2,4-Dioxa-7-aza-, 2,4-dioxa-8-aza-, and 2,4-dioxa-9-aza-3-phosphadecalins as rigid acetylcholine mimetics: Syntheses and characterization

Article abstract of DOI:10.1002/hlca.200490236

Phosphorylation of suitable piperidine precursors yielded a series of novel decalin-type O,N,P-heterocycles. The title compounds, P(3)-axially and P(3)-equatorially X-substituted, cis- and trans-configurated 2,4-dioxa-7-aza-, 2,4-dioxa-8-aza-, and 2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides (X = Cl, F, 4-nitrophenoxy, and 2,4-dinitrophenoxy), are configuratively fixed and conformationally constrained P-analogues of acetylcholine and as such represent acetylcholine (7-aza and 9-aza isomers) or γ-homo-acetylcholine mimetics (8-aza isomers). Being irreversible inhibitors of acetylcholinesterase (AChE), the compounds are considered to be suitable probes for the investigation of the stereochemical course of the inhibition reaction by ³¹P-NMR spectroscopy. Moreover, the design of these mimetics will enable studies of molecular interactions with AChE, in particular, the recognition conformation of acetylcholine.

Full text of DOI:10.1002/hlca.200490236

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2,4-Dioxa-7-aza-, 2,4-Dioxa-8-aza-, and 2,4-Dioxa-9-aza-3-phosphadecalins
as Rigid Acetylcholine Mimetics: Syntheses and Characterization
by Stefan Furegati, Walter Ganci, Fabrizio Gorla, Urs Ringeisen, and Peter R¸edi*
Organisch-Chemisches Institut der Universit‰t Z¸rich,Winterthurerstrasse 190, CH-8057 Z¸rich
Phosphorylation of suitable piperidine precursors yielded a series of novel decalin-type O,N,P-heterocycles.
The title compounds, P(3)-axially and P(3)-equatorially X-substituted, cis- and trans-configurated 2,4-dioxa-7-
aza-, 2,4-dioxa-8-aza-, and 2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides (X ˆ Cl, F, 4-nitrophenoxy,
and 2,4-dinitrophenoxy), are configuratively fixed and conformationally constrained P-analogues of acetylcho-
line and as such represent acetylcholine (7-aza and 9-aza isomers) or g-homo-acetylcholine mimetics (8-aza
isomers). Being irreversible inhibitors of acetylcholinesterase (AChE), the compounds are considered to be
suitable probes for the investigation of the stereochemical course of the inhibition reaction by 31P-NMR
spectroscopy. Moreover, the design of these mimetics will enable studies of molecular interactions with AChE,
in particular, the recognition conformation of acetylcholine.
1. Introduction. The acute toxicity of organophosphorus compounds is mainly due
to their inhibitory action on acetylcholinesterase and related serine hydrolases such as
chymotrypsin (Scheme 1) [1]. Hence, the exact knowledge of the chemical reaction
mechanisms is the prerequisite for the understanding of organophosphorus poisoning
and its prophylaxis and therapy. Since the phosphorylated enzymes are considered to
represent stable transition-state analogues [2], organophosphorus compounds are
unique active-site probes of serine hydrolases and enable direct 31P-NMR spectroscopic
studies of the inhibited enzyme species [3].
Scheme 1. E ˆ Enzyme: Serine hydrolase, e.g. chymotrypsin ,acetylcholinesterase
As a result of recent investigations of the regio- and stereochemical pathways of the
irreversible inhibition of serine hydrolases with configuratively fixed and conforma-
tionally restricted organophosphates, we had reported on the inhibition of d-
chymotrypsin with the enantiomerically pure 3-epimers of 3-(2,4-dinitrophenoxy)-
substituted cis- and trans-configurated 2,4-dioxa-3-phosphabicyclo[4.4.0]decane 3-
oxides (ˆ hexahydro-4H-1,3,2-benzodioxaphosphorin 3-oxides IV (Scheme 2)) [4 6].
According to kinetic measurements, all trans-compounds inhibited the enzyme
¹ 2004 Verlag Helvetica Chimica Acta AG, Z¸rich

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Scheme 2
For each structural type (I IV): cis-, trans-, axially and equatorially P-substituted isomers.
X ˆ electron withdrawing group, e.g., F, Cl, 4-nitrophenoxy, 2,4-dinitrophenoxy, or amino acid derivatives
(model compounds).
R1, R2 ˆ :(tert-amines, free bases), H, Me, Ph CH2; R1 ˆ R2 or R1=R2.
irreversibly, the (SP)-enantiomers reacting significantly faster. In the cis-series, only the
(À)-enantiomer of the equatorially substituted 3-epimer was an irreversible inhibitor.
The decisive stereochemical experiments were designed so that the enzyme and the
inhibitors reacted in stoichiometric amounts to monitor the inhibition reaction directly
by 31P-NMR spectroscopy. The results have evidenced that the irreversible inhibition of
d-chymotrypsin follows different stereochemical pathways yielding diastereoisomeric
phosphorylated derivatives of d-chymotrypsin. Depending on the isomer, neat
inversion (trans, XÀP axial), inversion and retention (trans, XÀP equatorial) [4],
and neat retention (cis, XÀP equatorial) [5] of the configuration at the P-atom took
place. This result clearly showed the unexpected dependence of an enzyme×s
stereochemical pathway on the structure of the substrate. The covalent nature of the
enzymeÀP bond was later established by means of a deuterated inhibitor ((Æ)-trans-3-
(2,4-dinitrophenoxy)-(1,5,5-2H3)-2,4-dioxa-3-phosphabicyclo[4.4.0]decane 3-oxide),

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where 1H-correlated 31P{2H}-NMR spectra of the enzymeÀinhibitor adduct revealed a
cross signal of the Ser195-H2 with the P-atom of the inhibitor [6].
Similar experiments with acetylcholinesterase (AChE) were not successful [7].
Although kinetics revealed the organophosphates IV to be potent irreversible
inhibitors of AChE, only complex, not clearly interpretable 31P-NMR spectra of the
inhibited enzyme could be obtained when the inhibitors were applied in excess1). This
fact might be mainly due to postinhibitory phenomena [8] with concomitant loss of the
stereochemical information2). These findings prompted us to search for more-suitable
inhibitors that would bind more tightly to AChE and are less prone to hydrolysis and
dealkylation [8]. For this purpose, the novel O,N,P-heterocycles of the types I, II, and
III (Scheme 2) seemed promising compounds, and their syntheses were envisaged. As
exemplified in the generalized Scheme 2, the 9-, 8-, or 7-aza-3-phosphadecalins I, II,
and III are configuratively fixed and conformationally constrained P-analogues of
acetylcholine. Representing acetylcholine (see I and III) or g-homoacetylcholine
mimetics (see II), these novel organophosphates are considered to be better suited for
the attempted 31P-NMR investigations. Moreover, the design of these mimetics will
enable studies of molecular interactions with AChE, in particular the recognition
conformation of acetylcholine [9 12]3).
2. Syntheses of the Acetylcholine Mimetics of Type I and II (9- and 8-Aza-3-
phosphadecalins).
2.1. General. As outlined in Scheme 3, the synthesis of both
compound types principially follows the same protocols, the main difference being the
significantly different chemical and physical behaviors of the individual isomers.
Keysteps in the syntheses of the starting 3-hydroxypiperidine-4-methanols 4 and 8 and
4-hydroxypiperidine-3-methanols 6 and 10 (Scheme 3) are the generation of a
favorable ratio of the cis/trans-isomers that are formed by the reduction of the
oxopiperidinecarboxylates 1 [10][14] and 2 [11][14] and, in particular, efficient
separation methods. For these purposes, the procedures in [10][11][14] had to be
modified and optimized [15 17]. The 8- and 9-aza-3-phosphadecalins 19 26 (Fig. 1)
and 35 42 (Fig. 2) are prepared by cyclization of the corresponding hydroxypiper-
idinemethanol with the appropriate P-reagent (according to the desired substituent X),
thus affording a ratio of the P-epimers of ca. 1:1)4). In all cases, the formation of both
epimers (a ˆ axial, b ˆ equatorial) is evidenced by 31P-NMR spectroscopy [4][5][19]
(see Sect. 4). However, when X ˆ Cl and X ˆ 2,4-dinitrophenoxy, only the respective
axial epimers could be isolated, as the equatorial ones rapidly epimerize during
workup. The N-benzyl-N-methylammonium compounds 27 29, 31 33 (Fig. 1), 43
45, and 47 49 (Fig. 2) are prepared by methylating the respective N-benzyl derivatives
with methyl trifluoromethanesulfonate (TfOMe) in abs. CHCl3 or MeCN and are
isolated as inseparable N-epimer mixtures. The final target N,N-dimethylammonium
1
)
Compared to d-chymotrypsin, AChE is a far more complex enzyme, and stoichiometric inhibiton was a
priori not considered to provide reliable results.
2
3
4
)
)
)
For exper. details and tentative interpretations of the results, see [7].
This topic is discussed in one of our following papers [13].
The alternative way via nucleophilic reactions at the corresponding phosphorochloridates (prepared by
cyclization of the hydroxypiperidinemethanols with POCl3), showed strong diastereoselectivity in favor of
the axial epimers; therefore, the equatorial epimers could be isolated in only minor amounts, see also [18].

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Scheme 3. Synthesis of the Type-I and Type-II Compounds
X ˆ Cl, F, 4-NO2C6H4O, 2,4-(NO2)2C6H3O; Me(CF3SO3À) as counter-ion (ammonium compounds).
a) NaBH4, MeOH, 08 (cis/trans ca. 3 :2 from 1). b) NaBH4, iPrOH, r.t., then LiAlH4, Et2O, r.t. (cis/trans ca. 1 :1
from 2). c) Ac2O, pyridine, r.t. d) Chromatography (SiO2, hexane/AcOEt ! 3 ‡ 7). e) 2n NaOH/MeOH, 408 !
4 ‡ 8. f) (Me)2C(OMe)2, TsOH, CH2Cl2, 5 08. g) Chromatography (SiO2, hexane/Et2O ! 5 ‡ 9). h) 1n HCl,
608 ! 6 ‡ 10. i) Cl2P(O)X, Et3N, CH2Cl2 or Et2O, 08. j) Chromatography (SiO2, hexane/Et2O or hexane/
AcOEt). k) CF3SO3Me, CHCl3, r.t. l) H2, Pd/C, EtOH, r.t. m) Cl2P(O)X, CHCl3, 808. n) 2n NaOH/sat. NaCl/
CHCl3, extraction, < 1 min (!), r.t.

Helvetica Chimica Acta Vol. 87 (2004)
2633
congeners (e.g., 30a; Fig. 1) could not be prepared as expected after hydrogenolysis of
the corresponding N-benzyl-N-methylammonium compounds (e.g., 29a; Fig. 1) and
methylation of the intermediate N-methylazaphosphadecalins. The X-substituent at
the P-atom was either removed or reduced, and the equatorial derivatives were
completely epimerized. Moreover, being very strong bases, the N-methylazaphospha-
decalins could not be deprotonated easily, and their high nucleophilicity resulted in
uncontrollable reactivity. Therefore the N,N-dimethylammonium compounds had to be
prepared from the respective hydroxy-1-methylpiperidinemethanols 12, 16, 14, and 18
(Scheme 3) via the 3-X-substituted 8- or 9-methyl-2,4-dioxa-8- or -9-aza-3-phosphabi-
cyclo[4.4.0]decane 3-oxides followed by methylation (TfOMe) of the latter in situ. Due
to their physical and chemical characteristics, the ammonium compounds could not be
purified, and the reaction conditions had to be chosen so that either the pure
component or the by-products preciptitated. The characterized compounds are
compiled in the Figs. 1 3.
Fig. 1. Prepared 9-aza-actylcholine mimetics (Type I)
2.2. 9-Azaphosphadecalins (trans- and cis-Iax,Ieq, Scheme 3, Fig. 1) [14 16].
Modifying the procedures in [10][13], ethyl 1-benzyl-3-oxopiperidine-4-carboxylate
(1) was reduced (NaBH4, MeOH, 08), the resulting ca. 2 :3 mixture of the
hydroxypiperidinemethanols 4/8 were acetylated and the diacetates 3/7 separated by
column chromatography (Scheme 3). Saponification of the pure diastereoisomers 3
and 7 afforded the trans- and cis-1-benzyl-3-hydroxypiperidine-4-methanols 4 and 8,
respectively. Reaction with selected phosphoric trihalides or phosphorodichloridates
(Cl2P(O)X, X ˆ Cl, F, 4-(NO2)C6H4O, 2,4-(NO2)2C6H3O) and chromatographic
separation of the epimer mixtures gave the respective 3-X-substituted cis- and trans-
9-benzyl-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides 19 26. Methylation
(TfOMe) of the latter yielded the corresponding N-benzyl-N-methylammonium
compounds 27 29 and 31 33. The target N,N-dimethylammonium trifluoromethane-

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Helvetica Chimica Acta Vol. 87 (2004)
Fig. 2. Prepared 8-aza-acetylcholine mimetics (Type II g-homoacetylcholine)
Fig. 3. Prepared 7-aza-acetylcholine mimetics (Type III)
sulfonates 30a and 34a5) were prepared from the 3-hydroxy-1-methylpiperidine-4-
methanols 12 and 16 that had been obtained after methylation (TfOMe) of 4 and 8 to
yield the N-benzyl-N-methylammonium salts 11 and 13, respectively, followed by
hydrogenolysis. Cyclization of 12 and 16 with 2,4-dinitrophenyl phosphorodichloridate
and methylation (TfOMe) finally furnished 30a and 34a.
2.3. 8-Azaphosphadecalins (trans- and cis-IIax,IIeq, Scheme 3, Fig. 2) [15 17].
Similarly, modifying the procedures of [11][14], ethyl 1-benzyl-4-oxopiperidine-3-
i
carboxylate (2) was reduced (NaBH4, PrOH, room temperature, then LiAlH4, Et2O,
5
)
Kinetic investigations showed that both the 2,4-dinitrophenoxy-substituted N-benzyl-N-methylammonium
and N,N-dimethylammonium compounds are only weak reversible inhibitors of AChE of comparable
strength (Ki ꢀ ca. 10À6 m) [15][16]. Due to this finding, together with the fact that the preparation of the
N,N-dimethylammonium compounds was not satisfyingly reproducible, only selected congeners have been
characterized [16].

Helvetica Chimica Acta Vol. 87 (2004)
2635
08), the resulting ca. 1:1 mixture 6/10 of the hydroypiperidinemethanols was
transformed into the acetonides 5/9 that could easily be separated by column
chromatography. Hydrolysis of the pure diastereoisomers 5 and 9 afforded the trans-
and cis-1-benzyl-4-hydroxypiperidine-3-methanols 6 and 10. The g-homoacetylcholine
mimetics 35 42, the respective N-benzyl-N-methylammonium trifluoromethanesulfo-
nates 43 45 and 47 49, as well as the target N,N-dimethylammonium compounds 46a
and 50a5) were prepared as described above. The latter were obtained after cyclization
of the respective 4-hydroxy-1-methylpiperidine-3-methanols 14 and 18 with 2,4-
dinitrophenyl phosphorodichloridate and methylation (TfOMe).
3. Synthesis of the Acetylcholine Mimetics of Type III (7-Aza-3-phospadecalins).
3.1. General. Starting from the 3-hydroxypiperidine-2-methanols 52 and 58, the 7-aza-3-
phosphadecalins were made analogously to the 8- and 9-aza compounds as described
above [21]. But the syntheses of 52 and 58 were not as straightforward. Though their
precursor ethyl 1-benzyl-3-oxopiperidine-2-carboxylate (ˆethyl 1-benzyl-3-oxopipe-
colate; 55) is accessible as the kinetic product of the Dieckmann condensation of ethyl
4-[benzyl(2-ethoxy-2-oxoethyl)amino]butanoate [15], its preparation is not satisfac-
tory6). As a consequence, we followed the alternative route depicted in Scheme 4. In
the course of our work with the acetylcholine mimetics of the types I and II, it became
evident that almost all of the chloro-, (4-nitrophenoxy)-, and (2,4-dinitrophenoxy)-
azaphosphadecalins were only weak reversible inhibitors of AChE [15][16] (see [also
13]). Moreover, due to facile epimerization of the chloro- and (2,4-dinitrophenoxy)-
substituted compounds, the equatorial epimers of only the 4-nitrophenoxy derivatives
could be isolated and characterized. In contrast to this finding, the corresponding
phosphorofluoridates turned out to be well suited for our purposes. They are
irreversible inhibitors of AChE, and both epimers of all three types are accessible, a
fact that allows cross-link comparisons of their inhibition characterisics. For these
reasons, only the fluoridates for the type-III congeners were synthesized [21].
Unfortunately, in spite of extensive exploration, all attempts to reliably prepare the
N,N-dimethylammonium derivatives were not successful in this series. In particular, the
protocol elaborated for the 8- and 9-aza isomers was not applicable. Since kinetic
investigations exhibited no significant difference between the free bases and the
ammonium compounds [16][21] (see also [13]), only the corresponding N-benzyl
derivatives of the type-III acetylcholine mimetics were characterized.
3.2. 7-Azaphosphadecalins (trans- and cis-IIIax,IIIeq, Scheme 4, Fig. 3) [21]. The
key 3-hydroxypiperidine-2-methanols 52 and 58 were prepared by hydrogenation
(Rh/Alox, 60 bar H2, pH 3) and in situ benzylation of 3-hydroxypyridine-2-methanol
(51). The predominantly resulting cis-hydroxypiperidinemethanol 52 was transformed
into the pivaloate 537) and the latter oxidized (Swern) to afford the 3-oxopiperidine-2-
6
)
The thermodynamic product is ethyl 1-benzyl-3-oxopiperidine-4-carboxylate (1). Ethyl 1-benzyl-3-
oxopiperidine-2-carboxylate (55) was accidentally isolated in 44% yield [15]. However, the procedure
was not reproducible, and in spite of ample attempts to optimize the reaction conditions in favor of 55, the
yield never exceeded an unsatisfactory 30% (see also [20]). Moreover, 55 underwent a retro-reaction on
storage for a while, yielding 1-benzylpyrrolidin-2-one.
7
)
The combination of both the acetic and pivalic acid esters was the most appropriate for an efficient
chromatographic separation.

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Scheme 4. Synthesis of the Type-III Compounds
Me(CF3SO3À) as counter-ion (ammonium compounds)
a) H2, Rh/Alox, 60 bar, H2O, pH 3, 358. b) BnBr, K2CO3, EtOH, reflux. c) tBuCOCl, pyridine, À208.
d) (COCl)2, DMSO, CH2Cl2, À608 (from 53). e) NaBH4, EtOH, À158 (cis/trans ca. 1:1 from 54). f) Ac2O,
pyridine, r.t. g) Chromatography (SiO2, hexane/AcOEt). h) KOH, EtOH/H2O, r.t. i) Cl2P(O)X, Et3N, CH2Cl2
or Et2O, 08. j) Chromatography (SiO2, hexane/Et2O or hexane/AcOEt). k) CF3SO3Me, MeCN, 1008. l) H2,
Pd/C, EtOH, r.t. m) CF3SO3Me, Li2CO3, MeCN, sonication, r.t. n) CF3SO3Me (neat), sonication, r.t.
o) CF3SO3Me, CHCl3, r.t. p) Cl2P(O)F, THF, r.t.

Helvetica Chimica Acta Vol. 87 (2004)
2637
methyl pivaloate 54 that was reduced (NaBH4, EtOH, À158) to yield a ca. 1:1 mixture
of the 3-hydroxy pivaloates 56. Acetylation7), chromatographic separation of 57, and
saponification of the pure diastereoisomers furnished the cis- and trans-1-benzyl-3-
hydroxypiperidine-2-methanols 52 and 58. The 3-fluoro-7-aza-3-phosphadecalins 59a,b
and 60a,b were obtained after cyclization with phosphoric dichloride fluoride [22] and
chromatographic separation of the P-epimers. Experiments to prepare the correspond-
ing ammonium compounds were performed with the trans-isomers since 59a was the
most-stable substrate in the series. The N-benzyl-N-methylammonium derivative 61
that was obtained after usual methylation of 59a could be hydrogenolyzed and
methylated in situ under special conditions (TfOMe, Li2CO3, sonication) to afford the
N,N-dimethylammonium derivative 62 as a main component of a mixture8). But the
product was only tentatively characterized by virtue of the 13C- and 31P-NMR signals
anticipated for 62. A similarly meager result was obtained when trans-3-hydroxy-2-
(hydroxymethyl)-1,1-dimethyl-piperidinium (64) was cyclized with the phosphorus
reagent. Though the N,N-dimethylammonium derivative 62 could be evidenced, the
compound was again present in a inseparable mixture8)9). In contrast, the protocol for
the types I and II, i.e., starting from 3-hydroxy-1-methylpiperidine-2-methanol (63),
was not successful at all, and the target 62 could not be isolated. As demonstrated for
59b and 60b, hydrogenolytic removal of the N-benzyl group always resulted in
quantitative epimerization at the P-atom, and only the axially substituted secondary
ammonium salts 65 and 66 could be isolated. Generally, the outcome of all these N-
alkylations is heavily dependent on the individual conditions and most significantly
on both the reaction and workup time. In spite of ample exploration, we were not able
to establish a reliable procedure to synthesize the target N,N-dimethylammonium
compounds of the type-III acetylcholine mimetics.
4. Spectroscopic Properties. The spectral characteristics of the novel azaphos-
phadecalins are very similar to those of the type-IV compounds, and all the structures
can be assigned unequivocally. In particular, the 31P-NMR spectra are most meaningful
and exhibit the same essential features as discussed in [4][5][19]. Normally, the 31P-
NMR resonance of the axial epimer is shifted upfield with respect to the equatorial
3
1
one10), and the magnitude of J(P,H) in the H-coupled 31P-NMR is indicative of the
conformation of the heterocyclic ring11). Due to the anomeric effect, electronegative
substituents X occupy the stereoelectronically favored axial position. As a conse-
8
)
Depending on the individual reaction conditions, the predominant products are trans-3-chloro-2-
(chloromethyl)-1,1-dimethylpiperidinium chloride and phosphorofluoridic acid (POF(OH)2) besides N-
methyl- and N-demethylamines in variable concentrations. Obviously, the liberated chloride from POCl2F
easily undergoes nucleophilic substitution reactions in the nonaqueous medium. In the course of all the
trials, we encountered a series of surprising results that are not discussed further in this context. Although
insufficient, the procedures indicated in the Exper. Part gave the best results and were reproducible to
some extent.
9
)
Probably also the equatorial epimer is present (see Exper. Part).
10
)
)
The magnitude of the chemical shift difference (Dd ˆ deq À dax) is indirectly proportional to the
electronegativity of the P-substituent; we found a typical range of ca. 0.5 7 ppm [4][5][7].
The axial epimers show 3J(P,HaxÀC(5)) ꢀ 0 and 3J(P,HeqÀC(5)) ꢀ 25Hz, whereas the equatorial ones have
11
3
3J(P,HaxÀC(5)) ꢀ J(P,HeqÀC(5)) ꢀ 10 15Hz. Hence, the axial epimers exhibit
a d-type and the
equatorial ones a m-type splitting pattern.

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Helvetica Chimica Acta Vol. 87 (2004)
quence, axially substituted cyclic phosphates adopt the chair and its equatorial
counterparts a twist-boat conformation. Surprisingly, the 31P-NMR chemical shifts of
the fluoridates of the cis-series do not follow the general rule mentioned above and
display an inverse behavior (Dd < 0)12). This finding can be explained by the F-atom
being the substituent with the strongest electronegativity, and the enhanced flexibility
of the cis-fused decalins allows facile conformational changes to render the anomeric
effect most operative13).
5. Remarks. The presented report summarizes the results of extensive preparative
efforts during several years. Although the compounds look very similar, each isomer
has individual, significantly different physical and chemical properties that cannot be
anticipated, and each compound has to be treated adequately. Despite their
pronounced reactivity, the N-benzyl derivatives of the acetylcholine mimetics I and
III as well as the g-homoacetylcholine mimetics II can well be handled. Unresolved
problems are caused by the cationic compounds, especially the original target N,N-
dimethylammonium congeners that constitute the real acetylcholine mimetics. Though
the N-benzyl-N-methyl cations are accessible, the respective N-methyl-azaphospha-
decalins cannot be isolated. Being highly basic and nucleophilic intermediates, they are
extremely reactive substances that have to be transformed in situ. The quaternary
ammonium salts proved to be rather tedious to handle. They are very hygroscopic and
significantly more reactive than the free amines, and the fact that they cannot be
purified is an additional drawback. Moreover, the equatorially substituted epimers are
not accessible when a catalytic hydrogenation step is involved. Although not all of the
congeners originally aimed at could be synthesized, the phosphorofluoridates of the
types I, II, and III, i.e., 19a,b, 23a,b, 35a,b, 39a,b, 59a,b and 60a,b, constitute a consistent
set of closely related acetylcholinesterase inhibitors that enabled cross-linked inves-
tigations [13].
The authors are indebted to the Swiss National Science Foundation for the financial support and to the
analytical department of our institute, especially the NMR team (Martin Binder, Dr. Gudrun Hopp-Rentsch,
Simon Jurt, and Nadja Walch) for the ready completion of our special desires.
Experimental Part
1. General. Continuous extraction of H2O-soluble compounds (hydroxypiperidinemethanols, etc.) with
Et2O, from the H2O soln. sat. with NaCl. The organophosphorus compounds were handled in a glove box
(Mecaplex type 2201) under dry N2. Handling of volatile F-compounds in glassware with Teflon junctions; care
must be taken when cleaning such glassware: prior to contact with alcohols (generation of dialkyl
phosphorofluoridates), soaking in aq. NaOH soln. is indispensable. pH Determinations: Knick Portamess 762
Calimatic, Mettler InLab-423-S7 electrode; calibration: Mettler standard buffers pH 4.01 and pH 7.00;
electrolyte: Mettler standard, 3m KCl sat. with AgCl; measurements at 228, accuracy Æ 0.02 pH units. TLC:
Merck 60 F254 silica-gel plates; detection by UV254 light, by spraying with −mostain× soln. ((NH4)6Mo7O24 ¥ 4 H2O
(40 g), Ce(SO4)2 (0.8 g), 10% H2SO4 soln. (800 ml)) and heating (blue spots) or Schlittler×s reagent (soln. A:
H2PtCl6 (1 g), H2O (6 ml), 2n HCl (20 ml); soln. B: KI (22.5g) in H 2O (250 ml); soln. A ‡ B diluted to
1000 ml). Standard column chromatography (CC): alumina 90 (63 200 mm, Merck 101097, act. II III) or silica
gel 60 (40 63 mm, Merck 109385); CC of the hydrolytically labile azaphosphadecalins on modified silica gel 60
12
)
)
The same holds for the fluoridates of the type-IV cis-compounds [13].
For a discussion of conformational analysis, see a following paper [23].
13

