Lewis acid-mediated rearrangement of activated cyclic amines: A facile synthetic protocol for the preparation of amino carbonyl compounds

Article abstract of DOI:10.1021/jo702044k

(Chemical Equation Presented) Ring opening of activated cyclic amines to produce amino carbonyl compounds has been studied in the presence of Lewis acids. Whereas five- and six-membered rings cleave and rearrange via a 1,2-hydride shift, reaction in three

Full text of DOI:10.1021/jo702044k

Lewis Acid-Mediated Rearrangement of Activated Cyclic Amines:
A Facile Synthetic Protocol for the Preparation of Amino Carbonyl
Compounds
Sermadurai Selvakumar, Sivaraj Baktharaman, and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Vinodks@iitk.ac.in
ReceiVed September 18, 2007
Ring opening of activated cyclic amines to produce amino carbonyl compounds has been studied in the
presence of Lewis acids. Whereas five- and six-membered rings cleave and rearrange via a 1,2-hydride
shift, reaction in three- and four-membered rings takes place via a C-C bond migration. In the case of
a three-membered ring, a wide variety of Lewis acids proved to be effective for the reaction. Base-
induced ring opening of activated R,R-disubstituted azetidinemethanol and its mechanistic aspects have
been studied.
Introduction
these methods, at times, suffer from poor regio- and stereose-
lectivity. Very few examples of rearrangements or fragmenta-
tions of activated cyclic amines for the synthesis of amino
carbonyl compounds are known.6 During our ongoing investiga-
tions on Lewis acid-mediated reactions of activated aziridines
and azetidines,7 we found that activated cyclic amines having
cyclopropanol at the R-position produced an interesting sub-
stituted cyclobutanone via a C-C bond migration (Scheme 1).8
Organic compounds having amino and carbonyl functional-
ities are prevalent in a variety of biologically important natural
products.1 They are also versatile intermediates in organic
synthesis.2 Development of methods for the synthesis of such
motifs with high regio- and stereoselectivity is one of the
important challenges in organic synthesis. Among these, the
construction of â- and γ-amino carbonyl compounds is of great
interest because of their use in medicinal chemistry.3 Since these
are also versatile precursors for the synthesis of unnatural amino
acids,4 a number of elegant approaches have been described
for the acquisition of amino carbonyl compounds.5 Many of
(5) (a) Arend, M.; Westermann, B.; Risch, N. Angew. Chem., Int. Ed.
1998, 37, 1044-1070. (b) Co´rdova, A. Acc. Chem. Res. 2004, 37, 102-
