2Cl2 1:2; 3 – 4 drops of Et3N added to 100 ml of solvent) afforded 17g (1.24 g, 72%). For anal.
purposes, a sample was recrystallized (2ꢁ) from hexane/CH2Cl2 (3 :1) at ꢀ 208. Colorless powder. M.p.
218 – 2218 ([25a]: M.p. > 2208). [a]Dr:t: ¼ ꢀ161.5 (c ¼ 0.91, CHCl3) ([25a]: [a]rD:t: ¼ ꢀ151 (c ¼ 0.69,
CHCl3)). IR (CHCl3): 3061w, 3039w, 3008m, 2889w, 2839w, 1600w, 1498m, 1447s, 1383m, 1372w, 1292w,
1
1165m, 1086m, 1050s, 1000m, 976s, 918w, 879s, 825m, 640w. H-NMR (300 MHz, CDCl3): 0.32 (s, Me);
1.30 (s, Me); 2.76 (d, J(H,P) ¼ 10.4, 2 Me); 4.85 (d, J ¼ 8.7, CH); 5.21 (dd, J(H,H) ¼ 8.7, J(H,P) ¼ 2.9,
CH); 7.21 – 7.51 (m, 16 arom. H); 7.53 – 7.65 (m, 2 arom. H); 7.72 – 7.79 (m, 2 arom. H). 13C-NMR
(75 MHz, CDCl3): 25.35, 27.48, 35.10, 35.48, 81.13, 81.29, 81.95, 82.11, 82.49, 111.73, 127.03, 127.13, 127.25,
127.44, 127.67, 128.08, 128.59, 128.71, 128.81, 129.00, 141.86, 142.21, 146.56, 146.90. 31P-NMR (122 MHz,
CDCl3): 140.04. FAB-MS: 540 (4, [M þ 1]þ), 432 (6), 431 (19), 289 (7), 288 (9), 267 (6), 265 (12), 238
(11), 237 (47), 207 (17), 195 (12), 191 (10), 179 (100), 178 (51). Anal. calc. for. C33H34NO4P (539.62): C
73.45, H 6.35, N 2.60; found: C 73.61, H 6.38, N 2.49. NMR and MS data match those in [25a][26].
(3aR,8aR)-N,N-Dicyclohexyltetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]di-
oxaphosphepin-6-amine (17h). TADDOL (1; 1.50 g, 3.21 mmol) was treated with Et3N (0.90 ml,
6.42 mmol) and PCl3 (0.28 ml, 3.21 mmol), and then with Et3N (0.45 ml, 3.21 mmol) and dicyclohexyl-
amine (0.63 ml, 3.21 mmol) according to GP 4. Purification of the crude product (2.12 g) by FC (hexane/
Et2O 3 :1; 3 – 4 drops of Et3N added to 100 ml of solvent) afforded 17h (1.72 g, 79%). For anal. purposes,
a sample was recrystallized from hexane/Et2O (15 :1) at ꢀ 208. Colorless powder. M.p. 192 – 1948.
[a]rD:t: ¼ ꢀ77.9 (c ¼ 1.36, CHCl3) ([27]: [a]Dr:t: ¼ ꢀ60.6 (c ¼ 1, CH2Cl2)). IR (CHCl3): 3064w, 3039w, 3002w,
2933s, 2853s, 1599w, 1493m, 1448s, 1383m, 1372w, 1163s, 1119w, 1084m, 1077m, 1050s, 1038s, 1021s, 981s,
918w, 877s, 854w, 822m, 650w, 640w, 611w. 1H-NMR (300 MHz, CDCl3): 0.23 (s, Me); 1.44 (s, Me); 1.29 –
1.49 (m, 10 H, CH2); 1.77 – 1.89 (m, 10 H, CH2); 3.42 – 3.58 (m, 2 H, NCH); 4.63 (d, J ¼ 8.7, CH); 5.16 (dd,
J(H,H) ¼ 8.7, J(H,P) ¼ 3.4, CH); 7.17 – 7.33 (m, 12 arom. H); 7.45 (d, J ¼ 7.5, 4 arom. H); 7.63 (d, J ¼ 7.2, 2
arom. H); 7.82 – 7.85 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 25.00, 25.51, 26.81, 26.91, 27.73, 34.94,
35.06, 35.19, 35.32, 53.57, 53.83, 80.65, 80.94, 81.13, 82.49, 82.87, 83.10, 83.16, 111.00, 126.78, 126.87, 127.10,
127.19, 127.32, 127.44, 127.54, 127.79, 128.62, 128.71, 129.03, 142.24, 142.81, 147.00, 147.51. 31P-NMR
(122 MHz, CDCl3): 140.99. FAB-MS: 675 (1, Mþ), 422 (5), 238 (12), 237 (61), 228 (7), 207 (12), 180 (17),
179 (100), 178 (18), 167 (37). Anal. calc. for. C43H50NO4P (675.86): C 76.42, H 7.46, N 2.07; found: C
76.60, H 7.53, N 1.97. Anal. data match those in [27].

Helvetica Chimica Acta – Vol. 95 (2012)
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1-[(3aR,8aR)-Tetrahydro-2,2-dimethyl-6-oxido-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]diox-
aphosphepin-6-yl]piperidine (18a). Compound 17a (150 mg, 0.26 mmol) was treated with H2O2 (0.04 ml,
1.31 mmol) according to GP 5. FC (hexane/CH2Cl2 1:3) afforded 18a (109 mg, 71%). Colorless powder.
1H-NMR (300 MHz, CDCl3): 0.59 (s, Me); 0.76 (s, Me); 1.48 – 1.53 (m, 3 CH2); 3.01 – 3.09 (m, 2 NCH2);
5.08 (d, J ¼ 8.1, CH); 5.46 (d, J ¼ 8.1, CH); 7.24 – 7.40 (m, 14 arom. H); 7.52 – 7.59 (m, 6 arom. H).
13C-NMR (75 MHz, CDCl3): 24.43, 25.73, 25.83, 26.59, 26.72, 78.30, 79.60, 84.78, 84.91, 88.94, 89.10,
113.13, 126.75, 127.10, 127.44, 127.79, 127.89, 128.05, 128.62, 129.73, 140.02, 140.08, 140.33, 140.52, 144.14,
145.06, 145.19. 31P-NMR (122 MHz, CDCl3): 0.65. FAB-MS: 1193 (10, [2 M]þ), 1192 (14), 759 (5), 597
(10), 596 (23, Mþ), 432 (37), 431 (100), 373 (17), 345 (24), 207 (11), 195 (15), 179 (25).
4-[(3aR,8aR)-Tetrahydro-2,2-dimethyl-6-oxido-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]diox-
aphosphepin-6-yl]morpholine (18b). Compound 17b (180 mg, 0.31 mmol) was treated with H2O2
(0.10 ml, 3.26 mmol) according to GP 5. Purification of the crude product by recrystallization from
hexane/CH2Cl2 3 :1 at ꢀ 208 afforded 18b (110 mg, 59%). Colorless powder. 1H-NMR (300 MHz,
CDCl3): 0.63 (s, Me); 0.71 (s, Me); 3.00 – 3.07 (m, NCH2); 3.13 – 3.21 (m, NCH2); 3.57 – 3.64 (m,
2 OCH2); 5.10 (d, J ¼ 8.4, CH); 5.48 (d, J ¼ 8.1, CH); 7.22 – 7.41 (m, 12 arom. H); 7.54 – 7.61 (m, 8 arom.
H). 13C-NMR (75 MHz, CDCl3): 26.59, 44.60, 66.81, 78.26, 79.44, 85.20, 85.28, 89.57, 89.70, 113.48, 126.86,
127.20, 127.27, 127.69, 128.07, 128.20, 128.30, 128.62, 129.82, 132.91, 139.87, 140.16, 140.30, 143.93, 145.03.
31P-NMR (122 MHz, CDCl3): 0.30.
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-N,N-bis(phenylmethyl)-1,3-dioxolo[4,5-
e][1,3,2]dioxaphosphepin-6-amine 6-Oxide (18c). Compound 17c (120 mg, 0.17 mmol) was treated with
H2O2 (0.05 ml, 1.63 mmol) according to GP 5. FC (hexane/Et2O 3 :1) afforded 18c (144 mg, 66%).
