Reactivity and diastereoselectivity in the thermal and Lewis acid- catalyzed Diels-Alder reactions of N-sulfinylphosphoramidates

Article abstract of DOI:10.1021/jo970186t

The [4 + 2] cycloaddition reactions of N-sulfinylphosphoromidates, prepared from the corresponding phosphoramidates by treatment with N- (chlorosulfinyl)imidazole, and 1,3-cyclohexadiene were found to be diastereoselective in the absence (>90:10) and presence (> 95:5) of Lewis acid. The sulfur configuration of the major adduct from the cycloaddition reaction has been established unambiguously by X-ray crystallography. The use of Lewis acids improved the diastereoselectivity and yield, as Well as shortened reaction times. Based on the intermediacy of a tin chelate, and the absence of phosphoryl secondary orbital interactions, a mechanism for the cycloaddition reactions is discussed.

Full text of DOI:10.1021/jo970186t

1
372
J . Org. Chem. 1998, 63, 1372-1378
Articles
Rea ctivity a n d Dia ster eoselectivity in th e Th er m a l a n d Lew is
Acid -Ca ta lyzed Diels-Ald er Rea ction s of
N-Su lfin ylp h osp h or a m id a tes1
,
†
,‡
Yinsheng Zhang* and Christopher J . Flann*
Department of Chemistry, University of Montana, Missoula, Montana 59812
Received February 3, 1997 (Revised Manuscript Received December 31, 1997)
The [4 + 2] cycloaddition reactions of N-sulfinylphosphoramidates, prepared from the corresponding
phosphoramidates by treatment with N-(chlorosulfinyl)imidazole, and 1,3-cyclohexadiene were found
to be diastereoselective in the absence (>90:10) and presence (>95:5) of Lewis acid. The sulfur
configuration of the major adduct from the cycloaddition reaction has been established unambigu-
ously by X-ray crystallography. The use of Lewis acids improved the diastereoselectivity and yield,
as well as shortened reaction times. Based on the intermediacy of a tin chelate, and the absence
of phosphoryl secondary orbital interactions, a mechanism for the cycloaddition reactions is
discussed.
6
In tr od u ction
organophosphorus compounds, we undertook a system-
atic study of the [4 + 2] cycloaddition of N-sulfinylphos-
phoramidates 3a -f with various dienes. The reactivity
and diastereoselectivity of this [4 + 2] cycloaddition in
the absence and presence of a Lewis acid is reported
herein.
The Diels-Alder chemistry of phosphoryl activated
N-sulfinyl compounds had previously seen little research.
2
In 1963, Wieczorkowski reported the first example of a
Diels-Alder reaction between diethyl N-sulfinylphos-
phoramidate (G ) P(O)(OEt) ) and a 1,3-diene to afford
2
a 3,6-dihydro-2H-1,2-thiazine 1-oxide (eq 1). Subsequent
studies, notably by Kataev and Bal’on, showed that this
dienophile exhibited reasonable levels of reactivity and
Resu lts
P r ep a r a tion of N-Su lfin ylp h osp h or a m id a tes 3a -
f. The N-sulfinyl compounds are usually prepared from
their corresponding amides.5 Phosphoramidates 2a -c
were prepared in good yield by the reaction of phospho-
c
rines 1a -c (commercially available) with CCl
gas at room temperature.7 Cyclic phosphoramidates
d -f were obtained in high yield from the treatment of
corresponding chlorides 1d -f with NH gas in benzene.
4 3
and NH
2
regioselectivity with various dienes.3,4 These isolated
reports represent the extent of research in this area. This
dearth of studies on the phosphoryl variant of Diels-
Alder reactions featuring N-sulfinyl dienophiles (eq 1)
stands in stark contrast to the many studies in which
3
Little is known about N-sulfinylphosphoramidates, but
the preparation of other N-sulfinyl compounds has been
5c
investigated. Compounds 3a -c were readily prepared
2
by the reaction of amides 2a -c with SOCl in the absence
the sulfonamide (G ) SO Ph) and the carbamate (G )
2
or presence of pyridine. The acid sensitivity of com-
pounds 3d -f suggested that modification of this method
by addition of tertiary amine bases, such as pyridine and
triethylamine, might be beneficial. However, such modi-
fication provided very poor yields of N-sulfinylphosphor-
amidates 3d -f (25% to 40%).
COOR) serve as the activating group.5
a-c
As part of our interest in the development of new
methodology for asymmetric synthesis via homochiral
†
Current address: Le Research, Inc., 2715 Upper Afton Road, St.
Paul, MN 55119.
‡
The substitution of N-(chlorosulfinyl)imidazole for
Current address: Moulton, Bellingham, Longo & Mather, P. C.,
1
900 Sheraton Plaza, P.O. Box 2559, Billings, MT 59103-2559.
1) Presented at the 47th Northwest Regional Meeting of ACS,
Missoula, MT, 1992, ORGN 116.
SOCl , however, afforded the desired compounds 3a -f
2
(
8
in good yields. N-(Chlorosulfinyl)imidazole, formed by
a direct treatment of imidazole with excess thionyl
chloride, was used in situ for the synthesis of the
N-sulfinylphosphoramidates 3a -f.
(
2) Wieczorkowski, J . Chem. Ind. 1963, 825.
(3) Kataev, E. G.; Plemenkov, V. V.; Markin, V. V. Dokl. Akad. Nauk.
SSSR 1965, 165, 1313.
4) Levchenko, E. S.; Bal’on, Ya G.; Kirsanov, A. V. Zh. Org. Khim.
967, 30, 1883.
5) These reactions have been widely investigated from a synthetic
(
1
(
(6) Flann, C. J . Book of Abstracts; ACS 32nd National Organic
Chemistry Symposium, American Chemical Society: Washington, DC,
1991, p 288.
(7) Atherton, F. R.; Openshaw, T. H.; Todd, A. R. J . Org. Chem.
1945, 663.
and mechanistic perspective. For comprehensive reviews see: (a)
Weinreb, S. M. Acc. Chem. Res. 1988, 21, 313. (b) Boger, D. L.;
Weinreb, S. M. In Hetero Diels-Alder Methodology in Organic Syn-
thesis; Academic: San Diego, 1987; p 1. (c) Bussas, P.; Kresze, G.;
Munsterer, H.; Schwobel, A. Sulf. Rep. 1983, 2, 215.
(8) Kim, Y. H.; Shin, J . M. Tetrahedron Lett. 1985, 26, 3821.
S0022-3263(97)00186-2 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/18/1998

Diels-Alder Reactions of N-Sulfinylphosphoramidates
Ta ble 1. Cycloa d d ition s of N-Su lfin ylp h osp h or a m id a te
J . Org. Chem., Vol. 63, No. 5, 1998 1373
Sch em e 1
3
d a n d Dien es
Sch em e 2
Compounds 3a and 3b were purified by distillation.
Thermally unstable and moisture sensitive compounds
3
c-f were used as formed in situ.