112. (c) Aziz, N.; Torkiyan, L.; Saidi, M. R. Org. Lett. 2006, 10, 2079-
2082. (d) Tramontini, M.; Angiolini, L. Tetrahedron 1990, 46, 1791-1837.
(e) Xu, L.-W.; Xia, C.-G. Eur. J. Org. Chem. 2005, 633-639. (f) Spencer,
J. B.; Gaunt, M. J. Org. Lett. 2001, 3, 25-28. (g) Enders, D.; Wahl, H.;
Bettray, W. Angew. Chem., Int. Ed. 1995, 34, 455-457. (h) Kobayashi, S.;
Kakumoto, K.; Sugiura, M. Org. Lett. 2002, 4, 1319-1322. (i) Myers, J.
K.; Jacobson, E. N. J. Am. Chem. Soc. 1999, 121, 8959-8960. (j) Miura,
K.; Tamaki, K.; Nakagawa, T.; Hosomi, A. Angew. Chem., Int. Ed. 2000,
39, 1958-1960. (k) Ishitani, H.; Ueno, M.; Kobayashi, S. J. Am. Chem.
Soc. 2000, 122, 8180-8186 and references cited therein.
(6) (a) Wang, B. M.; Song, Z. L.; Fan, C. A.; Tu, Y. Q.; Shi, Y. Org.
Lett. 2002, 4, 363-366. (b) Song, Z. L.; Wang, B. M.; Tu, Y. Q.; Fan, C.
A.; Zhang, S. Y. Org. Lett. 2003, 5, 2319-2321. (c) Molander, G. A.;
Stengel, P. J. Tetrahedron 1997, 53, 8887-8912. (d) For a related example
of rearrangement of epoxy alcohol for the preparation of â-hydroxy carbonyl
compounds, see: Shimazaki, M.; Hara, H.; Suzuki, K.; Tsuchihashi, G.-I.
Tetrahedron Lett. 1987, 28, 5891-5894.
(7) (a) Prasad, B. A. B.; Bisai, A.; Singh, V. K. Org. Lett. 2004, 6, 4829-
4831. (b) Gandhi, S.; Bisai, A.; Prasad, B. A. B.; Singh, V. K. J. Org.
Chem. 2007, 72, 2133-2142.
* To whom correspondence should be addressed. Fax: +91-512-2597436.
(1) (a) Seebach, D.; Matthews, J. L. J. Chem. Soc., Chem. Commun.
1997, 2015-2022. (b) Juaristi, E. In Enantioselective Synthesis of â-amino
acids; John Wiley & Sons: New York, 1997.
(2) (a) Davis, F. A.; Santhanaraman, M. J. Org. Chem. 2006, 71, 4222-
4226. (b) Davis, F. A.; Yang, B. Org. Lett. 2003, 5, 5011-5014. (c) Notz,
W.; Tanaka, F.; Watanabe, S.-I.; Chowdari, N. S.; Turner, J. M.; Th-
ayumanavan, R.; Barbas, C. F. J. Org. Chem. 2003, 68, 9624-9634.
(3) (a) Dimmock, J. R.; Sidhu, K. K.; Chen, M.; Reid, R. S.; Allen, T.
M.; Kao, G. Y.; Truitt, G. A. Eur. J. Med. Chem. 1993, 28, 313-322. (b)
Traxler, P.; Trinks, U.; Buchdunger, E.; Mett, H.; Meyer, T.; Mu¨ller, M.;
Regenass, U.; Ro¨sel, N.; Lydon, N. J. Med. Chem. 1995, 38, 2441-2448.
(4) (a) Abele, S.; Seebach, D. Eur. J. Org. Chem. 2000, 1-15. (b) Cheng,
R. P.; Gellman, S. H.; Degrado, W. F. Chem. ReV. 2001, 101, 3219-3232.
(c) Ma, J.-A. Angew. Chem., Int. Ed. 2003, 42, 4290-4299. (d) Cole, D.
C. Tetrahedron 1994, 50, 9517-9582. (e) Mario, O.; Carlos, C. Tetrahe-
dron: Asymmetry 2007, 18, 3-99.
10.1021/jo702044k CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/29/2007
J. Org. Chem. 2007, 72, 10141-10146
10141