Colorless powder. 1H-NMR (300 MHz, CDCl3): 0.60 (s, Me); 0.80 (s, Me); 4.07 (dd, J(H,H) ¼ 12.1,
J(H,P) ¼ 4.7, 2 CH2); 5.13 (d, J ¼ 8.1, CH); 5.65 (d, J ¼ 8.1, CH); 7.17 – 7.46 (m, 26 arom. H); 7.58 – 7.61
(m, 2 arom. H); 7.74 – 7.77 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 26.46, 26.75, 48.64, 78.02, 79.35,
85.67, 85.75, 89.40, 89.51, 113.26, 127.17, 127.23, 127.35, 127.56, 127.64, 127.99, 128.09, 128.40, 128.66, 128.92,
130.03, 137.44, 137.47, 140.29, 144.09, 144.90. 31P-NMR (122 MHz, CDCl3): 2.38.
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-N,N-diprop-2-en-1-yl-1,3-dioxolo[4,5-
e][1,3,2]dioxaphosphepin-6-amine 6-Oxide (18d). Compound 17d (70 mg, 0.12 mmol) was treated with
H2O2 (0.04 ml, 1.31 mmol) according to GP 5. FC (hexane/Et2O 3 :1) afforded 18d (52 mg, 72%).
Colorless powder. 1H-NMR (300 MHz, CDCl3): 0.60 (s, Me); 0.75 (s, Me); 3.54 – 3.62 (m, 2 NCH2); 5.05
(d, J ¼ 8.1, CH); 5.09 – 5.20 (m, 2 CH2); 5.49 (d, J ¼ 8.1, CH); 5.68 – 5.79 (m, 2 CH); 7.19 – 7.39 (m, 12
arom. H); 7.49 – 7.66 (m, 8 arom. H). 13C-NMR (75 MHz, CDCl3): 26.59, 26.81, 48.08, 78.24, 79.41, 85.21,
85.32, 89.25, 89.46, 113.13, 117.51, 126.90, 127.10, 127.32, 127.48, 127.86, 127.98, 128.08, 128.78, 129.92,
134.43, 140.11, 140.52, 144.17, 145.00. 31P-NMR (122 MHz, CDCl3): 2.00.
(3aR,8aR)-Tetrahydro-2,2-dimethyl-N,N-bis(1-methylethyl)-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-
e][1,3,2]dioxaphosphepin-6-amine 6-Oxide (18e). Compound 17e (70 mg, 0.12 mmol) was treated with
H2O2 (0.04 ml, 1.31 mmol) according to GP 5. FC (hexane/Et2O 3 :1) afforded 18e (61 mg, 85%).
Colorless powder. 1H-NMR (300 MHz, CDCl3): 0.57 (s, Me); 0.81 (s, Me); 1.15 (d, J ¼ 6.9, Me); 1.23 (d,
J ¼ 6.9, Me); 3.35 – 3.47 (m, 2 NCH); 5.07 (d, J ¼ 8.1, CH); 5.52 (d, J ¼ 8.1, CH); 7.18 – 7.38 (m, 12 arom.
H); 7.51 – 7.70 (m, 6 arom. H); 7.71 – 7.73 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 21.95, 22.30, 26.35,
26.77, 46.57, 78.26, 79.62, 84.86, 84.93, 88.58, 88.72, 112.80, 127.12, 127.18, 127.44, 127.72, 127.83, 127.90,
127.98, 128.50, 130.06, 140.58, 140.82, 140.97, 144.80, 145.59. 31P-NMR (122 MHz, CDCl3): ꢀ 0.04. FAB-
MS: 1224 (2, [2 M]þ), 613 (28), 612 (67, Mþ), 432 (35), 431 (100), 373 (19), 346 (15), 345 (31), 265 (17),
237 (18), 207 (30), 195 (32), 179 (50).
(3aR,8aR)-N,N-Diethyltetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]diox-
aphosphepin-6-amine 6-Oxide (18f). Compound 17f (100 mg, 0.18 mmol) was treated with H2O2
(0.05 ml, 1.63 mmol) according to GP 5. FC (hexane/Et2O 3 :1) afforded 18f (82 mg, 80%). Colorless
powder. M.p. 194 – 1958. [a]rD:t: ¼ ꢀ229.7 (c ¼ 1.00, CHCl3). IR (CHCl3): 3050w, 3008m, 2935w, 1601w,
1448m, 1382w, 1364w, 1259m, 1167w, 1092w, 1064w, 1034m, 1019s, 960w, 916 m, 832w, 824w, 640m, 629m,
1
619m. H-NMR (300 MHz, CDCl3): 0.61 (s, Me); 0.75 (s, Me); 1.05 (t, J ¼ 7.5, 2 Me); 3.08 (m, J ¼ 6.5,
2 NCH); 5.11 (d, J ¼ 8.3, CH); 5.52 (d, J ¼ 8.3, CH); 7.20 – 7.39 (m, 14 arom. H); 7.50 – 7.57 (m, 4 arom.
H); 7.64 – 7.73 (m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 13.96, 26.53, 26.72, 39.89, 39.95, 78.23, 79.48,
84.22, 84.93, 89.01, 89.04, 113.08, 127.01, 127.14, 127.17, 127.39, 127.49, 127.85, 127.93, 128.04, 128.07, 128.85,

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Helvetica Chimica Acta – Vol. 95 (2012)
130.08, 140.43, 140.71, 140.85, 144.53, 145.36, 145.47. 31P-NMR (122 MHz, CDCl3): 2.34. Anal. calc. for.
C35H38NO5P (583.65): C 72.03, H 6.56, N 2.40; found: C 72.11, H 6.57, N 2.34.
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphosphepin 6-
Oxide (19). To a soln. of TADDOL (1; 1.00 g, 2.14 mmol) in Et2O (30 ml) was added pyridine (0.36 ml,
4.46 mmol) at ꢀ 158, and then PCl3 (0.19 ml, 2.14 mmol) was added dropwise over 15 min. The mixture
(which contained a colorless precipitate) was slowly warmed to r.t. (ca. 1 h) and stirred for further 2 h at
r.t. Sat. aq. NaCl soln. (50 ml) and sat. aq. NaHCO3 soln. (20 ml) were added, the org. layer was
separated, and the aq. layer was extracted with Et2O (2 ꢁ 30 ml). The combined org. layers were dried
(MgSO4) and concentrated under reduced pressure. The crude product was purified by FC (hexane/
CH2Cl2 1:3) to afford 19 (0.89 g, 81%). For anal. purposes, a sample was recrystallized from pentane/
Et2O 1:5 at ꢀ 208. Colorless powder. M.p. 181 – 1838 ([25a]: M.p. 226 – 2278 (dec.)). [a]rD:t: ¼ ꢀ299.16
(c ¼ 1.07, CHCl3; [25a]: [a]rD:t: ¼ ꢀ289.9 (c ¼ 1.56, CHCl3)). IR (CHCl3): 3064w, 3008m, 2937w, 1600w,
1496m, 1448s, 1384w, 1374w, 1354w, 1270s, 1167m, 1092s, 1073s, 1054s, 1035m, 982s, 955s, 900w, 857w,
654w, 641w. 1H-NMR (200 MHz, CDCl3): 0.68 (s, Me); 0.88 (s, Me); 1.36 (d, J ¼ 5.3, OH); 5.23 (d, J ¼ 8.1,
CH); 5.38 (d, J ¼ 8.1, CH); 7.26 – 7.45 (m, 16 arom. H); 7.59 – 7.64 (m, 4 arom. H). 13C-NMR (50 MHz,
CDCl3): 26.18, 26.65, 79.73, 79.98, 80.05, 88.56, 88.71, 114.30, 126.71, 126.81, 127.29, 127.44, 127.83, 127.92,
128.14, 128.24, 128.40, 128.62, 128.75, 138.84, 139.00, 139.19, 143.13, 143.57. 31P-NMR (122 MHz, CDCl3):
ꢀ 3.92. FAB-MS: 1027 (16), 1026 (26), 513 (1, Mþ), 432 (40), 431 (100), 345 (18), 265 (11), 237 (59), 207
(44), 179 (79). Anal. calc. for C31H29O5P (512.55): C 72.65, H 5.70, P 6.04; found: C 72.60, H 5.88, P 5.93.
Anal. data match those in [25a].