Rea ctivity of N-Su lfin ylp h osp h or a m id a tes in [4
+
2] Cycloa d d ition s. The previous studies indicated
these compounds underwent the [4 + 2] cycloaddition
reaction, but under conditions suggesting low dieneophile
reactivity.2 Wieczorkowski reported that diethyl N-sul-
Sch em e 3
-4
finylphosphoramidate 3a only reacted with dienes at 60-
2
7
0 °C in benzene. However, we found the cycloaddition
of compounds 3a -f took place at room temperature in
CH Cl in fair to good yields. The examples of [4 + 2]
2
2
cycloaddition reactions of compound 3d with various
dienes are shown in Table 1.
In addition to cycloaddition adducts, phosphoramides
were also formed. If compound 3d was generated with-
out purification, a cycloaddition reaction with cyclohexa-
diene afforded the desired adduct 7d and a byproduct
from a [3 + 2] cycloaddition. However, a more reasonable
which has been identified as 8d based on 1H, C,
13
31
P
explanation is a [2,3]-sigmatropic rearrangement after
NMR and elemental analysis. This same product was
the [4 + 2] cycloaddition reaction, as shown in Scheme
obtained by the treatment of adduct 7d with HCl or
10,11
3
.
4
caustic soda, indicating that the byproduct was formed
Regioselectivity a n d Dia ster eoselectivity. Ka-
from the adduct 7d by loss of SO
2
(Scheme 2). These
3
taev examined the regioselectivity of the cycloaddition
of 3a and 2-substituted 1,3-butadienes and suggested
that the major product was a 4-substituted thiazine oxide
results illustrate that the adducts can be readily con-
verted to â-aminoalkenes 8d .
The dienophiles showed reactivity with a broad range
of dienes. The relatively unreactive butadiene provides
an adduct in good yield, while the most reactive diene,
cyclopentadiene, affords a complicated mixture from
which 9d can be isolated. This product appears to result
1
4
on the basis of low resolution H NMR. Later, Bal’on
corrected the major product as a 5-substituted thiazine
oxide. We also studied the reaction of isoprene with
compounds 3a and 3d and found only one isomer in each
1
13
case. Based on the analysis of H and C NMR, the
structures of the adducts are consistent with 5-methyl-
(9) (a) Kashman, Y.; Awerbough, O. Tetrahedron 1971, 5593. (b)
2
thiazine oxide 5a (G ) (EtO) ) and 5d (Table 1).
In the cycloaddition reactions of dienes and N-sulfinyl
compounds, adducts epimeric at sulfur can be formed.
Pankiewicz, Z.; Kinas, R.; Stec, W. J . J . Am. Chem. Soc. 1979, 101,
7
1
2
712. (c) Cerioni, G.; Piras, P. J . Chem. Soc., Perkin Trans. 2 1981,
449. (d) McClure, C. K.; Hansen, K. B. Tetrahedron Lett. 1996, 37,
049. To our knowledge, the effects of SnCl
4
on the chemical shifts of
P NMR spectroscopy were not studied before; however, the effects of
common chemical shift reagents, such as Eu(dpm) and Eu(tfc) , on
on H and C NMR of carbonyl
3
1
3
3
(10) We could not characterize compounds formed in the cycload-
dition since they were extremely unstable.
the 31P NMR and Lewis acid SnCl
1
13
4
compounds have been investigated. Our results were consistent with
previous reports cited above.
(11) Natsugari, H.; Whittle, R. R.; Weinreb, S. M. J . Am. Chem. Soc.
1984, 106, 7867.

1
374 J . Org. Chem., Vol. 63, No. 5, 1998
Zhang and Flann
Ta ble 2. Dia ster eoselectivity in th e Cycloa d d ition s of
N-Su lfin ylp h osp h or a m id a tes (3a -f)
endo/exo isolated
ratioa
yield, %
b
entry dienophile
conditions
4 h, rt
1
2
3
4
5
6
7
8
9
0
3a
91:9
>95:5
>95:5
74
83
80
90
78
78
80
50
68
45
60
55
63
41
55
20 min, BF3‚Et2O, rt
o
15 min, TiCl4, -78 C
o
15 min, SnCl4, -78 C >95:5
o
15 min, SnCl4, 5 C
4 h, rt
>95:5
92:8
F igu r e 1. Endo/exo sulfur epimers.
3b
3c
3d
3e
3f
o
15 min, SnCl4, -78 C >95:5
4 h, rt 90:10
15 min, SnCl4, -78 C >95:5
8 h, rt 93:7
20 min, SnCl4, -78 C >95:5
8 h, rt
20 min, SnCl4, -78 C >95:5
8 h, rt
20 min, SnCl4, -78 C >95:5
Previous studies of these cycloadducts disclose a lack of
stereoselectivity at sulfur.5a Mock and Weinreb noted
the absence of stereoselectivity in the thermal cycload-
dition of benzyl N-sulfinyl carbamate and N-sulfinylben-
zenesulfonamide with cyclohexadiene. This apparent
general lack of selectivity perhaps precluded development
of reactions based on sulfur stereoselectivity or studies
to improve or explain the observed selectivity.
In contrast to the N-sulfinylcarbamates and -sulfon-
amides, N-sulfinylphosphoramidates 3a -f exhibit great
selectivity in the thermal Diels-Alder reaction, providing
a >90:10 ratio of sulfur epimers. Furthermore, these
isomers were chromatographically separable (3a and 3b).
As this new methodology allowed the selective prepara-
tion and separation of the sulfur epimers, the configu-
ration of the isomers at sulfur was investigated (Figure
12
13
o
1
o
11
1
1
1
1
2
3
4
5
o
o
a
The endo/exo ratio was determinated by 31P and 1H NMR of
the crude. b Isolated yields are based on the N-phosphoramides
a -f.
2
Sch em e 4
1
). Complete NMR spectral information for the two
sulfur epimers 7a , 7a ′ and 7b, 7b′ is given in the
Experimental Section.
The spectra of the major and minor isomers show
differences in the chemical shifts of H2,3 and H5-8, which
facilitate identification of the stereoisomeric adducts. The
chemical shifts of protons H6′,8′ are particularly affected;
protons H6′,8′ (2.90, 2.31 ppm) in the minor isomer are
significantly downfield from those protons H6,8 (1.80, 1.75
ppm) in the major isomer. Moreover, the difference of
Sch em e 5
2 3
chemical shifts between H (6.95 ppm) and H (6.28 ppm)
in the major isomer (∆δ ) 0.67 ppm) is larger than that
between H2′ (6.75 ppm) and H3′ (6.29 ppm) in the minor
(
“
∆δ ) 0.46 ppm). Considering the shielding effect of the
SdO” group,1
2,14a,b
the assignment of the major isomer
as the endo sulfur epimer seems reasonable. Eu(dpm)
3
NMR shift experiments supported this hypothesis.11,13a,b
From the relative magnitude of the induced shift of the
respective protons shown in parentheses in Figure 1 (i.e.
the slope of a plot of chemical shift vs mole ratio of
Eu(dpm)
3
/sample), the pertinent observation is that the
prompted us to examine the diastereoselectivity derived
from phosphorus chiral center through the racemic
N-sulfinylphosphoramidates 3e and 3f. The cycloaddi-
tion reactions of 3e (propyl) and 3f (tert-butyl) with
protons H2,3 in the major isomer are approximately
equally shifted, and both are more strongly affected than
the same protons in the minor isomer. In both isomers
1
6
the bridge head protons (H
1
/H
4
) are similarly strongly
cyclohexadiene provided two endo sulfur epimers
shifted. Recognizing the Lewis acidity of Eu(dpm)
3
(Scheme 5) as major adducts, which were unseparable
diastereomers in 56:44 and 69:31 ratio, respectively.