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2639
(15 40 mm, Merck. 115111): silica gel (200 g) was washed with 1n HCl, thoroughly neutralized with H2O, and
reactivated by stepwise washing with EtOH and hexane and drying at 1208 (pH of a 10% aq. slurry, 5.6),
adsorbent/substance ca. 15 30 :1, all separations within ca. 15min (!). M.p.: Mettler FP 5/52; not corrected.
UV: Perkin-Elmer Lambda-9- UV/VIS/NIR spectrophotometer, Hewlett-Packard 8452A diode-array spectro-
photometer; lmax (log e) in nm. IR: Perkin-Elmer 1600-FT-IR, Perkin-Elmer Paragon-1000PC-FT-IR
spectrometer; in cmÀ1 1H-, 13C-, and 31P-NMR: Bruker AC-300 or ARX-300 (300.0, 75.4, and 121.4 MHz,
.
resp.), AMX-400 (400.0, 100.6, and 161.9 MHz, resp.), DRX-500 (500.0, 125.7, and 202.4 MHz, resp.), AMX-600
or DRX-600 (600.0, 150.9, and 242.9 MHz, resp.; at 564.5 MHz for 19F) spectrometers; chemical shifts d in ppm
rel. to the assigned solvent (Me4Si as internal, H3PO4 (85% in D2O) as external standard (0 ppm), coupling
1
constants J in Hz; all assignments based on extensive interpretations of 1H-, H{19F}-, 1H{31P}-, 1H,1H-COSY,
1H,1H-, 1H,19F-NOESY, 13C{1H}-, DEPT90, DEPT135, 1H,13C-COSY (HSQC), 1H,13C- (HMBC), 19F-, 31P-, and
31P{1H}-NMR experiments; complex spin systems are interpreted according to 1st-order approximation,
although, in several complex cases, the intensities show higher-order spectra; the signals are characterized
according to their appearance and the relative intensities of the individual lines (i.e., ddd=dt, although, in the
latter case, three different coupling partners may be present, too). The specification of Hax and Heq in the
phosphadecalins is strictly valid only for compounds adopting double-chair conformations, i.e., for all
compounds with axial X at the P-atom; for reasons of simplicity, this terminology is maintained also for the
compounds with equatorial X, although the O,P-heterocyclic moiety adopts non-chair conformations. Due to
the flexibility of the latter and the concomitant coalescence phenomena, high-field NMR spectra are often less
resolved than expected. GC/MS: Hewlett-Packard HP-5980 series II (GC), HP-5971 MSD (mass-selective
detector, EI; 70 eV), column HP-5, 25 m 0.2 mm, 0.33 mm; injector 1808, detector 3308; temp. program: 1508
(2 min), 1008 2408 (rate 308/min), 2908 (5min). MS: Varian MAT 112s, Varian MAT 90, electron impact (EI),
70 eV; Varian MAT 7011, Finnigan MAT SSQ 700, chemical ionization (CI) with NH3, unless otherwise stated;
Finnigan MAT TSQ 7000, electrospray ionization (ESI).
2. Piperidine Precursors 3 18 (for 9- and 8-Azaphosphadecalins I and II (Scheme 3). (Æ)-trans- and (Æ)-
cis-1-Benzyl-3-hydroxypiperidine-4-methanol (4 and 8 resp.). A soln. of ethyl 1-benzyl-3-oxopiperidine-4-
carboxylate hydrochloride (1; 10 g; Aldrich. 14,320-O) in MeOH (200 ml) was added dropwise to NaBH4 (25g)
under vigourous stirring (KPG) at 08 [10]. After completing the addition, stirring of the heterogeneous mixture
was continued at r.t. (20 h). H2O (200 ml) was added, the mixture stirred for another 5h at r.t., when MeOH was
removed and the residue subjected to continuous extraction. After workup and drying (308/0.05Torr), 4/8 ca.
2 :3 (GC) was obtained as a yellow oil (7.32 g, 98%). An aliquot (2 g) was subjected to CC (alumina, 2% MeOH/
CH2Cl2): cis-isomer 8 (1.1 g), followed by the trans-isomer 4 (0.6 g). As this separation was not easily
reproducible, crude 4/8 (4 g) was dissolved in anh. pyridine (20 ml) and Ac2O (10 ml) and kept at r.t. (15h).
Usual workup afforded the mixture of the diacetates 3 and 7 (5.5 g, 99%). CC (SiO2, hexane/AcOEt 2 :3) gave a
neat separation of (Æ)-trans-1-benzyl-3-(acetyloxy)piperidine-4-methanol acetate (3; 2.2 g) from the later
eluting (Æ)-cis-1-benzyl-3-(acetyloxy)piperidine-4-methanol acetate (7; 3.0 g), both as yellowish, viscous oils.
Data of 3: Rf (hexane/AcOEt 2 :1) 0.44. IR (CHCl3): 3030w, 2951w, 2810w, 2769w, 2360m, 2341w, 1733s,
1653w, 1466w, 1455w, 1370m, 1248s, 1115w, 1031m, 606w. 1H-NMR (300 MHz, CDCl3): 7.31 7.23 (m, HÀC(2')
to HÀC(6')); 4.81 (dt, 3J(3,2ax) ˆ 3J(3,4) ˆ 9.8, 3J(3,2eq) ˆ 4.7, HÀC(3)); 4.03 (AB of ABX, not resolved,
CH2OCOMe); 3.54, 3.48 (AB, 2J ˆ 13.3, PhCH2); 3.09 (m, dd-like, 2J ˆ 1, HeqÀC(2)); 2.81 (m, dt-like, 2J ˆ 11.2,
HeqÀC(6)); 2.04, 2.02 (each s, COMe); 1.96 1.87 (m, HaxÀC(2), HaxÀC(6)); 1.78 1.73 (m, HÀC(4),
HeqÀC(5)); 1.53 (m, dq-like, w1/2 ꢀ 25, HaxÀC(5)). 13C-NMR (75.4 MHz, CDCl3): 170.9, 170.2 (COMe); 137.8
(C(1'); 128.8 (C(3'), C(5')); 128.2 (C(2'), C(6')); 127.0 (C(4')); 70.2 (C(3)); 64.6 (C(2)); 62.4 (C(6)); 56.7
‡
(PhCH2); 52.1 (CH2OCOMe); 40.2 (C(4)); 27.1 (C(5)); 20.9, 20.7 (COMe). CI-MS: 307 (17, [M ‡ 2 H] ), 306
‡
(100, [M ‡ H] ).
Data of 7: Rf (hexane/AcOEt 2 :1) 0.26. IR (CHCl3): 3030m, 2950m, 2807m, 2360w, 1732s, 1494w, 1454m,
1
1370s, 1248s, 1150w, 1107w, 1040s, 977w, 947w, 85 4w, 693w, 607w. H-NMR (300 MHz, CDCl3): 7.30 7.23 (m,
HÀC(2') to HÀC(6')); 5.00 (br. s, w1/2 ꢀ 10, HÀC(4)); 4.03 (A of ABX, 2J ˆ 11.0, 3J ˆ 8.3, CHAOCOMe); 3.99
(B of ABX, 2J ˆ 11.0, 3J ˆ 6.3, CHBOCOMe); 3.60, 3.50 (AB, 2J ˆ 13.4, PhCH2); 3.03 (m, dd-like, 2J ˆ 11,
HeqÀC(2)); 2.90 (m, dt-like, 2J ˆ 11.3, HeqÀC(6)); 2.1 2.0 (m, HaxÀC(2)); 2.09, 2.02 (each s, COMe); 1.90 (m,
w1/2 ꢀ 25, HaxÀC(6)); 1.71 (m, q-like, CH2(5)); 1.55 ( X of ABX, dt-like, w1/2 ꢀ 20, HÀC(4)). 13C-NMR
(75.4 MHz, CDCl3): 170.9, 170.6 (COMe); 137.6 (C(1'); 128.8 (C(3'), C(5')); 128.1 (C(2'), C(6')); 127.0 (C(4'));
67.8 (C(3)); 64.4 (C(2)); 62.4 (C(6)); 55.4 (PhCH2); 52.2 (CH2OCOMe); 37.6 (C(4)); 24.0 (C(5)); 21.0, 20.7
‡
‡
(COMe). CI-MS: 307 (18, [M ‡ 2 H] ), 306 (100, [M ‡ H] ).
Saponification (2n NaOH in MeOH, 408, TLC control) of 3 (2.2 g) and 7 (3.2 g) and continuous extraction
afforded 4 (1.50 g, 97%) and 8 (2.20 g, 96%), both as colorless crystals.

2640
Helvetica Chimica Acta Vol. 87 (2004)
Data of 4: M.p. 111 1128. IR (KBr): 3379s (br.), 3091s (br.), 2909s, 2818s, 2362m, 1496m, 1444m, 1410m,
1366s, 1351m, 1294m, 1251m, 1204m, 1138m, 1102s, 1055s, 1003s, 95 6s, 874m, 789m, 75 9s, 705s. 1H-NMR
(300 MHz, CDCl3): 7.33 7.26 (m, HÀC(2') to HÀC(6')); 3.78 3.66 (m, CH2OH, HÀC(3)); 3.56, 3.51 (AB, 2J ˆ
13.0, PhCH2); 3.00 (ddd, 2J ˆ 10.5, 3J(6eq,5ax) ˆ 4.5, 3J(6eq,5eq) ˆ 1.5, HeqÀC(6)); 2.84 (dd, 2J ˆ 10.0,
3J(2eq,3ax) ˆ 4.0, HeqÀC(2)); 2.00 (dt, 2J ˆ 3J(6ax,5ax) ˆ 10.5, 3J(6eq,5ax) ˆ 2.5, HaxÀC(6)); 1.96 (t, 2J ˆ
3J(2ax,3ax) ˆ 10.0, HaxÀC(2)); 1.60 1.55 (m, CH2(5)); 1.30 (X of ABX, dq-like, w1/2 ꢀ 20, HÀC(4)).
13C-NMR (75.4 MHz, CDCl3): 139.0 (C(1')); 130.7 (C(3'), C(5')); 129.6 (C(2'), C(6')); 128.4 (C(4')); 73.5
(C(3)); 68.5(CH 2OH); 64.1 (PhCH2); 61.4 (C(2)); 54.0 (C(6)); 45.7 (C(4)); 27.5 (C(5)). CI-MS: 222 (100, [M ‡
‡
H] ). See also [10][14].
Data of 8: M.p. 82 848. IR (KBr): 3375s (br.), 3085s (br.), 2916s, 2820s, 2362m, 1496m, 1468 m, 1410m,
1366m, 1340m, 1294m, 1251m, 1203m, 1132m, 1099s, 1046s, 1027s, 1008s, 95 6s, 921m, 775m, 75 9s, 705s. 1H-NMR
(300 MHz, CDCl3): 7.37 7.25( m, HÀC(2') to HÀC(6')); 3.95( s, w1/2 ꢀ 8, HÀC(3)); 3.74 (A of ABX, 2J ˆ 10.9,
3J ˆ 4.2, CHAOH); 3.67 (B of ABX, 2J ˆ 10.9, 3J ˆ 5.7, CHBOH); 3.528, 3.532 (AB, 2J ˆ 13.0, PhCH2); 2.98 2.87
(m, HeqÀC(2), HeqÀC(6), OH); 2.19 (dd, 2J ˆ 11.5, 3J(2ax,3) ˆ 1.5, HaxÀC(2)); 2.05( ddd, 2J ˆ 13.5,
3
3J(6ax,5ax) ˆ 9.5, J(6eq,6ax) ˆ 3.0, HaxÀC(6)); 1.81 (X of ABX, dq-like, w1/2 ꢀ 20, HÀC(4)); 1.57 1.46 (m, t-
like, CH2(5)). 13C-NMR (75.4 MHz, CDCl3): 137.8 (C(1')); 128.8 (C(3'), C(5')); 128.1 (C(2'), C(6')); 127.0
(C(4')); 66.9 (C(3)); 64.7 (CH2OH); 62.4 (PhCH2); 59.4 (C(2)); 52.6 (C(6)); 41.3 (C(4)); 22.8 (C(5)). CI-MS:
‡
222 (100, [M ‡ ] ). See also [10][14].
(Æ)-trans- and (Æ)-cis-1-Benzyl-4-hydroxypiperidine-3-methanol (6 and 10) Ethyl 1-benzyl-4-oxopiper-
idine-3-carboxylate hydrochloride (2; 12 g; Aldrich 49,597-2) was dissolved in sat. Na2CO3 soln. (100 ml) and
extracted with Et2O. After workup, the resulting free base (9.7 g, 92%) was dissolved in iPrOH (15ml), added
dropwise to a suspension of anh. Na2CO3 (1.5g) and NaBH 4 (1.95g) in iPrOH (35ml), and stirred at r.t. (3 h).
Then 1n HCl (150 ml) was added and the mixture stirred at 408 (30 min), set to pH 10 with sat. Na2CO3 soln.,
and extracted with Et2O. The resulting crude cis-/trans-4-hydroxy esters (7.5g, 77%; ca. 1:1 (GC), not further
characterized) in Et2O (30 ml) were added to LiAlH4 (2.1 g) in Et2O (30 ml) at ca. 58 over 20 min, and the
suspension was stirred at r.t. (2 h). Then 2,2',2''-nitrilotris[ethanol] (8 g) was added slowly at ca. 58, and after
30 min, H2O (2 ml) was added and the mixture stirred for 15h at r.t. The resulting suspension was filtered over
Celite and afforded, after drying at 308/0.05Torr, crude 6/10 ca. 1:1 (GC) as a yellow oil (6.6 g, 99%). CC
(alumina, several solvents) of 6/10 or CC (silica gel) of the corresponding diacetates was feasible but resulted in
only moderate resolution. Therefore, the corresponding acetonides were prepared: 2,2-dimethoxypropane
(25g), TsOH ¥ H 2O (5.5 g) and crude 6/10 (6.6 g) in CH2Cl2 (50 ml) were stirred at 508 for 30 min (TLC
control). After workup (evaporation of the solvent, addition of sat. Na2CO3 soln. (pH 10), extraction with Et2O,
drying), 5/9 1:1 (GC) (7.2 g, 93%) was obtained. CC (SiO2, hexane/Et2O 1:1 ! Et2O) of an aliquot (6 g) gave a
neat separation of trans-(1RS,6SR)-8-benzyl-3,3-dimethyl-2,4-dioxa-8-azabicyclo[4.4.0]decane (ˆtrans-6-ben-
zylhexahydro-2,2-dimethyl-4H-1,3-dioxino[5,4-c]pyridine, 5; 2.8 g) from the later eluting cis-(1RS,6RS)-8-
benzyl-3,3-dimethyl-2,4-dioxa-8-azabicyclo[4.4.0]decane (ˆcis-6-benzyl-hexahydro-2,2-dimethyl-4H-1,3-dioxi-
no[5,4-c]pyridine; 9; 3.0 g), both as colorless crystals.
Data of 5: Rf (AcOEt) 0.42. M.p. 59.5 608. IR (KBr): 3033w, 2998m, 2937s, 2905m, 2873m, 2804s, 2756m,
1495w, 1454m, 1362m, 1339m, 1310w, 1270m, 1258m, 1240w, 1219m, 1199s, 1169s, 1131m, 1116m, 1102s, 1061s,
1031m, 972m, 934m, 901w, 862s, 793m, 748s, 701s, 626w, 5 42w, 5 30w. 1H-NMR (600 MHz, CDCl3): 7.32 7.27
(4 H), 7.26 7.23 (1 H) (each m, HÀC(2') to HÀC(6')); 3.64 (A of ABX, 2J ˆ 11.3, 3J(5eq,6) ˆ 4.8, HeqÀC(5));
3.57 (B of ABX, 2J ˆ 11.3, 3J(5ax,6) ˆ 11.3, HaxÀC(5)); 3.52, 3.47 (AB, 2J ˆ 13.0, PhCH2); 3.51 (dt, 3J(1,6) ˆ
3J(1,10ax) ˆ 10.5, 3J(1,10eq) ˆ 4.5, HÀC(1)); 2.96 (dquint., 2J ˆ 11.9, 3J(9eq,10ax) ˆ 2.6, 3J(9eq,10eq) ˆ
2
3
4
2
4J(9eq,7eq) ˆ 1.3, HeqÀC(9)); 2.66 (ddd, J ˆ 11.1, J(7eq,6) ˆ 3.4, J(7eq,9eq) ˆ 1.3, HeqÀC(7)); 2.11 (dt, J ˆ
3J(9ax,10ax) ˆ 11.9, 3J(9ax,10e) ˆ 2.9, HaxÀC(9)); 1.89 (X of ABX, 3J(6,5ax) ˆ 11.3, 3J(6,7ax) ˆ 11.1, 3J(6,1) ˆ
10.5, 3J(6,5eq) ˆ 4.8, HÀC(6)); 1.75( m, dq-like, 2J ˆ 11.5, 3J(10eq,1) ꢀ J(10eq,9ax) ꢀ J(10eq,9eq) ˆ 4.5,
3
3
HeqÀC(10)); 1.70 (m, dq-like, 2J ꢀ J(10ax,1) ꢀ J(10ax,9ax) ˆ 11.5 3J(10ax,9eq) ˆ 2.6, HaxÀC(10)); 1.67 (t, 2J
ˆ 3J(7ax,6) ˆ 11.1, HaxÀC(7)); 1.46 (s, MeaxÀC(3)); 1.40 (s, MeeqÀC(3)). 13C-NMR (150.9 MHz, CDCl3): 138.2
(C(1')); 128.9 (C(3'), C(5')); 128.2 (C(2')), C(6')); 127.0 (C(4')); 89.9 (C(3)); 72.6 (C(1)); 62.9 (C(5)); 62.7
(C(13)); 52.7; (C(7)); 52.3 (C(9)); 39.8 (C(6)); 31.4 (C(10)); 29.9 (MeeqÀC(3)); 19.3 (MeaxÀC(3)). EI-MS: 261
3
3
.
‡
‡
‡
(1, M ), 246 (7, [M À Me] ), 203 (9), 174 (3), 146 (7), 132 (7), 119 (16), 112 (24), 106 (27), 91 (100, PhCH2 ),
84 (8), 65(12), 56 (11).
Data of 9: Rf (AcOEt) 0.14. M.p. 45.5 468. IR (KBr): 3060w, 3022w, 2988m, 2943m, 2916s, 2874m, 2815m,
1495w, 1467w, 1454m, 1432w, 1401w, 1378m 1366s, 1328w, 1318w, 1292w, 1279w, 1240m, 1222s, 1204s, 1167m,
1130m, 1104s, 1091s, 1060m, 1006m, 987w, 931w, 918w, 85 4w, 790w, 765w, 740m, 697m, 647w, 614w, 5 18w.
1H-NMR (600 MHz, CDCl3): 7.33 7.27 (4 H), 7.26 7.23 (1 H) (each m, HÀC(2') to HÀC(6')); 4.13 (q,

Helvetica Chimica Acta Vol. 87 (2004)
2641
3J(1,10eq) ˆ 3J(1,10ax) ˆ 3J(1,6) ˆ 2.7, HÀC(1)); 4.06 (A of ABX, 2J ˆ 12.0, 3J(5eq,6) ˆ 3.2, HeqÀC(5)); 3.54,
2
2
3
2
3.45( AB, J ˆ 13.0, PhCH2); 3.46 (B of ABX, J ˆ 12.0, J(5ax,6) ꢀ 1, HaxÀC(5)); 2.62 (t, J ˆ 3J(7ax,6) ˆ 11.2,
HaxÀC(7)); 2.61 (dq-like, not resolved, 2J ˆ 11.3, HeqÀC(9)); 2.53 (ddd, 2J ˆ 11.2, 3J(7eq,6) ˆ 4.7, 4J(7eq,9eq) ˆ
2
3
3
2
1.0, HeqÀC(7)); 2.28 (ddd, J ˆ 11.3, J(9ax,10ax) ˆ 13.6, J(9ax,10eq) ˆ 2.8, HaxÀC(9)); 1.82 (m, ddt-like, J ꢀ
3J(10ax,9ax) ˆ 13.8, 3J(10ax,6) ꢀ J(10ax,9eq) ˆ 4.0, HaxÀC(10)); 1.69 (dq, 2J ˆ 13.8, 3J(10eq,9ax) ˆ 3J(10eq,9eq)
3
ˆ 3J(10eq,1) ˆ 2.7, HeqÀC(10)); 1.60 (X of ABX, m, w1/2 ꢀ 20, HÀC(6)); 1.44 (s, MeaxÀC(3)); 1.40 (s,
MeeqÀC(3)). 13C-NMR (150.9 MHz, CDCl3): 138.9 (C(1')); 129.2 (C(3'), C(5')); 128.3 (C(2'), C(6')); 127.0
(C(4')); 98.4 (C(3)); 64.5(C(1)); 63.7 (Ph CH2); 63.2 (C(5)); 51.7 (C(7)); 48.1 (C(9)); 34.6 (C(6)); 31.4 (C(10));
.
‡
‡
30.0 (MeeqÀC(3)); 19.0 (MeaxÀC(3)). EI-MS: 261 (5, M ), 246 (3, [M À Me] ), 202 (4), 203 (4), 174 (30), 172
‡
(16), 158 (11), 146 (4), 120 (10), 91 (100, PhCH2 ), 82 (7), 65(12), 56 (4).
Hydrolysis of 3 and 7 was performed by suspending 3 or 7 (each 1.65g) in H 2O/1n HCl 1:1 (15ml) and
stirring at 608 for 2 h (TLC control). Workup afforded 6 (1.30 g, 93%) and 10 (1.30 g, 93%), both as colorless
crystals.
Data of 6: M.p. 71 738. IR (CHCl3): 3379s (br.), 3007s, 2945s, 2808s, 1454m, 1365m, 1342m, 1092s, 1074m,
1046s, 1027s. 1H-NMR (300 MHz, CDCl3): 7.34 7.23 (m, HÀC(2') to HÀC(6')); 3.64 (AB of ABX, d-like,
3
CH2OH); 3.61 (dt, 3J(4,3) ꢀ J(4,5ax) ꢀ 8, 3J(4,5eq) ˆ 4.5, HÀC(4)); 3.495, 3.49 (AB, 2J ˆ 13.0, PhCH2); 2.80 (m,
t-like, w1/2 ꢀ 25, HeqÀC(2), HeqÀC(6)); 2.06 (dt, 2J ˆ 3J(6ax,5ax) ˆ 11.5, 3J(6ax,5eq) ˆ 3.7, HaxÀC(6)); 1.94 1.73
(m, HaxÀC(2), HÀC(3), HeqÀC(5)); 1.64 (dq, 2J ˆ 3J(5ax,4) ˆ 3J(5ax,6ax) ˆ 11.5, 3J(5ax,6eq) ˆ 3.7, HaxÀC(5)).
13C-NMR (75.4 MHz, CDCl3): 137.6 (C(1')); 129.1 (C(3'), C(5')); 128.2 (C(2'), C(6')); 127.1 (C(4')); 72.9 (C(4));
‡
65.3 (CH2OH); 62.7 (PhCH2); 53.8 (C(2)); 51.3 (C(6)); 44.5 (C(3)); 33.5 (C(5)). CI-MS: 222 ([M ‡ H] ). See
also [14].
Data of 10: M.p. 135 136 8. IR (KBr): 3357s (br.), 3066s (br.), 2953s, 2940s, 2859s, 2818s, 2360s, 1498s,
1472s, 1458s, 1423m, 1297s, 1266s, 1146s, 1118s, 1073s, 1058s, 1021s, 998s, 971s, 790s, 747s, 700s. 1H-NMR
2
(300 MHz, CDCl3): 7.32 7.25( m, HÀC(2') to HÀC(6')); 4.04 (m, w1/2 ꢀ 12, HÀC(4)); 3.90 (A of ABX, J ˆ
3
2
3
11.0, J ˆ 3.5, CHAOH); 3.86 (B of ABX, J ˆ 11.0, J ˆ 5.5, CHBOH); 3.49 (s, PhCH2); 2.9 2.7 (br. s, 2 OH);
2.67 2.63 (m, HeqÀC(2), HeqÀC(6)); 2.44 (br. d-like, w1/2 ꢀ 25, HaxÀC(2)); 2.37 (m, w1/2 ꢀ 25, HaxÀC(6));
1.93 1.82 (m, HÀC(3), CH2(5)). 13C-NMR (75.4 MHz, CDCl3): 137.6 (C(1')); 128.9 (C(3'), C(5')); 128.2
(C(2'), C(6')); 127.0 (C(4')); 69.0 (C(4)); 64.0 (CH2OH); 63.0 (PhCH2); 53.3 (C(2)); 49.8 (C(6)); 41.4 (C(3));
‡
32.5(C(5)). CI-MS: 222 ([ M ‡ H] ). See also [14].
(Æ)-trans- and (Æ)-cis-1-Benzyl-3-hydroxy-4-(hydroxymethyl)-1-methylpiperidinium Trifluoromethanesul-
fonates (11 and 15, resp.). Methyl trifluoromethanesulfonate (300 ml) was added to a soln. of 4 (520 mg) in
CHCl3 (15ml), heated with a fan ( ca. 1 min) and kept at r.t. (2 h) when a yellowish oil separated. After
decanting the solvent, washing the residue with CHCl3, and drying (508/0.05Torr), pure 11 (850 mg, 94%) was
1
obtained. Colorless viscous oil. H- and 13C-NMR: mixture of N-epimers (Meax/Meeq ca. 2.5:1).
Analogous methylation of 8 (440 mg) afforded 15 (750 mg, 98%), mixture of N-epimers (Meax/Meeq ca.
5:1). Colorless viscous oil.
Data of 11: IR (KBr): 3550 3200m, 2934w, 2360w, 1699w, 1653w, 1558w, 1458m, 1259s, 1225m, 1165m,
1064w, 1029s, 881w, 767w, 705m, 639s, 5 74w, 5 18m. 1H-NMR (300 MHz, (CD3)2CO): 7.79 7.72 (2 H), 7.65 7.56
(3 H) (each m, HÀC(2') to HÀC(6')); 4.93, 4.90 (each s, PhCH2), 4.47, 4.20 (dt, 3J(3,2ax) ˆ 3J(3,4) ˆ 10.3,
3J(3,2eq) ˆ 4.5, HÀC(3)); 3.90 3.20 (m, CH2OH, HeqÀC(2), HeqÀC(6), OH); 3.43, 3.28 (each s, MeN); 2.20
1.81 (m, HaxÀC(2), HaxÀC(6), CH2(4)). 13C-NMR (75.4 MHz, (CD3)2CO): 133.3 (C(3'), C(5')); 130.6, 130.5
1
(C(4')); 128.6 (C(2'), C(6')); 127.0 (C(1')); 121.4 (q, J(C,F) ˆ 220, CF3SO3); 71.6, 70.7 (PhCH2); 64.6 (C(3));
62.3, 61.2, 60.9, 60.6, 59.3 (CH2OH, C(2), C(6)); 45.9, 43.4 (MeN); 29.2 (C(4)); 20.8, 19.5 (C(5)). CI-MS: 236 (6,
.
‡
‡
M
), 222 (100, [M ‡ H À Me] )).
Data of 15: IR (KBr): 3600 3450m, 2948w, 2360w, 1700w, 1684w, 1653w, 1558w, 1540w, 1481m, 1457w,
1277s, 1225s, 1165m, 1092w, 1029s, 1004m, 919w, 882w, 764m, 707m, 639s, 5 74m, 5 17m. 1H-NMR (300 MHz,
(CD3)2CO): 7.70 7.57 (2 H), 7.56 7.50 (3 H) (each m, HÀC(2') to HÀC(6')); 4.77, 4.74 (AB, 2J ˆ 13,
CH2C6H5); 4.57, 4.45 (each br. s, w1/2 ꢀ 10, HÀ(C(3)); 4.23 (dd, J ˆ 12.1, 3J(2eq,3) ˆ 2.8, HeqÀC(2)); 3.88 (dd,
2
2J ˆ 13.9, 3J(6eq,5ax) ˆ 2.9, HeqÀC(6)); 3.83 3.49 (m, CH2OH, OH, HaxÀC(2), HaxÀC(6)); 3.36 (s, MeN); 2.60
(m, q-like, w1/2 ꢀ 20, HÀC(4)); 1.92 (m, t-like, w1/2 ꢀ 20, CH2(5)). 13C-NMR (75.4 MHz, (CD3)2CO): 133.4
(C(3'), C(5')); 130.5C(4 ')); 128.9 (C(2'), C(6')); 127.3 (C(1')); 121.1 (q, 1J(C,F) ˆ 221, CF3SO3); 72.6, 71.7
(PhCH2); 64.6, 64.1 (C(3)); 62.5, 62.2 (CH2OH, C(2)); 60.4, 59.6 (C(6)); 47.3, 39.6 (MeN); 30.1, 29.1 (C(4));
.
‡
‡
‡
18.8, 18.4 (C(5)). CI-MS: 236 (10, M ), 222 (100, [M ‡ H À Me] ), 146 (8, [M À Bn] ).
(Æ)-trans- and (Æ)-cis-1-Benzyl-4-hydroxy-3-(hydroxymethyl)-1-methylpiperidinium Trifluoromethanesul-
fonates (13 and 17, resp.). As described for 11 and 15, with 6 (1.6 g) or 10 (1.1 g): 13 (2.7 g, 97%), mixture of N-