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-6-[(3aR,8aR)-tetrahydro-2,2-dimethyl-
4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphosphepin-6-yl]-1,3-dioxolo[4,5-e][1,3,2]dioxaphos-
phepin 6-Oxide (20). To a soln. of TADDOL (1; 2.32 g, 4.96 mmol) and Et3N (1.40 ml, 9.99 mmol) in
CH2Cl2 (40 ml) under Ar at – 508 was added slowly (15 min) PCl3 (0.43 ml, 4.93 mmol). After warming up
to ꢀ 208 (100 min) and recooling to ꢀ 508, again Et3N (0.68 ml, 4.85 mmol) and phenothiazin (0.97 g,
4.87 mmol) were added. After warming up to r.t., the mixture was stirred for further 72 h at r.t. During
this period, a brownish precipitate was formed. For workup, the mixture was diluted with CH2Cl2
(100 ml), washed with sat. NaCl (50 ml) and sat. NaHCO3 (5 ml), dried (MgSO4), and the solvent was
removed under reduced pressure. Purification by FC (CH2Cl2, 1% Et3N) afforded 20 (231 mg, 9%).
Colorless powder. M.p. 171 – 173. IR (CHCl3): 3061w, 3008m, 1600w, 1495m, 1448s, 1384m, 1377w, 1252s,
1165m, 1093m, 1086m, 1047w, 1030m, 997s, 919m, 878m, 838w, 641w. 1H-NMR (300 MHz, CDCl3): 0.21
(s, Me); 0.59 (s, Me); 0.95 (s, Me); 1.58 (s, Me); 4.71 (d, J ¼ 8.30, CH); 5.25 (d, J ¼ 7.89, CH); 5.43 (quint.,
J(H,H) ¼ 8.30, J(H,P) ¼ 4.15, J(H,P) ¼ 3.73, CH); 5.63 (d, J ¼ 7.89, CH); 7.25 – 7.42 (m, 24 arom. H);
7.48 – 7.87 (m, 16 arom. H). 13C-NMR (75 MHz, CDCl3): 24.56, 26.33, 27.03, 27.73, 80.02, 80.11, 80.27,
83.03, 83.45, 80.60, 83.70, 84.05, 84.15, 84.24, 84.38, 84.70, 86.87, 87.16, 91.51, 91.88, 112.02, 113.64, 126.46,
127.16, 127.25, 127,38, 127.63, 127.73, 127.86, 128.02, 128.14, 128.33, 128.71, 129.25, 129.98, 139.31, 139.41,
139.50, 140.05, 140.46, 143.98, 144.33, 144.41, 144.87, 145.03, 145.73. 31P-NMR (122 MHz, CDCl3): 157.96
(d, J(P,P) ¼ 189.98), 13.51 (d, J(P,P) ¼ 189.98). FAB-MS: 1616 (1), 1552 (1), 1125 (1), 1024 (1), 1007 (1,
Mþ), 432 (39), 431 (100), 373 (15), 345 (21), 237 (26). MALDI-MS: 1029.6 ([M þ Na]þ), 1045.6 ([M þ
O þ Na]þ), 1061.7 ([M þ O þ K]þ).
(3aR,8aR)-Tetrahydro-2,2,6-trimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphosphepin
6-Oxide (21a). To a soln. of TADDOL (1; 2.33 g, 5.0 mmol) in THF (20 ml) was added BuLi (6.88 ml,
11.0 mmol) at ꢀ 788. The soln. was warmed to r.t. and stirred for 1 h, then cooled to ꢀ 788 again, and
MeP(O)Cl2 (0.55 ml, 6.0 mmol) was added. The mixture was warmed to r.t. and stirred for 3.5 h. The
solvent was removed under reduced pressure, and the residue purified by FC (hexane/EtOAc 2 :1 ! 1:1)
to afford 21a (2.54 g, 96%). Colorless solid. M.p. 240 – 2428. [a]rD:t: ¼ ꢀ287.5 (c ¼ 0.76, CHCl3). IR
(CHCl3): 3002m, 1495m, 1448m, 1373w, 1313m, 1166m, 1090m, 1056s, 1009m, 942s, 902m, 641w. 1H-NMR
(400 MHz, CDCl3): 0.58 (s, Me); 0.65 (s, Me); 1.46 (d, J ¼ 18.1, MeP); 5.21 (d, J ¼ 8.0, CH); 5.51 (d, J ¼
8.0, CH); 7.21 – 7.41 (m, 14 arom. H); 7.46 – 7.49 (m, 2 arom. H); 7.54 – 7.61 (m, 4 arom. H). 13C-NMR
(100 MHz, CDCl3): 13.2; 14.7; 26.6 (d, J ¼ 5.2); 79.1 (d, J ¼ 2.3); 79.7 (d, J ¼ 2.2); 87.2 (d, J ¼ 8.6); 88.7 (d,
J ¼ 10.7); 114.2; 126.8; 127.08; 127.14; 127.2; 127.58; 127.61; 128.18; 128.22; 128.3; 128.4; 129.2; 139.77;
139.82; 139.84; 140.0; 143.4; 144.16; 144.19. 31P-NMR (162 MHz, CDCl3): 22.2. MALDI-FT-ICR-MS:

Helvetica Chimica Acta – Vol. 95 (2012)
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549.2 (72, [M þ Na]þ), 431 (70), 345 (77), 267 (82), 105 (100). Anal. calc. for C32H31O5P (526.57): C
72.99, H 5.93; found: C 73.01, H 6.12.
(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-6-(phenylmethyl)-1,3-dioxolo[4,5-e][1,3,
2]dioxaphosphepin 6-Oxide (21b). To a soln. of TADDOL (1; 1.87 g, 4.0 mmol) in THF (16 ml) was
added BuLi (5.50 ml, 8.8 mmol) at ꢀ 788. The soln. was warmed to r.t. and stirred for 1 h, then cooled to
ꢀ 788 again, and a soln. of BnP(O)Cl2 (1.05 g, 5.0 mmol) in THF (4 ml) was added. The mixture was
warmed to r.t. and stirred for 3 h. The mixture was diluted with AcOEt, the org. layer was washed with
sat. aq. NaHCO3 soln. (2ꢁ) and sat. aq. NaCl soln., dried (MgSO4), filtered, and the solvent was removed
under reduced pressure. Recrystallization of the residue from hexane/AcOEt afforded 21b (1.58 g, 66%).
Colorless solid. M.p. 245 – 2468. [a]rD:t: ¼ ꢀ220.1 (c ¼ 0.84, CHCl3). IR (CHCl3): 3063w, 3003m, 1495m,
1448m, 1373m, 1271m, 1166m, 1090m, 1055s, 1042s, 996s, 939m, 924m, 882w, 641w. 1H-NMR (400 MHz,
CDCl3): 0.46 (s, Me); 0.77 (s, Me); 3.21 – 3.36 (m, CH2); 4.95 (d, J ¼ 8.0, CH); 5.46 (d, J ¼ 8.0, CH); 6.86 –
6.89 (m, 2 arom. H); 7.05 – 7.08 (m, 2 arom. H); 7.11 – 7.31 (m, 12 arom. H); 7.32 – 7.42 (m, 7 arom. H);
7.50 – 7.65 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 26.4; 26.9; 35.6 (d, J ¼ 146.5); 78.9 (d, J ¼ 2.6);
79.4 (d, J ¼ 2.5); 86.1 (d, J ¼ 8.4); 90.3 (d, J ¼ 13.1); 113.5; 126.58; 126.64; 127.0; 127.1; 127.2; 127.4; 127.56;
127.59; 128.0; 128.05; 128.06; 128.10; 128.29; 128.32; 128.7; 129.9; 130.0; 131.7; 131.8; 139.72; 139.73;
139.8; 139.9; 143.7; 144.66; 144.73. 31P-NMR (162 MHz, CDCl3): 19.9. MALDI-FT-ICR-MS: 625.2 (56,
[M þ Na]þ), 431 (33), 345 (48), 273 (65), 267 (58), 195 (100), 105 (52). Anal. calc. for C38H35O5P
(602.67): C 75.73, H 5.85; found: C 75.77, H 5.87.