Th e Effect of Lew is Acid s on Ster eoselectivity of
reagent and the strong dipolar characters of both sulfinyl
and phosphoryl groups, these induced shifts may indicate
a Eu3 complex with the sulfinyl oxygen
+
12,14a,b
and the
17
18
th e Cycloa d d ition s. Both Weinreb and Whitesell
phosphoryl oxygen.9
a,b,d
X-ray crystallographic analysis
reported the endo/exo selective [4 + 2] cycloaddition of
homochiral N-sulfinylcarbamates with 1,3-cyclohexadi-
ene and (E,E)-hexa-2,4-diene in the presence of either
of the major isomer confirmed an endo configuration at
sulfur. X-ray crystal structures of 7b and 7c are shown
in Figure 2.15
The high selectivity at sulfur observed in the thermal
cycloaddition of achiral N-sulfinyl compounds 3a -d
(15) The author has deposited atomic coordinates for these struc-
tures with the Cambridge Crystallographic Data Centre. The coordi-
nates can be obtained, on request, from the Director, the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge, CB2, 1EZ,
UK.
(
(
12) Mock, W. L.; Nugent, R. M. J . Am. Chem. Soc. 1975, 97, 6521.
13) Garigipati, R. S.; Cordova, R.; Parvez, M.; Weinreb, S. M.
1
(16) The determination of endo sulfur epimers was based on the H
1
3
Tetrahedron 1986, 42, 2979.
14) (a) Garigipati R. S.; Freyer, A. J .; Whittle, R. R.; Weinreb, S.
and C NMR of known endo sulfur epimers 7a ,b,c. The structure
details of these compounds will be published elsewhere.
(17) Remiszewski, S. W.; Yang, J .; Weinreb, S. M. Tetrahedron Lett.
1986, 27, 1853.
(
M. J . Am. Chem. Soc. 1984, 106, 7861. (b) Bell, S. I.; Parvez, M.;
Weinreb, S. M. J . Org. Chem. 1991, 56, 373.

Diels-Alder Reactions of N-Sulfinylphosphoramidates
J . Org. Chem., Vol. 63, No. 5, 1998 1375
F igu r e 2. X-ray crystal structures of adducts 7b (X ) Y ) MeO) and 7c (X ) Y ) Ph).
Sch em e 6
TiCl
4 4
or SnCl . They noted that Lewis acid plays an
important role in asymmetric induction, probably by
chelation with N-sulfinylcarbamate dienophiles.1
7,18
To
our knowledge, there are no reports of Lewis acid-
catalyzed cycloadditions featuring N-sulfinylphosphor-
amidates. We examined the effect of Lewis acids, such
as BF
3
2 4 4
‚Et O, SnCl , and TiCl , on the stereochemistry of
the cycloaddition reactions which are shown in Table 2.
Lewis acid-catalyzed cycloadditions afforded a single
1
31
sulfur epimer (based on H and P NMR assay) in high
yield. This adduct showed the same configuration at
sulfur as the major isomer from the thermal reaction.
This selectivity extended to reactions involving racemic
N-sulfinylphosphoramidates 3e and 3f and provided
additional diastereoselctivity at phosphorus (33:67 and
Sch em e 7
1
7:83) over the thermal cycloaddition (Scheme 5).
Lewis acid enhancement of reactivity and stereoselec-
tivity led us to spectroscopically examine the mixtures
of Lewis acids and N-sulfinylphosphoramides for the
evidence of chelates. Due to the presence of Lewis base
sites, such as N, S, O, or π-NdS, in N-sulfinylphosphor-
amidates, several 1:1 and 2:1 solution complexes are
theoretically possible. Putative intermediates 10-12
should exhibit enhanced electrophilic character, espe-
cially intermediate 12, which features a six-member ring
system similar to that proposed by Castellino for the tin
a single crystal of 15 for unambiguous structure deter-
chelate of oxazolidinone.1
9a
No chelates, 10-12, were
119
13
1
31
mination. However, based on
and elemental analysis, a (1:1) SnCl
Sn, C, H, P NMR
/adduct chelate with
ever isolated. However, 31P and
mixture of SnCl (1 equiv) and compound 3a showed a
change in phosphorus chemical shift from -10.9 ppm to
119
Sn NMR study of a
4
4
structure 15 is suggested in Scheme 7. Comparison of
1
the H NMR spectra of 15 with adduct 7a showed
-
18.2 ppm,9b and a Sn signal at -1050 ppm.
119
19b
While
substantial change in the chemical shifts of all protons,
especially alkene protons H2,3 and bridgehead protons
not directly supporting chelates such as 10-12, it is
worthwhile to note that upon anhydrous workup, the
H
1,4. These shifts are consistent with proposed structure
4
SnCl -catalyzed cycloaddition of diethyl N-sulfinylphos-
phoramidate (3a ) with cyclohexadiene produced 15, a
white solid product (Scheme 7), which could also be
1
5 and are not dissimilar to those seen in the Eu(dmp)
3
study of 7a . The chemical shift differences between H
2
3 1 4
and H , H and H in 15 are also reduced. A sharp
obtained by adding SnCl
a (a clear oil) in CH Cl
4
(1 equiv) to a solution of adduct
. We were not able to prepare
119
resonance ( Sn) at -952 ppm is observed and consistent
7
2
2
19a,b
with a six-coordinate tin species.
(
18) Whitesell, J . K.; J ames, D.; Carpenter, J . F. J . Chem. Soc.,
Discu ssion
Chem. Commun. 1985, 1449. In Whitesell’s proposal, the transition
states are labeled exo or endo with respect to the carbamate group. In
our application of these possible transition states 17-20 endo refers
to the sulfinyl group.
Having established the likely operation of a dienophile/
Lewis acid chelate as the reactive intermediate in these
cycloadditions, the rationale for the observed stereose-
lectivity can be explored through this hypothesis. For
reactions involving N-sulfinylcarbamates, Whitesell pro-
(
19) (a) Castellino, S. J . Org. Chem. 1990, 55, 5197 and also see
references cited there. (b) Wrackmeyer, B. In Annual Reports on NMR
Spectroscopy: 119Sn NMR Parameters; Academic Press: London, 1985;
p 73.