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Helvetica Chimica Acta Vol. 87 (2004)
epimers (Meax/Meeq ca. 2 :1), and 17 (1.9 g, 99%), mixture of N-epimers (Meax/Meeq ca. 3 :1), resp., both as
yellowish viscous oils.
Data of 13: 1H-NMR (300 MHz, (CD3)2CO): 7.71 7.69 (2 H), 7.57 7.53 (each m, HÀC(2') to HÀC(6'));
4.79 (AB, not resolved, PhCH2); 4.25, 4.15 (each ddd, 3J(4,3ax) ˆ 3J(4,5) ˆ 10.5, 3J(4,3eq) ˆ 5.4, HÀC(4)); 3.98
3.23 (m, CH2OH, HeqÀC(2), HeqÀC(6)); 3.30, 3.26 (each s, MeN); 2.61 1.87 (m, HaxÀC(2), CH2(3),
HaxÀC(6)). 13C-NMR (CD3)2CO): 133.3, 132.9 (C(3'), C(5')); 130.5(C(4 ')); 129.2, 129.1 (C(2'), C(6')); 127.4,
127.3 (C(1')); 121.1 (q, 1J(C,F) ˆ 220, CF3SO3); 71.2, 71.0 (PhCH2); 68.6, 65.6 (C(4)); 61.6, 60.9, 60.7, 59.9, 59.7,
.
‡
59.1 (CH2OH, C(2), C(6)); 44.7, 44.2 (MeN); 40.7, 34.6 (C(5)); 28.6, 28.2 (C(3)). CI-MS: 236 (9, M ), 222 (100,
‡
[M ‡ H À Me] ).
Data of 17: 1H-NMR (300 MHz, (CD3)2CO): 7.8 7.5( m, HÀC(2') to HÀC(6')); 4.90, 4.84 (AB, 2J ˆ 11.3,
PhCH2), 4.89 (s, PhCH2); 4.39 (br. s, w1/2 ꢀ 10, HÀC(4)); 4.29 (dd, 2 J ˆ 12.5, 3J(6eq,5) ˆ 3, HeqÀC(6)); 3.98 (dd,
2J ˆ 3J(6ax,5) ˆ 12.5, HaxÀC(6)); 3.75 3.42 ( m, CH2OH, CH2(2)); 3.31, 3.24 (each s, MeN); 2.89 1.80 (m,
HÀC(3), CH2(5)). 13C-NMR ((CD3)2CO): 133.4, 132.8 (C(3'), C(5')); 131.3, 129.1 (C(4')), 128.9 (C(2'), C(6'));
127.2 (C(1')); 120.9 (q, 1J(C,F) ˆ 220, CF3SO3); 71.2, 68.4 (PhCH2); 61.1 (C(4)); 60.5(CH 2OH); 56.5 (2C), 54.5,
.
‡
54.0 (C(2), C(6)); 52.3, 44.4 (MeN); 28.9 (2C), 25.5, 25.3 (C(3), (C(5)). CI-MS: 236 (2, M ), 222 (100, [M ‡
‡
H À Me] ).
(Æ)-trans- and (Æ)-cis-3-Hydroxy-1-methylpiperidine-4-methanol (12 and 16, resp.; free amines). A soln. of
11 (770 mg) in EtOH (15ml) and 10% Pd/C (530 mg) was hydrogenolyzed by gentle stirring under a slight
pressure of H2 (rubber balloon, 15h). The catalyst was removed by filtration over Celite, the residue washed
with EtOH, the filtrate evaporated, and the residue dissolved in 2n NaOH. Continuous extraction yielded 12
(185mg, 64%) as a colorless, viscous oil.
Analogous treatment of 15 (1.52 g) afforded 16 (350 mg, 61%) as a yellowish powder.
Data of 12: IR (KBr): 3609w, 3482m, 3007m, 2942s, 2795m, 1602w, 1466m, 448m, 1381m, 1348w, 1251m,
1
1140m, 1090m, 1072m, 1049m, 1012m, 986m, 916m, 835m, 695w, 65 7m. H-NMR (300 MHz, CDCl3): 3.74 (dt,
3J(3,2ax) ˆ 3J(3,4) ˆ 11, 3J(3,2eq) ˆ 4.5), HÀC(3)); 3.68 3.62 (AB of ABX, not resolved, CH2OH); 2.96 (ddd,
3
2J ˆ 10.5, J(2eq,3) ˆ 4.5, 4J(3eq,4) ˆ 1.5, HeqÀC(2)); 2.77 (m, dt-like, 2J ˆ 11, HeqÀC(6)); 2.28 (s, MeN); 1.93
(dt, 2J ˆ 3J(6ax,5ax) ˆ 11.6, 3J(6ax,5eq) ˆ 2.7, HaxÀC(6)); 1.84 (dd, 2J ˆ 3J(2ax,3) ˆ 10.5, HaxÀC(2)); 1.62 1.56
2
3
(m, HÀC(4), HeqÀC(5)); 1.30 (ddt, J ˆ 3J(5ax,4) ˆ 3J(5ax,6ax) ˆ 12.5, J(5ax,6eq) ˆ 4, HaxÀC(5)). 13C-NMR
(75.4 MHz, CDCl3): 72.0 (C(3)); 67.2 (CH2OH); 62.3 (C(2)); 54.8 (C(6)); 45.9 (N-Me); 43.8 (C(4)); 26.2 (C(5)).
.
‡
‡
EI-MS: 145(80,
(100).
M
), 128 (11, [M À 2 H À Me)] ), 114 (29), 101 (17), 96 (31), 86 (11), 71 (46), 70 (18), 58
Data of 16: M.p. 103 1048. IR (KBr): 3361s, 3061m, 2940s, 2918s, 2846m, 201m, 1450m, 1406m, 1379m,
1360m,1325m, 1308m, 1263m, 1206m, 1183m, 1140m, 1099m, 1074m, 1044m, 1022s, 1009s, 971w, 95 6w, 922m,
891m, 816w, 760m, 668w, 5 30w, 5 01w. 1H-NMR (300 MHz, CDCl3): 3.96 (br. s, w1/2 ꢀ 10, HÀC(3)); 3.68 (AB of
ABX, not resolved, CH2OH); 3.34 3.19 (br., 2 OH); 2.86 (m, t-like, HeqÀC(2), HeqÀC(6)); 2.26 (s, MeN); 2.08
(dd, 2J ˆ 11.5, 3J(2ax,3) ˆ 1.1, HaxÀC(2)); 1.96 (dd, 2J ˆ 3J(6ax,5ax) ˆ 12, 3J(6ax,5eq) ˆ 2.5, HaxÀC(6)); 1.76 (ddt,
2J ˆ 3J(5ax,6ax) ˆ 3J(5ax,4) ˆ 12, 3J(5ax,6eq) ˆ 3.5, HaxÀC(5)); 1.30 (ddt, 2J ˆ 3J(5ax,4) ˆ 3J(5ax,6ax) ˆ 12.5,
3J(5ax,6eq) ˆ 4, HaxÀC(5)). 1.52 1.44 (m, HÀC(4), HeqÀC(5)). 13C-NMR (75.4 MHz, CDCl3): 67.1 (C(3));
‡
66.3 (CH2OH); 61.8 (C(2)); 55.1 (C(6)); 46.0 (MeN); 40.7 (C(4)); 22.8 (C(5)). CI-MS: 146 (84, [M ‡ H] ). EI-
.
‡
‡
MS: 145(84, M ), 128 (12, [M À 2 H À Me)] ), 114 (20), 101 (20), 96 (24), 86 (14), 71 (40), 70 (14), 58 (100).
(Æ)-trans- and (Æ)-cis-4-hydroxy-1-methylpiperidine-3-methanol (14 and 18, resp.; free amines). As
described for 12 and 16, with 13 (1.25g) or 17 (1.60 g): 14 (390 mg, 83%) and 18 (526 mg, 85%), resp., both as
colorless viscous oils.
Data of 14: 1H-NMR (300 MHz, CDCl3): 4.05(br., 2 OH); 3.69 ( A of ABX, 2J ˆ 10.8, 3J ˆ 7, CHAOH); 3.65
2
3
3
3
(B of ABX, J ˆ 10.8, J ˆ 4.5, CHBOH); 3.48 (dt, J(4,3) ˆ 3J(4,5ax) ˆ 9.5, J(4,5eq) ˆ 4.5, HÀC(4)); 2.81 (m,
w1/2 ꢀ 20, HeqÀC(2), HeqÀC(6)); 2.25( s, MeN); 2.04 1.59 (m, HaxÀC(2), HÀC(3), CH2(5), HaxÀC(6)).
13C-NMR (75.4 MHz, CDCl3): 74.4 (C(4)); 64.8 (CH2OH); 56.4, 53.9 (C(2), C(6)); 45.8 (C(3)); 45.0 (MeN);
.
‡
‡
‡
33.9 (C(5)). CI-MS: 146 (100, [M ‡ H] ), 145(27, M ), 144 (20, [M À H] ).
Data of 18: 1H-NMR (300 MHz, (CD3)2CO): 4.24 (m, q-like, 3J(4,3) ꢀ J(4,5ax) ꢀ J(4,5eq) ꢀ 3.5,
HÀC(4)); 4.00 (A of ABX, 2J ˆ 10.8, 3J ˆ 6.0, CHAOH); 3.93 (B of ABX, 2J ˆ 10.8, 3J ˆ 6.0, CHBOH); 2.69
(m, w1/2 ꢀ 25, HeqÀC(2), HeqÀC(6)); 2.38 (s, MeN); 2.38 2.33 (m, HaxÀC(2), HeqÀC(5), HaxÀC(6)); 2.13 (X of
ABX, m, w1/2 ꢀ 18, HÀC(3)); 2.01 (m, q-like, HaxÀC(5)). 13C-NMR (75.4 MHz, (CD3)2CO): 66.5(C(4)); 63.2
3
3
‡
(CH2OH); 54.8, 51.7 (C(2), C(6)); 46.5 (C(3)); 43.5 (MeN); 33.4 (C(5)). CI-MS: 146 (100, [M ‡ H] ), 145(25,
.
‡
‡
M
), 144 (16, [M À H] ).
3. Piperidine Precursors 52 54, 56 58, 63, and 64 (for 7-Azaphosphadecalins (Scheme 4), III). (Æ)-trans-
and (Æ)-cis-1-Benzyl-3-hydroxypiperidine-2-methanol (58 and 52, resp.) and (Æ)-cis-1-Benzyl-3-hydroxypiper-

Helvetica Chimica Acta Vol. 87 (2004)
2643
idin-2-yl-methyl 2,2-Dimethylpropanoate (53). A soln. of 3-hydroxypyridine-2-methanol hydrochloride (5.0 g;
Aldrich H3,153-0; techn. 85%) in H2O (30 ml; pH 3.0 (HCl)) was hydrogenated for 18 h over 5% Rh/Alox
(1.16 g) at 358, 60 bar H2. The catalyst was removed by filtration over Celite. To the filtrate, H2O (5 0 ml),
Na2CO3 (7.0 g), EtOH (80 ml), and benzyl bromide (3.5ml) were added, and the mixture was refluxed for
30 min. After evporation of EtOH, the aq. phase was extracted with Et2O and dried to afford crude 52 (5.25 g,
1
77%) containing ca. 6% of 58 (by H- and 13C-NMR).
To a soln. of crude 52 (9.60 g) in pyridine (25ml), a soln. of pivaloyl chloride (5.61 ml) in pyridine (25ml)
was added dropwise at À308, and the mixture was kept at À208 for 2 d. After evaporation, the residue was
dissolved in CH2Cl2, the soln. washed with 2n NaOH (30 ml) and evaporated, and the residue dried at 508/0.05
Torr to afford crude 53 (12.8 g, 97%) as a brownish oil. CC (SiO2, hexane/AcOEt 2 :1) of an aliquot (2 g) yielded
pure 53 (1.85g). Colorless solid. M.p. 58 8. Rf (AcOEt) 0.51. IR (film): 3467m (br.), 3085w, 3062w, 3027w, 2958s,
2936s, 2871m, 2801m, 2724w, 1729s, 1603w, 1540w, 1495m, 1480s, 1453s, 1397m, 1366m, 1284s, 1228m, 1161s,
1073m, 1029m, 1001m, 983m, 960w, 940w, 911w, 868w, 841w, 802w, 771w, 737m, 699m, 626w, 5 71w, 5 48w, 5 39w,
523w, 5 11w. 1H-NMR (300 MHz, CDCl3): 7.32 7.22 (m, HÀC(2') to HÀC(6')); 4.37 (d, 3J ˆ 5.1, CH2OC-
OCMe3); 3.99, 3.26 (AB, 2J ˆ 13.6, PhCH2); 3.93 (m, quint.-like, w1/2 ꢀ 10, HÀC(3)); 2.71 (ddt, 2J ˆ 11.8,
3J(6eq,5ax) ˆ 3J(6eq,5eq) ˆ 3.7, 4J ˆ 1.2, HeqÀC(6)); 2.63 (dd, 3J(2,3) ˆ 2.2, 3J ˆ 5.1, HÀC(2)); 2.03 (ddd, 2J ˆ
11.8, 3J(6ax,5ax) ˆ 10.3, 3J(6ax,5eq) ˆ 3.3, HaxÀC(6)); 1.82 1.63 (m, HeqÀC(4), HeqÀC(5)); 1.57 1.39 (m,
HaxÀC(4), HaxÀC(5)); 1.21 (s, Me3C). 13C-NMR (75.4 MHz, CDCl3): 178.3 (COCMe3); 139.2 (C(1')); 128.5
(C(3'), C(5')); 128.3 (C(2'), C(6')); 127.0 (C(4')); 67.9 (C(3)); 65.0 (C(2)); 64.5 (CH2OCOCMe3); 58.2 (PhCH2);
.
‡
51.4 (C(6)); 38.7 (Me3C); 30.9 (C(4)); 27.1 (Me3C); 20.6 (C(5)). EI-MS: 305 (1, M ), 190 (100), 91 (71,
‡
PhCH2 ), 57 (14). Anal. calc. for C18H27NO3 (305.45): C 69.41, H 8.41, N 4.03; found: C 68.93, H 8.22, N 4.00.
[(Æ)-1-Benzyl-3-oxopiperidin-2-yl]methyl 2,2-Dimethylpropanoate (54). Crude 53 (12.8 g) in CH2Cl2
(33 ml) was added to a soln. of (COCl)2 (4.30 ml) and DMSO (6.54 ml) in CH2Cl2 (33 ml) at À788 and the
mixture was stirred at À608 for 10 min. Then Et3N (28 ml) was added, and the mixture was warmed to r.t. within
20 min and further stirred at r.t. for 20 min. After drying at 358/0.05Torr, the residue was dissolved in 2 n NaOH
and extracted with Et2O. Rapid CC (SiO2, AcOEt) afforded 54 (12.2 g, 96%). Colorless oil that quickly
decomposed at r.t. in air. Rf (AcOEt) 0.62. 1H-NMR (300 MHz, CDCl3): 7.32 7.22 (m, HÀC(2') to HÀC(6'));
4.61 (A of ABX, 2J ˆ 11.7, 3J ˆ 5.0, CHAOCOCMe3); 4.34 (B of ABX, 2J ˆ 11.7, 3J ˆ 4.7, CHBOCOCMe3); 3.92,
3
2
3.58 (AB, 2J ˆ 13.6, PhCH2); 3.32 (X of ABX, 3J(2,HA) ˆ 5.0, J (2,HB) ˆ 4.7, HÀC(2)); 3.02 (dt, J ˆ 11.8, 3J ˆ
6.6, 4.5, HeqÀC(6)); 2.62 2.34 (m, 3 H); 1.95( m, sext.-like, w1/2 ꢀ 20, 2 H); 1.20 (s, Me3C). 13C-NMR (300 MHz,
CDCl3): 207.8 (C(3)); 178.1 (COCMe3); 138.2 (C(1')); 128.6 (C(3'), C(5')); 128.3 (C(2'), C(6')); 127.2 (C(4'));
69.6 (C(2)); 61.4 (CH2OCOCMe3); 58.3 (PhCH2); 47.4 (C(6)); 38.6 (Me3C); 38.3 (C(4)); 27.1 (Me3C); 23.2
‡
‡
(C(5)). EI-MS: 301 (1, [M À 2 H] ), 201 (25), 188 (28), 160 (43), 91 (100, PhCH2 ), 57 (26).
(Æ)-trans- and (Æ)-cis-3-(Acetyloxy)-1-benzylpiperidine-2-yl-methyl 2,2-Dimethylpropanoate (trans- and
cis-57, resp.). To a soln. of 54 (12.2 g) in EtOH (200 ml) was added NaBH4 (2.85g) in portions keeping the temp.
below À108 (6 portions within 1 h). After workup (addition of 10% H2SO4 soln. (140 ml), stirring at r.t.
(15min), evaporation of EtOH, addition of conc. NaOH soln. extraction with Et 2O, drying (K2CO3), and
evaporation, drying at 508/0.05Torr yielded cis/trans-56 (12.3 g, 96%) as a yellow oil. Acetylation (Ac2O (17 ml)
in pyridine (50 ml), r.t., 15 h) of 56 (11.05g) and usual workup afforded cis-/trans-57 1:1 (12.4 g, 99%) as a
brownish oil. CC (SiO2, hexane/AcOEt 87:13) gave a neat separation of trans-57 (5.41 g, 43%), colorless solid,
from the later eluting cis-57 (5.16 g, 41%), colorless oil.
Data of trans-57: M.p. 518. Rf (hexane/AcOEt 4 :1) 0.25. IR (film): 3085w, 3063w, 3028w, 2961s, 2873m,
2801m, 1731s, 1603w, 1495m, 1481m, 1454m, 1398m, 1368m, 1315w, 1282s, 1241s, 1155s, 1109m, 1072m, 1055m,
1036s, 985m, 947w, 924w, 845w, 804w, 770w, 738m, 699m, 603w, 5 84w, 5 26m, 5 10s. 1H-NMR (300 MHz, CDCl3):
7.24 7.14 (m, HÀC(2') to HÀC(6')); 4.80 (ddd, 3J(3,4ax) ˆ 8.3, 3J(3,2) ˆ 7.5, 3J(3,4eq) ˆ 4.4, HÀC(3)); 4.29 (A
of ABX, 2J ˆ 12.2, 3J ˆ 3.7, CHAOCOCMe3); 4.19 (B of ABX, 2J ˆ 12.2, 3J ˆ 4.1, CHBOCOCMe3); 3.97, 3.32 (AB,
2J ˆ 13.7, PhCH2); 2.67 (m, w1/2 ꢀ 20, HeqÀC(6)); 2.61 (X of ABX, 3J(2,HB) ˆ 4,1, 3J(2,HA) 3.7, 3J(2,3) ˆ 7.6,
HÀC(2)); 2.11 2.02 (m, HaxÀC(6)); 2.00 (s, COMe); 2.00 1.91, 1.64 1.54 (2 m, HeqÀC(4), HeqÀC(5)); 1.49
1.32 (m, HaxÀC(4), HaxÀC(5)); 1.14 (s, Me3C). 13C-NMR (75.4 MHz, CDCl3): 178.3 (COCMe3); 170.2
(COMe); 139.5(C(1 ')); 128.4 (C(3'), C(5')); 128.2 (C(2'), C(6')); 126.7 (C(4')); 69.8 (C(3)); 63.4 (C(2)); 60.5
(CH2OCOCMe3); 57.8 (PhCH2); 50.1 (C(6)); 38.8 (Me3C); 28.6 (C(4)); 27.1 (Me3C); 21.7 (C(5)); 21.2 (COMe).
.
‡
‡
‡
EI-MS: 347 (1, M ), 287 (3, [M À AcOH] ), 232 (100), 91 (52, PhCH2 ). Anal. calc. for C20H29NO4 (347.4):
C 69.41, H 8.41, N 4.03; found: C 68.99, H 8.03, N 3.93.
Data of cis-57: Rf (AcOEt/hexane 1:4) 0.20. IR (film): 3062w, 3027w, 2970s, 2869m, 2798m, 2721w, 1732s,
1603w, 1495m, 1481m, 1453m, 1398m, 1369s, 1316w, 1284s, 1239s, 1155s, 1123m, 1112m, 1067m, 1049m, 1030m,
982w, 965w, 939w, 911w, 85 5w, 808w, 769w, 739m, 699m, 65 1w, 606w, 5 85w, 5 43m, 5 11s, 5 03s. 1H-NMR (300 MHz,

2644
Helvetica Chimica Acta Vol. 87 (2004)
CDCl3): 7.32 7.20 (m, HÀC(2') to HÀC(6')); 5.09 (dt, 3J(3,4ax) ˆ 8.3, 3J(3,4eq) ˆ 3J(3,2) ˆ 4.4, HÀC(3)); 4.50
(A of ABX, 2J ˆ 11.6, 3J ˆ 6.4, CHAOCOCMe3), 4.22 (B of ABX, 2J ˆ 11.6, 3J ˆ 4.4, CHBOCOCMe3); 3.79, 3.68
(AB, 2J ˆ 14.0, PhCH2); 3.14 (X of ABX, 3J(2,HA) ˆ 6.4, 3J(2,HB) ˆ 4.4, 3J(2,3) ˆ 4.4, HÀC(2)); 2.60 (ddd, 2J ˆ
12.5, 3J ˆ 8.9, 3.1, HeqÀC(6)); 2.38 2.29 (m, HaxÀC(6)); 2.07 (s, COMe); 1.75 1.45( m, CH2(4), CH2(5)); 1.20
(s, Me3C). 13C-NMR (75.4 MHz, CDCl3): 178.3 (COCMe3); 170.3 (COMe); 139.2 (C(1')); 128.4 (C(3'), C(5'));
128.2 (C(2'), C(6')); 126.9 (C(4')); 70.5(C(3)); 60.6 ( CH2COCMe3); 60.4 (C(2)); 58.9 (PhCH2)); 47.1 (C(6));
.
‡
‡
38.6 (Me3C); 27.1 (Me3C); 26.8 (C(4)); 22.1 (C(5)); 21.2 (COMe). EI-MS: 347 (1, M ), 287 (1, [M À AcOH] ),
‡
232 (100), 91 (55, PhCH2 ). Anal. calc. for C20H29NO4 (347.4): C 69.41, H 8.41, N 4.03; found: C 68.93, H 8.22,
N 4.00.
Saponification of trans- or cis-57 (each 4.00 g) in EtOH (20 ml) with KOH (5.0 g) in H2O (20 ml) at r.t.
(30 min), usual workup and bulb-to-bulb distillation at 1508/0.05Torr gave (Æ)-trans-1-benzyl-3-hydroxypiper-
idine-2-methanol (58; 2.54 g, 99%) and (Æ)-cis-1-benzyl-3-hydroxypiperidine-2-methanol (52; 2.54 g, 99%),
resp., both as colorless crystals.
Data of 58: M.p. 808. Rf (AcOEt) ca. 0.18 (tailing). IR (KBr): 3304s (br.), 3218s (br.), 3063m, 3029m,
2925s, 2896m, 2855m, 2805s, 2785s, 2715w, 1603w, 1494m, 1480w, 1453m, 1443m, 1399m, 1381m, 1354w, 1321m,
1275w, 1252w, 1223w, 1179w, 1157w, 1119s, 1107s, 1070s, 1037s, 1027m, 1013s, 1001m, 969w, 932w, 923w, 906w,
1
875w, 85 0w, 797w, 738s, 695s, 624w, 5 76w, 5 41w, 5 08w. H-NMR (600 MHz, CDCl3): 7.34 7.22 (m, HÀC(2') to
HÀC(6')); 4.04, 3.37 (AB, 2J ˆ 13.6, PhCH2); 4.01 (A of ABX, 2J ˆ 11.3, 3J ˆ 3.0, CHAOH), 3.91 (B of ABX, 2J ˆ
3
3
3
3
11.3, J ˆ 4.5, CHBOH); 3.76 (ddd, J(3,4ax) ˆ 9.3, J(3,2) ˆ 7.6, J(3,4eq) ˆ 4.5, HÀC(3)); 2.83 (br. s, 2 OH);
2.78 (dt, 2J ˆ 11.9, J(6eq,5ax) ˆ 3J(6eq,5eq) ˆ 4.2, HeqÀC(6)); 2.29 (X of ABX, J(2,HB) ˆ 4.5, 3J(2,HA) ˆ 3.0,
3
3
3J(2,3) ˆ 7.5, H ÀC(2)); 2.13 (ddd, J ˆ 11.9, J(6ax,5ax) ˆ 10.5, J(6ax,5eq) ˆ 3.0, HaxÀC(6)); 1.95( m, dq-like,
2
3
3
2J ˆ 11.5, 3J(4eq,3) ˆ 4.5, 3J(4eq,5ax) ꢀ (4eq,5eq) ˆ 4.2, HeqÀC(4)); 1.65( m, dquint.-like, 2J ˆ 11.5,
3
3J(5eq,6eq) ˆ 4.2, 3J(5eq,6ax) ꢀ J(5eq,4ax) ˆ 3.0 HeqÀC(5)); 1.43 (m, tt-like, 2J ˆ 11.5, 3J(5ax,6ax) ꢀ
3
3J(5ax,4ax) ˆ 10.5, 3J(5ax,6eq) ˆ 4.2, HaxÀC(5)); 1.39 (m, tt-like, 2J ˆ 11.5, 3J(4ax,5ax) ˆ 10.5, 3J(4ax,3) ˆ 9.3,
3J(4ax,5eq) ˆ 3.0, HaxÀC(4)). 13C-NMR (150.9 MHz, CDCl3): 138.8 (C(1')); 128.9 (C(3'), C(5')); 128.5(C(2 '),
C(6')); 127.2 (C(4')); 68.0 (C(3)); 67.9 (C(2)); 59.1 (CH2OH); 58.2 (PhCH2); 51.0 (C(6)); 32.5 (C(4)); 22.2
.
‡
‡
‡
(C(5)). EI-MS: 221 (<1, M ), 190 (45, [M À CH2OH] ), 91 (100, PhCH2 ), 65(15). Anal. calc. for C 13H19NO2
(221.3): C 70.56, H 8.65, N 6.33; found: C 70.50, H 8.22, N 5.95.
Data of 52: M.p. 60.58. Rf (AcOEt) ca. 0.18 (tailing). IR (film): 3383s (br.), 3085w, 3061m, 3027m, 2936s,
2801s, 1602w, 1585w, 1495m, 1452s, 1367m, 1266w, 1221m, 1186w, 1116m, 1065s, 1028s, 989m, 95 5m, 916w, 885w,
842w, 796w, 737s, 699s, 5 25s, 5 04s. 1H-NMR (600 MHz, CDCl3): 7.36 7.30 (3 H), 7.29 7.22 (2 H) (each m,
HÀC(2') to HÀC(6')); 4.19, 3.52 (AB, 2J ˆ 13.4, PhCH2); 4.05( m, not resolved, HÀC(3)); 4.01 (A of ABX, 2J ˆ
11.6, 3J ˆ 5.6, CHAOH); 3.88 (B of ABX, 2J ˆ 11.6, 3J ˆ 4.0, CHBOH); 2.99 (br. s, 2 OH); 2.75( dt, 2J ˆ 11.7,
3J(6eq,5ax) ˆ 3J(6eq,5eq) ˆ 4.7, HeqÀC(6)); 2.49 (X of ABX, 3J(2,HA) ˆ 5.6, 3J(2,HB) ˆ 4.0, 3J(2,3) ˆ 2.5,
HÀC(2)); 2.10 (ddd, 2J ˆ 11.7, 3J(6ax,5ax) ˆ 9.7, 3J(6ax,5eq) ˆ 3.3, HaxÀC(6)); 1.84 1.65( m, HeqÀC(4),
HeqÀC(5)); 1.59 1.44 (m, HaxÀC(4), HaxÀC(5)). 13C-NMR (150.9 MHz, CDCl3): 139.0 (C(1')); 128.7 (C(3'),
C(5')); 128.3 (C(2'), C(6')); 127.0 (C(4')); 69.2 (C(3)); 64.9 (C(2)); 61.8 (CH2OH); 57.8 (PhCH2)); 50.8 (C(6));
.
‡
‡
‡
30.9 (C(4)); 20.4 (C(5)). EI-MS: 221 (1, M ), 190 (100, [M À CH2OH] ), 91 (91, PhCH2 ), 65(15). Anal. calc.
for C13H19NO2 (221.3): C 70.56, H 8.65, N 6.33; found: C 69.97, H 8.17, N 5.96.
(Æ)-trans-3-Hydroxy-1-methylpiperidine-2-methanol (63). Methyl trifluoromethanesulfonate (265 ml) was
added to trans-57 (168 mg). The flask was sonicated at r.t. (5min) to homogenize the mixture when colorless
drops began to separate; the reaction was complete within 30 min. After washing the residue with CHCl3 and
drying at 508/0.05Torr, the crude product was hydrogenolyzed in EtOH (2 ml) with 10% Pd/C (100 mg) by
vigorous stirring under a slight pressure of H2 (rubber balloon, 1 h). The catalyst was removed by filtration over
Celite, the residue washed with EtOH, the filtrate evaporated, and the resulting viscous oil dissolved in a soln. of
KOH (290 mg) in EtOH/H2O 1:1 (2.5ml) and stirred at r.t. (45min). Continuous extraction afforded 63
(64 mg, 63%). Colorless viscous oil that slowly solidified. M.p. 758. Rf (AcOEt) 0.06. IR (film): 3374m (br.),
2939s, 2859m, 2794s, 2712w, 1461m, 1449m, 1425w, 1373w, 1347w, 1303w, 1279m, 1227w, 1203w, 1181w, 1127m,
1
2
3
1065s, 1023s, 977w, 924w, 85 2w, 811w, 732m. H-NMR (600 MHz, CDCl3): 3.98 (A of ABX, J ˆ 11.6, J ˆ 2.1,
CHAOH); 3.81 (B of ABX, 2J ˆ 11.6, 3J ˆ 4.1, CHBOH); 3.68 (ddd, 3J(3,4ax) ˆ 11.7, 3J(3,2) ˆ 8.9, 3J(3,4eq) ˆ 4.7,
HÀC(3)); 3.52 (br. s, 2 OH); 2.81 (m, d-like, w1/2 ꢀ 15, 2J ˆ 11.3, HeqÀC(6)); 2.32 (s, MeN); 2.13 (dt, 2J ˆ
3J(6ax,5ax) ˆ 11.3, 3J(6ax,5eq) ˆ 3.7, HaxÀC(6)); 2.01 (m, dq-like, 2J ˆ 11.7, 3J(4eq,3) ˆ 4.7, 3J(4eq,5ax) ꢀ
3J(4eq,5eq) ꢀ 4.5, HeqÀC(4)); 1.79 (X of ABX, 3J(2,HB) ˆ 4.1, 3J(2,HA) ˆ 2.1, 3J(2,3) ˆ 8.9, HÀC(2)); 1.71
2
3
3
3
1.50 (m, CH2(5)); 1.31 (m, dq-like, J ꢀ J(4ax,3) ꢀ J(4ax,5ax) ˆ 11.7, J(4ax,5eq) ˆ 2.0, HaxÀC(4)). 13C-NMR
(150.9 MHz, CDCl3): 70.4 (C(2)); 67.8 (C(3)); 59.1 (CH2OH); 56.2 (C(6)); 42.6 (MeN); 33.3 (C(4)); 23.1
(C(5)). EI-MS: 145 (<1, M ), 128 (<1, [M À OH] ), 114 (100, [M À CH2OH] ), 86 (17).
.
‡
‡
‡