Methyl (3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphos-
phepin-6-acetate 6-Oxide (22). To a soln. of 21a (263 mg, 0.50 mmol) in THF (10 ml) was added BuLi
(1.25 ml, 2.0 mmol) at ꢀ 788, and the mixture was stirred for 3.5 h. At the same temp., NCCOOMe
(0.16 ml, 2.0 mmol) was added, and stirring continued for another 1 h before quenching the reaction with
H2O. The mixture was diluted with AcOEt, the org. layers were washed with sat. aq. K2CO3 soln. (2ꢁ)
and sat. aq. NaCl soln., dried (MgSO4), filtered, and the solvent was removed under reduced pressure.
FC of the residue (hexane/AcOEt 3 :1 ! 1:1) afforded 22 (134 mg, 46%). Colorless glass. [a]rD:t: ¼ ꢀ244.0
(c ¼ 0.77, CHCl3). IR (CHCl3): 3007m, 1740s, 1496m, 1448m, 1384m, 1273s, 1167m, 1117m, 1089m, 1055s,
1040s, 1010s, 942m, 642m. 1H-NMR (400 MHz, CDCl3): 0.57 (s, Me); 0.75 (s, Me); 3.00 – 3.19 (m, CH2);
3.35 (d, J ¼ 0.5, MeO); 5.22 (d, J ¼ 7.9, CH); 5.49 (d, J ¼ 7.9, CH); 7.22 – 7.40 (m, 14 arom. H); 7.46 – 7.61
(m, 6 arom. H). 13C-NMR (100 MHz, CDCl3): 26.5; 26.9; 36.0 (d, J ¼ 146.0); 52.2; 79.0 (d, J ¼ 2.5); 79.5
(d, J ¼ 2.5); 87.5 (d, J ¼ 7.9 ) ; 91.0 (d, J ¼ 11.9); 114.1; 126.7; 127.2; 127.3; 127.70; 127.73; 128.1; 128.18;
128.23; 128.7; 129.6; 139.42; 139.44; 139.5; 139.7; 143.4; 144.07; 144.13; 165.6; 165.7. 31P-NMR (162 MHz,
CDCl3): 12.6. MALDI-FT-ICR-MS: 607.2 (31, [M þ Na]þ), 431 (18), 345 (16), 267 (16), 105 (17).
(3aR,8aR)-6-Chlorotetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphos-
phepin 6-Oxide (23). To a soln. of TADDOL (1; 2.33 g, 5.0 mmol) in THF (25 ml) was added BuLi
(6.88 ml, 11.0 mmol) at ꢀ 788. The mixture was warmed to r.t. and stirred for 1 h, then again cooled to
ꢀ 788 before addition of POCl3 (0.60 ml, 6.50 mmol). The mixture was stirred for 3 h at ꢀ 788, the
reaction was quenched with sat. aq. NaHCO3 soln., and the mixture was diluted with Et2O. The org. layer
was washed with sat. aq. NaHCO3 soln. (2ꢁ) and sat. aq. NaCl soln., dried (MgSO4), filtered, and the
solvent was removed under reduced pressure. The residue was purified by recrystallization from hexane/
AcOEt to afford 23 (1.37 g, 50%). Colorless solid. M.p. 1348 (dec.). [a]rD:t: ¼ ꢀ319.9 (c ¼ 0.67, CHCl3).
IR: 3008m, 1496m, 1448m, 1374m, 1293s, 1167m, 1089m, 1055m, 1036s, 1019s, 998s, 654m, 641m. 1H-NMR
(400 MHz, CDCl3): 0.58 (s, Me); 0.64 (s, Me); 5.33 (d, J ¼ 7.9, CH); 5.38 (d, J ¼ 7.9, CH); 7.25 – 7.44 (m, 16
arom. H); 7.56 – 7.61 (m, 4 arom. H). 13C-NMR (100 MHz, CDCl3): 26.5 (Me); 26.6 (Me); 78.6, 79.4, 91.6
(d, 2J(C,P) ¼ 10.8); 92.5 (d, 2J(C,P) ¼ 9.3); 115.1 (C); 126.6, 127.3, 127.5, 127.5, 128.1, 128.1, 128.3, 128.4,
128.5, 128.8, 128.8, 128.9, 138.6 (d, 3J(C,P) ¼ 11.4, C); 138.8 (d, 3J(C,P) ¼ 10.6, C); 141.4 (C); 142.1 (C).
31P-NMR (162 MHz, CDCl3): ꢀ 9.1. ESI-MS (pos.): 564 (100, [M þ NH4]þ). ESI-MS (neg.): 577 (100,
[M þ MeO]ꢀ). Anal. calc. for C31H28O5PCl (546.99): C 68.07, H 5.16; found: C 68.03, H 5.34.
(3aR,8aR)-Tetrahydro-6-methoxy-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]diox-
aphosphepin 6-Oxide (24). To a soln. of 23 (820 mg, 1.5 mmol) in THF (30 ml) was added a soln. of
MeONa (160 mg, 3 mmol) in MeOH (5 ml). After stirring for 1 d at r.t., sat. aq. NaHCO3 soln. was
added, the org. layer was separated, and the aq. layer was extracted with CH2Cl2. The combined org.
layers were washed with sat. aq. NaCl soln., dried (MgSO4), and concentrated under reduced pressure to

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Helvetica Chimica Acta – Vol. 95 (2012)
afford 24 (800 mg, 98%). White foam. M.p. 176 – 1798. [a]rD:t: ¼ ꢀ235.5 (c ¼ 0.52, CHCl3). IR (CHCl3):
3008m, 1496m, 1448s, 1384m, 1380m, 1279s, 1167m, 1037s, 1021s, 941m, 901m, 640m. 1H-NMR (400 MHz,
CDCl3): 0.58 (s, Me); 0.73 (s, Me); 3.34 (d, J ¼ 11.8, MeO); 5.25 (d, J ¼ 8.1, CH); 5.32 (d, J ¼ 8.1, CH);
7.23 – 7.42 (m, 16 arom. H); 7.54 – 7.58 (m, 4 arom. H). 13C-NMR (100 MHz, CDCl3): 26.4; 26.7; 54.4 (d,
J ¼ 6.0); 78.6; 79.6; 87.7 (d, J ¼ 6.5); 88.1 (d, J ¼ 8.3); 113.8; 126.9; 127.17; 127.22; 127.3; 127.71; 127.73;
128.21; 128.24; 128.4; 129.0; 129.1; 139.4; 139.5; 139.8; 139.9; 143.2; 143.3; 143.91; 143.93. 31P-NMR
(162 MHz, CDCl3): ꢀ 9.8. ESI-MS (pos.): 560 (100, [M þ NH4]þ). ESI-MS (neg.): 527 (100, [M ꢀ
Me]ꢀ).
Sodium (3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxaphos-
phepin-6-olate 6-Oxide (25). To a soln. of 23 (0.5 g, 0.91 mmol) in THF (20 ml) were added H2O (10 ml)
and NaOH (91 mg, 2.3 mmol). After stirring for 10 h at r.t., the solvent was removed under reduced
pressure, and then the residue was dissolved in AcOEt. The soln. was filtered and concentrated under
reduced pressure to afford, after drying under h.v., 25 (490 mg, 97%). Colorless solid. M.p. 329 – 3308
(dec.). [a]rD:t: ¼ ꢀ153.2 (c ¼ 1.05, MeOH). IR (KBr): 3059w, 2989w, 2935w, 1636.3br. m, 1495s, 1447s,
1
1382m, 1372m, 1240br. s, 1166s, 1082s, 1057s, 1022s, 899s, 858w, 804w, 743s, 699s, 592m, 549s. H-NMR
(400 MHz, CD3OD): 0.68 (s, Me); 5.30 (s, CH); 7.16 – 7.29 (m, 12 arom. H); 7.53 – 7.56 (m, 8 arom. H).
2
13C-NMR (100 MHz, CD3OD): 27.0 (Me); 82.1 (CH); 84.8 (d, J (C,P) ¼ 6.6), 113.0 (C); 127.9, 128.0,
128.08, 128.13, 128.4, 128.7, 130.4 (CH); 143.4, 143.5, 147.4, 147.5 (C). 31P-NMR (120 MHz, CD3OD):
ꢀ 7.57. MALDI-FT-ICR-MS: 573.1 (46, [M þ Na]þ); 381.2 (100), 345.2 (44), 273.0 (94), 267.1 (92), 105.0
(51). ESI-MS (neg.): 527.2 [M ꢀ Na]ꢀ.