1
376 J . Org. Chem., Vol. 63, No. 5, 1998
Zhang and Flann
effect in the different reactive intermediates, 17 and 19.
Indeed, the thermal reaction of 3f provides a 69:31
mixture of diastereomers at phosphorus, while the Lewis
acid-catalyzed reaction provides a 83:17 mixture. The
albeit modest extra stereocontrol afforded by the Lewis
acid is not readily explained by a reactive intermediate
such as 19; rather, 17 enforced as a cyclic intermediate
1
6 seems the more likely source of selectivity. Under this
analysis, the stereoselectivity at phosphorus results from
facial selectivity of the diene reacting in endo mode with
a rigid phosphorus chelate. This result and hypothesis
suggest that by appropriate manipulation of the environ-
ment surrounding phosphorus, the facial selectivity could
be improved to synthetically useful levels. Moreover, if
the environment surrounding phosphorus that provides
the observed stereoselectivity can be prepared from a
single chirality, this methodology would be useful for
asymmetric synthesis.
F igu r e 3. [4 + 2] Cycloaddition modes.
posed the scheme illustrated in Figure 3.18 This proposal
recognizes that the endo/exo selectivity and E-, Z-
dienophile stereoisomers can both influence stereoselec-
tivity. The N-sulfinylphosphoramidates can correspond-
ingly react with the diene through any one of the four
possible cycloaddition modes. However, only two modes,
Con clu sion
In contrast to N-sulfinylcarbamates and sulfonamides,
the cycloaddition reactions of N-sulfinylphosphorami-
dates and cyclohexadiene showed great diastereoselec-
tivity at sulfur under either thermal (90:10) or Lewis acid
1
7 and 19, can provide the observed stereoselectivity. On
the basis of evidence for the presence of a chelate, such
as 13, it seems likely that the cycloaddition proceeds not
through the mode exemplified by 19, but through 17,
enforced through the agency of the Lewis acid as cycload-
dition mode 16.
(>95:5) conditions. This sulfur stereoselectivity trans-
lates into stereoselectivity in the compounds derived from
the cycloadducts. A cyclic diene chelate, coupled with the
absence of secondary stereoelectronic factors in the
dienophile, is proposed to explain this selectivity. We are
currently extending these studies to asymmetric cycload-
ditions by using homochiral N-sulfinylphosphoramidates
to further test this hypothesis and planning to transform
the cycloadducts to useful nitrogen-containing com-
pounds.
While the stereoselectivity of the Lewis acid-catalyzed
cycloaddition may be readily explained by this model, the
operative mode of the thermal reaction is less clear. In
the absence of chelation enforcing an endo, syn mode,
illustrated by 16, the predominant stereochemistry is
explained equally as well by the endo, anti mode 19 as it
is by the endo, syn mode 17. Regardless of the mode the
reaction follows, it is unusual in that the corresponding
N-sulfinylcarbamate reacts nonstereospecifically. One
possible explanation for this phenomena is the absence
of a secondary orbital interaction in dienophiles activated
by a phosphoryl group. Earlier studies have shown that
dienophiles, in which the phosphoryl group is the sole
Exp er im en ta l Section
Gen er a l. All reactions were carried out under an atmo-
sphere of dry nitrogen. Solvents and commercial reagents
1
were used as received without additional purification.
H
13
NMR (270 MHz) and C NMR (90 MHz) spectra were recorded
31
in CDCl
3
/TMS solutions, unless otherwise stated. P NMR
2
0a,b
source of activation, are completely nonstereospecific.
(90 MHz) spectra were recorded in CDCl with 85% H PO as
3
3
4
This lack of secondary orbital interaction stands in stark
contrast to that found in dienophiles activated by a
carbonyl moiety. This lack of selectivity with N-carbam-
ate dienophiles, perhaps, can be explained through
conflicting secondary orbital interactions between the
carbonyl group and the sulfinyl group. In contrast with
the N-phosphoryl dienophile, the sulfinyl secondary
orbital interactions are not opposed and are perhaps
reinforced through steric effects. Whatever the basis for
this stereoselection, further studies are planned to elu-
cidate it further by utilizing it in the development of new
synthetic methods.
The logic inherent in the above mechanistic proposal
can be extended to cycloaddition reactions involving
chiral dienophiles. For the achiral dienophiles 3a -d , the
reactive intermediate, in either E or Z form, produces
the same sulfur epimer. However, the introduction of
chirality in dienophiles 3e,f creates the possibility that
the remote phosphorus chiral center may have a different
an external standard. Flash chromatography was carried out
using 32-63 mm silica gel, and TLC on Merck silica gel plates
6
0, S254. Elemental analyses were performed by the University
of Arizona Microanalytic Service Laboratory. Melting points
are uncorrected.
Ma t er ia ls. Compounds 1a -c were bought from Aldrich
Company. P h osp h or a m id es 2a -c were prepared according
7
to literature. Dieth yl p h osp h or a m id a te (2a ): mp 51-52
°C (lit.7 49-50 °C); P NMR δ 6.5. Dim et h yl p h osp h or -
31
2
1
a m id e (2b): bp 98-100 °C/0.5 Torr (lit. bp 98 °C/0.5 Torr);
3
1
1
P NMR δ 12.5; H NMR δ 3.69 (d, J ) 11.7 Hz, 6H), 3.2 (bs,
2
°
(
H). P ,P -Dip h en yl p h osp h in ic a m id e (2c): mp 144-145
3
1
1
C; P NMR δ 21.6; H NMR δ 7.86-7.94 (m, 5H), 7.41-7.47
m, 5H), 4.12 (bs, 2H).4
-Am in o-2-oxo-5,5-d im et h yl-1,3,2-d ioxa za p h osp h or i-
2
21
n a n (2d ) was prepared according to literature: mp 126-
1
J ) 6.1 Hz), 32.0 (d, J ) 4.9 Hz), 21.6, 20.0. N-Su lfin yl-2-
oxo-5,5-d im eth yl-1,3,2-d ioxa za p h osp h or a m id a te (3d ) was
generated by adopting Kim’s procedure. Yield (crude): 83%;
yellow oil; H NMR δ 4.20 (m, 2H), 3.95 (m, 2H), 1.35 (s, 3H),
0
21
31
13
28 °C (lit. 125-127 °C); P NMR δ 6.4; C NMR δ 76.5 (d,
8
1
.92 (s, 3H); 13C NMR δ 78.5 (d, J ) 9.0 Hz), 32.3 (d, J ) 6.1
31
Hz), 21.8, 20.0; P NMR δ -13.4.
(20) (a) Bodalski, R.; Koszak, J .; Krawczyk, H.; Pietrusiewicz, K.
M. J . Org. Chem. 1982, 47, 2219. (b) Daniewski, W. M.; Griffin, C. E.
J . Org. Chem. 1966, 31, 3236.
(21) Zwierzak, A.; Koziara, A. Tetrahedron 1970, 26, 3521.