Helvetica Chimica Acta Vol. 87 (2004)
2645
(Æ)-trans-3-Hydroxy-2-(hydroxymethyl)-1,1-dimethylpiperidinium Trifluoromethanesulfonate (64). Methyl
trifluoromethanesulfonate (330 ml) in CHCl3 (1 ml) was added to a soln. of 63 (303 mg) in CHCl3 (1 ml) at r.t.
(10 min) when a yellowish oil separated. After decanting the solvent and washing the residue twice with CHCl3,
drying at 508/0.05Torr gave pure 64 (640 mg, 99%). Colorless viscous oil. IR (film): 3447m (br.), 2853w, 1701w,
1485m, 1459m, 1422w, 1369w, 1252s, 1225s, 1163s, 1112m, 1187m, 1067m, 1053m, 1029s, 998w, 869w, 947m, 907w,
845w, 807w, 75 9w, 640m, 5 79w. 1H-NMR (600 MHz, (CD3)2CO): 4.34 (A of ABX, 2J ˆ 13.9, 3J ˆ 2.0, CHAOH);
4.24 4.18 (B of ABX, 2J ˆ 14, 3J ˆ 4.5, and m, not resolved, CHBOH, HÀC(3)); 3.66 (ddt, 2J ˆ 12.7,
3J(6eq,5ax) ˆ 3J(6eq,5eq) ˆ 3.8, 4J (6eq,4eq) ˆ 1.3, HeqÀC(6)); 3.60 (dt, 2J ˆ 3J(6ax,5ax) ˆ 12.4, 3J(6ax,5eq) ˆ
3.5, HaxÀC(6)); 3.47 (s, MeeqÀN); 3.31 (X of ABX, 3J(2,HB) ˆ 4.5, 3J(2,HA) ˆ 2.0, 3J(2,3) ˆ 9.5, HÀC(2)); 3.30
(s, MeaxÀN); 2.22 2.18 (m, dq-like, HeqÀC(4)); 2.15 2.09, 2.03 1.98 (2 m, CH2(5)); 1.68 (ddt, 2J ˆ 12.6,
3J(4ax,3) ˆ 3J(4ax,5ax) ˆ 10.5, 3J(4ax,5eq) ˆ 4.7, HaxÀC(4)). 13C-NMR (150.9 MHz, (CD3)2CO): 121.9 (q,
1J(C,F) ˆ 321, CÀF3SO3); 77.2 (C(2)); 66.3 (C(6)); 63.5(C(3)); 65.9 (CH 2OH); 55.8 (MeeqÀN); 47.4
.
‡
‡
(MeaxÀN); 31.8 (C(4)); 19.1 (C(5)). CI-MS: 147 (7, M ), 146 (100, [M ‡ H À Me] ).
4. Phosphorus Heterocycles 19 50, 59 62, 65, and 66 (Figs. 1 3). General Procedures. 4.1. Cyclizations. To
the soln. of the hydroxypiperidinemethanol (1 equiv.) and Et3N (2 equiv.) in anh. CH2Cl2 prepared at 08 in a
glove box under N2, the respective phosphorus reagent (1 equiv.) in anh. CH2Cl2 was added, and the mixture was
stirred at 08 (1 min to 6 h, according to the reactivity; TLC control). The volatile components were evaporated,
and the residue was dissolved in the appropriate solvent and purified by CC (SiO2, pH 5.6; see General). In most
cases, the axial epimer was eluted faster, although there were exceptions (37a,b, 39a,b, 60a,b). Yields of pure
compounds were generally ca. 20% per epimer, depending on several parameters, the most important ones
being the reactivity of the starting materials and the rate of epimerization of the products (4-nitrophenoxy <
F ꢁ 2,4-dinitrophenoxy < Cl). Therefore, both the reaction, separation, and workup times as well as the ratio
adsorbent/substance had to be optimized for each individual preparation. The axial epimers were stable when
stored as such (<08, Ar), but in soln. they slowly decomposed. Although being reasonably stable when stored as
such (<08, Ar), the equatorial epimers gradually epimerized.
4.2. Phosphorus Reagents. 4-Nitrophenyl phosphorodichloridate is commercially available (Aldrich 15,540-
3). The 2,4-dinitrophenyl phosphorodichloridate was prepared according to [24]: POCl3 (5ml), anh. NaCl
(7 mg), and 2,4-dinitrophenol were heated under reflux (ca. 1208) in a glove box under N2 (48 h). After filtration
and distilling off excess POCl3 (bulb-to-bulb), the viscous residue crystallized (1.87 g, 92%). The product
consisted of Cl2P(O)OC6H3(NO2)2 (85%, 31P-NMR (CDCl3): 5.0) and ClP(O)[OC6H3(NO2)2]2 (15%, 31P-
NMR(CDCl3): À6.5) and was not purified further.
POCl2F was prepared according to [22]: POCl3 (100 g) and dry, finely crystalline NH4F (48 g; Fluka 09737,
puriss. p.a.) were heated at 1108 for 15h in a flask fitted with a condenser. The volatile fluorinated compounds
passing through the condenser (POCl2F (b.p. 5 48) POClF2 (b.p. 38) and POF3 (b.p. À408)) were trapped at
À788. The mixture from the cold trap was fractionally distilled (Vigreux, 50 cm) to afford POCl2F as a colorless
liquid (11.6 g, 13%). B.p. 528. 31P-NMR (CDCl3): 1.80 (d, 1J(P,F) ˆ 1191). The compound was stable for a long
period when stored in the refrigerator and handled in a rigourously dry atmosphere, see also General.
4.3. N-Benzyl-N-methylammonium Trifluoromethanesulfonates 27 29, 31 33, 43 45, and 47 49. They
were prepared by adding methyl trifluoromethanesulfonate (neat, 1.1 equiv.) to the soln. of the respective N-
benzyl compound in abs. CHCl3 or MeCN in a dry flask under dry N2 and heating with a fan to homogenize (ca.
1
2 min). The mixture was stirred at r.t. until viscous yellowish drops began to separate. After completion of
the reaction (1 2 h; TLC control) the supernatant was decanted, the oily residue washed twice with the
respective solvent, evaporated, and dried at 508/0.05Torr to afford the quaternary ammonium compounds.
4.4. N,N-Dimethylammonium Trifluoromethanesulfonates 30a, 34a, 46a, and 50a. They were prepared from
the corresponding hydroxy-1-methylpiperidinemethanols 12, 16, 14, and 18, resp., via the 3-(2,4-dinitrophen-
oxy)-8- or -9-methyl-2,4-dioxa-8- or -9-aza-3-phosphabicyclo[4.4.0]decane 3-oxides (not isolated, preparation
as described above). The crude products were dissolved in CHCl3, shaken (<1 min!) with an ice-cold soln. of
sat. NaCl/2n NaOH (pH > 11) and extracted with CHCl3. The org. phase was washed with H2O to neutrality,
dried (Na2SO4), filtered, and evaporated and the residue dried at 308/0.05Torr to afford the crude free amines as
yellowish oils. The deprotonation reaction and the workup procedure must be performed as quickly as possible
since the yields strongly depended on the speed of operation. Methylation of the crude free amines as described
above afforded the N,N-dimethylammonium compounds. Special conditions had to be applied to the 7-
azaphosphadecalins as their reaction characteristics were significantly different from the 8- and 9-aza series (see
below, compounds 61 and 62). All the cationic compounds are very hygroscopic, more reactive than the free
amines, and quite tedious to handle.

2646
Helvetica Chimica Acta Vol. 87 (2004)
5. 2,4-Dioxa-9-aza-3-phosphadecalins 19 34 of Type I. (1RS,3SR,6RS)-9-Benzyl-3-fluoro-2,4-dioxa-9-aza-
3-phosphabicyclo[4.4.0]decane 3-Oxide (19a). Colorless viscous oil (34%). Rf (Et2O) 0.18. IR (CHCl3): 2951m,
2928m, 2816m, 2774m, 1952w, 1877w, 1825w, 1602w, 1495m, 1468m, 1454m, 1444m, 1334s, 1306m, 1160m, 1096s,
1072s, 1045s, 1009s, 982s, 933m, 899s, 882s, 85 8m. 1H-NMR (600 MHz, CDCl3): 7.27 7.19 (m, HÀC(2') to
HÀC(6')); 4.30 (A of ABXÀP, 2J ˆ 11.2, 3J(5eq,P)ˆ 24.3, 3J(5eq,6)ˆ 4.4, HeqÀC(5)); 4.24 (td, 3J(1,6) ˆ
3J(1,10ax) ˆ 10.9, 3J(1,10eq) ˆ 4.2, HÀC(1)); 4.10 (B of ABXÀP, 2J ˆ 3J(5ax,6) ˆ 11.2, HaxÀC(5)); 3.53, 3.51
(AB, 2J ˆ 13.1, PhCH2); 3.11 (ddd, 2J ˆ 10.5, 3J(10eq,1) ˆ 4.2, 4J(10eq,8eq) ˆ 1.5, (HeqÀC(10)); 2.85( dquint.-
3
like, 2J ˆ 11.5, 3J(8eq,7ax) ꢀ J(8eq,7eq) ˆ 4.3, 4J(8eq,10eq) ˆ 1.5, HeqÀC(8)); 2.09 (t, 2J ˆ 3J(10ax,1) ˆ 10.5,
3
HaxÀC(10)); 2.02 (ddd, 2J ˆ 11.5, 3J(8ax,7ax) ˆ 12.4, J(8ax,7eq) ˆ 4.0, HaxÀC(8)); 1.92 (X of ABXÀP, qt-like,
3
3
w1/2 ꢀ 25, HÀC(6)); 1.59 (dq, 2J ˆ 12.4, 3J(7eq,6) ꢀ J(7eq,8ax) ꢀ J(7eq,8eq) ꢀ 4, HeqÀC(7)); 1.23 (qd, 2J ˆ
3J(7ax,6) ˆ 3J(7ax,8ax) ˆ 12.4, 3J(7ax,8eq) ˆ 4.3, HaxÀC(7)). 13C-NMR (150.9 MHz, CDCl3): 137.3 (C(1'));
128.8 (C(3'), C(5')); 128.3 (C(2'), C(6')); 127.4 (C(4')); 80.6 (d, 2J(1,P) ˆ 6.4, C(1)); 73.7 (d, 2J(5,P) ˆ 7.5, C(5));
62.1 (PhCH2); 56.6 (d, 3J(10,P) ˆ 11.9, C(10)); 51.7 (C(8)); 39.6 (d, 3J(6,P) ˆ 6.3, C(6)); 24.3 (C(7)). 31P-NMR
.
‡
(121.4 MHz, CDCl3): À16.5( dd, 1J(P,F) ˆ 1008, 3J(P,HeqÀC(5)) ˆ 24.3). EI-MS: 285(7,
M
), 194 (9, [M À
‡
‡
PhCH2] ); 171 (18), 160 (23), 91 (100, PhCH2 ), 65(19). Anal. calc. for C 13H17FNO3P (285.24): C 54.75, H 6.01,
N 4.91; found: C 54.45, H 5.58, N 4.83.
(1RS,3RS,6RS)-9-Benzyl-3-fluoro-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (19b). Color-
less prisms (32%). M.p. 88 928. Rf (Et2O) 0.09. IR (CHCl3): 2950m, 2930m, 2815m, 2773m, 1952w, 1878w,
1820w, 1711w, 1602w, 1494m, 1474m, 1468m, 1454m, 1332s, 1302m, 1159m, 1103m, 1053s, 1013s, 980s, 897s, 879s.
1H-NMR (600 MHz, CDCl3): 7.36 7.24 (m, HÀC(2') to HÀC(6')); 4.50 4.37 (A of ABXÀP and m, not
resolved, HeqÀC(5), HÀC(1)); 4.21 (B of ABXÀP, 2J ˆ 3J(5ax,P) ˆ 3J(5ax,6) ˆ 10.5, 4J(5ax,F) ˆ 4.0,
HaxÀC(5)); 3.59, 3.585 (AB, 2J ˆ 13.2, PhCH2); 3.22 (ddd, 2J ˆ 10.6, 3J(10eq,1) ˆ 4.6, 4J(10eq,8eq) ˆ 1.5,
3
HeqÀC(10)); 2.91 (dquint.-like, 2J ˆ 11.6, 3J(8eq,7ax) ꢀ J(8eq,7eq) ˆ 4.0, 4J(8eq,10eq) ˆ 1.5, HeqÀC(8)); 2.15
(X of ABXÀP, qt-like, w1/2 ꢀ 25, HÀC(6)); 2.13 2.03 (m, HaxÀC(8), HaxÀC(10)); 1.70 (dq, 2J ˆ 12.3,
3
3
3J(7eq,6) ꢀ J(7eq,8ax) ꢀ J(7eq,8eq) ꢀ 4, HeqÀC(7)); 1.33 (qd, 2J ˆ 3J(7ax,6) ˆ 3J(7ax,8ax) ˆ 12.3,
3J(7ax,8eq) ˆ 4.3, HaxÀC(7)). 13C-NMR (150.9 MHz, CDCl3): 137.1 (C(1')); 128.8 (C(3'), C(5')); 128.3 (C(2'),
C(6')); 127.4 (C(4')); 80.2 (d, 2J(1,P) ˆ 5.3, C(1)); 73.6 (d, 2J(5,P) ˆ 7.2, C(5)); 62.0 (PhCH2); 56.9 (d, 3J(10,P) ˆ
3
8.9, C(10)); 51.5 (C(8)); 38.4 (d, J(6,P) ˆ 13.1, C(6)); 24.3 (C(7)). 31P-NMR (121.4 MHz, CDCl3): À15.9 (dt,
.
‡
‡
1J(P,F) ˆ 1002, 3J(P,HaxÀC(5)) ˆ 3J(P,HeqÀC(5)) ˆ 10.5). EI-MS: 285 (9, M ), 194 (5, [M À PhCH2] ), 171
‡
(11), 160 (21), 91 (100, PhCH2 ), 65(12). Anal. calc. for C 13H17FNO3P (285.24): C 54.75, H 6.01, N 4.91; found: C
54.63, H 5.88, N 5.04.
(1RS,3SR,6RS)-9-Benzyl-3-chloro-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (20a)14).
Slightly yellow oil (78%). IR (CHCl3): 3361w (br.), 2934m, 2497m, 1474m, 1469m, 1319s, 1254m, 1146m,
1095s, 1047s, 1014s, 987m, 972s, 946m, 938m, 796s, 75 3s, 697s, 5 70s, 5 5 s8, 5 25m. 1H-NMR (300 MHz, CDCl3):
7.29 7.18 (m, HÀC(2') to HÀC(6')); 4.29 (A of ABXÀP, 2J ˆ 11.3, 3J(5eq,P) ˆ 28.5, 3J(5eq,6) ˆ 4.4, HeqÀC(5));
4.28 (m, not resolved, HÀC(1)); 4.11 (B of ABXÀP, 2J ˆ 3J(5ax,6) ˆ11.3, 3J(5ax,P) ˆ 2.3, HaxÀC(5)); 3.525,
3.52 (AB, 2J ˆ 13, PhCH2); 3.09 (ddd, 2J ˆ 10.5, 3J(10eq,1) ˆ 4.5, 4J(10eq, 8eq) ˆ 1.5, HeqÀC(10)); 2.86 (dquint.-
3
like, 2J ˆ 11.5, 3J(8eq,7ax) ꢀ J(8eq,7eq) ꢀ 4.5, 4J(8eq,10eq) ˆ 1.5, HeqÀC(8)); 2.11 (t, 2J ˆ 3J(10ax,1) ˆ 10.3,
HaxÀC(10)); 2.06 1.92 (m, HÀC(6), HaxÀC(8)); 1.59 (dq, 2J ˆ 12.5, 3J(7eq,6) ˆ 4.0, 3J(7eq,8ax) ˆ
3
3
3J(7eq,8eq) ˆ 2.5, HeqÀC(7)); 1.59 (dq-like, 2J ˆ 12.5, 3J(7eq,6) ꢀ J(7eq,8ax) ꢀ J(7eq,8eq) ꢀ 4, HeqÀC(7));
1.26 (qd, 2J ˆ 3J(7ax,6) ˆ 3J(7ax,8ax) ˆ 12.5, 3J(7ax,8eq) ˆ 4.2, HaxÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 137.0
(C(1')); 128.8 (C(3'), C(5')); 128.3 (C(2'), C(6')); 127.4 (C(4')); 80.6 (d, 2J(1,P) ˆ 7.3, C(1)); 73.5( d, 2J(5,P) ˆ 8.3,
C(5)); 62.1 (PhCH2); 56.4 (d, 3J(10,P) ˆ 12.7, C(10)); 51.6 (C(8)); 39.7 (d, 3J(6,P) ˆ 6.6, C(6)); 24.2 (C(7)). 31P-
‡
NMR (161.9 MHz, CDCl3): À2.4 (d, 3J(P,HeqÀC(5)) ˆ 28.5). CI-MS: 321 (9, [M(37Cl) ‡ NH4] ), 319 (27,
‡
‡
‡
[M(35Cl) ‡ NH4] ), 304 (32, [M(37Cl) ‡ H] ), 302 (100, [M(35Cl) ‡ H] ), 244 (19), 235(20), 219 (46), 218 (85).
(1RS,3SR,6RS)-9-Benzyl-3-(4-nitrophenoxy)-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(21a). Yellow viscous oil (32%). IR (CHCl3): 3005w, 2950w, 2860w, 2815w, 1614m, 1593m, 1526s, 1493m,
1
1348s, 1304m, 1160m, 1094m, 1040s, 1008s, 978s, 934s. H-NMR (300 MHz, CDCl3): 8.25( AA' of AA'BB', J ˆ
9.2, HÀC(3'), HÀC(5')); 7.41 (BB' of AA'BB', J ˆ 9.2, HÀC(2'), HÀC(6')); 7.39 7.26 (m, HÀC(2'') to
HÀC(6'')); 4.36 (A of ABXÀP, 2J ˆ 10.9, 3J(5eq,P) ˆ 23.5, J(5eq,6) ˆ 4.4, HeqÀC(5)); 4.35 (m, not resolved,
3
14
)
There is no evidence of the presence of the equatorially substituted epimer when the phosphorylation is
performed under standard conditions. However, at low temperatures and short reaction times (<08, ca.
1 min), the product shows a concomitant, paramagnetically shifted 31P-NMR signal that can be tentatively
assigned to the equatorial epimer.

Helvetica Chimica Acta Vol. 87 (2004)
2647
2
3
HÀC(1)); 4,19 (B of ABXÀP, J ˆ 3J(5ax,6) ˆ 11.1, J(5ax,P) < 1, HaxÀC(5)); 3.59 (s, PhCH2); 3.18 (ddd, 2J ˆ
10.3, J(10eq,1) ˆ 4.5, J(10eq, 8eq) ˆ 1.5, HeqÀC(10)); 2.94 (dquint.-like, 2J ˆ 11.5, 3J(8eq,7ax) ꢀ J(8eq,7eq) ꢀ
3
4
3
4.5, 4J(8eq,10eq) ˆ 1.5, HeqÀC(8)); 2.20 (t, 2J ˆ 3J(10ax,1) ˆ 10.3, HaxÀC(10)); 2.14 1.99 (m, HÀC(6),
HaxÀC(8)); 1.68 (dq-like, 2J ˆ 12.5, 3J(7eq,6) ꢀ J(7eq,8ax) ꢀ J(7eq,8eq) ꢀ 4.5, HeqÀC(7)); 1.32 (qd, 2J ˆ
3J(7ax,6) ˆ 3J(7ax,8ax) ˆ 12.5, 3J(7ax,8eq) ˆ 4.3, HaxÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 155.4 (d,
2J(1',P) ˆ 6.1, C(1')); 144.6 (C(4')); 137.1 (C(1'')); 128.8 (C(3''), C(5'')); 128.2 (C(2''), C(6'')); 127.2 (C(4''));
125.6 (C(3'), C(5')); 120.0 (d, 3J(2' and 6',P) ˆ 5.4, C(2'), C(6')); 80.3 (d, 2J(1,P) ˆ 6.9, C(1)); 73.2 (d, 2J(5,P) ˆ
7.8, C(5)); 62.1 (PhCH2); 56.7 (d, 3J(10,P) ˆ 11.4, C(10)); 51.7 (C(8)); 39.7 (d, 3J(6,P) ˆ 6.5, C(6)); 24.2 (C(7)).
3
3
31P-NMR (161.9 MHz, CDCl3): À14.6 (br. d, 3J(P,HeqÀC(5)) ˆ 23.5). CI-MS: 405 (100, [ M ‡ H] ).
‡
(1RS,3RS,6RS)-9-Benzyl-3-(4-nitrophenoxy)-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(21b). Slightly yellow powder (25%). IR (CHCl3): 2927w, 1615m, 1594s, 1526s, 1494m, 1467w, 1348s, 1291s,
1248s, 1160s, 1098s, 1073m, 1047s, 1005s, 976s, 936s. 1H-NMR (300 MHz, CDCl3): 8.24 (AA' of AA'BB', J ˆ 9.3,
HÀC(3'), HÀC(5')); 7.37 (BB' of AA'BB', J ˆ 9.3, HÀC(2'), HÀC(6')); 7.39 7.26 (m, HÀC(2'') to HÀC(6''));
7.37 7.26 (m, HÀC(2'') to HÀC(6'')); 4.49 (tdd, 3J(1,6) ꢀ J(1,10ax) ꢀ 10, 3J(1,10eq) ˆ 4.5, 4J(1,P) ˆ 1.5,
3
HÀC(1)); 4.40 (A of ABXÀP, 2J ˆ 10.8, 3J(5eq,P) ˆ 15.5, 3J(5eq,6) ˆ 5.0, HeqÀC(5)); 4.30 (B of ABXÀP,
2J ˆ 3J(5ax,6) ˆ 10.8, 3J(5ax,P) ˆ 6.5, HaxÀC(5)); 3.62, 3.56 (AB, 2J ˆ 13.2, PhCH2); 3.21 (ddd, 2J ˆ 10.5,
3J(10eq,1) ˆ 4.5, 4J(10eq,8eq) ˆ 1.5, HeqÀC(10)); 2.92 (dquint.-like, 2J ˆ 11.5, 3J(8eq,7ax) ꢀ J(8eq,7eq) ˆ 4.0,
3
4J(8eq,10eq) ˆ 1.5, HeqÀC(8)); 2.01 2.12 (m, HÀC(6), HaxÀC(8), HaxÀC(10); 1.68 (dq-like, 2J ˆ 13.1,
3J(7eq,6) ꢀ J(7eq,8ax) ꢀ J(7eq,8eq) ꢀ 4, HeqÀC(7)); 1.35( qd, 2J ˆ 3J(7ax,6) ˆ 3J(7ax,8ax) ˆ 13.1,
3J(7ax,8eq) ˆ 4.3, HaxÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 155.2 (d, 2J(1',P) ˆ 6.2, C(1')); 144.3 (C(4'));
137.2 (C(1'')); 128.7 (C(3''), C(5'')); 128.2 (C(2''), C(6'')); 127.3 (C(4'')); 125.5 (C(3'), C(5')); 120.6 (d, 3J(2' and
6',P) ˆ 5.5, C(2'), C(6')); 79.3 (d, 2J(1,P) ˆ 65.4, C(1)); 72.9 (d, 2J(5,P) ˆ 6.8, C(5)); 62.0 (PhCH2); 56.9 (d,
3
3
3J(10,P) ˆ 10.2, C(10)); 51.7 (C(8)); 39.0 (d, J(6,P) ˆ 9.5, C(6)); 25.0 (C(7)). 31P-NMR (161.9 MHz, CDCl3):
3
3
3
‡
À12.1 (dd, J(P,HeqÀC(5)) ˆ 15.5, J(P,HaxÀC(5)) ˆ 6.5). CI-MS: 405 (100, [M ‡ H] ).
(1RS,3SR,6RS)-9-Benzyl-3-(2,4-dinitrophenoxy)-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(22a). Slightly yellow foam (29%). IR (CHCl3): 3065w, 3030w, 2927w, 2815m, 1609s, 1593m, 1541s, 1485m,
1455m, 1347s, 1318s, 1265s, 1159m, 1095m, 1070s, 1037s, 981s, 936s. 1H-NMR (300 MHz, CDCl3): 8.77 (dd,
4J(3',5') ˆ 2.8, 5J(3',6') ˆ 1.2, HÀC(3')); 8.38 (dd, 3J(5',6') ˆ 9.2, 4J(5',3') ˆ 2.8, HÀC(5')); 8.02 (d, 3J(6',5') ˆ 9.2,
5J(6',3') ˆ 1.2, HÀC(6')); 7.29 7.18 (m, HÀC(2'') to HÀC(6'')); 4.43 (td, 3J(1,6) ˆ 3J(1,10ax) ˆ 10.2, 3J(1,10eq) ˆ
4.5, HÀC(1)); 4.33 (AB of ABXÀP, 2J ꢀ J(5ax,6) ꢀ 11, 3J(5eq,P) ˆ 25, 3J(5eq,6) ꢀ 5 , CH(5)); 3.52, 3.515 (AB,
3
2
2J ˆ 13.4, PhCH2)); 3.09 (ddd, 2J ˆ 10.5, 3J(10eq,1) ˆ 5.5, 4J(10eq, 8eq) ˆ 1.3, HeqÀC(10)); 2.87 (dquint.-like,
2J ˆ 11.5, 3J(8eq,7ax) ꢀ J(8eq,7eq) ꢀ 4.5, 4J(8eq,10eq) ˆ 1.5, HeqÀC(8)); 2.11 (t, 2J ˆ 3J(10ax,1) ˆ 10.5,
3
HaxÀC(10)); 2.06 1.97 (m, HÀC(6), HaxÀC(8)); 1.62 (dq-like, 2J ˆ 13.0, 3J(7eq,6) ꢀ J(7eq,8ax) ꢀ
3
3J(7eq,8eq) ꢀ 4.5, HeqÀC(7)); 1.33 (qd, 2J ˆ 3J(7ax,6) ˆ 3J(7ax,8ax) ˆ 13.0, 3J(7ax,8eq) ˆ 4.3, HaxÀC(7)).
13C-NMR (75.4 MHz, CDCl3): 148.3 (d, 2J(1',P) ˆ 5.6, C(1')); 145.1 (C(4')); 141.9 (d, 3J(2',P) ˆ 7.5, C(2'));
3
137.2 (C(1'')); 128.9 (C(5')); 128.8 (C(2''), C(6'')); 128.3 (C(3''), C(5'')); 127.2 (C(4'')); 122.8 (d, J(6',P) ˆ 2.2,
C(6'));121.7 (C(3')); 80.9 (d, 2J(1,P) ˆ 7.0, C(1)); 73.8 (d, 2J(5,P) ˆ 7.9, C(5)); 62.1 (PhCH2); 56.8 (d, 3J(10,P) ˆ
11.6, C(10)); 51.7 (C(8)); 39.9 (d, 3J(6,P) ˆ 6.7, C(6)); 24.2 (d, 4J(7,P) ˆ 1, C(7)). 31P-NMR (161.9 MHz, CDCl3):
3
‡
À15.4 (br. d, J(P,HeqÀC(5)) ˆ 25). CI-MS: 450 (100, [ M ‡ H] ).
(1RS,3RS,6RS)-9-Benzyl-3-(2,4-dinitrophenoxy)-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(22b)15). Yellow viscous oil (ca. 10%). 31P-NMR (161.9 MHz, CDCl3): À14.7 (m, w1/2 ꢀ 35).
(1RS,3SR,6SR)-9-Benzyl-3-fluoro-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (23a). Color-
less oil (24%). Rf (Et2O) 0.13. IR (CHCl3): 2953s, 2812s, 2768s, 1955w, 1877w, 1816w, 1758w, 1601w, 1586w,
1495s, 1454s, 1444s, 1371s, 1337s, 1272s, 1168s, 1125s, 1092s, 1075s, 1026s, 981s, 881s. 1H-NMR (600 MHz, CDCl3):
7.33 7.24 (m, HÀC(2') to HÀC(6')); 4.70 (m, w1/2 ꢀ 6, HÀC(1)); 4.56 (A of ABXÀP, 2J ˆ 11.4, 3J(5ax,6) ˆ 2.5,
HaxÀC(5)); 4.27 (B of ABXÀP, 2J ˆ 11.4, 3J(5eq,P) ˆ 24.8, 3J(5eq,6) ˆ 1.2, HeqÀC(5)); 3.58, 3.55 (AB, 2J ˆ 13.5,
PhCH2); 3.18 (dt, 2J ˆ 13.0, 3J(10eq,1) ˆ 4J(10eq,8eq) ˆ 2.1, HeqÀC(10)); 3.00 (dquint.-like, 2J ˆ 12,
3J(8eq,7ax) ꢀ J(8eq,7eq) ꢀ 4.5, J(8eq,10eq) ˆ 2.1, HeqÀC(8)); 2.29 (qd, J ˆ 3J(7ax,8ax) ˆ 12.0, J(7ax,8eq) ˆ
3
4
2
3
4.3, HaxÀC(7)); 2.26 (ddd, J ˆ 13.0, J(10ax,1) ˆ 1.8, J(10ax,P) ˆ 5.9, HaxÀC(10)); 2.12 (td, J ˆ 3J(8ax,7ax) ˆ
2
3
4
2
11.7, 3J(8ax,7eq) ˆ 2.4, HaxÀC(8)); 1.77 (X of ABXÀP, dquint.-like, w1/2 ꢀ 25, HÀC(6)); 1.56 (m, dq-like, w1/2
ꢀ
25, HeqÀC(7)). 13C-NMR (150.9 MHz, CDCl3): 137.5(C(1 ')); 128.7 (C(3'), C(5')); 128.2 (C(2'), C(6')); 127.1
15
)
The formation of the minor, equatorially substituted P-epimer is evidenced by TLC. Due to epimerization
during workup, it was characterized only in the mixture by 31P-NMR and its amount estimated from the
relative intensities of the signals.