(3aR,8aR,3’aR,8’aR)-6,6’-Oxybis[tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,
3,2]dioxaphosphepin] 6,6’-Dioxide (26). Compound 23 (125 mg, 0.23 mmol) and 25 (126 mg, 0.23 mmol)
were dissolved in THF (2 ml), and the mixture was stirred for 3 d. The soln. (which contained a fine
precipitate) was concentrated under reduced pressure, and the residue was recrystallized from CH2Cl2/
hexane by slow evaporation of the solvent to afford 26 (170 mg, 72%). Colorless needles. M.p. 215 – 2188.
[a]Dr:t: ¼ ꢀ266.9 (c ¼ 1.05, CHCl3). IR (CHCl3): 3066w, 3008m, 2927m, 1496m, 1448m, 1394w, 1309s,
1
1167w, 1096m (br.), 1020s, 961s, 902w. H-NMR (400 MHz, CDCl3): 0.46 (s, Me); 0.74 (s, Me); 5.28 (d,
J ¼ 8.0, CH); 5.32 (d, J ¼ 8.0, CH); 7.22 – 7.30 (m, 12 arom. H); 7.37 – 7.45 (m, 6 arom. H); 7.51 – 7.53 (m, 2
arom. H). 13C-NMR (100 MHz, CDCl3): 26.1, 26.8 (Me); 79.2, 79.4 (CH); 89.4 (d, 2J(C,P) ¼ 2.6), 90.0 (d,
2J(C,P) ¼ 4.3), 114.2 (C); 127.0, 127.2, 127.3, 127.5, 127.7, 127.8, 128.1, 128.3, 128.40, 128.41, 128.8, 128.9
(CH); 139.1, 142.1, 142.4 (C). 31P-NMR (162 MHz, CDCl3): ꢀ 24.99. HR-MS: 1061.3193 ([M þ Na]þ,
C62H56NaO11P2; calc. 1061.3196 (ꢀ0.28 ppm)). MALDI-FT-ICR-MS: 1061.3 (10, [M þ Na]þ); 431.2
(97), 345.2 (65), 273.0 (100), 200.9 (63). Anal. calc. for C62H56O11P2 (1039.05): C 71.67, H 5.43; found: C
71.23, H 5.65.
6. Products 31, 32, 34, 36 – 41 of Experiments Aimed at Preparation of C,P-Derivatives. (3R)-3-(2,2-
Diphenylethenyl)-2,2-diphenyloxirane (31). To a suspension of 3 in DMF (15 ml) under Ar, LiPH2
(0.14g, 3.51 mmol) was added. The dark brown mixture was stirred for 10 min at r.t., 15 h at 808, and again
at r.t. for 13 h, then H2O (degassed, 30 ml) and Et2O (60 ml) were added. The org. layer was washed with
aq. NaCl soln. and dried (Na2SO4), the solvent was removed under reduced pressure to afford 31 (0.32 g,
86%), which was recrystallized from acetone at ꢀ 208. Colorless powder. [a]rD:t: ¼ ꢀ35.8 (c ¼ 1.25,
CHCl3). IR (CHCl3): 3083w, 3062m, 3008s, 1952w, 1893w, 1812w, 1658w, 1600m, 1495s, 1447s, 1319w,
1280w, 1075m, 1030m, 941w, 910w, 628m. 1H-NMR (200 MHz, CDCl3): 3.91 (d, J ¼ 8.72, CH); 5.52 (d, J ¼
8.27, CH); 7.09 – 7.56 (m, 20 arom. H). 13C-NMR (50 MHz, CDCl3): 64.24, 68.24, 124.02, 126.84, 127.16,
127.25, 127.70, 127.76, 127.86, 127.95, 128.14, 128.27, 128.36, 128.75, 130.14, 130.71, 137.57, 138.84, 140.71,
141.53, 148.40. FAB-MS: 374 (1, Mþ), 372 (2), 358, (7), 344 (16), 270 (25), 269 (100), 191 (73). Anal. data
match those of rac-31 in [35].
1,1’,1’’,1’’’-(Buta-1,3-diene-1,4-diylidene)tetrakisbenzene (32). At r.t. in an autoclave (7 ml) under Ar,
3 (2.05g, 4.07 mmol) and ZnCl2 · Et2O (2 ml, 2.00 mmol) were mixed and cooled to ꢀ 1968. PH3 Gas was
condensed in (4 ꢁ ca. 20 ml each, 20 bar), and the temp. was allowed to rise to r.t. within 3 h (12 bar);
after further 16 h at r.t., the temp. was increased to 908 for 2 h (130 bar) and then kept at 708 for 16 h
(70 bar). After flushing several times with N2, the yellow suspension was washed with Et2O (10 ml),
CH2Cl2 (10 ml), H2O (20 ml), and Et2O (50 ml) to afford 32 (1.16 g, 80%). 1H-NMR (200 MHz, CDCl3):
6.80 (s, 2 CH); 7.15 – 7.27 (m, 10 arom. H); 7.30 – 7.44 (m, 10 arom. H).

Helvetica Chimica Acta – Vol. 95 (2012)
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(3aR,8aR)-Tetrahydro-2,2-dimethyl-4,4,8,8-tetraphenyl-1,3-dioxolo[4,5-e][1,3,2]dioxathiepin 6,6-Di-
oxide (34). Compound 33 [3] (3.05 g, 5.95 mmol) was dissolved in CCl4/MeCN/H2O (8 :8 :12 ml), and
the mixture was cooled to 08. NaIO4 (2.60 g, 12.2 mmol) and RuCl3 (15 mg, 0.07 mmol) were added, and
the mixture was stirred at 08 for 6.5 h. CH2Cl2 (10 ml) was added, and the phases were separated. The aq.
layer was extracted with CH2Cl2, and the combined org. layers were washed with ice-cooled H2O and sat.
aq. NaCl soln., and dried (Na2SO4). The solvent was removed under reduced pressure to afford 34
1
(2.97 g, 95%) as black solid foam (pure according to H-NMR). To remove the color, the product was
dissolved in CH2Cl2 (30 ml), charcoal (ca. 5 g) was added, and the mixture was stirred for 1 h at r.t. After
filtration through Celite, the resulting orange soln. was concentrated under reduced pressure, where upon
crystallization occurred. Trituration of the beige solid with Et2O (15 ml) for 2 h afforded 34 (2.55 g, 81%).
Colorless solid. Caution: Sulfate 34 is very prone to hydrolysis on a TLC plate. It should be stored at
ꢀ 188. M.p. > 958 (dec.). [a]rD:t: ¼ ꢀ67.5 (c ¼ 1.1, CHCl3). IR (CHCl3): 3062w, 2995w, 2941w, 1600w,
1496m, 1448m, 1407s, 1385m, 1375w, 1165m, 1090m, 1052w, 1029w, 976m, 958m, 881s. 1H-NMR
(400 MHz, CDCl3): 0.87 (s, 2 Me); 5.42 (s, 2 CH); 7.27 – 7.37 (m, 12 arom. H); 7.43 – 7.47 (m, 4 arom. H);
7.54 – 7.58 (m, 4 arom. H). 13C-NMR (100 MHz, CDCl3): 26.00 (Me); 80.17 (CH); 92.35, 111.97 (C);
126.90, 127.84, 128.29, 128.36, 128.45, 128.56 (CH); 137.78, 142.10 (C). ESI-MS (pos.): 1625 (4, [3 M þ
K þ 2]þ), 1609 (26, [3 M þ Na þ 2]þ), 1095 (22, [2 M þ K]þ), 1079 (100, [2 M þ Na]þ), 1074 (7, [2 M þ
NH4]þ), 592 (18, [M þ MeCN þ Na]þ), 494 (8, [M ꢀ SO4 ꢀ 2 þ MeCN þ Na]þ), 431 (14, [M ꢀ SO4 ꢀ
2]þ). ESI-MS (neg.): 559 (8, [M þ H2O þ OH]ꢀ), 545 (100, [M þ OH]ꢀ), 527 (2, [M ꢀ 1]ꢀ). Anal.
calc. for C31H28O6S (528.62): C 70.44, H 5.34, S 6.07; found: C 70.33, H 5.45, S 6.03.