Diels-Alder Reactions of N-Sulfinylphosphoramidates
-Am in o-3-n -p r op yl-2-oxo-1,3,2-oxa za p h osp h or in a n e
J . Org. Chem., Vol. 63, No. 5, 1998 1377
2
1094, 1017 (s) cm-1; HRMS calcd for C10
found 281.0853.
4
H20NO SP 281.0846,
(
2e) a n d 2-Am in o-3-ter t-bu tyl-2-oxo-1,3,2-oxa za p h osp h o-
r in a n e (2f). To a cooled (-35 °C) solution of (N-alkylamino)-
en d o-3-Aza -N-(d iet h oxylp h osp h or yl)-2-oxo-2-t h ia b i-
cyclo[2.2.2]oct-5-en e (7a , m a jor su lfu r ep im er ). Oil; 68%;
eluting (2/5 hex/THF); H NMR δ 6.94-6.90 (m, 1H), 6.28 (t,
J ) 7.4 Hz, 1H), 4.67-4.61 (m, 1H), 4.35-4.32 (m, 1H), 4.21-
propan-1-ol (3-(N-n-propylamino)propanol and 3-(N-tert-butyl-
2
2a
amino)propanol were synthesized according to Israil’s and
1
2
2b
Deyrup’s
mmol) in CH
P(O)Cl (23.0 mmol) in CH
procedures, 23.0 mmol) and triethylamine (48.0
Cl (60 mL) was added dropwise a solution of
Cl (15 mL) at -25 to -30 °C.
2
2
4
.08 (m, 4H), 1.85-1.75 (m, 2H), 1.61-1.52 (m, 1H), 1.35 (t, J
3
2
2
13
)
7.0 Hz, 6H), 1.27-1.15 (m, 1H); C NMR (DMSO-d ) δ 136.5
6
Stirring of the reaction mixture was continued for 2 h at room
temperature. Precipitated triethylamine hydrochloride was
filtered off, and the filtrate was concentrated. The residual
3
2
(
d, J P-C ) 4.9 Hz), 125.8, 62.6 (d, J P-C ) 12.2 Hz), 62.8 (d, J
2
3
)
2
1
12.2 Hz), 54.8 (d, J P-C ) 4.9 Hz), 49.2 (d, J P-C ) 2.4 Hz),
3 31
4.0, 15.9 (d, J P-C ) 6.2 Hz), 14.5 (s); P NMR δ 4.7; IR (neat)
253 (s), 1116 (s), 1032 (s) cm ; MS (EI) 279 (M , 0.3), 126
SP
crude product was dissolved in dry C
6
H
6
(60 mL), and then
-1
+
dry NH gas was passed through the reaction mixture at room
3
(40), 98 (73), 80 (100), 78 (79); HRMS calcd for C10
H
18NO
4
temperature for 4 h. The crude product 2e or 2f was collected
by filtration, and pure product was obtained from recrystal-
lization (EtOAc).
2
79.0690, found 279.0693.
exo-3-Aza-N-(dieth oxylph osph or yl)-2-oxo-2-th iabicyclo-
1
[
2.2.2]oct-5-en e (7a ′, m in or su lfu r ep im er ). Oil; 6%; H
Da ta for 2e: white powder; 80% (overall yields); mp 73-
NMR δ 6.79-6.74 (m, 1H), 6.33-6.27 (m, 1H), 4.09-4.03 (m,
1
7
(
2
4
5 °C; H NMR δ 4.37-4.19 (m, 2H), 3.18-3.05 (m, 2H), 2.98
1
2
H), 4.10-4.02 (m, 4H), 3.99-3.93 (m, 1H), 2.85-2.78 (m, 1H),
bs, 2H), 2.89-2.82 (m, 2H), 1.94-1.87 (m, 2H), 1.59-1.53 (m,
13
.28-2.2 (m, 1H), 1.52-1.34 (m, 2H), 1.29-1.24 (m, 6H);
C
H), 0.90 (t, J ) 7.3 Hz, 3H); 13C NMR δ 67.1 (d, J ) 7.3 Hz),
31
NMR δ 139.5 (d, J ) 4.9 Hz), 127.5, 62.7 (d, J ) 12.2 Hz),
6
NMR δ 4.9; IR (neat) 1264 (s), 1114 (s), 1024 (s) cm ; MS (EI)
2
9.8, 46.3, 26.4 (d, J ) 3.7 Hz), 21.1 (d, J ) 4.9 Hz), 11.2;
P
3
1
2.4 (d, J ) 12.2 Hz), 54.8 (d), 48.3, 24.1, 15.0 (d), 10.5;
P
-
1
NMR δ 13.9; IR (KBr) 3250 (b), 1211(s), 1058(s) cm . Anal.
-
1
Calcd for C P: C, 40.43; H, 8.47; N, 15.73. Found:
6
15 2 2
H N O
+
79 (M , 0.3), 126 (37), 98 (63), 80 (100), 79 (56).
C, 40.74; H, 8.25; N, 15.45.
en d o-3-Aza -N-(d im eth oxylp h osp h or yl)-2-oxo-2-th ia bi-
cyclo[2.2.2]oct-5-en e (7b, m a jor su lfu r ep im er ). White
crystals; 72%; eluting (2/5 hex/THF); mp 96-97.5 °C (EtOAc);
Da ta for 2f: white powder; 75% (overall yields); mp 100-
1
1
3
1
(
2
01 °C; H NMR δ 4.35-4.21 (m, 1H), 4.20-4.15 (m, 1H),
.32-3.19 (m, 1H), 3.17-3.05 (m, 1H), 2.75 (br, 2H), 2.10-
1
2
.95 (m, 1H), 1.95-1.85 (m, 1H), 1.38 (s, 9H); 13C NMR δ 64.9
H NMR δ 6.97-6.92 (m, 1H), 6.28 (t, J H-H ) 7.4 Hz, 1H),
2
4
.68-4.65 (m, 1H), 4.36-4.31 (m, 1H), 3.81 (d, J P-H ) 12.9
d, J ) 7.3 Hz), 54.9 (d, J ) 3.7 Hz), 41.7, 29.0 (d, J ) 3.7 Hz),
2
7.3 (d, J ) 4.9 Hz); 3 P NMR δ 9.6; IR (KBr) 3255 (b), 1240
1
1
Hz, 3H), 3.77 (d,
J P-H ) 12.9 Hz, 3H), 1.84-1.72 (m, 2H),
13
-
1.62-1.51 (m, 1H), 1.24-1.13 (m, 1H); C NMR δ 137.0 (d,
(
7 17 2 2
s), 1106, 1037 (s) cm . Anal. Calcd for C H N O P: C,
3
2
2
J
C-P ) 4.9 Hz), 125.4, 55.5 (d, J ) 4.9 Hz), 54.3 (d, J ) 6.1
3 3 31
4
3.72; H, 8.92; N, 14.58. Found: C, 43.88; H, 8.73; N, 14.47.