2648
Helvetica Chimica Acta Vol. 87 (2004)
2
3
(C(4')); 78.5( d, 2J(1,P) ˆ 7.2, C(1)); 73.1 (d, J(5,P) ˆ 7.1, C(5)); 61.9 (PhCH2); 56.4 (d, J(9,P) ˆ 9.1, C(10));
51.7 (C(8)); 34.3 (d, 3J(6,P) ˆ 5.6, C(6)); 22.8 (C(7)). 31P-NMR (121.4 MHz, CDCl3): À16.5( ddd, 1J(P,F) ˆ
.
3
4
‡
‡
1006, J(P,HeqÀC(5)) ˆ 24.8, J(P,HaxÀC(10)) ˆ 5.9). EI-MS: 285 (14, M ), 194 (4, [M À PhCH2] ), 160 (65),
‡
147 (22), 118 (22), 91 (100, PhCH2 ), 80 (22). Anal. calc. for C13H17FNO3P (285.24): C 54.75, H 6.01, N 4.91;
found: C 54.98, H 6.32, N 5.24.
(1RS,3RS,6SR)-9-Benzyl-3-fluoro-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (23b). Color-
less plates (55%). M.p. 95 988. Rf (Et2O) 0.07. IR (CHCl3): 2953s, 2930s, 2813s, 2787s, 2768s, 1954w, 1876w,
1
1816w, 1737w, 1602w, 1586w, 1495m, 1454s, 1443s, 1370s, 1329s, 1093s, 1076s, 1012s, 984s, 949s, 886s. H-NMR
(600 MHz, CDCl3): 7.36 7.24 (m, HÀC(2') to HÀC(6')); 4.80 (m, w1/2 ꢀ 30, HÀC(1)); 4.53 (A of ABXÀP, 2J ˆ
11.4, 3J(5ax,P) ˆ 16.4, 3J(5ax,6) ˆ 3.5, HaxÀC(5)); 4.39 (B of ABXÀP, 2J ˆ 11.4, 3J(5eq,P) ˆ 16.4, 3J(5eq,6) ˆ
2
2
4.8, HeqÀC(5)); 3.58 (s, PhCH2); 2.84 (m, dt-like, J ˆ 11.8, HeqÀC(8)); 2.70 (m, td-like, J ˆ 11.8, HeqÀC(8));
2.44 (m, w1/2 ꢀ 20, CH2(10)); 2.30 (X of ABXÀP, m, w1/2 ꢀ 30, HÀC(6)); 1.82 (m, q-like, w1/2 ꢀ 15, CH2(7)).
13C-NMR (150.9 MHz, CDCl3): 137.2 (C(1')); 128.7 (C(3'), C(5')); 128.3 (C(2'), C(6')); 127.3 (C(4')); 79.2
(2J(1,P) ˆ 7.7, C(1)); 69.7 (d, 2J(5,P) ˆ 6.4, C(5)); 62.2 (PhCH2); 53.6 (C(10)); 49.3 (C(8)); 32.8 (d, 3J(6,P) ˆ 8.1,
C(6)); 24.3 (C(7)). 31P-NMR (121.4 MHz, CDCl3): À16.9 (dtd, 1J(P,F) ˆ 997, 3J(P,HeqÀC(5)) ˆ
.
‡
‡
3J(P,HaxÀC(5) ˆ 16.4, 3J(P,1) ˆ 7.5). EI-MS: 285 (7, M ); 194 (8, [M À PhCH2] ), 171 (13), 160 (25), 91
.
‡
‡
‡
(100, PhCH2 ), 65(14). EI-MS: 285(16,
M
), 194 (24, [M À PhCH2] ), 160 (48), 147 (19), 118 (25), 91 (100,
‡
PhCH2 ), 80 (29). Anal. calc. for C13H17FNO3P (285.24): C 54.75, H 6.01, N 4.91; found: C 54.52, H 5.81, N 4.69.
(1RS,3SR,6SR)-9-Benzyl-3-chloro-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (24a)14). Col-
orless oil (80%). IR (CHCl3): 3420w (br.), 2991m, 2901m, 2501m, 1496w, 1449m, 1412s, 1304s, 1250m, 1229m,
1205m, 1103s, 1069s, 994s, 968s, 932w, 814m, 777s, 742m, 725m, 700s, 669s, 5 71s, 5 40s. 1H-NMR (300 MHz,
CDCl3): 7.26 7.17 (m, HÀC(2') to HÀC(6')); 4.64 (q-like, w1/2 ꢀ 6, HÀC(1)); 4.52 (A of ABXÀP, 2J ˆ 11.0,
3J(5ax,6) ˆ 2.5, 3J(5ax,P) ꢀ 3, HaxÀC(5)); 4.18 (B of ABXÀP, 2J ˆ 11.0, 3J(5eq,P) ˆ 29.8, 3J(5eq,6) ˆ 1.5,
HeqÀC(5)); 3.52, 3.44 (AB, 2J ˆ 13.5, PhCH2); 3.09 (dt-like, 2J ˆ 13.1, 3J(10eq,1) ꢀ J(10eq,8eq) ꢀ 2, HeqÀC(10));
4
2.92 (dquint.-like, 2J ˆ 11.0, 3J(8eq,7ax) ꢀ J(8eq,7eq) ꢀ 3.5, 4J(8eq,10eq) ꢀ 2, HeqÀC(8)); 2.28 2.15( m,
3
2
3
HaxÀC(7), HaxÀC(10)); 2.04 (td, J ˆ 3J(8ax,7ax) ˆ 11.0, J(8ax,7eq) ˆ 2.5, HaxÀC(8)); 1.71 (X of ABXÀP, d-
like, w1/2 ꢀ 20, HÀC(6)); 1.49 (m, dsext.-like, w1/2 ꢀ 20, HeqÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 137.5(C(1 '));
128.6 (C(3'), C(5')); 128.1 (C(2'), C(6')); 127.0 (C(4')); 78.7 (d, 2J(1,P) ˆ 8.3, C(1)); 73.2 (d, 2J(4,P) ˆ 7.6, C(5));
61.8 (PhCH2); 56.3 (d, J(10,P) ˆ 9.9, C(10)); 51.8 (C(8)); 34.3 (d, J(6,P) ˆ 5.8, C(6)); 23.1 (C(7)). 31P-NMR
3
3
(161.9 MHz, CDCl3): À2.6 (d, 3J(P,HeqÀC(5)) ˆ 29.8). CI-MS: 304 (34, [M(37Cl) ‡ H] ); 302 (100, [M(35Cl) ‡
‡
‡
H] ).
(1RS,3SR,6SR)-9-Benzyl-3-(4-nitrophenoxy)-2,4-dioxa-9-aza-3-phospha-bicyclo[4.4.0]decane 3-Oxide
(25a). Yellow foam (41%). IR (CHCl3): 2952w, 2916w, 2811w, 2765w, 1615w, 1594m, 1525s, 1493s, 1348s,
1311s, 1110s, 1093m, 1075m, 1043m, 1026m, 1005s, 988s, 926s. 1H-NMR (300 MHz, CDCl3): 8.23 (AA' of
AA'BB', J ˆ 9.1, HÀC(3'), HÀC(5')); 7.40 (BB' of AA'BB', J ˆ 9.1, HÀC(2'), HÀC(6')); 7.42 7.22 (m,
HÀC(2'') to HÀC(6'')); 4.75( s, w1/2 ꢀ 6, HÀC(1)); 4.59 (A of ABXÀP, 2J ˆ 11.4, 3J(5ax,6) ˆ 2.5, 3J(5ax,P) ˆ 1.5,
HaxÀC(5)); 4.28 (B of ABXÀP, 2J ˆ 11.4, 3J(5eq,P) ˆ 24.5, 3J(5eq,6) ˆ 1.2, HeqÀC(5)); 3.60, 3.56 (AB, 2J ˆ 13.5,
4
PhCH2); 3.18 (dt-like, 2J ˆ 13.0, 3J(10eq,1) ꢀ J(10eq,8eq) ꢀ 2, HeqÀC(10)); 3.01 (dquint.-like, 2J ˆ 11.5,
3
3J(8eq,7ax) ꢀ J(8eq,7eq) ꢀ 3.5, 4J(8eq,10eq) ꢀ 2, HeqÀC(8)); 2.36 (qd, 2J ˆ 3J(7ax,6) ˆ 3J(7ax,8ax) ˆ 11.8,
3J(7ax,8eq) ˆ 4.0, HaxÀC(7)); 2.27 (ddd, 2J ˆ 13.0, 3J(10ax,1) ˆ 1.8, 4J(10ax,P) ˆ 7.0, HaxÀC(10)); 2.12 (td,
2J ˆ 3J(8ax,7ax) ˆ 11.8, 3J(8ax,7eq) ˆ 2.4, HaxÀC(8)); 1.79 (X of ABXÀP, m, w1/2 ꢀ 20, HÀC(6)); 1.58 (m, d-like,
w1/2 ꢀ 20, HeqÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 155.5 (d, 2J(1',P) ˆ 6.0, C(1')); 144.3 (C(4')); 137.4 (C(1''));
128.7 (C(3''), C(5'')); 128.2 (C(2''), C(6'')); 127.0 (C(4'')); 125.6 (C(3'), C(5')); 120.0 (d, 3J(2' and 6',P) ˆ 5.5,
C(2'), C(6')); 78.1 (d, 2J(1,P) ˆ 7.6, C(1)); 72.7 (d, 2J(5,P) ˆ 7.2, C(5)); 61.9 (PhCH2); 56.5 (d, 3J(10,P) ˆ 8.9,
C(10)); 51.7 (C(8)); 34.3 (d, 3J(6,P) ˆ 5.7, C(6)); 22.9 (C(7)). 31P-NMR (161.9 MHz, CDCl3): À14.5( dd,
3
‡
3J(P,HeqÀC(5)) ˆ 24.5, J(P,HaxÀC(10)) ˆ 7.0). CI-MS: 405(100, [ M ‡ H] ).
(1RS,3RS,6SR)-9-Benzyl-3-(4-nitrophenoxy)-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(25b). Slightly brown viscous oil (31%). IR (CHCl3): 3080w, 2953w, 2919w, 2813w, 1613s, 1526s, 1493s, 1349s,
1286s, 1248m, 1165m, 1110m, 1092m, 1072s, 1051m, 1027m, 1003s, 984s, 95 1s, 930s. 1H-NMR (300 MHz, CDCl3):
8.24 (AA' of AA'BB', J ˆ 9.0, HÀC(3'), HÀC(5')); 7.47 (BB' of AA'BB', J ˆ 9.0, HÀC(2'), HÀC(6')); 7.37 7.25
(m, HÀC(2'') to HÀC(6'')); 4,87 (sept.-like, 3J(1,6) ꢀ J(1,10ax) ꢀ J(1,10eq) ꢀ 3, 3J(1,P) ꢀ 2.5, HÀC(1)); 4.60
(A of ABXÀP, 2J ˆ11.6, 3J(5ax,P) ˆ 8.6, 3J(5ax,6) ˆ 3.5, HaxÀC(5)); 4.31 (B of ABXÀP, 2J ˆ 11.6, 3J(5eq,P) ˆ
16.7, 3J(5eq,6) ˆ 4.7, HeqÀC(5)); 3.57, 3.51 (AB, 2J ˆ 13.2, PhCH2); 3.03 (dd, 2J ˆ 12.3, 3J(10eq,1) ˆ 5.3,
HeqÀC(10)); 2.61 (m, w1/2 ꢀ 20, HaxÀC(10)); 2.51 (ddd, 2J ˆ 12.4, 3J(8eq,7ax) ˆ 4.6, 3J(8eq,7eq) ˆ 3.0,
HeqÀC(8)); 2.19 (ddd, 2J ˆ 12.0, 3J(8ax,7ax) ˆ 9.5, 3J(8ax,7eq) ˆ 3.5, HaxÀC(8)); 2.05( X of ABXÀP, m,
3
3
w1/2 ꢀ 25, HÀC(6)); 1.76 (dddd, 2J ˆ 13.5, 3J(7ax,6) ꢀ J(7ax,8ax) ˆ 9.5, 3J(7ax,8eq) ˆ 4.0, HaxÀC(7)); 1.61 1.88
3

Helvetica Chimica Acta Vol. 87 (2004)
2649
(m, HeqÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 156.1 (d, 2J(1',P) ˆ 5.8, C(1')); 143.2 (C(4')); 137.4 (C(1'')); 128.6
3
(C(3''), C(5'')); 128.2 (C(2''), C(6'')); 127.3 (C(4'')); 125.4 (C(3'), C(5')); 120.1 (d, J(2' and 6',P) ˆ 5.3, C(2'),
2
2
3
C(6')); 77.6 (d, J(1,P) ˆ 6.6, C(1)); 70.6 (d, J(5,P) ˆ 5.8, C(5)); 62.1 (PhCH2); 55.7 (d, J(10,P) ˆ 5.8, C(10));
50.5 (C(8)); 33.7 (d, 3J(6,P) ˆ 6.2, C(6)); 23.7 (C(7)). 31P-NMR (161.9 MHz, CDCl3): À12.5( m, w1/2 ˆ 32). CI-
‡
MS: 405(100, [ M ‡ H] ).
(1RS,3SR,6SR)-9-Benzyl-3-(2,4-dinitrophenoxy)-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(26a). Slightly yellow powder (35%). IR (CHCl3): 2927w, 2854w, 2812w, 1609s, 1541s, 1485m, 1455m, 1347s,
1316s, 1270m, 1091m, 1069m, 1007s, 983m, 935s. 1H-NMR (300 MHz, CDCl3): 8.75( dd, 4J(3',5') ˆ 2.8, 5J(3',6') ˆ
1.2, HÀC(3')); 8.39 (dd, 3J(5',6') ˆ 9.2, 4J(5',3') ˆ 2.8, HÀC(5')); 8.10 (dd, 3J(6',5') ˆ 9.2, 5J(6',3') ˆ 1.2,
HÀC(6')); 7.28 7.18 (m, HÀC(2'') to HÀC(6'')); 4.80 (s, w1/2 ꢀ 6, HÀC(1)); 4.68 (A of ABXÀP, 2J ˆ 11.3,
3J(5ax,6)ˆ 2.4, 3J(5ax,P)ꢀ 1, HaxÀC(5)); 4.21 (B of ABXÀP, 2J ˆ 11.3, 3J(5eq,P)ˆ 25, 3J(5eq,6) ꢀ 1,
HeqÀC(5)); 3.53, 3.47 (AB, 2J ˆ 13.4, PhCH2); 3.08 (dt-like, 2J ˆ 13.0, 3J(10eq,1) ꢀ J(10eq,8eq) ꢀ 2, HeqÀC(10));
4
2.96 (dquint.-like, 2J ˆ 11.5, 3J(8eq,7ax) ꢀ J(8eq,7eq) ꢀ 3.5, 4J(8eq,10eq) ꢀ 2, HeqÀC(8)); 2.27 (qd, 2J ˆ
3
3J(7ax,6) ˆ 3J(7ax,8ax) ˆ 12.8, 3J(7ax,8eq) ˆ 4.0, HaxÀC(7)); 2.27 (ddd, 2J ˆ 13.0, 3J(10ax,1) ˆ 1.8,
4J(10ax,P) ˆ 7, HaxÀC(10)); 2.06 (td, 2J ˆ 3J(8ax,7ax) ˆ 11.5, 3J(8ax,7eq) ˆ 2.5, HaxÀC(8)); 1.77 (X of ABXÀP,
d-like, w1/2 ꢀ 20, HÀC(6)); 1.52 (m, d-like, w1/2 ꢀ 20, HeqÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 148.2 (d,
2J(1',P) ˆ 5.1, C(1')); 144.8 (C(4')), 141.9 (br., C(2')); 137.4 (C(1'')); 129.0 (C(5')); 128.7 (C(2''), C(6'')); 128.2
(C(3''), C(5'')); 127.1 (C(4'')); 122.7 (d, 3J(6',P) ˆ 2.3, C(6')); 121.5(C(3 ')); 78.7 (d, 2J(1,P) ˆ 7.7, C(1)); 73.3 (d,
2J(5,P) ˆ 7.2, C(5)); 61.8 (PhCH2); 56.3 (d, 3J(10,P) ˆ 9.0, C(10)); 51.6 (C(8)); 34.3 (d, 3J(6,P) ˆ 5.7, C(6)); 22.8
(C(7)). 31P-NMR (161.9 MHz, CDCl3): À15.5 (dd, 3J(P,HeqÀC(5)) ˆ 25, 3J(P,HaxÀC(10)) ˆ 7). CI-MS: 450
‡
(100, [M ‡ H] ), 289 (93), 243 (15), 222 (27), 204 (47), 186 (40).
(1RS,3RS,6SR)-9-Benzyl-3-(2,4-dinitrophenoxy)-2,4-dioxa-9-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(26b)15). Yellow viscous oil (ca. 15%). 31P-NMR (161.9 MHz, CDCl3): À15.0 (m, w1/2 ꢀ 35).
(1RS,3SR,6RS,9RS)-9-Benzyl-3-chloro-9-methyl-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]decane 3-Ox-
ide Trifluoromethanesulfonate (27a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 2 :1). White powder
(40%). H-NMR (300 MHz, (CD3)2SO)16): 7.73 7.58 (m, HÀC(2') to HÀC(6')); 5.27 5.15 (m, not resolved,
1
HÀC(1)); 4.96 (br. s, PhCH2); 4.72 4,62 (AB of ABXÀP, not resolved, CH2(5)); 3.90 3.86 (m, CH2(8),
CH2(10)); 3.44 (s, MeaxÀN); 3.37 (s, MeeqÀN); 2.80 1.83 (m, HÀC(6), CH2(7)). 31P-NMR (121.4 MHz,
(CD3)2SO): À3.3 (d, 3J(P,HeqÀC(5)) ˆ 30). ESI-MS: 318 (33, [M(37Cl) À CF3SO3] ), 316 (100, [M(35Cl) À
‡
‡
CF3SO3] ).
(1RS,3SR,6RS,9RS)-9-Benzyl-9-methyl-3-(4-nitrophenoxy)-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (28a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 5 :1).
White foam (56%). 1H-NMR (300 MHz, (CD3)2CO)16): 8.27 (AA' of AA'BB', J ˆ 9.2, HÀC(3'), HÀC(5')); 7.72
(BB' of AA'BB', J ˆ 9.2, HÀC(2'), HÀC(6')); 7.58 7.46 (m, HÀC(2'') to HÀC(6'')); 5.32 (td, 3J(1,6) ˆ
3J(1,10eq) ˆ 10.9, 3J(1,10eq) ˆ 4.6, HÀC(1)); 4.98 (s, PhCH2, (B)); 4.93 (s, PhCH2, (A)); 4.74 4.55 (AB of
ABXÀP, not resolved, CH2(5)); 3.99 3.78 (m, CH2(8), CH2(10)); 3.39 (s, MeaxÀN); 3.33 (s, MeeqÀN); 2.62 (X
of ABXÀP, oct.-like, w1/2 ꢀ 20, HÀC(6)); 2.25 2.17 ( m, CH2(7)). 31P-NMR (121.4 MHz, (CD3)2CO): À14.3 (d,
‡
3J(P,HeqÀC(5)) ˆ 22.5). ESI-MS: 419 (100, [M À CF3SO3] ).
(1RS,3RS,6RS,9RS)-9-Benzyl-9-methyl-3-(4-nitrophenoxy)-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (28b). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 4 :1).
Yellow viscous oil (27%). 1H-NMR (300 MHz, (CD3)2CO)16): 8.32 (AA' of AA'BB', J ˆ 8.8, HÀC(3'),
HÀC(5')); 7.73 (BB' of AA'BB', J ˆ 8.8, HÀC(2'), HÀC(6')); 7.60 7.54 (m, HÀC(2'') to HÀC(6'')); 5.27 (td,
3J(1,6) ˆ 3J(1,10eq) ˆ 11.0, 3J(1,10eq) ˆ 4.7, HÀC(1)); 5.01 (s, PhCH2 (B)); 4.95( s, PhCH2 (A)); 4.85 4.53 ( AB
of ABXÀP, CH2(5)); 4.05 3.92 (m, CH2(8), CH2(10)); 3.42 (s, MeaxÀN); 3.34 (s, MeeqÀN); 2.87 (X of ABXÀP,
oct.-like, w1/2 ꢀ 30, HÀC(6)); 2.31 2.09 (m, CH2(7)). 31P-NMR (121.4 MHz, (CD3)2CO): À12.9 (A), À13.0 (B)
3
3
‡
(each t-like, J(P,HeqÀC(5)) ꢀ J(P,HaxÀC(5)) ꢀ 10). ESI-MS: 419 (100, [M À CF3SO3] ).
(1RS,3SR,6RS,9RS)-9-Benzyl-3-(2,4-dinitrophenoxy)-9-methyl-2,4-dioxa-9-azonia-3-phosphabicyclo-
[4.4.0]decane 3-Oxide Trifluoromethanesulfonate (29a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca.
3 :1). White foam (92%). IR (KBr): 3500w, 1725w, 1710w, 1691w, 1658w, 1641w, 1611m, 1546m, 1536m, 1483m,
1441m, 1350m, 1262s, 1165m, 1053m, 1030s, 939m, 906m, 835m. H-NMR (300 MHz, (CD3)2CO)16): 8.88 (dd,
1
4J(3',5') ˆ 2.9, 5J(3',6') ˆ 1.0, HÀC(3')); 8.62 (dd, 3J(5',6') ˆ 9.2, 4J(5',3') ˆ 2.9, HÀC(5')); 7.97 (dd, 3J(6',5') ˆ 9.2,
16
)
For reasons of simplicity, the chemical shifts are given for the predominant epimer A, and only the MeN
groups are specified. The epimer B exhibits paramagnetic shifts of the respective H-atoms (ca. 0.1
0.3 ppm)).

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Helvetica Chimica Acta Vol. 87 (2004)
5J(6',3') ˆ 1.0, HÀC(6')); 7.77 7.54 (m, HÀC(2'') to HÀC(6'')); 5.37 (td, 3J(1,6) ˆ 3J(1,10ax) ˆ 10.8, 3J(1,10eq) ˆ
4.8, HÀC(1)); 4.98 (s, PhCH2)); 4.80 4.71 (AB of ABXÀP, not resolved, CH2(5)); 4.05 3.81 (m, CH2(8),
CH2(10)); 3.39 (s, MeaxÀN); 3.37 (s, MeeqÀN); 2.73 (X of ABXÀP, oct.-like, w1/2 ꢀ 30, HÀC(6)); 2.31 2.06 (m,
CH2(7)). 13C-NMR (75.4 MHz, CDCl3): epimer A: 148.3 (d, 2J(1',P) ˆ 5.6, C(1')); 145.1 (C(4'); 141.9 (d,
3J(2',P) ˆ 7.5, C(2')); 134.5(C(2 ''), C(6'')); 131.9 (C(4'')); 130.4 (C(5')); 130.2 (C(3''), C(5'')); 127.7 (C(1'')); 124.6
3
1
2
(d, J(6',P) ˆ 2.5, C(6')); 122.8 (C(3')); 122.1 (q, J(C,F) ˆ 320, CF3SO3); 75.7 (d, J(1,P) ˆ 6.4, C(1)); 74.0 (d,
2J(5,P) ˆ 7.5, C(5)); 73.1 (PhCH2); 61.0 (C(8)); 60.6 (d, J(10,P) ˆ 8.9, C(10)); 46.7 (MeN); 38.9 (d, J(6,P) ˆ
3
3
2
3
6.4, C(6)); 20.1 (C(7)); epimer B: 148.3 (d, J(1',P) ˆ 5.6, C(1')); 145.1 (C(4')); 141.9 (d, J(2',P) ˆ 7.5, C(2'));
3
134.0 (C(2''), C(6'')); 132.0 (C(4'')); 130.5(C(3 ''), C(5'')); 130.4 (C(5')); 128.0 (C(1'')); 124.6 (d, J(6',P) ˆ 2.5,
C(6')); 122.9 (C(3')); 122.1 (q, 1J(C,F) ˆ 320, CF3SO3); 75.0 (d, 2J(1,P) ˆ 6.7, C(1)); 74.1 (d, 2J(5,P) ˆ 7.1, C(5));
73.1 (PhCH2); 63.6 (C(8)); 60.7 (d, 3J(10,P) ˆ 9.5, C(10)); 53.7 (MeN); 38.8 (d, 3J(6,P) ˆ 6.8, C(6)); 20.3 (C(7)).
31P-NMR (121.4 MHz, (CD3)2CO): À15.0 (A), À15.1 (B) (each d, 3J(P,HeqÀC(5)) ˆ 27.0). ESI-MS: 464 (100,
‡
[M À CF3SO3] ). Anal. calc. for C15H19F3N3O11PS ¥ 2 H2O (573.36): C 31.40, H 4.04, N 7.33; found: C 31.28,
H 4.35, N 7.68.
(1RS,3SR,6RS)-3-(2,4-Dinitrophenoxy)-9,9-dimethyl-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]decane 3-
Oxide Trifluoromethanesulfonate (30a). White foam (90%). IR (CHCl3): 1H-NMR (300 MHz, (CD3)2CO): 8.90
(d, 4J(3',5') ˆ 3.0, HÀC(3')); 8.67 (dd, 3J(5',6') ˆ 9.2, 4J(5',3') ˆ 3.0, HÀC(5')); 7.99 (d, 3J(6',5') ˆ 9.2, HÀC(6'));
5.37 (td, 3J(1,6) ˆ 3J(1,10ax) ˆ 11.1, 3J(1,10eq) ˆ 4.5, HÀC(1)); 4.82 4.64 (AB of ABXÀP, not resolved,
CH2(5)); 3.95 3.75 ( m, CH2(8), CH2(10)); 3.58 (s, MeaxÀN); 3.51 (s, MeeqÀN); 2.69 (X of ABXÀP, oct.-like,
w1/2 ꢀ 30, HÀC(6)); 2.29 2.17 (m, CH2(7)). 13C-NMR (75.4 MHz, CDCl3): 147.2 (d, 2J(1',P) ˆ 5.9, C(1')); 144.1
(C(4')); 140.9 (m, w1/2 ꢀ 6, C(2')); 129.4 (C(5')); 123.6 (d, 3J(6',P) ˆ 2.5, C(6')); 121.8 (C(3')); 121.0 (q, 1J(C,F) ˆ
2
2
3
321, CF3SO3); 74.4 (d, J(1,P) ˆ 5.9, C(1)); 73.0 (d, J(5,P) ˆ 7.9, C(5)); 61.8 (br. d, J(10,P) ꢀ 10, C(10)); 61.7
(C(8)); 56.6 (MeaxÀN); 48.0 (MeeqÀN); 37.6 (d, 3J(6,P) ˆ 6.4, C(6)); 19.3 (C(7)). 31P-NMR (121.4 MHz,
(CD3)2CO): À15.0 (br. d, 3J(P,HeqÀC(5)) ꢀ 25). ESI-MS: 388 (100, [M À CF3SO3] ). Anal. calc. for
‡
C21H23F3N3O11PS ¥ H2O (631.44): C 39.94, H 3.39, N 6.65; found: C 40.12, H 3.65, N 6.53.
(1RS,3RS,6RS)-3-(2,4-Dinitrophenoxy)-9,9-dimethyl-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]decane 3-
3
Oxide Trifluoromethanesulfonate (30b)17). 31P-NMR (121.4 MHz, CDCl3): À14.0 (t-like, J(P,H) ꢀ 11).
(1RS,3SR,6SR,9SR)-9-Benzyl-3-chloro-9-methyl-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]decane 3-Ox-
ide Trifluoromethanesulfonate (31a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 3 :1). White powder
(50%). 1H-NMR (300 MHz, (CD3)2SO)16): 7.61 7.48 (m, HÀC(2') to HÀC(6')); 4.91 (s, w1/2 ꢀ 8, HÀC(1));
4.65, 4.64 (AB, 2J ˆ 12.6, PhCH2); 4.40, 4.12 (AB of ABXÀP, CH2(5)); 3.77 3.33 (m, CH2(8), CH2(10)); 3.08 (s,
MeaxÀN); 2.91 (s, MeeqÀN); 2.23 1.82 (m, HÀC(6), CH2(7). 13C-NMR (75.4 MHz, (CD3)2SO): epimer A:
133.7 (C(3'), C(5')); 130.8 (C(4')); 129.3 (C(2'), C(6')); 127.4 (C(1')); 120.0 (q, 1J(C,F) ˆ 322, CF3SO3); 73.5( d,
2J(1,P) ˆ 5.5 C(1)); 71.0 (PhCH2); 70.0 (d, 2J(5,P) ˆ 6.1, C(5)); 62.0 (d, 3J(10,P) ˆ 8.8, C(10)); 58.6 (C(8)); 47.3
(MeN); 31.5( d, 3J(6,P) ˆ 4.2, C(6)); 18.1 (C(7)); epimer B: 133.7 (C(3'), C(5')); 130.8 (C(4')); 129.3 (C(2'),
C(6')); 127.4 (C(1')); 120.0 (q, 1J(C,F) ˆ 322, CF3SO3); 73.2 (d, 2J(1,P) ˆ 6.2, C(1)); 70.3 (d, 2J(5,P) ˆ 6.2, C(5));
63.4 (PhCH2); 60.7 (d, 3J(10,P) ˆ 8.2, C(10)); 59.6 (C(8)); 52.3 (MeN); 31.7 (d, 3J(6,P) ˆ 4.3, C(6)); 20.3 (C(7)).
31P-NMR (121.4 MHz, (CD3)2SO): À7.5(A ) , À7.2 (B) (each d, 3J(P,HeqÀC(5)) ꢀ 24). ESI-MS: 318 (29,
‡
‡
[M(37Cl) À CF3SO3] ), 316 (100, [M(35Cl) À CF3SO3] ).
(1RS,3SR,6SR,9SR)-9-Benzyl-9-methyl-3-(4-nitrophenoxy)-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (32a). N-Epimer B (Meeq) not detectable. Slightly yellow pasty foam
(53%). IR (KBr): 2961w, 1614m, 1589s, 1531s, 1487s, 1462m, 1348s, 1315s, 1280s, 1226s, 1192m, 1151s, 1116m,
1070m, 1031s, 1007s, 982s, 970s, 934s, 866m, 840m, 812m, 787m, 771m, 75 8m, 743m, 727m, 706m, 671w, 639s.
1H-NMR (300 MHz, (CD3)2CO): 8.30 (AA' of AA'BB', J ˆ 9.3, HÀC(3'), HÀC(5')); 7.60 (BB' of AA'BB', J ˆ
9.3, HÀC(2'), HÀC(6')); 7.61 7.50 (m, HÀC(2'') to HÀC(6'')); 5.52 (s, w1/2 ꢀ 6, HÀC(1)); 4.96 (A of ABXÀP,
3
2J ˆ 12.0, 3J(5ax,6) ꢀ J(5ax,P) ꢀ 1, HaxÀC(5)); 4.87, 4.86 (AB, 2J ˆ 13.0, PhCH2); 4.56 (B of ABXÀP, 2J ˆ 12.0,
3J(5ax,P) ˆ 25.5, HeqÀC(5)); 4.16 (m, d-like, w1/2 ꢀ 20, HeqÀC(10)); 4.03 3.92 (m, HeqÀC(8), HaxÀC(10)); 3.82
(br. d, 2J ˆ 12.8, w1/2 ꢀ 15, HaxÀC(8)); 3.39 (s, MeN); 2.70 2.55 (m, HÀC(6), HeqÀC(7)); 2.22 (m, d-like, w1/2
ꢀ
20, HaxÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 155.6 (d, 2J(1',P) ˆ 6.2, C(1')); 145.6 (C(4')); 134.1 (C(3''),
C(5'')); 131.4 (C(4'')); 129.7 (C(2''), C(6'')); 127.4 (C(1'')); 126.3 (C(3'), C(5')); 126.9 (q, 1J(C,F) ˆ 322, CF3SO3);
121.3 (d, 3J(2' and 6',P) ˆ 5.5, C(2'), C(6')); 77.0 (d, 2J(1,P) ˆ 6.8, C(1)); 72.95( d, 2J(5,P) ˆ 7.2, C(5)); 72.9
The formation of the minor, equatorially substituted P-epimer is evidenced by 31P-NMR of the crude
reaction mixture and its amount estimated from the relative intensity of the signals (ca. 1:2). Due to fast
epimerization, it could not be isolated.
17
)