(3aR,7aR)-Tetrahydro-6-methoxy-2,2-dimethyl-4,4,7,7-tetraphenyl-4H-1,3-dioxolo[4,5-d][1,2]oxa-
phosphorin 6-Oxide (36). Compound 3 (500 mg, 0.99 mmol) was treated with P(OMe)3 (2 ml, 17 mmol)
in DMF (4 ml) at 1208 according to GP 6. FC (SiO2 (60 g); pentane/Et2O 3 :2) afforded 36 (170 mg,
32%). Colorless solid. M.p. 227 – 2298. Rf (hexane/AcOEt 2 :1) 0.35. [a]rD:t: ¼ ꢀ122.0 (c ¼ 1.05, CHCl3). IR
(CHCl3): 3450w (br.), 3063w, 3007m, 2955w, 1600w, 1495m, 1448m, 1384m, 1375m, 1258s, 1171m, 1128m,
1095s, 1077m, 1056s, 985s, 947m, 926m, 912m, 892w, 874w. 1H-NMR (400 MHz, CDCl3): 0.79 (s, Me); 1.69
(s, Me); 2.87 (d, 3J(H,P) ¼ 10.9, Me); 4.24 (dd, J ¼ 10.0, 4J(H,P) ¼ 0.7, CH); 5.33 (dd, J ¼ 10.0, 3J(H,P) ¼
1.2, CH); 7.16 – 7.35 (m, 12 arom. H); 7.47 – 7.53 (m, 4 arom. H); 7.56 – 7.60 (m, 2 arom. H); 7.87 – 7.91 (m, 2
arom. H). 13C-NMR (100 MHz, CDCl3): 25.88, 27.38, 53.53 (d, 2J(C,P) ¼ 8.0) (Me); 58.83 (d, 1J(C,P) ¼
2
117.8) (C); 75.49 (d, J(C,P) ¼ 2.6), 80.79 (d, J(C,P) ¼ 5.4) (CH); 85.85 (d, J(C,P) ¼ 8.4), 111.58 (C);
125.29, 126.81, 126.99, 127.02, 127.11, 127.39, 127.53, 127.55, 127.62, 127.99, 128.09, 128.11, 129.13, 129.19,
132.19, 132.29 (CH) (C,P couplings!); 137.36 (d, J(C,P) ¼ 2.3), 139.57 (d, J(C,P) ¼ 8.9), 140.24, 144.31 (d,
J(C,P) ¼ 8.7) (C). 31P-NMR (121 MHz, CDCl3): 21.26. MALDI-FT-ICR-MS: 549.2 (24, [M þ Na]þ),
491.1 (7), 469.2 (11), 455.2 (19), 451.1 (17), 437.2 (18), 431.2 (20), 397.2 (88), 373.2 (41), 355.1 (100). HR-
MS: 549.1774 ([M þ Na]þ, C32H31NaO5Pþ; calc. 549.1801 (ꢀ4.9 ppm)). Anal. calc. for C32H31O5P
(526.57): C 72.99, H 5.93; found: C 72.97, H 6.13.
(3aR,6R,7aR)- and (3aR,6S,7aR)-Tetrahydro-2,2-dimethyl-4,4,6,7,7-pentaphenyl-4H-1,3-dioxo-
lo[4,5-d][1,2]oxaphosphorin 6-Oxide ((RP)-37 and (SP)-37, resp.). Compound 3 (250 mg, 0.50 mmol)
was treated with PhP(OMe)2 (0.4 ml, 2.52 mmol) in DMF (4 ml) at 1208 according to GP 6. FC (SiO2
(20 g); pentane/Et2O 8 :2 ! Et2O) afforded (RP)-37 (61 mg, 22%) and (SP)-37 (35 mg, 12%). Colorless
solids.
Data of (RP)-37. M.p. 208 – 2108. Rf (hexane/AcOEt 2 :1) 0.37. [a]rD:t: ¼ ꢀ189.9 (c ¼ 1.04, CHCl3). IR
(CHCl3): 3404br. w, 3064w, 2991m, 2935w, 1599w, 1495m, 1448m, 1438w, 1384m, 1374w, 1170m, 1126m,
1108s, 1094s, 1036w, 1005s, 989s, 935w, 924w, 905m, 865m. 1H-NMR (400 MHz, CDCl3): 0.62 (s, Me); 1.58
(s, Me); 4.91 (dd, J ¼ 10.0, J(H,P) ¼ 0.6, CH); 5.49 (dd, J ¼ 10.0, J(H,P) ¼ 0.8, CH); 6.85 – 7.13 (m, 8
arom. H); 7.16 – 7.40 (m, 11 arom. H); 7.61 – 7.66 (m, 4 arom. H); 7.69 – 7.75 (m, 2 arom. H). 13C-NMR
(100 MHz, CDCl3): 25.77, 27.41 (Me); 61.75 (d, 1J(C,P) ¼ 73.2) (C); 76.29 (d, J(C,P) ¼ 7.1), 80.23 (d,
2
J(C,P) ¼ 7.8) (CH); 87.46 (d, J(C,P) ¼ 10.3), 112.15 (C); 125.46, 126.81, 126.85, 126.88, 126.91, 127.04,
127.17, 127.67, 127.91, 127.95, 128.11, 128.35, 129.54, 129.61, 130.95, 130.98, 131.95, 132.05, 133.46, 133.53
(CH) (C,P couplings!); 130.81 (d, 1J(C,P) ¼ 138.4), 138.28 (d, J(C,P) ¼ 4.1), 140.26 (d, J(C,P) ¼ 2.3),
140.68 (d, J(C,P) ¼ 3.4), 145.03 (d, J(C,P) ¼ 4.1) (C). 31P-NMR (121 MHz, CDCl3): 37.90. MALDI-FT-
ICR-MS: 611.2 (3, [M þ K]þ), 595.2 (26, [M þ Na]þ), 455.2 (10), 431.2 (13), 397.2 (100), 357.2 (9), 330.1

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Helvetica Chimica Acta – Vol. 95 (2012)
(49), 321.1 (16). HR-MS: 595.1981 ([M þ Na]þ, C37H33NaO4Pþ; calc. 595.2008 (ꢀ4.5 ppm)). Anal. calc.
for C37H33O4P (572.64): C 77.61, H 5.81; found: C 77.66, H 5.97.
Data of (SP)-37. M.p. 239 – 2408 (dec.). Rf (hexane/AcOEt 2 :1) 0.25. [a]rD:t: ¼ ꢀ124.8 (c ¼ 0.69,
CHCl3). IR (CHCl3): 3426w (br.), 3058w, 2991m, 1600w, 1496m, 1449m, 1437w, 1383m, 1374w, 1170m,
1116m, 1094s, 1075m, 1034w, 1102m, 981s, 940m, 921w, 903m, 864m. 1H-NMR (300 MHz, CDCl3): 0.92 (s,
Me); 1.42 (s, Me); 4.64 (d, J ¼ 9.8, CH); 5.58 (dd, J ¼ 9.8, J(H,P) ¼ 1.9, CH); 7.02 – 7.56 (m, 19 arom. H);
7.61 – 7.67 (m, 2 arom. H); 7.78 – 7.87 (m, 2 arom. H); 7.91 – 7.97 (m, 2 arom. H). 13C-NMR (100 MHz,
1
CDCl3): 26.23, 26.75 (Me); 62.34 (d, J(C,P) ¼ 75.6) (C); 74.22, 79.14 (d, J(C,P) ¼ 4.9) (CH); 90.11 (d,
2J(C,P) ¼ 8.6), 110.76 (C); 125.70, 126.83, 126.93, 127.20, 127.23, 127.48, 127.65, 127.91, 128.03, 128.20,
128.28, 128.38, 128.61, 129.92, 129.98, 132.64, 132.75, 134.32, 134.45 (CH) (C,P couplings!); 130.10 (d,
1J(C,P) ¼ 136.7), 138.02, 139.33, 140.30 (d, J(C,P) ¼ 6.1), 145.66 (d, J(C,P) ¼ 7.3 ) (C ) . 31P-NMR
(121 MHz, CDCl3): 35.37. MALDI-FT-ICR-MS: 611.2 (7, [M þ K]þ), 595.2 (64, [M þ Na]þ), 455.2
(9), 431.2 (21), 397.2 (100), 357.2 (9), 330.1 (45), 321.1 (12). HR-MS: 595.1966 ([M þ Na]þ,
C37H33NaO4Pþ; calc. 595.2008 (ꢀ 7.1 ppm)).