Hz), 53.9 (d, J ) 4.9 Hz), 49.8 (d, J ) 2.4 Hz), 24.4, 14.8;
P
Dieth yl N-Su lfin ylp h osp h or a m id a te (3a ) a n d Dim eth -
-
1
NMR δ 7.6; IR (KBr) 1267 (s), 1106 (s), 1012 (s) cm . Anal.
Calcd for C SP: C, 38.25; H, 5.62; N, 5.58. Found: C,
8.34; H, 5.66; N, 5.61.
exo-3-Aza -N-(d im et h oxylp h osp h or yl)-2-oxo-2-t h ia b i-
yl N-Su lfin ylp h osp h or a m id a te (3b). A reaction mixture
of dialkyl phosphoramidate (50 mmol), SOCl (55 mmol), and
anhydrous C (25 mL) was heated at 65 °C until the
8
H14NO
4
2
3
6
H
6
evolution of HCl ceased. The benzene and excess thionyl
chloride were distilled off in vacuo. The residue was fraction-
cyclo[2.2.2]oct-5-en e (7b ′, m in or su lfu r ep im er ). Oil; 6%;
1
2
H NMR δ 6.77-6.72 (m, 1H), 6.29 (t, J ) 7.52 Hz, 1H), 4.39-
ally distilled. 3a : yield 70%; bp 85 °C/1.5 Torr (lit. 78%, 77
3
1
4.35 (m, 1H), 3.95-3.90 (m, 1H), 3.77 (d, J ) 11.43 Hz, 3H),
3.75 (d, J ) 11.5 Hz, 3H), 2.83-2.75 (m, 1H), 2.26-2.18 (m,
°
C/1 Torr), P NMR δ -10.9; 3b: yield 68%; bp 115 °C/2 Torr;
3
1
1
P NMR δ -8.2; H NMR δ 3.84 (d, J ) 12.0 Hz).
1
4
H), 1.62-1.40 (m, 2H); 13C NMR δ 140.8, 128.6, 56.0 (d, J )
.9 Hz), 55.1 (d, J ) 4.9 Hz), 53.7 (d, J ) 4.9 Hz), 49.5, 25.2
Th er m a l Cycloa d d ition Rea ction s. Meth od a : Gen -
er a l P r oced u r e for th e P r ep a r a tion of Ad d u cts (5a , 6a ,
a , 7b). The 1,3-diene (25 mmol) was added dropwise to a
solution of freshly distilled dialkyl N-sulfinylphosphoramidate
20 mmol) and CH Cl (25 mL) at 5 °C. The resulting solution
was stirred for 3 to 8 h at room temperature. The CH Cl and
3
1
(d, J ) 4.9 Hz), 11.5; P NMR δ 7.8; IR (neat) 1233 (s), 1100
7
-
1
(s), 1032 (s) cm
.
(
2
2
Meth od b: Gen er a l P r oced u r e for Ad d u cts (7c, 4d -
8
7d , 7e, 7f). Freshly prepared N-(chlorosulfinyl)imidazole (15
2
2
excess diene were distilled off in vacuo. The residue consisted
of an adduct and a small amount of dialkyl phosphoramidate
in the form of a light-yellow liquid which could not be purified
further by distillation at 0.05 Torr. Purification of the residue
mmol) was added to a solution of phosphoramidate (15 mmol)
2 2
and CH Cl (10 mL) at -40 °C. The resulting mixture was
stirred at room temperature for 2-6 h. After removal of the
salt and solvent, the residue was dissolved in anhydrous
by silica gel column chromatography (CHCl
hexane) gave the [4 + 2] adducts as colorless oils or white
crystals.
3
/CH
3
OH or THF/
2 2 2 2
CH Cl (10 mL). A diene (20 mmol) was added to the CH Cl
solution, and then the mixture was stirred at room tempera-
ture for 5-10 h. Workup and purification was carried out as
those for method a.
2
-(Dieth oxyp h osp h in yl)-5-m eth yl-3,6-d ih yd r o-2H-1,2-
th ia zin e 1-Oxid e (5a ). Oil; 75%; eluting (2% MeOH/CHCl );
H NMR δ 5.72 (bs, 1H), 4.30-4.25 (m, 1H), 4.21-4.06 (m,
H), 3.89 (bd, 1H), 3.54 (bd, 1H, J ) 6.5 Hz), 3.16 (bd, 1H, J
3
en do-3-Aza-N-(diph en ylph osph or yl)-2-oxo-2-th iabicyclo-
[2.2.2]oct-5-en e (7c). White powders; 50%; eluting (1.5%
1
1
4
)
1
MeOH/CHCl ); mp 134-135 °C (EtOAc); H NMR δ 8.02-7.95
3
1
3
6.5 Hz), 1.84 (s, 3H), 1.42-1.30 (m, 6H); C NMR δ 122.7,
(m, 4H), 7.85-7.78 (m, J ) 12.8 Hz, 3H), 7.62-7.41 (m, 3H),
6.89 (t, J ) 7.2 Hz, 1H), 6.31 (t, J ) 7.4 Hz, 1H), 4.62-4.56
(m, 1H), 4.28 (br, 1H), 2.14-2.08 (m, 1H), 1.75-1.61 (m, 2H),
17.8 (d, J ) 7.3 Hz), 63.9 (d, J ) 3.7 Hz), 63.5 (d, J ) 3.7
31
Hz), 52.2 (d, J ) 4.9 Hz), 37.5, 24.4, 15.8 (d, J ) 7.2 Hz);
NMR δ 2.4; IR (neat) 1255 (s), 1164 (m), 1037 (s) cm ; HRMS
P
-
1
13
1.25-1.11 (m, 1H); C NMR δ 137.3, 137.2, 133.3, 132.8, 132.6,
calcd for C
-(Dieth oxyp h osp h in yl)-4,5-d im eth yl-3,6-d ih yd r o-2H-
,2-th ia zin e 1-Oxid e (6a ). Oil; 80%; eluting (2% MeOH/
9
H
18NO
4
SP 267.0690, found 267.0695.
129.2, 128.6, 128.1, 126.3, 56.1 (d, J ) 3.7 Hz), 49.9 (d, J )
2
4.9 Hz), 25.1, 15.2; 31P NMR δ 29.5; IR (KBr) 1212 (s), 1154,
-
1
1
1118 (s), 1053 (s) cm
62.94; H, 5.28; N, 4.08. Found: C, 63.14; H, 5.32; N, 4.18.