Helvetica Chimica Acta Vol. 87 (2004)
2651
(PhCH2); 62.3 (br. d, 3J(10,P) ꢀ 10, C(10)); 60.0 (C(8)); 48.0 (MeN); 32.1 (d, 3J(6,P) ˆ 5.2, C(6)); 18.6 (C(7)).
‡
31P-NMR (121.4 MHz, (CD3)2CO): À15.2 (d, 3J(P,HeqÀC(5)) ˆ 25.5). ESI-MS: 419 (100, [M À CF3SO3] ).
(1RS,3RS,6SR,9SR)-9-Benzyl-9-methyl-3-(4-nitrophenoxy)-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (32b). N-Epimer B (Meeq) not detectable. Yellow viscous oil (28%).
1H-NMR (300 MHz, (CD3)2CO)18): 8.30 (AA' of AA'BB', J ˆ 9.1 HÀC(3'), HÀC(5')); 7.67 7.48 (m, HÀC(2'),
HÀC(6'), HÀC(2'') to HÀC(6'')); 5.48 (s, w1/2 ꢀ 6, HÀC(1)); 4.96 (A of ABXÀP, not resolved, HaxÀC(5)); 4.82,
3
4.81 (AB, 2J ˆ 12.8, PhCH2); 4.60 (B of ABXÀP, 2J ˆ 12.0, J(5eq,P) ˆ 20.5, HeqÀC(5)); 4.13 (m, d-like, w1/2
ꢀ
20, HeqÀC(10)); 3.98 3.82 (m, HeqÀC(8), HaxÀC(10)); 3.82 (br. d, 2J ˆ 12.8, w1/2 ꢀ 20, HaxÀC(8)); 3.18 (s,
MeN); 2.61 (m, d-like, w1/2 ꢀ 20, HeqÀC(7)); 2.34 (X of ABXÀP, m, w1/2 ꢀ 30, HÀC(6)); 2.23 (m, t-like, w1/2 ꢀ 30,
HaxÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 154.7 (d, J(1',P) ˆ 6.2, C(1')); 145.3 (C(4')); 133.3 (C(3''), C(5''));
2
130.7 (C(4'')); 129.0 (C(2''), C(6'')); 126.6 (C(1'')); 125.7 (C(3'), C(5')); 126.4 (q, 1J(C,F) ˆ 320, CF3SO3); 121.5
3
2
2
(d, J(2' and 6',P) ˆ 5.5, C(2'), C(6')); 75.0 (d, J(1,P) ˆ 4.2, C(1)); 71.4 (PhCH2); 70.9 (d, J(5,P) ˆ 5.5, C(5));
61.2 (br. d, J(10,P) ꢀ 10, C(10)); 58.8 (C(8)); 47.3 (MeN); 31.6 (d, J(6,P) ˆ 4.5, C(6)); 18.4 (C(7)). 31P-NMR
3
3
(121.4 MHz, (CD3)2CO)18): À10.9 (d, 3J(P,HeqÀC(5)) ˆ 20.5). ESI-MS: 419 (100, [M À CF3SO3] ).
‡
(1RS,3SR,6SR,9SR)-9-Benzyl-3-(2,4-dinitrophenoxy)-9-methyl-2,4-dioxa-9-azonia-3-phosphabicyclo-
[4.4.0]decane 3-Oxide Trifluoromethanesulfonate (33a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca.
1.5:1). Colorless fine needles (73%). M.p. 110 113 8. IR (KBr): ca. 3750 3400m, 3113m, 2362w, 1610m, 1540w,
1482m, 1349s, 1321m, 1263s, 1225m, 1160m, 1069m, 1031s, 1009m, 975m, 939m, 904m, 835m, 788m, 741m, 727m,
705m, 638s, 5 74m, 5 18m, 471m. 1H-NMR (300 MHz, (CD3)2CO)16): 8.89 (dd, 4J(3',5') ˆ 2.8, 5J(3',6') ˆ 1.0,
HÀC(3')); 8.64 (dd, 3J(5',6') ˆ 9.2, 4J(5',3') ˆ 2.8, HÀC(5')); 8.02 (dd, 3J(6',5') ˆ 9.2, 5J(6',3') ˆ 1.0, HÀC(6'));
7.79 7.45( m, HÀC(2'') to HÀC(6'')); 5.48 (s, w1/2 ꢀ 6, HÀC(1)); 5.05 4.75 (m, not resolved, HaxÀC(5),
PhCH2); 4.66 (B of ABXÀP, 2J ˆ 11.9, 3J(5ax,P) ˆ 25.5, HeqÀC(5)); 4.25 4.19 (m, HeqÀC(10)); 4.05 3.85( m,
CH2(8), HaxÀC(10)); 3.42 (s, MeaxÀN); 3.37 (s, MeeqÀN); 2.80 2.48 (m, HeqÀC(7)); 2.37 2.22 (m, HÀC(6),
HaxÀC(7)). 13C-NMR (75.4 MHz, CDCl3): epimer A: 148.2 (d, 2J(1',P) ˆ 5.1, C(1')); 144.9 (C(4')); 141.2 (d,
3J(2',P) ˆ 6.6, C(2')); 134.2 (C(2''), C(6'')); 131.9 (C(4'')); 130.1 (C(5')); 129.9 (C(3''), C(5'')); 127.7 (C(1''));
124.6 (d, 3J(6',P) ˆ 2.2, C(6')); 122.7 (C(3')); 121.7 (q, 1J(C,F) ˆ 321, CF3SO3); 77.8 (d, 2J(1,P) ˆ 5.8, C(1)); 73.7
(d, 2J(5,P) ˆ 7.4, C(5)); 73.2 (PhCH2); 62.4 (d, 3J(10,P) ˆ 8.6, C(10)); 60.1 (C(8)); 48.3 (MeN); 32.2 (d,
3J(6,P) ˆ 5.3, C(6)); 18.8 (C(7)); epimer B: 148.2 (d, 2J(1',P) ˆ 5.1, C(1')); 144.9 (C(4'); 141.2 (d, 3J(2',P) ˆ 6.6,
C(2')); 134.2 (C(2''), C(6'')); 131.9 (C(4'')); 130.1 (C(5')); 129.9 (C(3''), C(5'')); 127.7 (C(1'')); 124.6 (d, 3J(6',P) ˆ
1
2
2
2.2, C(6')); 122.7 (C(3')); 121.7 (q, J(C,F) ˆ 321, CF3SO3); 77.3 (d, J(1,P) ˆ 6.2, C(1)); 72.6 (d, J(5,P) ˆ 6.8,
3
3
C(5)); 69.9 (PhCH2); 60.6 (br. d, J(10,P) ꢀ 10, C(10)); 63.8 (C(8)); 52.2 (MeN); 32.1 (d, J(6,P) ˆ 5.1, C(6));
19.1 (C(7)). 31P-NMR (121.4 MHz, (CD3)2CO): À15.8 (B), À16.0 (A) (each d, J(P,HeqÀC(5)) ˆ 25.5). ESI-
3
‡
‡
MS: 464 (100, [M À CF3SO3] ), 450 (20, [M À CF3SO3 À Me] ). Anal. calc. for C21H23F3N3O11PS ¥ H2O (631.44):
C 39.94, H 3.99, N 6.65; found: C 39.94, H 3.85, N 6.60.
(1RS,3SR,6SR)-3-(2,4-Dinitrophenoxy)-9,9-dimethyl-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]decane 3-
Oxide Trifluoromethanesulfonate (34a). Colorless resin (23%). 1H-NMR (300 MHz, (CD3)2CO): 8.90 (dd,
4J(3',5') ˆ 2.4, 5J(3',6') ˆ 1.0, HÀC(3')); 8.66 (dd, 3J(5',6') ˆ 9.1, 4J(5',3') ˆ 2.7, HÀC(5')); 8.05( dd, 3J(6',5') ˆ 9.1,
5J(6',3') ˆ 1.0, HÀC(6')); 5.50 (s, w1/2 ꢀ 6, HÀC(1)); 4.99 (A of ABXÀP, 2J ˆ 11.8, HaxÀC(5)); 4.66 (B of
2
3
ABXÀP, J ˆ 11.8, J(5eq,P) ˆ 25.8, HeqÀC(5)); 4.18 3.83 (m, CH2(8), CH2(10)); 3.52 (s, MeaxÀN)); 3.48 (s,
MeeqÀN)); 2.71 2.46 (m, HÀC(6), HeqÀC(7)); 2.24 (m, t-like, w1/2 ꢀ 30, HaxÀC(7)). 13C-NMR (75.4 MHz,
CDCl3): 148.2 (d, 2J(1',P) ˆ 5.0, C(1')); 144.9 (C(4')); 141.1 (br. d, w1/2 ꢀ 5, C(2')); 130.3 (C(5')); 123.8 (d,
3J(6',P) ˆ 2.4, C(6')); 122.6 (C(3')); 122.0 (q, 1J(C,F) ˆ 321, CF3SO3); 77.9 (d, 2J(1,P) ˆ 5.9, C(1)); 73.7 (d,
2J(5,P) ˆ 7.5, C(5)); 64.1 (d, 3J(10,P) ˆ 8.9, C(10)); 62.2 (C(8)); 58.0 (MeeqÀN); 51.6 (MeaxÀN); 31.9 (d,
3J(6,P) ˆ 5.2 C(6)); 19.0 (C(7)). 31P-NMR (121.4 MHz, (CD3)2CO): À15.9 (d, 3J(P,HeqÀC(5)) ˆ 25.8). ESI-MS:
‡
388 (100, [M À CF3SO3] ), 374 (10). Anal. calc. for C15H19F3N3O11PS ¥ 2 H2O (573.36): C 31.40, H 4.04, N 7.33;
found: C 31.75, H 4.31, N 7.69.
(1RS,3RS,6SR)-3-(2,4-Dinitrophenoxy)-9,9-dimethyl-2,4-dioxa-9-azonia-3-phosphabicyclo[4.4.0]decane 3-
Oxide Trifluoromethanesulfonate (34b)17). 31P-NMR (121.4 MHz, CDCl3): À15.4 (dd, 3J(P,H) ꢀ 26, 7)18).
6. 2,4-Dioxa-8-aza-3-phosphadecalins 35 50 of Type II. (1RS,3RS,6SR)-8-Benzyl-3-fluoro-2,4-dioxa-8-
aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (35a). Colorless prisms (25%). M.p. 173.58. Rf (Et2O) 0.36. IR
(KBr): 3062w, 3027m, 3006w, 2958m, 2936m 2867w, 2818m, 2802m, 2775m, 2726w, 1495m, 1484w, 1471w, 1446m,
1391w, 1368w, 1320s, 1262w, 1220m, 1185m, 1142m, 1130w, 1100m, 1079w, 1069m, 1042s, 994s, 975m, 963m, 915m,
1
According to H- and 31P-NMR spectra, the conformation of the P-heterocycle is rather chair-like than a
18
)
twist-boat.

2652
Helvetica Chimica Acta Vol. 87 (2004)
894s, 876m, 846w, 797m, 783m, 741m, 694m, 65 9m, 626w, 5 70m, 5 32m, 5 04w. 1H-NMR (600 MHz, CDCl3): 7.36
7.24 (m, HÀC(2') to HÀC(6')); 4.28 (A of ABXÀP, 2J ˆ 11.0, 3J(5eq,P) ˆ 24.5, 3J(5eq,6) ˆ 4.5, HeqÀC(5)); 4.18
(td, 3J(1,6) ˆ 3J(1,10ax) ˆ 12.1, 3J(1,10eq) ˆ 4.7, HÀC(1)); 4.10 (B of ABXÀP, 2J ˆ 3J(5ax,6) ˆ 11.0, 3J(5ax,P) ˆ
1.0, HaxÀC(5)); 3.58, 3.46 (AB, 2J ˆ 13.2, PhCH2); 3.01 (dsext.-like, 2J ˆ 12.1, 3J(9eq,10ax) ˆ 4.5, 3J(9eq,10eq) ˆ
2.5, 4J(9eq,7eq) ˆ 2.2, HeqÀC(9)); 2.81 (ddd, 2J ˆ 11.2, 3J(7eq,6) ˆ 3.7, 4J(7eq,9eq) ˆ 2.2, HeqÀC(7)); 2.34 (X of
ABXÀP, 3J(6,1) ˆ 12.1, 3J(6,5ax) ˆ 11.0, 3J(6,5eq) ˆ 4.5, 3J(6,7ax) ˆ 11.2, 3J(6,7eq) ˆ 3.7, HÀC(6)); 2.12 (td, 2J ˆ
3J(9ax,10ax) ˆ 12.1, 3J(9ax,10eq) ˆ 2.5, HaxÀC(9)); 2.08 (ddt, 2J ˆ 12.1, 3J(10eq,1) ˆ 4.7, 3J(10eq,9ax) ˆ
3J(10eq,9eq) ˆ 2.5, HeqÀC(10)); 1.94 (qd, 2J ˆ 3J(10ax,1) ˆ 3J(10ax,9ax) ˆ 12.1, 3J(10ax,9eq) ˆ 4.5, HaxÀC(10));
1.70 (t, 2J ˆ 3J(7ax,6) ˆ 11.2, HaxÀC(7)). 13C-NMR (150.9 MHz, CDCl3): 137.4 (C(1')); 128.7 (C(3'), C(5'));
128.3 (C(2'), C(6')); 127.4 (C(4')); 83.0 (d, 2J(1,P) ˆ 6.5, C(1)); 71.8 (d, 2J(5,P) ˆ 7.6, C(5)); 62.9 (PhCH2); 51.1
(C(9)); 51.0 (C(7)); 39.6 (d, 3J(6,P) ˆ 6.2, C(6)); 31.6 (d, 3J(10,P) ˆ 9.2, C(10)). 31P-NMR (121.4 MHz, CDCl3):
.
‡
‡
À19.9 (dd, 1J(P,F) ˆ 1010, 3J(P,HeqÀC(5)) ˆ 24.5. EI-MS: 285 (20, M ), 208 (10), 194 (8, [M À PhCH2] ), 186
‡
(14), 185(13), 172 (12), 126 (15), 94 (21), 92 (26), 91 (100, PhCH 2 ), 65(17). Anal. calc. for C 13H17FNO3P
(285.24): C 54.75, H 6.01, N 4.91; found: C 54.45, H 5.88, N 4.83.
(1RS,3SR,6SR)-8-Benzyl-3-fluoro-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (35b). Color-
less prisms (20%). M.p. 113 1148. Rf (Et2O) 0.28. IR (KBr): 3062w, 3025w, 2976w, 2941w, 2917w, 2873w, 2825m,
2777w, 1602w, 1495m, 1477w, 1452m, 1392m, 1368m, 1342s, 1324s, 1278w, 1220w, 1200w, 1185w, 1175w, 1144w,
1128w, 1105m, 1080m, 1065m, 1045s, 1002m, 973m, 956m, 912m, 894s, 871m, 846m, 794w, 769m, 747m, 702w,
675m, 630w, 5 70m, 5 32m. 1H-NMR (600 MHz, CDCl3): 7.36 7.24 (m, HÀC(2') to HÀC(6')); 4.37 (A of
3
ABXÀP, 2J ˆ 3J(5eq,P) ˆ 10.5, 3J(5eq,6) ˆ 5.7, HeqÀC(5)); 4.31 (dddd, J(1,10ax) ˆ 3J(1,6) ˆ 11.5, 3J(1,10eq) ˆ
4.5, 4J(1,F) ˆ 2.0, HÀC(1)); 4.13 (B of ABXÀP, 2J ˆ 3J(5ax,P) ˆ 3J(5ax,6) ˆ 10.5, 4J(5ax,F) ˆ 3.7, HaxÀC(5));
2
2
3
3
4
3.58, 3.46 (AB, J ˆ 13.2, CH2); 3.01 (dsext.-like, J ˆ 11.5, J(9eq,10ax) ˆ 4.2, J(9eq,10eq) ˆ 2.5, J(9eq,7eq) ˆ
2.3, HeqÀC(9)); 2.84 (ddd, 2J ˆ 11.0, 3J(7eq,6) ˆ 3.8, 4J(7eq,9eq) ˆ 2.3, HeqÀC(7)); 2.48 (X of ABXÀP,
3J(6,1) ˆ 11.5, 3J(6,5ax) ˆ 10.5, 3J(6,5eq) ˆ 5.7, 3J(6,7ax) ˆ 11.0, 3J(6,7eq) ˆ 3.8, HÀC(6)); 2.15( m, not resolved,
HeqÀC(10)); 2.12 (td, 2J ˆ 3J(9ax,10ax) ˆ 11.5, 3J(9ax,10eq) ˆ 2.5, HaxÀC(9)); 1.90 (qd, 2J ˆ 3J(10ax,1) ˆ
3J(10ax,9ax) ˆ 11.5, 3J(10ax,9eq) ˆ 4.2, HaxÀC(10)); 1.72 (t, 2J ˆ 3J(7ax,6) ˆ 11.0, HaxÀC(7)). 13C-NMR
(150.9 MHz, CDCl3): 137.4 (C(1')); 128.7 (C(3'), C(5')); 128.3 (C(2'), C(6')); 127.4 (C(4')); 82.3 (d, 2J(1,P) ˆ
6.6, C(1)); 71.4 (d, 2J(5,P) ˆ 7.1, C(5)); 62.0 (PhCH2; 52.0 (C(7)); 51.0 (C(9)); 38.5 (d, 3J(6,P) ˆ 12.6, C(6)); 32.0,
3J(10,P) ˆ 7.1 (C(10)) . 31P-NMR (121.4 MHz, CDCl3): À15.6 (dt, 1J(P,F) ˆ 998, 3J(P,HaxÀC(5) ˆ
.
‡
‡
3J(P,HeqÀC(5)) ˆ 10.5). EI-MS: 285 (19, M ), 208 (12), 194 (34, [M À PhCH2] ), 186 (3), 172 (3), 160 (3),
‡
132 (7), 126 (14); 112 (15), 94 (10), 92 (26), 91 (100, PhCH2 ), 67 (8), 65(17), 5(5). Anal. calc. for
C13H17FNO3P (285.24): C 54.75, H 6.01, N 4.91; found: C 54.59, H 5.72, N 4.79.
(1RS,3RS,6SR)-8-Benzyl-3-chloro-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (36a)14). Color-
1
less viscous oil (55%). H-NMR (300 MHz, CDCl3): 7.30 7.19 (m, HÀC(2') to HÀC(6')); 4.22 (A of ABXÀP,
2J ˆ 11.1, 3J(5eq,P)ˆ 28.5, 3J(5eq,6) ˆ 4.5, HeqÀC(5)); 4.19 4.08 (m, not resolved, HÀC(1)); 4.08 (B of ABXÀP,
2J ˆ 3J(5ax,6)ˆ 11.1, 3J(5ax,P)ˆ 2.5, HaxÀC(5)); 3.52, 3.42 (AB, 2J ˆ 13.1, PhCH2); 2.99 (dsext.-like, 2J ˆ 12,
3
4
2
3
4
3J(9eq,10ax) ꢀ J(9eq,10eq) ꢀ J(9eq,7eq) ꢀ 2, HeqÀC(9)); 2.75( ddd, J ˆ 11.4, J(7eq,6) ˆ 3.7, J(7eq,9eq) ˆ 2.2,
HeqÀC(7)); 2.29 (X of ABXÀP, 3J(6,1)ˆ 3J(6,5ax) ˆ 3J(6,7ax) ˆ 11.1, J(6,5eq) ˆ 4.5, J(6,7eq) ˆ 3.5, HÀC(6));
2.11 1.86 (m, HaxÀC(7), HaxÀC(9), CH2(10)). 13C-NMR (75.4 MHz, CDCl3): 137.7 (C(1')); 128.7 (C(3'), C(5'));
128.3 (C(2'), C(6')); 127.3 (C(4')); 83.0 (d, 2J(1,P) ˆ 7.8, C(1)); 71.7 (d, 2J(5,P)ˆ 8.6, C(5)); 61.9 (PhCH2); 51.1, 51.0
(C(7), C(9)); 39.6 (d, 3J(6,P) ˆ 6.6, C(6)); 31.3 (d, 3J(10,P)ˆ 9.8, C(10)). 31P-NMR (161.9 MHz, CDCl3): À2.3 (d,
3
3
3J(P,HeqÀC(5)) ˆ 28.5). CI-MS: 304 (31, [M(37Cl) ‡ H] ), 302 (100, [M(35Cl) ‡ H] ).
‡
‡
(1RS,3RS,6SR)-8-Benzyl-3-(4-nitrophenoxy)-2,4-dioxa-8-aza-3-phospha-bicyclo[4.4.0]decane 3-Oxide
(37a). Slightly yellow powder (31%). IR (CHCl3): 2952w, 2809w, 2766w, 1615m, 1594m, 1525s, 1493s, 1348s,
1311s, 1040s, 1012m, 968m, 931s. 1H-NMR (300 MHz, CDCl3): 8.26 (AA' of AA'BB', J ˆ 9.1, HÀC(3'),
HÀC(5')); 7.42 (BB' of AA'BB', J ˆ 9.1, HÀC(2'), HÀC(6')); 7.39 7.26 (m, HÀC(2'') to HÀC(6'')); 4.30 (A of
ABXÀP, 2J ˆ 10.9, 3J(5eq,P) ˆ 24.5, 3J(5eq,6) ˆ 4.5, HeqÀC(5)); 4.12 (sext.-like, 3J(1,10ax) ꢀ J(1,6) ꢀ 11,
3
3J(1,10eq) ꢀ 5 , HÀC(1)); 4.13 (B of ABXÀP, J ˆ 3J(5ax,6) ˆ 10.9, J(5ax,P) ˆ 1.0, HaxÀC(5)); 3.59, 3.49 (AB,
2J ˆ 13.2, PhCH2); 3.04 (m, dq-like, w1/2 ꢀ 18, HeqÀC(9)); 2.84 (ddd, 2J ˆ 11.3, 3J(7eq,6) ˆ 3.5, 4J(7eq,9eq) ˆ 2.2,
HeqÀC(7)); 2.41 (X of ABXÀP, 3J(6,1) ꢀ 11, 3J(6,5ax) ˆ 10.9, 3J(6,5eq) ˆ 4.5, 3J(6,7ax) ˆ 11.2, 3J(6,7eq) ˆ 3.5,
2
3
HÀC(6)); 2.17 1.99 (m, HaxÀC(9), HeqÀC(10)); 1.97 (qd-like, 2J ꢀ J(10ax,9ax) ꢀ J(10ax,1) ꢀ 11,
3
3
3J(10ax,9eq) ˆ 4.0, HaxÀC(10)); 1.73 (t, J ˆ 3J(7ax,6) ˆ 11.2, HaxÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 155.6
2
(d, 2J(1',P) ˆ 6, C(1')); 144.7 (C(4')); 137.3 (C(1''); 128.7 (C(3''), C(5'')); 128.3 (C(2''), C(6'')); 127.3 (C(4''));
125.7 (C(3'), C(5')); 120.0 (d, J(2' and 6',P) ˆ 5.6, C(2'), C(6')); 82.6 (d, 2J(1,P) ˆ 7.3, C(1)); 71.5( d, J(5,P) ˆ
3
2
8.0, C(5)); 62.1 (PhCH2); 51.1 (C(7)); 51.0 (C(9)); 39.7 (d, J(6,P) ˆ 6.4, C(6)); 31.7 (d, 3J(10,P) ˆ 6.1, C(10)).
3
31P-NMR (161.9 MHz, CDCl3): À14.2 (d, J(P,HeqÀC(5)) ˆ 24). CI-MS: 405(100, [ M ‡ H] ).
3
‡

Helvetica Chimica Acta Vol. 87 (2004)
2653
(1RS,3SR,6SR)-8-Benzyl-3-(4-nitrophenoxy)-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(37b). Yellow viscous oil (32%). IR (CHCl3): 3008w, 2962w, 2810w, 2766w, 1615m, 1593s; 1526s; 1493s;
1454m, 1365m, 1348s, 1294s, 1248m, 1171m, 1104s, 1079m, 1086s, 1044s, 1012s, 970s, 933s. 1H-NMR (300 MHz,
CDCl3): 8.23 (AA' of AA'BB', J ˆ 9.0, HÀC(3'), HÀC(5')); 7.38 (BB' of AA'BB', J ˆ 9.0, HÀC(2'), HÀC(6'));
7.34 7.24 (m, HÀC(2'') to HÀC(6'')); 4.17 4.42 (AB of ABXÀP and m, not resolved, HÀC(1), CH2(5)); 3.57,
3.46 (AB, 2J ˆ 13.1, PhCH2); 3.01 (m, dquint.-like, w1/2 ꢀ 20, HeqÀC(9)); 2.82 (ddd, 2J ˆ 11.3, 3J(7eq,6) ˆ 3.7,
4J(7eq,9eq) ˆ 2.2, HeqÀC(7)); 2.40 (X of ABX, ttq-like, w1/2 ꢀ 22, HÀC(6)); 2.16 2.08 (m, HaxÀC(9),
HeqÀC(10)); 1.86 (qd-like, 2J ꢀ J(10ax,1) ꢀ J(10ax,9ax) ꢀ 13, 3J(10ax,9eq) ꢀ 4, HaxÀC(10)); 1.73 (t, 2J ˆ
3J(7ax,6) ˆ 11.2, HaxÀC(7)). 13C-NMR (75.4 MHz, CDCl3): 155.7 (d, 2J(1',P) ˆ 6, C(1')); 144.9 (C(4')); 137.4
(C(1'')); 128.7 (C(3''), C(5'')); 128.3 (C(2''), C(6'')); 127.3 (C(4'')); 125.5 (C(3'), C(5')); 120.6 (d, 3J(2' and 6',P) ˆ
5.3, C(2'), C(6')); 81.5( d, 2J(1,P) ˆ 5.7, C(1)); 70.8 (d, 2J(5,P) ˆ 7.0, C(5)); 62.0 (PhCH2); 51.8 (d, 4J(7,P) ˆ 0.8,
C(7)); 51.1 (d, 4J(9,P) ˆ 2.1, C(9)); 39.0 (d, 3J(6,P) ˆ 9.0, C(6)); 31.9 (d, 3J(10,P) ˆ 7.8, C(10)). 31P-NMR
3
3
3
‡
(161.9 MHz, CDCl3): À12.0 (dd, J(P,HeqÀC(5)) ˆ 15, 3J(P,HaxÀC(5)) ˆ 8). CI-MS: 405(100, [ M ‡ H] ).
(1RS,3RS,6SR)-8-Benzyl-3-(2,4-dinitrophenoxy)-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(38a). Slightly yellow powder (48%). IR (CHCl3): 3030w, 2962w, 2811w, 2766w, 1609s, 1541s, 1485w, 1454m,
1347s, 1317s, 1266s, 1131m, 1094m, 1069s, 1037s, 995s, 935s, 901s. 1H-NMR (300 MHz, CDCl3): 8.83 (d,
4J(3',5') ˆ 2.9, HÀC(3')); 8.47 (dd, 3J(5',6') ˆ 9.2, 4J(5',3') ˆ 2.9, HÀC(5')); 8.13 (d, 3J(6',5') ˆ 9.2, HÀC(6'));
7.38 7.27 (m, HÀC(2'') to HÀC(6'')); 4.45( td, 3J(1,6) ˆ 3J(1,10ax) ˆ 10.2, 3J(1,10eq) ˆ 5.8, HÀC(1)); 4.36 4.25
(AB of ABXÀP, not resolved, CH2(5)); 3.67, 3.58 (AB, 2J ˆ 13.0, PhCH2); 3.11 (m, d-like, w1/2 ꢀ 20, HeqÀC(9));
2.92 (m, d-like, w1/2 ꢀ 20, HeqÀC(7)); 2.51 (X of ABXÀP, m, w1/2 ꢀ 30, HÀC(6)); 2.25(br. t, 2J ꢀ J(9ax,10ax) ꢀ
3
12, HaxÀC(9)); 2.07 (m, w1/2 ꢀ 20, CH2(10)), 1.89 (t, 2J ˆ 3J(7ax,6) ˆ 11.5, HaxÀC(7)). 13C-NMR (75.4 MHz,
CDCl3): 148.3 (d, 2J(1',P) ˆ 5.5, C(1')); 145.0 (C(4')); 141.9 (d, 3J(2',P) ˆ 7.2, C(2')); 137.5(C(1 '')); 129.3 (C(5'));
129.0 (C(2''), C(6'')); 128.6 (C(3''), C(5'')); 127.6 (C(4'')); 123.1 (d, 3J(6',P) ˆ 2, C(6')); 121.8 (C(3')); 83.3 (d,
2J(1,P) ˆ 7.3, C(1)); 72.2 (d, J(5,P) ˆ 8.0, C(5)); 62.2 (PhCH2); 51.4 (C(7)); 51.3 (C(9)); 39.9 (d, 3J(6,P) ˆ 6.4,
2
C(6)); 31.7 (d, 3J(10,P) ˆ 9.2, C(10)). 31P-NMR (161.9 MHz, CDCl3): À15.2 (br. d 3J(P,HeqÀC(5)) ˆ 26). CI-
‡
MS: 450 (100, [M ‡ H] ).
(1RS,3SR,6SR)-8-Benzyl-3-(2,4-dinitrophenoxy)-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(38b)15). 31P-NMR (161.9 MHz, CDCl3): À14.0 (t 3J(P,HaxÀC(5)) ꢀ J(P,HeqÀC(5)) ꢀ 11).
3
(1RS,3RS,6RS)-8-Benzyl-3-fluoro-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (39a). Color-
less prisms (30%). M.p. 112 112.58. Rf (AcOEt/MeOH 98 :2) 0.20. IR (KBr): 3086w, 3062w, 3026w, 2964m,
2923m, 2905m, 2829w, 2800m, 2779m, 1496w, 1480w, 1451w, 1420w, 1384w, 1370w, 1360w, 1352w, 1340m, 1309s,
1276w, 1215m, 1158w, 1129w, 1096m, 1073s, 1051m, 1023s, 992s, 970m, 948m, 909m, 891s, 85 2w, 832m, 786w,
770m, 742m, 722m, 697m, 641m, 5 46w, 5 12m. 1H-NMR (600 MHz, CDCl3): 7.34 7.25( m, HÀC(2') to HÀC(6'));
4.87 (q, 3J(1,6) ˆ 3J(1,10ax) ˆ 3J(1,10eq) ˆ 2.6, HÀC(1)); 4.53 (A of ABXÀP, 2J ˆ 11.7, 3J(5ax,6) ˆ 2.9,
2
3
3
2
HaxÀC(5)); 4.21 (B of ABXÀP, J ˆ 11.7, J(5eq,6) < 1, J(5eq,P) ˆ 24.8, HeqÀC(5)); 3.60, 3.50 (AB, J ˆ 13.0,
PhCH2); 2.72 (dquint.-like, 2J ˆ11.8, 3J(9eq,10ax) ꢀ J(9eq,10eq) ˆ 2.4, 4J(9eq,7eq) ꢀ 1, HeqÀC(9)); 2.69 (br.
3
dd, 2J ˆ 11.8, 3J(7eq,6) ˆ 4.6, 4J(7eq,9eq) ꢀ 1, HeqÀC(7)); 2.54 (t, 2J ˆ 3J(7ax,6) ˆ 11.8, HaxÀC(7)); 2.39 (td, 2J ˆ
3J(9ax,10ax) ˆ 11.8, 3J(9ax,10eq) ˆ 2.9, HaxÀC(9)); 2.06 (X of ABXÀP, 3J(6,1) ˆ 2.6, 3J(6,5ax) ˆ 2.9,
3J(6,5eq) < 1, 3J(6,7ax) ˆ 11.8, 3J(6,7eq) ˆ 4.6, HÀC(6)); 2.01 (br. dddd, 2J ˆ 14.5, 3J(10eq,1) ˆ 2.6,
3J(10eq,9ax) ˆ 2.9, 3J(10eq,9eq) ˆ 2.4, 4J(10eq,P) ꢀ 1, HeqÀC(10)); 1.96 (qdd-like, 2J ˆ 14.5, 3J(10ax,1) ˆ 2.6,
3J(10ax,9ax) ˆ 11.9, 3J(10ax,9eq) ˆ 2.4, 4J(10ax,P) ˆ 6.0, HaxÀC(10)19). 13C-NMR (150.9 MHz, CDCl3): 137.9
(C(1')); 129.0 (C(2'), C(6')); 128.3 (C(4')); 127.3 (C(2'), C(6')); 127.3 (C(4')); 78.5( d, 2J(1,P) ˆ 6.6, C(1)); 72.3 (d,
2J(5,P) ˆ 6.9, C(5)); 62.9 (PhCH2); 49.5(C(7)); 46.7 (C(9)); 35.5( d, 3J(6,P) ˆ 5.9, C(6)); 31.0 (d, 3J(10,P) ˆ 8.9,
C(10)). 31P-NMR (121.4 MHz, CDCl3): À16.6 (ddd, J(P,F) ˆ 1009, J(P,HeqÀC(5)) ˆ 24.8, J(P,HaxÀC(10)) ˆ
1
3
4
.
6.019). EI-MS: 285(9, M ), 208 (3), 194 (7, [M À PhCH2] ), 185(15), 172 (18), 144 (5), 132 (7), 118 (7), 94
‡
‡
‡
(18), 92 (10), 91 (100, PhCH2 ), 67 (10), 65(17). Anal. calc. for C 13H17FNO3P (285.24): C 54.75, H 6.01, N 4.91;
found: C 54.96, H 5.84, N 4.77.
(1RS,3SR,6RS)-8-Benzyl-3-fluoro-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (39b). Color-
less viscous oil (30%). Rf (AcOEt/MeOH 98 :2) 0.32. IR (KBr): 3026w, 2962m, 2815m, 1492m, 1474w, 1451m,
1400w, 1327s, 1236w, 1203w, 1170m, 1131m, 1055s, 1031s, 1002m, 970m, 939m, 910w, 878m, 867m, 848m, 797w,
19
)
This 4J(10,P) had been assigned to HeqÀC(10) in the cis-decalin series [5]. However, the 1H{31P}-NMR
4
spectra at 600 MHz clearly showed that it originates from HaxÀC(10). HeqÀC(10) exhibits a small J (ca.
1 Hz).