Dimethyl P-[{(4R,5R)-5-[(Hydroxy)(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}(diphenyl)-
methyl]phosphonate (38). Sulfate 34 (250 mg, 0.47 mmol) was treated with P(OMe)3 in DMF (3 ml)
at 808 according to GP 6. FC (SiO2 (70 g); pentane/Et2O 8 :2 ! pentane/Et2O 1:1) and subsequent
precipitation from CH2Cl2/hexane afforded 38 (136 mg, 51%). Colorless solid. M.p. 234 – 2378. Rf
(hexane/AcOEt 8 :2) 0.43. [a]rD:t: ¼ ꢀ117.6 (c ¼ 1.09, CHCl3). IR (CHCl3): 3324br. m, 3062w, 3007m,
2956m, 2853w, 1600w, 1495m, 1447m, 1380w, 1370w, 1166m, 1056s, 1035s, 875w, 830w, 658w, 632w.
1H-NMR (400 MHz, CDCl3): 0.25 (s, Me); 0.51 (s, Me); 3.55 (d, 3J(H,P) ¼ 10.9, Me); 3.64 (d, 3J(H,P) ¼
10.6, Me); 5.26 (dd, J ¼ 6.0, 4J(H,P) ¼ 0.6, CH); 5.81 (dd, J ¼ 6.0, 3J(H,P) ¼ 2.4, CH); 5.99 (br. s, OH);
7.17 – 7.34 (m, 12 arom. H); 7.44 – 7.51 (m, 4 arom. H); 7.55 – 7.60 (m, 2 arom. H); 7.71 – 7.76 (m, 2 arom.
2
2
H). 13C-NMR (100 MHz, CDCl3): 27.14, 27.99, 53.40 (d, J(C,P) ¼ 8.0), 54.72 (d, J(C,P) ¼ 7.3 ) ( Me ) ;
1
60.32 (d, J(C,P) ¼ 131.7) (C); 78.45 (d, J(C,P) ¼ 7.4) (CH); 78.49 (C); 83.27 (CH); 111.49 (C); 126.84,
126.85, 126.89, 126.92, 127.01, 127.04, 127.13, 127.32, 127.34, 127.57, 127.84, 129.48, 131.69, 131.74, 132.73,
2
2
132.81 (CH) (C,P couplings!); 137.19 (d, J(C,P) ¼ 2.1), 139.45 (d, J(C,P) ¼ 10.0), 143.66, 149.34 (C).
31P-NMR (121 MHz, CDCl3): 28.50. MALDI-FT-ICR-MS: 597.2 (3, [M þ K]þ), 581.2 (100, [M þ Na]þ),
483.2 (6), 431.2 (8), 373.2 (31), 355.1 (9), 341.1 (6), 305.1 (11), 298.1 (25), 289.1 (41). HR-MS: 581.2054
([M þ Na]þ, C33H35NaO6Pþ; calc. 581.2063 (ꢀ1.5 ppm)). Anal. calc. for C33H35O6P (558.61): C 70.96, H
6.32; found: C 70.92, H 6.48.
Dimethyl P-[{(4R,5R)-5-[(methoxy)(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}(diphenyl)-
methyl]phosphonate (39). Compound 35 [1a] (1.45 g, 2.91 mmol) was treated with P(OMe)3 (3.5 ml,
30 ml) in DMF (10 ml) at 1208 according to GP 6. The residue was dissolved in CH2Cl2 (15 ml), the soln.
was washed with H2O, and the org. layer was separated (tedious phase separation!). The aq. layer was
extracted with CH2Cl2 (3ꢁ), the combined org. layers were washed with H2O and sat. aq. NaCl soln.,
dried (Na2SO4), and concentrated under reduced pressure. The crude product (1.88 g) was triturated
with Et2O (ca. 10 ml) to afford 39 (990 mg, 59%). Slightly beige powder. For anal. purposes, a sample was
purified by FC (pentane/Et2O 4 :1 ! Et2O). Colorless powder. M.p. 225 – 2268. Rf (hexane/AcOEt 4 :1)
0.14. [a]rD:t: ¼ ꢀ3.2 (c ¼ 1.11, CHCl3). IR (CHCl3): 3389br. w, 3059w, 3002m, 2953m, 2850w, 1600w, 1494m,
1445m, 1380w, 1370w, 1170m, 1080s, 1035s, 909w, 881w. 1H-NMR (400 MHz, CDCl3): 0.80 (s, Me); 1.35 (s,
Me); 2.08 (s, MeO); 3.39 (d, 3J(H,P) ¼ 10.9, Me); 3.65 (d, 3J(H,P) ¼ 10.8, Me); 4.67 (dd, 3J(H,P) ¼ 18.7,
J ¼ 7.7, CH); 5.56 (d, J ¼ 7.7, CH); 7.10 – 7.16 (m, 2 arom. H); 7.21 – 7.35 (m, 14 arom. H); 7.55 – 7.60 (m, 2
arom. H); 7.67 – 7.72 (m, 2 arom. H). 13C-NMR (100 MHz, CDCl3): 27.30, 27.67, 51.38, 52.93 (d, 2J(C,P) ¼
7.9), 53.35 (d, 2J(C,P) ¼ 7.3) (Me); 60.75 (d, 1J(C,P) ¼ 134.8) (C); 80.62 (d, J(C,P) ¼ 5.9), 81.99 (d,
J(C,P) ¼ 6.5) (CH); 84.22, 108.58 (C); 126.64, 126.66, 126.72, 126.84, 126.88, 126.90, 127.27, 127.40, 127.48,
129.84, 131.10, 131.43, 131.49, 132.37, 132.45 (CH) (C,P couplings!); 137.61, 138.94, 140.48, 140.56 (C).
31P-NMR (121 MHz, CDCl3): 28.66. MALDI-FT-ICR-MS: 611.2 (5, [M þ K]þ), 595.2 (75, [M þ Na]þ),
373.2 (5), 298.1 (100). Anal. calc. for C34H37O6P (572.64): C 71.31, H 6.51; found: C 71.24, H 6.63.
[{(4R,5R)-5-[(Methoxy)(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}(diphenyl)methyl](di-
phenyl)phosphorane Oxide (40). Compound 34 (250 mg, 0.50 mmol) was treated with Ph2P(OMe)
(450 mg, 2.1 mmol) in DMF (4 ml) at 1208 according to GP 6. FC (SiO2 (50 g); pentane/Et2O 4 :1 !
Et2O) and subsequent trituration with Et2O afforded 40 (85 mg, 25%). Colorless powder. M.p. 183 –

Helvetica Chimica Acta – Vol. 95 (2012)
1299
1998. Rf (hexane/AcOEt 4 :1) 0.2. [a]rD:t: ¼ ꢀ57.3 (c ¼ 1.57, CHCl3). IR (CHCl3): 3326w (br.), 3058m,
2988m, 2827w, 1600w, 1495m, 1447m, 1437m, 1382m, 1372m, 1166s, 1091s, 1064s, 1036w, 1001w, 976w,
908w, 869m. 1H-NMR (400 MHz, CDCl3): 0.70 (s, Me); 0.97 (s, Me); 2.05 (s, MeO); 4.98 – 5.02 (m, CH);
5.37 (d, J ¼ 7.7, CH); 6.97 – 7.81 (m, 30 arom. H). 13C-NMR (100 MHz, CDCl3): 27.05, 27.23, 51.07 (Me);
1
3
2
62.96 (d, J(C,P) ¼ 60.7) (C); 80.35 (d, J(C,P) ¼ 8.0), 82.02 (d, J(C,P) ¼ 4.2) (CH); 83.99, 108.03 (C);
126.39, 126.79, 126.88, 127.00, 127.02, 127.10, 127.22, 127.33, 127.40, 127.50, 129.79, 130.33, 130.35, 130.48,
130.50, 131.01, 132.70, 132.75, 133.17, 133.20, 133.25, 133.30, 133.37 (CH) (C,P couplings!); 134.14 (d,
1J(C,P) ¼ 93.8), 134.57 (d, 1J(C,P) ¼ 90.9), 135.75, 137.72, 137.91 (d, 2J(C,P) ¼ 5.2), 140.54 (C). 31P-NMR
(121 MHz, CDCl3): 36.30. MALDI-FT-ICR-MS: 700.3 (2, [M þ K]þ), 687.3 (84, [M þ Na]þ), 431.2 (20),
390.1 (100), 368.1 (14). Anal. calc. for C44H41O4P (664.78): C 79.50, H 6.22; found: C 79.67, H 6.27.