-(5,5-Dim eth yl-2-oxo-1,3,2-d ioxa p h osp h or yl)-3,6-d ih y-
d r o-2H-1,2-th ia zin e 1-Oxid e (4d ). Oil; 40%; eluting (1%
2
. Anal. Calcd for C18H18NO SP: C,
1
CHCl
1
)
6
)
6
3
); H NMR δ 4.18-4.06 (m, 4H), 3.84 (bd, J ) 7.1 Hz,
H), 3.70-3.62 (m, 1H), 3.47 (bd, J ) 6.4 Hz, 1H), 3.10 (bd, J
2
6.4 Hz, 1H), 1.79 (s, 3H), 1.76 (s, 3H), 1.36 (t, J ) 7.1 Hz,
13
H); C NMR δ 124.4, 115.5, 63.8 (d, J ) 3.7 Hz), 63.7 (d, J
3.7 Hz), 53.7 (d, J ) 4.9 Hz), 41.5, 19.9, 17.1, 16.2 (d, J )
1
MeOH/CHCl
3
); H NMR δ 6.06-5.99 (m, 1H), 5.79-5.72 (m,
H), 4.35-4.27 (m, 2H), 4.09-3.96 (m, 2H), 3.92-3.67 (m, 2H),
1
3
3
3
1
.1 Hz); P NMR δ 2.3; IR (neat) 1259 (s), 1165, 1134 (m),
.53-3.44 (m, 1H), 3.33-3.27 (m, 1H), 1.22 (s, 3H), 1.00 (s,
H); 13C NMR δ 124.7 (d, J ) 6.1 Hz), 114.4, 77.5 (d, J ) 6.1
Hz), 76.7 (d, J ) 6.1 Hz), 48.3 (d, J ) 4.9 Hz), 37.0 (d, J ) 3.7
(22) (a) Israili, Z. H.; Perel, J . M. J . Med. Chem. 1972, 15, 709. (b)
Deyrup, J . A.; Moyer, C. L. J . Org. Chem. 1969, 34, 175.
Hz), 31.9, 21.9, 20.8; 31P NMR δ -1.4; IR (neat) 1261 (s), 1160

1
378 J . Org. Chem., Vol. 63, No. 5, 1998
Zhang and Flann
+
(
(
2
s), 1058, 1006 (s) cm-1; MS (EI) 265 (M , 13), 212 (29), 144
mL). The resulting solution was stirred for 30 min, cooled to
0 °C, and quenched by pouring into a mixture of 0.1 M HCl
and ether. The aqueous portion was extracted with ether, and
the combined organic extracts were washed with brine. The
35), 69 (100); HRMS calcd for C
65.0540.
-(5,5-Dim eth yl-2-oxo-1,3,2-d ioxa p h osp h or yl)-5-m eth -
yl-3,6-d ih yd r o-2H-1,2-th ia zin e 1-Oxid e (5d ). Oil; 52%;
9 4
H16NO SP 265.0534, found
2
solution was dried (MgSO
product. Flash chromatography of the crude (silica gel, 5%
MeOH/CHCl ) gave 0.1 g (61%) of 8d as a white solid.
4
) and concentrated to give crude
1
eluting (2% MeOH/CHCl
.25 (m, 2H), 4.24-4.00 (m, 2H), 3.99-3.92 (m, 2H), 3.46 (bd,
J ) 7.1 Hz, 1H), 3.13 (bd, 1H), 1.83 (br, 3H), 1.21 (s, 3H), 1.00
3
); H NMR δ 5.73 (br, 1H), 4.31-
4
3
Recrystallization from EtOAc: white crystals, mp 129-131 °C;
1
3
1
(
s, 3H); C NMR δ 132.1, 118.1 (d, J ) 6.1 Hz), 77.6 (d, J )
H NMR δ 5.68-5.55 (m, 2H), 4.33-4.28 (m, 2H), 3.85-3.74
6
3
.1 Hz), 76.9 (d, J ) 6.1 Hz), 52.3 (d, J ) 4.9 Hz), 37.6 (d, J )
(m, 2H), 3.48-3.41 (m, 1H), 2.89-2.82 (m, 1H), 2.41 (bd, J )
7.9 Hz, 1H), 2.15-2.13 (m, 1H), 1.99-1.89 (m, 2H), 1.67-1.54
.7 Hz), 32.4 (d, J ) 6.1 Hz), 24.7 (d, J ) 1.2 Hz), 21.9, 21.0;
3
1
-1
13
P NMR δ -1.4; IR (neat) 1283 (s), 1112 (s), 1013 (s) cm
;
(m, 2H), 1.21 (s, 3H), 0.88 (s, 3H); C NMR δ 125.1, 123.6,
HRMS calcd for C10
-(5,5-Dim et h yl-2-oxo-1,3,2-d ioxa p h osp h or yl)-4,5-d i-
m eth yl-3,6-d ih yd r o-2H-1,2-th ia zin e 1-Oxid e (6d ). White
H
18NO
4
SP 279.0694, found 279.0693.
74.4 (d, J ) 4.9 Hz), 46.1, 32.6 (d, J ) 6.1 Hz), 30.2, 29.4, 23.2,
3
1
2
19.6, 18.8; P NMR δ 5.2; IR (KBr) 1229 (s), 1057, 1014 (s)
1
-
3
cm . Anal. Calcd for C11H20NO P: C, 53.87; H, 8.22; N, 5.71.
1
powders; 65%; eluting (2% MeOH/CHCl
3
); mp 128-131 °C; H
NMR δ 4.33-4.24 (m, 2H), 4.06-3.92 (m, 2H), 3.88 (br, 2H),
Found: C, 53.82; H, 8.13; N, 5.71. The product was identical
with the byproduct from the cycloaddition reaction of 3d .
3
3
1
4
1
1
7
.52 (bd, J ) 6.8 Hz, 1H), 3.11 (bd, J ) 6.4 Hz, 1H), 1.79 (s,
H), 1.75 (s, 3H), 1.20 (s, 3H), 1.02 (s, 3H); 13C NMR δ 131.8,
16.9, 77.7 (d, J ) 4.9 Hz), 76.8 (d, J ) 4.9 Hz), 53.7 (d, J )
.9 Hz), 41.5 (d, J ) 3.7 Hz), 31.8 (d, J ) 4.9 Hz), 21.8, 21.0,
Lew is Acid -Ca ta lyzed Cycloa d d ition Rea ction s. Gen -
er a l p r oced u r e. To a solution of N-sulfinylphosphoramidate
(
2.0 mmol, freshly prepared in situ from the phosphorami-
dates) in CH Cl (5 mL) was added SnCl (1.8 mmol) at -78
C. After the mixture was stirred for 5 min, cyclohexadiene
4 mmol) was added, and the resultant mixture was stirred
for 10-20 min at -78 °C. The mixture was poured into water
10 mL) and extracted with CH Cl
(3 × 15 mL). The combined
organics were washed with brine and dried over Na SO . The
2
2
4
3
1
9.8, 17.0; P NMR δ -1.7; IR (KBr) 1258 (s), 1144 (s), 1094,
°
(
-
1
4
054 (s) cm . Anal. Calcd for C11H20NO SP: C, 43.11; H,
.07; N, 4.95. Found: C, 43.24; H, 6.92; N, 4.81.
en d o-3-Aza -3-(5,5-d im eth yl-2-oxo-1,3,2-d ioxa p h osp h o-
(
2
2
r yl)-3-oxo-3-th ia bicyclo[2.2.2]oct-5-en e (7d ). Oil; 45%;
eluting (2/5 hex/THF); H NMR δ 6.98-6.92 (m, 1H), 6.33-
6
4
1
3
2
4
1
same procedure was used for the separation and purification
as that for the thermal cycloaddition reactions. See Table 2
reaction conditions and isolated yields). In all case, the acid-
.28 (m, 1H), 4.69-4.67 (br, 1H), 4.36-4.35 (br, 1H), 4.32-
.25 (m, 1H), 4.18-4.03 (m, 3H), 2.13-1.96 (m, 1H), 1.76-
.70 (m, 1H), 1.68-1.54 (m, 1H), 1.30-1.27 (m, 1H), 1.17 (s,
H), 1.03 (s, 3H); 13C NMR δ 136.5, 125.4, 77.6 (d, J ) 4.9
(
catalyzed reactions provided only one isomer, and the purity
31
1
was checked by P and H NMR.