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Helvetica Chimica Acta Vol. 87 (2004)
1
779w, 737m, 700m, 671w, 628w, 5 68w, 5 16m. H-NMR (600 MHz, CDCl3)20): 7.33 7.30 (2 H), 7.29 7.24 (3 H)
(each m, HÀC(2') to HÀC(6')); 4.83 (X of ABXÀP, br. t-like, w1/2 ꢀ 30, HaxÀC(5)); 4.71 (quint.d-like, 3J(1,P) ˆ
3
18, 3J(1,6) ꢀ J(1,10ax) ꢀ 5, 3J(1,10eq) ꢀ 3, HÀC(1)); 4.36 (ddd, 3J(5eq,P) ˆ 18, 2J ˆ 11.5, 3J(5eq,6) ˆ 4.5,
HeqÀC(5)); 3.50, 3.40 (AB, 2J ˆ 13.0, PhCH2); 2.85( m, br. d-like, w1/2 ꢀ 25, 2J ˆ 11, HeqÀC(9)); 2.71 (ddd,
2J ˆ 12.5, 3J(7eq,6) ˆ 3.8, 4J(7eq,9eq) ˆ 1.6, HeqÀC(7)); 2.51 (X of ABXÀP, quint.-like, w1/2 ꢀ 20, HÀC(6)); 2.31
3
3
(dd, 2J ˆ 12.5, 3J(7ax,6) ˆ 3.5, HaxÀC(7)); 2.25( qt-like, 2J ꢀ J(10ax,9ax) ꢀ 11, 3J(10ax,1) ꢀ J(10ax,9eq) ꢀ 5,
HaxÀC(10)); 2.17 (br. t-like, 2J ꢀ J(9ax,10ax) ꢀ 11, HaxÀC(9)); 2.08 (m, w1/2 ꢀ 25, HeqÀC(10)). 13C-NMR
3
2
(150.9 MHz, CDCl3): 137.8 (C(1')); 128.6 (C(3'), C(5')); 128.4 (C(2'), C(6')); 127.4 (C(4')); 80.7 (dd, J(1,P) ˆ
6.5, 3J(1,F) ˆ 2, C(1)); 70.1 (d, 2J(5,P) ˆ 6.9, C(5)); 62.1 (PhCH2); 51.7 (C(7)); 50.9 (C(9)); 35.1 (d, 3J(6,P) ˆ 8.1,
C(6)); 28.5(C(10)).
31P-NMR (121.4 MHz, CDCl3)20): À17.0 (dt, 1J(P,F) ˆ 1002, 3J(P,HaxÀC(5)) ˆ
.
‡
‡
3J(P,HeqÀC(5)) ˆ 18). EI-MS: 285(19,
M
), 208 (15), 194 (26, [M À PhCH2] ), 172 (5), 133 (6), 132 (10),
‡
94 (17), 92 (22), 91 (100, PhCH2 ), 67 (10), 65(18). Anal. calc. for C 13H17FNO3P (285.24): C 54.75, H 6.01,
N 4.91; found: C 54.65, H 6.22, N 5.14.
(1RS,3RS,6RS)-8-Benzyl-3-chloro-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (40a)14). Col-
orless viscous oil (68%). IR (CHCl3): 3429w (br.), 3039w, 2941m, 2482s, 1498m, 1457s, 1412m, 1357m, 1356m,
1307s, 1264m, 1244m, 1202m, 1137m, 1086m, 1067s, 1013s, 968s, 925m, 823s, 790s, 75 1s, 726s, 700s, 643m, 603s,
554s. 1H-NMR (300 MHz, CDCl3): 7.26 7.19 (m, HÀC(2') to HÀC(6')); 4.81 (quint., 3J(1,6) ꢀ J(1,10ax) ꢀ
3
3J(1,10eq) ꢀ J(1,9eq) ꢀ 2, HÀC(1)); 4.48 (A of ABXÀP, 2J ˆ 12.0, 3J(5ax,6) ˆ 3J(5ax,P) ˆ 2.7, HaxÀC(5)); 4.11
4
(B of ABXÀP, 2J ˆ 12.0, 3J(5eq,6) ˆ 1.2, 3J(5eq,P) ˆ 29.7, HeqÀC(5)); 3.52, 3.40 (AB, 2J ˆ 13.0, PhCH2); 2.66
(m, dquint.-like, not resolved, HeqÀC(9)); 2.63 (br. dd, 2J ˆ 11.8, 3J(7eq,6) ꢀ 4.5, J(7eq,9eq) ꢀ 1, HeqÀC(7));
4
2.45( t, 2J ˆ 3J(7ax,6) ˆ 11.8, HaxÀC(7)); 2.39 (td-like, 2J ꢀ J(9ax,10ax) ꢀ 11, 3J(9ax,10eq) ꢀ 4, HaxÀC(9)); 1.98
3
(X of ABXÀP, br. d-like, w1/2 ꢀ 22, HÀC(6)); 1.91 (m, oct.-like, w1/2 ꢀ 10, CH2(10)). 13C-NMR (75.4 MHz,
CDCl3): 137.7 (C(1')); 128.9 (C(3'), C(5')); 128.2 (C(2'), C(6')); 127.1 (C(4')); 78.5( d, 2J(1,P) ˆ 8.2, C(1)); 72.2
(d, 2J(5,P) ˆ 7.8, C(5)); 62.8 (PhCH2); 49.7 (C(7)); 46.7 (C(9)); 35.5 (d, 3J(6,P) ˆ 5.9, C(6)); 30.8 (d, 3J(10,P) ˆ
9.5, C(10)). 31P-NMR (161.9 MHz, CDCl3): À2.5( d, 3J(P,HeqÀC(5)) ˆ 29.7). CI-MS: 304 (29, [M(37Cl) ‡ H] ),
‡
‡
302 (100, [M(35Cl) ‡ H] ).
(1RS,3RS,6RS)-8-Benzyl-3-(4-nitrophenoxy)-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(41a). Slightly yellow powder (29%). IR (CHCl3): 3086w, 3007w, 2954w, 2827w, 1615m, 1594s, 1526s, 1493s,
1470m, 1348s, 1310s, 1248m, 1165m, 1112m, 1096m, 1072s, 1050m, 1020s, 982s, 928s. 1H-NMR (600 MHz,
CDCl3): 8.24 (AA' of AA'BB', J ˆ 9.3 HÀC(3'), HÀC(5')); 7.42 (BB' of AA'BB', J ˆ 9.3, HÀC(2'), HÀC(6'));
7.35 7.31 (4 H), 7.29 7.26 (1 H) (each m, HÀC(2'') to HÀC(6'')); 4.91 (q, 3J(1,6) ˆ 3J(1,10ax) ˆ 3J(1,10eq) ˆ
2.6, HÀC(1)); 4.57 (A of ABXÀP, 2J ˆ 11.7, 3J(5ax,6) ˆ 2.8, 3J(5ax,P) ˆ 1.0, HaxÀC(5)); 4.22 (B of ABXÀP,
2J ˆ 11.7, 3J(5eq,6) ˆ 1.2, 3J(5eq,P) ˆ 24.5, HeqÀC(5)); 3.62, 3.52 (AB, 2J ˆ 13.0, PhCH2); 2.76 2.70 (m,
HeqÀC(7), HeqÀC(9)); 2.65( t, 2J ˆ 3J(7ax,6) ˆ 11.9, HaxÀC(7)); 2.43 (td, 2J ˆ 3J(9ax,10ax) ˆ 11.5,
3J(9ax,10eq) ˆ 4.3, HaxÀC(9)); 2.11 (X of ABXÀP, m, w1/2 ꢀ 25, HÀC(6)); 2.05 1.96 ( m, CH2(10)).
13C-NMR (150.9 MHz, CDCl3): 155.4 (d, 2J(1',P) ˆ 6, C(1')); 144.6 (C(4')); 137.8 (C(1'')); 128.9 (C(3''),
C(5'')); 128.2 (C(2''), C(6'')); 127.2 (C(4'')); 125.7 (C(3'), C(5')); 120.0 (d, 3J(2' and 6',P) ˆ 5.8, C(2'), C(6')); 77.8
2
2
3
(d, J(1,P) ˆ 7.4, C(1)); 71.9 (d, J(5,P) ˆ 7.4, C(5)); 62.8 (PhCH2); 49.6 (C(7)); 46.7 (C(9)); 35.6 (d, J(6,P) ˆ
5.6, C(6)); 31.0 (d, 3J(10,P) ˆ 8.6, C(10)). 31P-NMR (161.9 MHz, CDCl3): À14.5( dbr. d, 3J(P,HeqÀC(5)) ˆ 24.5,
3J(P,HaxÀC(5)) ˆ 3.5, J(P,HaxÀC(10)) ꢀ 1). CI-MS: 405(100, [ M ‡ H] ).
4
‡
(1RS,3SR,6RS)-8-Benzyl-3-(4-nitrophenoxy)-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(41b). Yellow viscous oil (26%). IR (CHCl3): 3030w, 2951w, 2816w, 1615m, 1594s, 1525s, 1493s, 1469w,
1374m,1348s, 1292s, 1248s, 1167m, 1112m, 1058s, 1020m, 974m, 933s. 1H-NMR (300 MHz, CDCl3): 8.26 (AA' of
AA'BB', J ˆ 9.0, HÀC(3'), HÀC(5')); 7.41 (BB' of AA'BB', J ˆ 9.0, HÀC(2'), HÀC(6')); 7.35 7.23 ( m,
HÀC(2'') to HÀC(6'')); 4.71 (m, oct.-like, w1/2 ꢀ 20, HÀC(1)); 4.62, 4.49 (AB of ABXÀP, not resolved, CH2(5));
3.48, 3.44 (AB, 2J ˆ 13.2, PhCH2); 2.59 2.18 (m, HÀC(6), CH2(7), CH2(9), HeqÀC(10)); 2.02 (m, w1/2 ꢀ 20,
HaxÀC(10)). 13C-NMR (75.4 MHz, CDCl3): 155.6 (d, 2J(1',P) ˆ 6, C(1')); 144.6 (C(4')); 137.1 (C(1'')); 128.7
3
(C(3''), C(5'')); 128.3 (C(2''), C(6'')); 127.4 (C(4'')); 125.9 (C(3'), C(5')); 120.8 (d, J(2' and 6',P) ˆ 5.2, C(2'),
C(6')); 78.9 (d, 2J(1,P) ˆ 6.9, C(1)); 70.2 (d, 2J(5,P) ˆ 6.2, C(5)); 62.3 (PhCH2); 50.9 (C(7)); 49.2 (C(9)); 35.2 (d,
3J(6,P) ˆ 7.1, C(6)); 29.2 (d, 3J(10,P) ˆ 4.1, C(10)). 31P-NMR (161.9 MHz, CDCl3): À13.4 (m, w1/2 ꢀ 35). CI-MS:
‡
405(100, [ M ‡ H] ).
According to 1H- and 31P-NMR spectra, the conformation of the P-heterocycle is neither a chair nor a
common twist-boat, see [23].
20
)

Helvetica Chimica Acta Vol. 87 (2004)
2655
(1RS,3RS,6RS)-8-Benzyl-3-(2,4-dinitrophenoxy)-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(42a). Slightly yellow powder (14%). IR (CHCl3): 2952w, 2826w, 1609s, 1541s, 1486m, 1455m, 1348s, 1316s,
1266m, 1165m, 1068s, 1020s, 985s, 936s, 924s, 918s, 894s. 1H-NMR (300 MHz, CDCl3): 8.83 (d, 4J(3',5') ˆ 2.7,
HÀC(3')); 8.47 (dd, 3J(5',6') ˆ 9.3, 4J(5',3') ˆ 2.7, HÀC(5')); 8.13 (d, 3J(6',5') ˆ 9.3, HÀC(6')); 7.36 7.26 (m,
HÀC(2'') to HÀC(6'')); 5.06 (q, 3J(1,6) ˆ 3J(1,10ax) ˆ 3J(1,10eq) ˆ 2.3, HÀC(1)); 4.71 (A of ABXÀP, 2J ˆ 11.6,
3J(5ax,6) ˆ 2.6, 3J(5ax,P)< 1, HaxÀC(5)); 4.22 (B of ABXÀP, 2J ˆ 11.6, 3J(5eq,6) ꢀ 1, 3J(5eq,P) ˆ 25.0,
2
HeqÀC(5)); 3.62, 3.53 (AB, J ˆ 13.0, PhCH2); 2.72 2.77 (m, HeqÀC(7), HeqÀC(9)); 2.60 (t, 2J ˆ 3J(7ax,6) ˆ
11.8, HaxÀC(7)); 2.40 (td, 2J ˆ 3J(9ax,10ax) ˆ 11.5, 3J(9ax,10eq) ˆ 4.5, HaxÀC(9)); 1.99 (X of ABXÀP, m, w1/
2
2 ꢀ 22, HÀC(6)); 2.01 1.98 (m, CH2(10)). 13C-NMR (75.4 MHz, CDCl3): 148.1 (d, J(1',P) ˆ 5.7, C(1')); 144.8
(C(4')); 142.0 (d, 3J(2',P) ˆ 7.5, C(2')); 137.4 (C(1'')); 129.1 (C(5')); 128.9 (C(2''), C(6'')); 128.3 (C(3''), C(5''));
127.3 (C(4'')); 122.9 (d, 3J(6',P) ˆ 2.2, C(6')); 121.6 (C(3')); 78.7 (d, 2J(1,P) ˆ 7.3, C(1)); 72.5( d, 2J(5,P) ˆ 7.3,
C(5)); 62.8 (PhCH2); 49.6 (C(7)); 46.7 (C(9)); 35.5 (d, 3J(6,P) ˆ 5.9, C(6)); 31.0 (d, 3J(10,P) ˆ 8.7, C(10)). 31P-
3
3
NMR (161.9 MHz, CDCl3): À15.7 (dd, J(P,HeqÀC(5)) ˆ 25.0, J(P,HaxÀC(5)) ˆ 4.2). CI-MS: 450 (100, [M ‡
‡
H] ).
(1RS,3SR,6RS)-8-Benzyl-3-(2,4-dinitrophenoxy)-2,4-dioxa-8-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide
(42b)15). Yellow viscous oil (ca. 5%). 31P-NMR (161.9 MHz, CDCl3): À14.8 (t-like, not resolved,
3
3J(P,HaxÀC(5)) ꢀ J(P,HeqÀC(5)) ꢀ 10).
(1RS,3RS,6SR,8SR)-8-Benzyl-3-chloro-8-methyl-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]decane 3-Ox-
ide Trifluoromethanesulfonate (43a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 2 :1). White powder
(25%). 1H-NMR (300 MHz, (CD3)2CO)16): 7.79 7.50 (m, HÀC(2') to HÀC(6')); 5.1 4.4 (m, not resolved,
HÀC(1), CH2(5), PhCH2); 4.0 3.5( m, CH2(7), CH2(9)); 3.43 (s, MeaxÀN); 3.39 (s, MeeqÀN); 3.5 2.4 ( m,
HÀC(6), CH2(10)). 31P-NMR (121.4 MHz, (CD3)2CO): À2.8 (d, 3J(P,HeqÀC(5)) ˆ 30). ESI-MS: 318 (28,
‡
‡
[M(37Cl) À CF3SO3] ), 316 (100, [M(35Cl) À CF3SO3] ).
(1RS,3RS,6SR,8SR)-8-Benzyl-8-methyl-3-(4-nitrophenoxy)-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (44a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 2 :1).
Slightly yellow powder (52%). 1H-NMR (300 MHz, (CD3)2CO)16
)
21): 8.31 (AA' of AA'BB', J ˆ 8.8, HÀC(3'),
HÀC(5')); 7.78 7.45( m, HÀC(2'), HÀC(6'), HÀC(2'') to HÀC(6'')); 5.23 5.03 (m, HÀC(1)); 4.92, 4.88 (AB,
2J ˆ 13, PhCH2)); 4.73 4.48 (AB of ABXÀP, not resolved, CH2(5)); 4.08 3.37 (m, CH2(7), CH2(9)); 3.44 (s,
MeaxÀN); 3.23 (s, MeeqÀN); 3.11, 2.89 (each m, w1/2 ꢀ 30, HÀC(6)); 2.69 2.27 (m, CH2(10)). 13C-NMR
(75.4 MHz, (CD3)2CO): epimer A: 156.2 (d, 2J(1',P) ˆ 6, C(1')); 146.2 (C(4')); 132.7 (C(3''), C(5'')); 130.4
(C(4'')); 130.3 (C(2''), C(6'')); 128.2 (C(1'')); 126.9 (C(3'), C(5')); 122.1 (q, 1J(C,F) ˆ 320, CF3SO3); 121.9 (d,
3J(2' and 6',P) ˆ 4.2, C(2'), C(6')); 77.8 (d, 2J(1,P) ˆ 6.9, C(1)); 71.5(Ph CH2); 70.1 (d, 3J(5,P) ˆ 7.9, C(5)); 58.5
(C(7)); 57.5 (C(9)); 44.8 (MeN); 34.5 (d, 3J(6,P) ˆ 5.9, C(6)); 26.1 (d, 3J(10,P) ˆ 10.2, C(10)); epimer B: 156.2
2
(d, J(1',P) ˆ 6, C(1')); 146.2 (C(4')); 132.7, (C(3''), C(5'')); 130.4 (C(4'')); 130.3 (C(2''), C(6'')); 128.2 (C(1''));
126.9 (C(3'), C(5')); 121.9 (d, 3J(2' and 6',P) ˆ 4.2, C(2'), C(6')); 77.9 (d, 2J(1,P) ˆ 7, C(1)); 71.5(Ph CH2); 70.1 (d,
3
3
3J(5,P) ˆ 7.9, C(5)); 61.7 (C(7)); 60.6 (C(9)); 52.2 (MeN); 37.5 (d, J(6,P) ˆ 5.9, C(6)); 28.9 (d, J(10,P) ˆ 9.9,
C(10)). 31P-NMR (121.4 MHz, (CD3)2CO): À14.2 (d, 3J(P,HeqÀC(5)) ˆ 22.5). ESI-MS: 419 (100, [M À
‡
‡
CF3SO3] ), 405(60, [ M ‡ H À Me] ).
(1RS,3SR,6SR,8SR)-8-Benzyl-8-methyl-3-(4-nitrophenoxy)-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (44b). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 3 :1).
Yellow viscous oil (47%). 1H-NMR (300 MHz, (CD3)2CO)16): 8.31 (AA' of AA'BB', J ˆ 9.1, HÀC(3'),
HÀC(5')); 7.70 (BB' of AA'BB', J ˆ 9.1, HÀC(2'), HÀC(6')); 7.65 7.48 ( m, HÀC(2'), HÀC(6'), HÀC(2'') to
HÀC(6'')); 5.02 4.92 (m, HÀC(1)); 4.88 (s, PhCH2)); 4.69 4.43 (AB of ABXÀP, not resolved, CH2(5)); 4.03
3.71 (m, HeqÀC(7), HeqÀC(9)); 3.41 (s, MeaxÀN); 3.24 (s, MeeqÀN); 3.56 3.14 (m, HÀC(6), HaxÀC(7),
HaxÀC(9)); 2.57 2.51 (m, CH2(10)). 13C-NMR (75.4 MHz, (CD3)2CO): epimer A: 155.0 (d, 2J(1',P) ˆ 6.8,
C(1')); 145.0 (C(4')); 133.3 (C(3''), C(5'')); 130.7 (C(4'')); 129.0 (C(2''), C(6'')); 126.8 (C(1'')); 125.6 (C(3'),
C(5')); 122.2 (q, 1J(C,F) ˆ 320, CF3SO3); 121.1 (d, 3J(2' and 6',P) ˆ 5.0, C(2'), C(6')); 77.0 (d, 2J(1,P) ˆ 5.3, C(1));
3
3
71.5(Ph CH2); 69.6 (d, J(5,P) ˆ 7.2, C(5)); 58.8 (C(7)); 57.9 (C(9)); 44.9 (MeN); 33.7 (d, J(6,P) ˆ 8.9, C(6));
26.4 (d, 3J(10,P) ˆ 9.4, C(10)); epimer B: 155.0 (d, 2J(1',P) ˆ 6.8, C(1')); 145.0 (C(4')); 133.3 (C(3''), C(5''));
1
130.7 (C(4'')); 29.0 (C(2''), C(6'')); 126.8 (C(1'')); 125.6 (C(3'), C(5')); 122.2 (q, J(C,F) ˆ 320, CF3SO3); 121.1
3
2
3
(d, J(2' and 6',P) ˆ 5.0, C(2'), C(6')); 77.2 (d, J(1,P) ˆ 5.7, C(1)); 68.6 (d, J(5,P) ˆ 6.5, C(5)); 65.1 (PhCH2);
61.7 (C(7)); 60.5(C(9)); 52.2 (MeN); 36.3 ( d, 3J(6,P) ˆ 10.0, C(6)); 28.9 (d, 3J(10,P) ˆ 7.5, C(10)). 31P-NMR
21
)
Due to partial overlapping and marginal resolution of the signals, only tentative assignments.