(4S,5R)-4-(Diphenylmethyl)-5-[(methoxy)(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolane (41). To a
suspension of CeCl3 (128 mg, 0.52 mmol) in THF (10 ml), 40 (150 mg, 0.22 mmol) and LiAlH4 (20 mg,
0.52 mmol) were added consecutively at r.t. After stirring for 2.5 h (TLC control), 1n aq. NaOH soln.
(1 ml), H2O (8 ml) and Et2O (10 ml) were added. The org. layer was separated, and the aq. layer was
extracted with Et2O. The combined org. layers were washed with sat. aq. NaCl soln., dried (Na2SO4), and
concentrated under reduced pressure. The residue was purified by FC (SiO2 (20 g); pentane/Et2O 4 :1) to
afford 41 (45 mg, 45%). White foam. M.p. 73 – 788. Rf (hexane/AcOEt 2 :1) 0.73. [a]rD:t: ¼ ꢀ19.1 (c ¼ 1.06,
Table 1. Crystallographic Data for 10, 12a, 12b, (R)-15, and 23
10
12a
12b
(R)-15
23
Formula
C43H40N2O2 C32H30N2Oþ3 O0.25 C32H30N2O2S C40H38N2O2S C31H28ClO5P
Formula weight [g/mol]
T [K]
Wavelength [ꢄ]
Source
616.81
293(2)
0.71069
MoKa
494.58
293(2)
0.71069
MoKa
506.64
293(2)
1.54178
CuKa
610.78
293(2)
1.54178
CuKa
546.95
293(2)
1.54184
CuKa
Crystal dimensions [mm] 0.4 ꢁ 0.3 ꢁ 0.3 0.4 ꢁ 0.3 ꢁ 0.3
0.3 ꢁ 0.2 ꢁ 0.1 0.5 ꢁ 0.3 ꢁ 0.1 0.4 ꢁ 0.3 ꢁ 0.2
Crystal system
Space group
q Range [8]
a [ꢄ]
monoclinic
orthorhombic
monoclinic
triclinic
orthorhombic
P21
P21212
P21
P1
P212121
1.9 < q < 26.0 1.8 < q < 25.0 4.3 < q < 50.0 4.4 < q < 50 3.7 < q < 65.0
9.472(1)
16.287(2)
11.194(2)
90
16.003(4)
14.252(2)
11.517(1)
90
8.30(1)
15.53(3)
10.34(2)
90
93.8(2)
90
8.826(6)
10.090(9)
10.687(7)
68.84(6)
80.04(5)
68.62(7)
825(1)
1
9.671(4)
16.355(8)
17.239(4)
90
90
90
b [ꢄ]
c [ꢄ]
a [8]
b [8]
99.82(1)
90
1701.6(3)
2
1.204
0.073
90
90
g [8]
V [ꢄ3]
Z
2626.7(8)
4
1.251
0.081
2616
1330(4)
2
2727(2)
4
1calc [g cmꢀ3
]
1.265
1.327
1441
1.229
1.157
1703
1.332
2.119
2663
m [mmꢀ1
]
Total reflections measured 3635
Independent reflections
Reflections observed
No. of variables
Criterion
3459
2451
584
I > 2s(I)
3.56
2616
1506
366
I > 2s(I)
4.81
1441
1383
335
I > 2s(I)
3.48
1703
1682
407
I > 2s(I)
3.67
2637
2139
343
I > 3s(I)
9.62
Final R [%]
wR2 [%]
9.90
1.093
14.94
1.137
9.41
1.012
8.96
1.123
28.38
2.343
Goodness-of-fit
D1 (max, min) [e ꢄꢀ3
CCDC No.
]
0.138, ꢀ 0.175 0.414, ꢀ 0.232 0.154, ꢀ 0.199 0.239, ꢀ 0.217 0.641, ꢀ 0.663
157927 157930 157931 157932 157934

1300
Helvetica Chimica Acta – Vol. 95 (2012)
CHCl3). IR (CHCl3): 3060m, 3007m, 2938m, 2832w, 1949w, 1885w, 1813w, 1652m, 1598m, 1494s, 1445s,
1383s, 1373m, 1326w, 1264s, 1177w, 1135s, 1072s, 1033w, 990w, 867m. 1H-NMR (300 MHz, CDCl3): 1.02 (s,
Me); 1.23 (s, Me); 3.18 (s, MeO); 3.24 (s, 1 H); 4.53 – 4.60 (m, 2 H); 7.09 – 7.35 (m, 18 arom. H); 7.42 – 7.47
(m, 2 arom. H). 13C-NMR (75 MHz, CDCl3): 26.96, 27.03 (Me); 51.76 (CH); 54.04 (Me); 79.41, 81.06
(CH); 83.49, 108.97 (C); 125.95, 126.41, 127.39, 127.56, 127.62, 128.09, 128.16, 128.66, 128.75, 129.93,
131.41 (CH); 140.27, 141.32, 142.80, 144.19 (C). MALDI-FT-ICR-MS: 487.2 (52, [M þ Na]þ), 413.3 (14,
[M ꢀ O2CMe2 þ Na]þ), 357.2 (6), 279.1 (8), 273.0 (100, matrix), 263.1 (29), 219.1 (22), 180.1 (24). HR-
MS: 487.2232 ([M þ Na]þ, C32H32NaOþ3 ; calc. 487.2244 (ꢀ2.5 ppm)).
7. X-Ray Data. See Tables 1 and 2.
Table 2. Crystallographic Data for 27, 34, (SP )-37, 38, and 39
27
34
(SP )-37
38
39
Formula
Formula weight [g/mol]
T [K]
Wavelength [ꢄ]
Source
C44H41N2O3P C31H28O6S
C37H33O4P
572.60
293(2)
0.71073
MoKa
C33H35O6P
558.58
293(2)
1.54178
CuKa
C34H37O6P
572.61
293(2)
0.71073
MoKa
676.76
293(2)
0.71073
MoKa
528.59
293(2)
0.71073
MoKa
Crystal dimensions [mm] 0.4 ꢁ 0.3 ꢁ 0.2 0.5 ꢁ 0.4 ꢁ 0.3 0.4 ꢁ 0.2 ꢁ 0.2 0.2 ꢁ 0.1 ꢁ 0.1 0.4 ꢁ 0.2 ꢁ 0.2
Crystal system
Space group
q Range [8]
a [ꢄ]
b [ꢄ]
c [ꢄ]
monoclinic
P21
monoclinic
P21
orthorhombic orthorhombic orthorhombic
P212121 P212121 P212121
1.8 < q < 20.0 1.8 < q < 20.0 1.7 < q < 21.6 3.5 < q < 50.0 1.9 < q < 20.0
10.657(4)
15.164(4)
11.728(4)
90
10.592(9)
16.26(2)
16.09(2)
90
9.661(5)
14.801(6)
21.172(6)
90
9.010(8)
16.45(2)
19.77(2)
90
11.683(7)
17.77(1)
18.373(8)
90
a [8]
b [8]
107.96(2)
90
1803(1)
2
1.247
0.120
107.76(7)
90
2639(5)
4
1.331
0.167
2710
90
90
90
90
90
90
g [8]
V [ꢄ3]
Z
3027(2)
4
1.256
0.130
1989
2925(5)
4
1.267
1.187
1735
2956(3)
4
1.287
0.138
1604
1calc [g cmꢀ3
]
m [mmꢀ1
]
Total reflections measured 1907
Independent reflections
Reflections observed
No. of variables
Criterion
Final R [%]
wR2 [%]
1785
1515
493
I > 2s(I)
2.52
2595
2304
690
I > 2s(I)
2.63
1989
1517
382
I > 2s(I)
2.69
1735
1469
362
I > 2s(I)
10.16
23.10
1.066
1604
1316
371
I > 2s(I)
2.83
5.64
0.810
5.70
0.957
5.31
0.761
5.93
0.918
Goodness-of-fit
D1 (max, min) [e ꢄꢀ3
CCDC No.
]
0.107, ꢀ 0.106 0.103, ꢀ 0.171 0.097, ꢀ 0.114 0.630, ꢀ 0.569 0.111, ꢀ 0.134
157933 157935 157936 157937 157938
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Received March 23, 2012