Tin ch ela te 15. SnCl (0.29 g, 1 equiv) was added to the
diethyl N-sulfinylphosphoramidate freshly distilled (3a , 0.2 g,
.15 mmol) and CH Cl (6 mL) at -78 °C under nitrogen. To
Hz), 76.8 (d, J ) 4.9 Hz), 54.2, 49.2, 24.5 (d, J ) 3.7 Hz), 21.6,
4
3
1
2
1
9
1.1, 15.6; P NMR δ -1.0; IR (neat) 1227 (s), 1123 (m), 1060,
1
-
+
011 (s) cm ; MS (EI) 291 (M ), 191 (87), 166 (68), 123 (53),
8 (100), 79 (50). A byproduct 8d was isolated in 20% yield.
en do-3-Aza-3-(3-n -pr opyl-1,3,2-oxazaph osph or yl)-2-oxo-
1
2
2
this stirred mixture was added dropwise a precooled (-30 °C)
solution of an excess (0.18 g, 2.5 equiv) of cyclohexadiene in
CH Cl (1 mL). The reaction mixture was stirred at -78 °C
2 2
for 30 min. The white precipitate was collected by filtration.
The mother liquor yielded more product after cooling the
2
-th ia bicyclo[2.2.2]oct-5-en e (7e). Oil; 55% (two diastere-
1
omers); eluting (2/5 hex/THF); H NMR δ 6.98-6.95 (m, 1H),
6
minor isomer), 4.41-4.25 (m, 3H), 3.51-3.44 (m, minor), 3.32-
3
1
1
1
.26 (t, J ) 7.3 Hz, 1H), 4.83-4.78 (m, 1H), 4.58-4.52 (m,
solution. Recrystallization from EtOAc gave 0.41 g (72%).
.30 (m, 1H), 3.18-3.03 (m, 2H), 2.95-2.78 (m, 1H), 2.06-
.97 (m, 2H), 1.90-1.72 (m, 2H), 1.69-1.56 (m, 3H), 1.20-
.12 (m, 1H), 0.94-0.86 (m, 3H, two isomers); 13C NMR δ
34.6, 127.6 (d, J ) 4.9 Hz), 67.7 (d, J ) 4.9 Hz), 54.9, 49.1 (d,
1
White powder; mp 112-114 °C; H NMR (CD
3
COCD
3
) δ 7.06-
7
4
1
1
.00 (m, 1H), 6.37-6.32 (m, 1H), 4.82 (br, 1H), 4.68 (br, 1H),
.38-4.25 (m, 4H), 1.90-1.81 (m, 2H), 1.76-1.65 (m, 1H),
.41-1.35 (m, 6H), 1.28-1.25 (m, 1H); C NMR (DMSO-d
36.4 (d, J ) 3.7 Hz), 125.7, 62.6 (d, J ) 12.2 Hz), 62.4 (d, J
12.2 Hz), 54.6 (d, J ) 4.9 Hz), 48.9, 23.8, 15.8 (d, J ) 6.1
13
6
) δ
J ) 3.7 Hz), 44.5, 25.1 (d, J ) 4.9 Hz), 23.4 (d, J ) 3.7 Hz),
2
0.2, 19.3 (d, J ) 3.7 Hz), 13.2; 31P NMR δ 6.4/6.8 (56:44); IR
)
-
1
(neat) 1254, 1243 (s), 1168, 1152 (m), 1005 (s) cm ; MS (ISP)
31
Hz), 14.3; P NMR (DMSO-d
6
) δ 4.4; IR (KBr) 1203 (s), 1161
Sn NMR (external SnCl ) δ -952. Anal.
NO SPSn: C, 22.23, H, 3.37 N, 2.60; Cl,
+
3
27 (M + Na, 58), 247 (36), 225 (86), 211 (33), 197 (100).
-1 119
(
m), 1028 (s) cm
;
4
en d o-3-Aza -3-(3-ter t-b u t yl-1,3,2-oxa za p h osp h or yl)-2-
Calcd for C10
H
18Cl
4
4
oxo-2-th ia bicyclo[2.2.2]oct-5-en e (7f). Oil; 41% (two dia-
stereomers); eluting (2/5 hex/THF); H NMR δ 6.93-6.87 (m,
2
5.96. Found: C, 21.82; H, 3.69; N, 2.43; Cl, 26.32.
1
1
4
3
1
1
5
1
H), 6.26 (t, J ) 7.2 Hz, 1H), 4.85-4.83 (m, minor), 4.61-
.54 (m, 1H), 4.25-4.20 (m, 1H), 4.18-4.11 (m, 1H), 3.91-
.86 (m, 1H), 3.40-3.14 (m, 2H), 2.02-1.85 (m, 2H), 1.84-
.70 (m, 2H), 1.54-1.43 (m, minor), 1.35 (s, 9H), 1.31 (s, 1H),
.15-1.01 (m, 1H); 13C NMR δ 136.7 (d, J ) 4.9 Hz), 124.5,
6.0 (d, J ) 6.1 Hz), 49.9 (d, J ) 2.4 Hz), 26.1 (d, J ) 7.3 Hz),
Ack n ow led gm en t. We are grateful to the Petro-
leum Research Fund for financial support of this
research.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
3
1
4.5; P NMR δ 4.1/4.8 (1:2); IR (neat) 1244 (s), 1155, 1104
13
4
5
d , 6a , 7a , 7a ′, 7b, 7b′, 7d , 7e, 7f, 9d and C NMR for 3d ,
a , 5d (13 pages). This material is contained in libraries on
-
1
+
(
(
m), 1023 (s) cm ; MS (ESI) 319 (M + 1, 19), 256 (100), 239
100), 223 (64), 193 (79), 137 (79), 112 (14).
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
N-(Cycloh exa -3-en yla m in o)-5,5-d im et h yl-2-oxo-1,3,2-
d ioxa p h osp h or in a n e (8d ). A NaHCO
mL, 1 mmol) was added dropwise at room temperature to a
solution of thiazine derivative (7d , 0.5 mmol) and CH Cl (5
3
0.1 M solution (10
2
2
J O970186T