2656
Helvetica Chimica Acta Vol. 87 (2004)
(121.4 MHz, (CD3)2CO): À11.3 (B), À11.8 (A) (each br. dd, 3J(P,HeqÀC(5)) ꢀ 15, 3J(P,HaxÀC(5)) ꢀ 10). ESI-
‡
‡
MS: 419 (100, [M À CF3SO3] ) 405(35, [ M ‡ H À Me] ).
(1RS,3RS,6SR,8SR)-8-Benzyl-3-(2,4-dinitrophenoxy)-8-methyl-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (45a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 3 :1).
White foam (92%). M.p. 97 988. IR (KBr): 3550 3200m, 1816w, 1765w, 1726w, 1710w, 1692w, 1658w, 1611m,
1546m, 1483m, 1350s, 1260s, 1159m, 1096m, 1050m, 1030s, 938m, 907m, 834m, 75 4m, 704w, 638m, 5 74w, 5 18m.
1H-NMR (300 MHz, (CD3)2CO)16): 8.93 (dd, 4J(3',5') ˆ 2.8, 5J(3',6') ꢀ 1, HÀC(3')); 8.67 (dd, 3J(5',6') ˆ 9.2,
4J(5',3') ˆ 2.8, HÀC(5')); 8.13 (dd, 3J(6',5') ˆ 9.2, 5J(6',3') ꢀ 1, HÀC(6')); 7.68 7.49 (m, HÀC(2'') to HÀC(6''));
5.04 (td, 3J(1,6) ˆ 3J(1,10ax) ˆ 11.0, 3J(1,10eq) ˆ 5.5, HÀC(1)); 4.895, 4.89 (AB, 2J ˆ 13.0, PhCH2); 4.69 4.60
(AB of ABXÀP, not resolved, CH2(5)); 4.09 3.76 (m, CH2(7), CH2(9)); 3.52 (s, MeaxÀN); 3.30 (s, MeeqÀN);
3.18 (X of ABXÀP, oct.-like, w1/2 ꢀ 30, HÀC(6)); 2.69 2.50 (m, CH2(10)). 13C-NMR (75.4 MHz, CDCl3):
2
3
epimer A: 147.4 (d, J(1',P) ˆ 5.5, C(1')); 144.0 (C(4')); 140.7 (br. d, J(2',P) ꢀ 7, C(2')); 133.4 (C(3''), C(5''));
130.7 (C(4'')); 129.4 (C(5')); 129.0 (C(2''), C(6'')); 126.9 (C(1'')); 123.2 (d, 3J(6',P) ꢀ 2, C(6')); 120.9 (q, 1J(C,F) ˆ
309, CF3SO3); 121.8 (C(3')); 78.6 (d, 2J(1,P) ˆ 7.1, C(1)); 71.5(Ph CH2); 70.6 (d, 2J(5,P) ˆ 8.4, C(5)); 58.9 (C(7));
57.5 (C(9)); 45.0 (MeN); 34.3 (d, 3J(6,P) ˆ 5.3, C(6)); 26.1 (d, 3J(10,P) ˆ 10, C(10)); epimer B: 147.4 (d,
3
2J(1',P) ˆ 5.5, C(1')); 144.0 (C(4')); 140.7 (br. d, J(2',P) ꢀ 7, C(2')); 133.4 (C(3''), C(5'')); 130.7 (C(4'')); 129.4
(C(5')); 129.0 (C(2'')), C(6'')); 126.9 (C(1'')); 123.2 (d, 3J(6',P) ꢀ 2, C(6')); 120.9 (q, 1J(C,F) ˆ 309, CF3SO3);
121.8 (C(3')); 78.6 (d, 2J(1,P) ˆ 7.1, C(1)); 71.5(Ph CH2); 70.6 (d, 2J(5,P) ˆ 8.0, C(5)); 61.7 (C(7)); 60.5 (C(9));
52.2 (MeN); 37.4 (d, 3J(6,P) ˆ 6.3, C(6)); 29.0 (d, 3J(10,P) ˆ 11, C(10)). 31P-NMR (121.4 MHz, (CD3)2CO):
‡
À14.7 (A), À14.8 (B) (each br. d, 3J(P,HeqÀC(5) ˆ 26). ESI-MS: 464 (100, [M À CF3SO3] ), 450 (5, ([M ‡ H À
‡
CF3SO3 À Me] ). Anal. calc. for C21H23F3N3O11PS ¥ H2O (631.44): C 39.94, H 3.39, N 6.65; found: C 39.36,
H 3.72, N 6.70.
(1RS,3RS,6SR)-3-(2,4-Dinitrophenoxy)-8,8-dimethyl-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]decane 3-
Oxide Trifluoromethanesulfonate (46a). White foam (30%). IR (KBr): 3550 3200m, 1820w, 1765w, 1723w,
1708w, 1695w, 1660w, 1610m, 1545m, 1480m, 1350s, 1260s, 1162m, 1098m, 1050m, 1032s, 940m, 905m, 830m,
758m, 707w, 640m, 5 7w0, 5 2m5 . 1H-NMR (300 MHz, (CD3)2CO): 8.90 (dd, 4J(3',5') ˆ 2.7, 5J(3',6') ˆ 1.2,
HÀC(3')); 8.65( dd, 3J(5',6') ˆ 9.2, 4J(5',3') ˆ 2.7, HÀC(5')); 8.02 (dd, 3J(6',5') ˆ 9.2, 5J(6',3') ˆ 1.2, HÀC(6'));
5.02 (td, 3J(1,6) ˆ 3J(1,10ax) ˆ 10.9, 3J(1,10eq) ˆ 5.2, HÀC(1)); 4.62 (A of ABXÀP, 2J ˆ 11.0, 3J(5eq,P) ˆ 23,
3J(5eq,6) ˆ 4.6, HeqÀC(5)); 4.56 ( B of ABXÀP, 2J ˆ 11.0, 3J(5ax,6)ˆ 11.8, HaxÀC(5)); 3.97 3.77 (m,
2
HeqÀC(7), CH2(9)); 3.70 (t, J ˆ 3J(7ax,6) ˆ 12.8, HaxÀC(7)); 3.60 (s, MeaxÀN); 3.51 (s, MeeqÀN); 3.29 (X of
ABXÀP, m, w1/2 ꢀ 30, HÀC(6)); 2.68 2.36 (m, CH2(10)). 13C-NMR (75.4 MHz, CDCl3): 147.1 (d, 2J(1',P) ˆ 4.8,
C(1')); 141.7 (C(4')); 138.5( m, w1/2 ꢀ 15, C(2')); 127.2 (C(5')); 121.0 (d, 3J(6',P) ˆ 2.2, C(6')); 119.6 (C(3')); 118.7
1
2
2
(q, J(C,F) ˆ 320, CF3SO3); 76.3 (d, J(1,P) ˆ 7.2, C(1)); 68.4 (d, J(5,P) ˆ 8.1, C(5)); 58.5 (C(7)); 57.6 (C(9));
54.0 (MeeqÀN); 46.1 (MeaxÀN); 32.4 (d, 3J(6,P) ˆ 5.9, C(6)); 24.2 (d, 3J(10,P) ˆ 10.0, C(10)). 31P-NMR
3
‡
(121.4 MHz, (CD3)2CO): À14.7 (d, J(P,HeqÀC(5)) ˆ 23). ESI-MS: 388 (100, [M À CF3SO3] ), 374 (18, [M ‡
‡
H À CF3SO3 À Me] ), 250 (15). Anal. calc. for C15H19F3N3O11PS ¥ 2 H2O (573.36): C 31.40, H 4.04, N 7.33;
found: C 31.60, H 4.20, N 7.47.
(1RS,3SR,6RS)-3-(2,4-Dinitrophenoxy)-8,8-dimethyl-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]decane 3-
Oxide Trifluoromethanesulfonate (46b)17). 31P-NMR (121.4 MHz, CDCl3): À13.7 (t-like, 3J(P,H) ꢀ 15).
(1RS,3RS,6RS,8RS)-8-Benzyl-3-chloro-8-methyl-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]decane 3-Ox-
ide Trifluoromethanesulfonate (47a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 5:1). White powder
(58%). M.p. 146 1488. IR (KBr): 3700 3300m, 2923w, 2360m, 2341m, 1734w, 1636w, 1558w, 1458m, 1311s,
1255s, 1226s, 1167m, 1083m, 1064m, 1033s, 995m, 968m, 946m, 873w, 830w, 794m. 1H-NMR (300 MHz,
(CD3)2CO)16): 7.81 7.77 (2 H), 7.61 7.53 (3 H) (each m, HÀC(2') to HÀC(6')); 5.24 (s, w1/2 ꢀ 8, HÀC(1)); 5.05
(s, PhCH2); 4.85( A of ABXÀP, 2J ˆ 12.6, 3J(5ax,6) ˆ 3J(5ax,P) ꢀ 2.7, HaxÀC(5)); 4.19 (B of ABXÀP, 2J ˆ 12.6,
3
3J(5eq,P) ˆ 30.2, J(5eq,6) ꢀ 1, HeqÀC(5)); 4.05 (t, 2J ˆ 3J(7ax,6) ˆ 13, HaxÀC(7)); 3.93 (td, 2J ˆ 3J(9ax,10ax) ˆ
3
13.5, J(9ax,10eq) ˆ 3.0, HaxÀC(9)); 3.84, 3.71 (each m, d-quint.-like, w1/2 ꢀ 20, HeqÀC(7), HeqÀC(9)); 3.33 (s,
MeN); (3.07 (m, d-like, w1/2 ꢀ 20, HeqÀC(10)); 2.78 (X of ABXÀP, m, w1/2 ꢀ 30, HÀC(6)); 2.37 (m, d-like, w1/2
ꢀ
20, HaxÀC(10)). 13C-NMR (75.4 MHz, (CD3)2CO): epimer A: 131.3 (C(3'), C(5')); 128.3 (C(4')); 126.8 (C(2'),
C(6')); 125.2 (C(1')); 118.6 (q, 1J(C,F) ˆ 322, CF3SO3); 69.1 (d, 2J(1,P) ˆ 5.6 C(1)); 68.1 (PhCH2); 65.8 (d,
3
3
2J(5,P) ˆ 6.2, C(5)); 53.5 (C(7)); 53.1 (C(9)); 41.4 (MeN); 27.5 (d, J(6,P) ˆ 4.1, C(6)); 23.1 (d, J(10,P) ˆ 8.7,
C(10)); epimer B: 131.3 (C(3'), C(5')); 128.3 (C(4')); 126.8 (C(2'), C(6')); 125.2 (C(1')); 118.6 (q, 1J(C,F) ˆ 322,
CF3SO3); 69.7 (d, 2J(1,P) ˆ 6, C(1)); 68.1 (PhCH2); 65.9 (d, 2J(5,P) ˆ 6, C(5)); 57.5 (C(7)); 57.0 (C(9)); 49.8
(MeN); 30.1 (d, 3J(6,P) ˆ 4, C(6)); 25.6 (d, 3J(10,P) ˆ 9, C(10)). 31P-NMR (121.4 MHz, (CD3)2CO): À3.4 (d,
‡
‡
3J(P,HeqÀC(5) ˆ 30.2). ESI-MS: 318 (28, [M(37Cl) À CF3SO3] ), 316 (100, [M(35Cl) À CF3SO3] ).

Helvetica Chimica Acta Vol. 87 (2004)
2657
(1RS,3RS,6RS,8RS)-8-Benzyl-8-methyl-3-(4-nitrophenoxy)-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (48a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 6 :1).
White powder (87%). 1H-NMR (300 MHz, (CD3)2CO)16): 8.27 (AA' of AA'BB', J ˆ 9.1, HÀC(3'), HÀC(5'));
7.73 (BB' of AA'BB', J ˆ 9.1, HÀC(2'), HÀC(6')); 7.58 7.45 (m, HÀC(2'') to HÀC(6'')); 5.29 (q, 3J(1,6) ꢀ
3
3J(1,10ax) ꢀ J(1,10eq) ꢀ 2, HÀC(1)); 4.99 (s, PhCH2); 4.91 (A of ABXÀP, 2J ˆ 12.2, 3J(5ax,6) ˆ 2.5, HaxÀC(5));
4.42 (B of ABXÀP, 2J ˆ 12.2, 3J(5eq,P) ˆ 25, HeqÀC(5)); 4.02 (t, 2J ˆ 3J(7ax,6) ˆ 13.1, HaxÀC(7)); 3.93 3.59
(m, HeqÀC(7), CH2(9)); 3.34 (s, MeaxÀN); 3.26 (s, MeeqÀN); 2.96 (m, d-like, w1/2 ꢀ 20, HeqÀC(10)); 2.66 (X of
ABXÀP, m, w1/2 ꢀ 30, HÀC(6)); 2.27 (m, d-like, w1/2 ꢀ 20, HaxÀC(10)). 13C-NMR (75.4 MHz, (CD3)2CO): 155.0
2
(d, J(1',P) ˆ 6, C(1')); 144.9 (C(4')); 133.4 (C(3''), C(5'')); 131.3 (C(4'')); 129.0 (C(2''), C(6'')); 126.9 (C(1''));
125.7 (C(3'), C(5')); 121.2 (q, 1J(C,F) ˆ 321, CF3SO3); 120.6 (d, 3J(2' and 6',P) ˆ 5.5, C(2'), C(6')); 74.5( d,
3
2J(1,P) ˆ 7.0, C(1)); 71.5(Ph CH2); 70.5( d, J(5,P) ˆ 7.9, C(5)); 55.5 (C(7)); 54.2 (C(9)); 52.4 (MeeqÀN); 43.6
(MeaxÀN); 30.1 (d, 3J(6,P) ˆ 5.0, C(6)); 25.4 (d, 3J(10,P) ˆ 9.0, C(10)). 31P-NMR (121.4 MHz, (CD3)2CO):
3
‡
À14.3 (A), À14.4 (B) (each d, J(P,HeqÀC(5) ˆ 25). ESI-MS: 419 (100, [M À CF3SO3] ), 405(15, [ M ‡ H À
‡
CF3SO3 À Me] ).
(1RS,3SR,6RS,8RS)-8-Benzyl-8-methyl-3-(4-nitrophenoxy)-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]-
decane 3-Oxide Trifluoromethanesulfonate (48b). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca. 6 :1).
Slightly yellow oil (64%). 1H-NMR (300 MHz, (CD3)2CO)16
)
18): 8.37 (AA' of AA'BB', J ˆ 9.1, HÀC(3'),
HÀC(5')); 7.69 (BB' of AA'BB', J ˆ 9.1, HÀC(2'), HÀC(6')); 7.60 7.46 (m, HÀC(2'') to HÀC(6'')); 5.25 (q,
3J(1,6) ꢀ J(1,10ax) ꢀ J(1,10eq) ꢀ 2.5, HÀC(1)); 4.93, 4.50 (AB of ABXÀP, not resolved, CH2(5)); 4.80 (s,
PhCH2); 3.80 3.58 (m, CH2(7), CH2(9)); 3.34 (s, MeaxÀN); 3.14 (s, MeeqÀN); 3.04 (m, d-like, w1/2 ꢀ 20,
HeqÀC(10)); 2.73 (X of ABXÀP, m, w1/2 ꢀ 30, HÀC(6)); 2.38 (m, t-like, w1/2 ꢀ 30, HaxÀC(10)). 13C-NMR
(75.4 MHz, (CD3)2CO): 154.7 (d, 2J(1',P) ˆ 5.8, C(1')); 145.3 (C(4')); 133.4 (C(3''), C(5'')); 130.7 (C(4'')); 129.0
(C(2''), C(6'')); 126.6 (C(1'')); 125.7 (C(3'), C(5')); 121.1 (q, 1J(C,F) ˆ 322, CF3SO3); 121.5( d, 3J(2' and 6',P) ˆ
4.5, C(2'), C(6')); 72.9 (d, 2J(1,P) ˆ 4.5, C(1)); 71.9 (PhCH2); 69.1 (d, 3J(5,P) ˆ 5.7, C(5)); 55.5 (C(7)); 53.7
(C(9)); 52.7 (MeeqÀN); 44.4 (MeaxÀN); 30.4 (d, 3J(6,P) ˆ 5.1, C(6)); 25.4 (d, 3J(10,P) ˆ 9.4, C(10)). 31P-NMR
3
3
(121.4 MHz, (CD3)2CO)18): À9.8 (B), À10.0 (A) (each br. d, J(P,HeqÀC(5)) ꢀ 20). ESI-MS: 419 (100, [M À
3
‡
‡
CF3SO3] ), 405(18, [ M ‡ H À CF3SO3 À Me] ).
(1RS,3RS,6RS,8RS)-8-Benzyl-3-(2,4-dinitrophenoxy)-8-methyl-2,4-dioxa-8-azonia-3-phosphabicyclo-
[4.4.0]decane 3-Oxide Trifluoromethanesulfonate (49a). Mixture of N-epimers (A ˆ Meax, B ˆ Meeq, A/B ca.
2 :1). White powder (57%). M.p. 88 908. IR (KBr): 3700 3300m, 1736w, 1611m, 1543m, 1483m, 1351s, 1261s,
1164m, 1085m, 1066m, 1030s, 972m, 939m, 904m, 873w, 803w, 75 6m, 741m, 710w, 638m, 5 74w, 5 5 4w, 5 18w, 476w.
1H-NMR (300 MHz, (CD3)2CO)16): 8.95( d, 4J(3',5') ˆ 2.5, HÀC(3')); 8.71 (dd, 3J(5',6') ˆ 9.2, 4J(5',3') ˆ 2.5,
HÀC(5')); 8.11 (d, 3J(6',5') ˆ 9.2, HÀC(6')); 7.85 7.63 ( m, HÀC(2'') to HÀC(6'')); 5.41 (q, 3J(1,6) ꢀ
3J(1,10ax) ꢀ J(1,10eq) ꢀ 2, HÀC(1)); 5.12 (s, PhCH2); 5.04 (A of ABXÀP, 2J ˆ 12.3, 3J(5ax,P) ˆ 7,
3
3J(5ax,6) ꢀ 2, HaxÀC(5)); 4.73 (B of ABXÀP, 2J ˆ 12.3, 3J(5eq,P) ˆ 25.5, HeqÀC(5)); 4.20 (t, 2J ˆ 3J(7ax,6) ˆ
13.0, HaxÀC(7)); 3.96 (td-like, 2J ꢀ 12, 3J(9eq,10ax) ꢀ J(9eq,10eq ꢀ 3, HeqÀC(9)); 3.91 3.61 (m, HeqÀC(7),
3
HaxÀC(9)); 3.41 (s, MeaxÀN); 3.29 (s, MeeqÀN); 3.18 (m, d-like, w1/2 ꢀ 20, HeqÀC(10)); 2.81 (X of ABXÀP, m,
w1/2 ꢀ 30, HÀC(6)); 2.31 (m, d-like, w1/2 ꢀ 25, HaxÀC(10)). 13C-NMR (75.4 MHz, (CD3)2CO): epimer A: 148.3
(d, 2J(1',P) ˆ 5.8, C(1')); 144.8 (C(4')); 141.4 (d, 3J(2',P) ˆ 6.8, C(2')); 133.3 (C(3''), C(5'')); 130.8 (C(4'')); 129.4
(C(5')); 129.1 (C(2''), C(6'')); 126.8 (C(1'')); 123.1 (d, 3J(6',P) ꢀ 2, C(6')); 119.9 (q, 1J(C,F) ˆ 322, CF3SO3); 121.9
2
2
(C(3')); 76.2 (d, J(1,P) ˆ 7.3, C(1)); 71.8 (d, J(5,P) ˆ 8.2, C(5)); 71.7 (PhCH2); 55.4 (C(7)); 54.1 (C(9)); 44.5
(MeN); 31.0 (d, 3J(6,P) ˆ 6.3, C(6)); 26.3 (d, 3J(10,P) ˆ 9.0, C(10)); epimer B: 148.3 (d, J(1',P) ˆ 5.8, C(1'));
2
144.8 (C(4')); 141.4 (d, 3J(2',P) ˆ 6.8, C(2')); 133.3 (C(3''), C(5'')); 130.8 (C(4'')); 129.4 (C(5')); 129.1 (C(2''),
C(6'')); 126.8 (C(1'')); 123.1 (d, 3J(6',P) ꢀ 2, C(6')); 119.9 (q, 1J(C,F) ˆ 322, CF3SO3); 121.9 (C(3')); 76.4 (d,
2J(1,P) ˆ 7.6, C(1)); 72.5( d, 2J(5,P) ꢀ 8, C(5)); 71.7 (PhCH2); 56.3 (C(7)); 55.8 (C(9)); 52.5 (MeN); 33.6 (d,
3J(6,P) ˆ 5.5, C(6)); 28.8 (d, J(10,P) ˆ 5.5, C(10)). 31P-NMR (121.4 MHz, (CD3)2CO): À15.0 (B), À15.2 (A)
3
(each dd, 3J(P,HeqÀC(5)) ˆ 25.5, 3J(P,HaxÀC(5)) ˆ 7). ESI-MS: 464 (100, [M À CF3SO3] ), 450 (18, [M ‡ H À
‡
‡
CF3SO3 À Me] ). Anal. calc. for C21H23F3N3O11PS ¥ 3 H2O (667.47): C 37.78, H 4.38, N 6.29; found: C 38.04,
H 4.01, N 6.10.
(1RS,3RS,6RS)-3-(2,4-Dinitrophenoxy)-8,8-dimethyl-2,4-dioxa-8-azonia-3-phosphabicyclo[4.4.0]decane 3-
Oxide Trifluoromethanesulfonate (50a)22). White foam (95%). 1H-NMR (300 MHz, (CD3)2CO): 8.90 (d,
4J(3',5') ˆ 2.7, HÀC(3')); 8.65( dd, 3J(5',6') ˆ 9.1, 4J(5',3') ˆ 2.7, HÀC(5')); 8.11 (d, 3J(6',5') ˆ 9.1, HÀC(6')); 5.35
3
2
3
(q, J(1,6) ˆ 3J(1,10ax) ˆ 3J(1,10eq) ˆ 2.3, HÀC(1)); 4.99 (A of ABXÀP, J ˆ 12.3, J(5ax,6) ˆ 2.5, HaxÀC(5));
22
)
The equatorially substituted P-epimer was not detected in the reaction mixture.

2658
Helvetica Chimica Acta Vol. 87 (2004)
4.55 (B of ABXÀP, 2J ˆ 12.3, 3J(5eq,P) ˆ 26.5, HeqÀC(5)); 4.01 3.02 (m, CH2(7), CH2(9)); 3.61 (s, MeaxÀN);
3.46 (s, MeeqÀN); 3.18 (m, dd-like, w1/2 ꢀ 20, HeqÀC(10)); 2.79 (X of ABXÀP, m, w1/2 ꢀ 30, HÀC(6)); 2.36 (m, d-
like, w1/2 ꢀ 25, HaxÀC(10)). 13C-NMR (75.4 MHz, (CD3)2CO): 148.4 (d, 2J(1',P) ˆ 6.0, C(1')); 144.8 (C(4'));
3
3
1
141.4 (d, J(2',P) ꢀ 7, C(2')); 130.3 (C(5')); 123.7 (d, J(6',P) ꢀ 2, C(6')); 122.7 (C(3')); 121.5( q, J(C,F) ˆ 320,
CF3SO3); 75.7 (d, 2J(1,P) ˆ 7.5, C(1)); 71.8 (d, 2J(5,P) ˆ 7.9, C(5)); 58.3 (C(7)); 57.2 (MeeqÀN); 56.8 (C(9)); 48.2
(MeaxÀN); 31.2 (d, 3J(6,P) ˆ 5.5, C(6)); 26.5 (d, 3J(10,P) ˆ 9.0, C(10)). 31P-NMR (121.4 MHz, (CD3)2CO):
À15.2 (d, 3J(P,HeqÀC(5)) ˆ 26). ESI-MS: 388 (100, [M À CF3SO3] ), 374 (20, [M ‡ H À CF3SO3 À Me] ), 349
(42), 248 (40), 174 (58). Anal. calc. for C15H19F3N3O11PS ¥ 2 H2O (573.36): C 31.40, H 4.04, N 7.33; found:
C 31.36, H 4.18, N 6.92.
‡
‡
7. 2,4-Dioxa-7-aza-3-phosphadecalins 59 66 of Type III. (1RS,3RS,6SR)-7-Benzyl-3-fluoro-2,4-dioxa-7-
aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (59a). Colorless prisms (22%). M.p. 116.5 118.5 8. Rf (hexane/
Et2O 1:2) 0.26. IR (KBr): 3027w, 2961m, 2918m, 2815m, 2723w, 1495w, 1455m, 1402w, 1335s, 1285m, 1146m,
1123m, 1103w, 1071m, 1051s, 1006s, 988m, 95 5w, 928w, 887s, 848w, 824w, 788m, 75 6s, 705m, 646w, 5 93m, 5 64m,
526m, 5 16w. 1H-NMR (600 MHz, CDCl3): 7.34 7.23 (m, HÀC(2') to HÀC(6')); 4.69 (A of ABXÀP, 2J ˆ 10.9,
3J(5eq,P)ˆ 25.2, 3J(5eq,6) ˆ 4.2, HeqÀC(5)); 4.33 (ddd, 3J(1,6) ˆ 10.5, 3J(1,10ax) ˆ 9.0, 3J(1,10eq) ˆ 4.8,
HÀC(1)); 4.21 (B of ABXÀP, 2J ˆ 3J(5ax,6) ˆ 10.8, 3J(5ax,P) ꢀ 1, HaxÀC(5)); 3.78, 3.36 (AB, 2J ˆ 13.8,
PhCH2); 2.83 (m, d-like, w1/2 ꢀ 15, 2J ꢀ 12, HeqÀC(8)); 2.66 (X of ABXÀP, 3J(6,1) ˆ 10.5, 3J(6,5ax) ˆ 10.8,
3J(6,5eq) ˆ 4.2, 5J(6,F) ˆ 1.2, HÀC(6)); 2.17 (m, w1/2 ꢀ 15, HeqÀC(10)); 2.12 (td, 2J ˆ 3J(8ax,9ax) ˆ 11.8,
3J(8ax,9eq) ˆ 3.0, HaxÀC(8)); 1.73 (m, d-like, w1/2 ꢀ 15, 2J ꢀ 11, 5J(9eq,P) ꢀ 2, HeqÀC(9)); 1.64 1.56 (m,
HaxÀC(9), HaxÀC(10)). 13C-NMR (150.9 MHz, CDCl3): 137.7 (C(1')); 128.5(C(3 '), C(5')); 128.2 (C(2'), C(6'));
127.5(C(4 ')); 81.0 (dd, 2J(1,P) ˆ 7.2, 3J(1,F) ˆ 1.9, C(1)); 72.2 (d, 2J(5,P) ˆ 7.8, C(5)); 61.4 (d, 3J(6,P) ˆ 4.8, C(6));
3
4
58.0 (PhCH2); 52.9 (C(8)); 30.9 (d, J(10,P) ˆ 9.6, C(10)); 22.9 (d, J(9,P) ˆ 2.5, C(9)). 31P-NMR (242.9 MHz,
CDCl3): À16.3 (dbr. d, 1J(P,F) ˆ 1013, 3J(P,HeqÀC(5)) ˆ 25.2, 5J(9eq,P) ꢀ 2). 19F{1H}-NMR (564.5 MHz,
.
1
‡
‡
CDCl3): À86.7 (d, J(F,P) ˆ 1013). EI-MS: 285(4, M ), 194 (4, [M À PhCH2] ), 171 (12), 160 (17), 91 (100,
‡
PhCH2 ), 65(14). Anal. calc. for C 13H17FNO3P (285.24): C 54.75, H 6.01, N 4.91; found: C 54.45 H 5.58, N 4.83.
(1RS,3SR,6SR)-7-Benzyl-3-fluoro-2,4-dioxa-7-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (59b). Color-
less plates (23%). M.p. 86 90.58. Rf (hexane/Et2O 1:2) 0.19. IR (KBr): 3062w, 3028w, 2961m, 2859m, 2723w,
1604w, 1494m, 1480m, 1455m, 1439m, 1398m, 1325s, 1292s, 1262m, 1228w, 1126m, 1080s, 1008s, 95 3m, 924m,
878s, 847m, 806w, 777m, 741s, 699s, 65 3m, 5 97m, 5 66m, 5 24m. 1H-NMR (600 MHz, CDCl3): 7.34 7.23 (m,
HÀC(2') to HÀC(6')); 4.74 (A of ABXÀP, 2J ˆ 10.2, 3J(5eq,P) ˆ 9.2, 3J(5eq,6) ˆ 5.5, HeqÀC(5)); 4.45 (sept.-
like, 3J(1,10ax)
ꢀ
3J(1,6) ꢀ 10, 3J(1,10eq) ˆ 4.5, 4J(1,F) ˆ 3.5, 3J(1,P)
ꢀ 1, H-C(1)); 4.38 (B of ABXÀP,
3J(5ax,P) ˆ 14.0, 2J ˆ 3J(5ax,6) ˆ 10.0, 4J(5ax,F) ˆ 2.8, HaxÀC(5)); 3.71, 3.25 (AB, 2J ˆ 13.6, PhCH2); 2.80 (m, d-
like, 2J ꢀ 12, HeqÀC(8)); 2.77 (X of ABX, 3J(6,1) ꢀ 10, 3J(6,5ax) ˆ 10.0, 3J(6,5eq) ˆ 5.5, 5J(6,F) ˆ 2.6, HÀC(6));
2.24 (m, w1/2 ꢀ 18, HeqÀC(10)); 2.12 (td, 2J ˆ 3J(8ax,9ax) ˆ 11.8, 3J(8ax,9eq) ˆ 2.7, HaxÀC(8)); 1.72 (m, d-like,
w1/2 ꢀ 15, 2J ꢀ 11, 5J(9eq,P) ꢀ 2, HeqÀC(9)); 1.63 1.50 (m, HaxÀC(9), HaxÀC(10)). 13C-NMR (105.9 MHz,
2
3
CDCl3): 137.4 (C(1')); 128.6 (C(3'), C(5')); 128.4 (C(2'), C(6')); 127.6 (C(4')); 80.9 (dd, J(1,)P ˆ 6.2, J(1,F) ˆ
1.6, C(1)); 72.7 (d, 2J(5,P) ˆ 7.6, C(5)); 60.5 (d, 3J(6,P) ˆ 9.8, C(6)); 58.1 (PhCH2); 52.4 (C(8)); 31.1 (d,
3J(10,P) ˆ 7.8, C(10)); 22.7 (d, 4J(9,P) ˆ 2.3, C(9)). 31P-NMR (124.9 MHz, CDCl3): À15.1 (dbr. dd, 1J(P,F) ˆ 997,
3J(P,HaxÀC(5) ˆ 14.0, 3J(P,HeqÀC(5)) ˆ 9.2, 5J(9eq,P) ꢀ 2). 19F{1H}-NMR (564.5 MHz, CDCl3): À72.8 (d,
1J(F,P) ˆ 997). 19F-NMR (564.5 MHz, CDCl3): À72.8 (dq, 1J(F,P) ˆ 997, 4J(F,HÀC(1)) ꢀ J(F,HaxÀC(5)) ꢀ
4
5J(F,HÀC(6)) ꢀ 3 (see 1H-NMR). CI-MS: 571 (99, [2M ‡ H] ), 303 (16, [M ‡ NH4] ); 286 (100, [M ‡ H] ).
‡
‡
‡
Anal. calc. for C13H17FNO3P (285.24): C 54.75, H 6.01, N 4.91; found: C 54.18, H 5.56, N 4.82.
(1RS,3RS,6RS)-7-Benzyl-3-fluoro-2,4-dioxa-7-aza-3-phosphabicyclo[4.4.0]decane 3-Oxide (60a). Color-
less prisms (23%). M.p. 107 110.58. Rf (hexane/AcOEt 1:1) 0.24. IR (KBr): 3082w, 3030w, 2969m, 2950m,
2807m, 2785m, 1606w, 1493m, 1450m, 1431w, 1381m, 1360m, 1343s, 1325s, 1252m, 1229m, 1203w, 1151s, 1121m,
1111m, 1085s, 1073m, 1058s, 1046s, 1033s, 988s, 968m, 930w, 904s, 884s, 869m, 848w, 827s, 760s, 730s, 700m, 649m,
1
2
538w, 5 24m. H-NMR (600 MHz, CDCl3): 7.35 7.24 ( m, HÀC(2') to HÀC(6')); 4.86 (A of ABXÀP, J ˆ 12.7,
3J(5eq,P) ˆ 25.5, 3J(5eq,6) ˆ 1.5, HeqÀC(5)); 4.79 (m, w1/2 ꢀ 6, HÀC(1)); 4.34 (B of ABXÀP, 2J ˆ 12.7,
3J(5ax,6) ˆ 3J(5ax,P) ˆ 1.5, HaxÀC(5)); 4.13, 3.29 (AB, 2J ˆ 13.6, PhCH2); 2.93 (m, dt-like, w1/2 ꢀ 15, 2J ˆ 12.5,
HeqÀC(8)); 2.48 (X of ABXÀP, 3J(6,1) ˆ 3J(6,5ax) ˆ 3J(6,5eq) ˆ 4J(6,P) ˆ 1.5, HÀC(6)); 2.12 (td, 2J ˆ
3J(8ax,9ax) ˆ 12.5, 3J(8ax,9eq) ˆ 2.5, HaxÀC(8)); 2.09 (m, d-like, w1/2 ꢀ 18, HeqÀC(10)); 1.97 (qt, 2J ˆ
3J(9ax,8ax) ˆ 3J(9ax,10ax) ˆ 12.5, 3J(9ax,8eq) ˆ 3J(9ax,10eq) ˆ 3.8, HaxÀC(9)); 1.63 (m, w1/2 ꢀ 30,
4J(10ax,P) ˆ 7.5, H axÀC(10)); 1.47 (m, dq-like, w1/2 ꢀ 18, 2J ˆ 12.5, HeqÀC(9)). 13C-NMR (150.9 MHz, CDCl3):
137.7 (C(1')); 128.6 (C(3'), C(5')); 128.4 (C(2'), C(6')); 127.2 (C(4')); 80.2 (d, 2J(1,P) ˆ 7.9, C(1)); 69.1 (dd,
2J(5,P) ˆ 6.9, 3J(5,F) ˆ 0.8, C(5)); 58.1 (d, 3J(6,P) ˆ 5.4, C(6)); 57.1 (PhCH2); 51.8 (C(8)); 30.0 (d, 3J(10,P) ˆ 8.8,
C(10)); 19.5( d, 4J(9,P) ˆ 2.5, C(9)). 31P-NMR (242.9 MHz, CDCl3): À16.7 (ddd, 1J(P,F) ˆ 997,