Selvakumar et al.
TABLE 2. Effect of Substituents on the Sulfonyl Group
SCHEME 1. Synthesis of 2-Substituted Cyclobutanone
entry
R
product
time, h
yield, %
1
2
3
4
5
6
7
8
4-MeC6H4
4-BrC6H4
4-FC6H4
4-OMeC6H4
2-NO2C6H4
4-NO2C6H4
Ph
2a
2b
2c
2d
2e
2f
10
10
20
24
20
24
20
10
72
77
88
SCHEME 2. Synthesis of Amino Carbonyl Compounds
79a
44a,b
48b
84
2g
2h
Me
80
a Based on recovered starting material. b Elimination product was also
observed.
TABLE 1. Effect of Lewis Acids on Rearrangement of
5-Membered N-Tosyl Cyclic Amine 1a
Cu(OTf)2 did not provide the above amino ketone. Instead, an
elimination product was obtained in modest yield (Table 1, entry
5). In(OTf)3 gave predominantly the elimination product 3a and
the amino ketone 2a was obtained only in 25% yield (entry 6).
Other Lewis acids, such as TiCl4 and Yb(OTf)3, did not initiate
the reaction under the above conditions.
yield, %
entry
Lewis acid
time, h
2a
3a
Having optimized the reaction conditions for Lewis acid-
induced rearrangement of 1a, we explored the scope of the
reaction by employing a variety of substituted sulfonyl com-
pounds 1a-h. The reaction tolerated a wide range of substituents
to afford corresponding γ-amino ketones 2a-h in moderate to
good yields (Table 2). For aryl sulfonates bearing the methoxy
or nitro substituents on the aromatic ring, the corresponding
products 2d-f were obtained in lower yields, with the recovery
of starting material under the optimized conditions (Table 2,
entries 4-6). This might be due to the chelation of Lewis acid
with the oxygen of the nitro or the methoxy group.
On the basis of the above experimental results, a possible
sequential mechanism of the reaction has been proposed
(Scheme 3). The chelation of a Lewis acid to the sulfonyl
oxygen weakens the C-N bond, facilitating intramolecular
attack of the OH group to provide an epoxide as an intermediate
and concomitant cleavage of the pyrrolidine ring. In the presence
of a Lewis acid, the epoxide ring cleaves12 to provide a stable
benzylic carbocation. Intramolecular 1,2-hydride shift affords
a γ-amino ketone 2 (Scheme 3). The driving force for the
hydride shift is the formation of the more stable carbocation
adjacent to the oxygen atom. Formation of 3 can be explained
simply by dehydration of tertiary alcohol.13
To substantiate the formation of an epoxide as an intermediate
in the above mechanism, the corresponding methyl ether 4a was
synthesized and exposed to a Lewis acid under the optimized
condition. Surprisingly, the same ring-opened product 2a was
obtained in the reaction (Table 3, entry 1). If the above
mechanism is to operate, this product should not have formed.
It occurred to us that there must be some residual moisture in
CH2Cl2 because of which the methyl ether was being hydrolyzed
to the corresponding alcohol under acidic conditions. To prevent
the hydrolysis of methyl ether from residual moisture, molecular
sieves were added to the reaction mixture. To our delight, the
addition of 4 Å molecular sieves (crushed) resulted in the
predominant formation of an elimination product 3a (Table 3,
1
2
3
4
5
6
7
8
Sn(OTf)2
Sc(OTf)3
BF3‚OEt2
Zn(OTf)2
Cu(OTf)2
In(OTf)3
TiCl4
10
10
48
48
48
5
72
64
32
23
50
72
25
48
48
Yb(OTf)3
We envisioned that if a cyclopropyl group is replaced by
phenyl groups, the rearrangement could be more facile due to
the involvement of phenonium ion as an intermediate. It was
indeed the case for 3- and 4-membered cyclic amines. However,
in the cases of 5- and 6-membered cyclic amines, the products
obtained were due to a hydride shift (Scheme 2). For the first
time, base-induced ring opening of activated R,R-disubstituted
azetidinemethanol has been studied. Herein, we wish to report
the details of our study.
Results and Discussion
At the outset, we examined the reaction of five-membered
cyclic amines. The requisite precursor 1a9 was synthesized by
sulfonylation of an amino alcohol10 derived from L-proline. On
treatment of 1a with 1 equiv of Sn(OTf)2 in CH2Cl2 at room
temperature for 10 h, a γ-amino pentanone derivative 2a was
obtained in 72% yield (Table 1).11 To optimize the reaction,
other Lewis acids were also evaluated. It was observed that Sc-
(OTf)3 facilitated the rearrangement to the same extent (Table
1, entry 2). On the other hand, BF3‚OEt2 and Zn(OTf)2 gave
the product 2a in low yields and led to the recovery of most of
the starting material (Table 1, entries 3 and 4). Interestingly,
(8) Baktharaman, S.; Selvakumar, S.; Singh, V. K. Org. Lett. 2006, 8,
4335-4338.
(9) Yang, S.-D.; Shi, Y.; Sun, Z.-H.; Zhao, Y.-B.; Liang, Y.-M.
Tetrahedron: Asymmetry 2006, 17, 1895-1900.
(10) Bhaskar Kanth, J. V.; Periasamy, M. Tetrahedron 1993, 49, 5127-
5132.
(12) Ranu, B. C.; Jana, U. J. Org. Chem. 1998, 63, 8212-8216.
(13) Nishizawa, M.; Asai, Y.; Imagawa, H. Org. Lett. 2006, 8, 5793-
5796.
(11) Under the specified condition, the reaction failed to give any ring-
opening product when diphenyl is replaced by dialkyl or monophenyl.
10142 J. Org. Chem., Vol. 72, No. 26, 2007

Preparation of Amino Carbonyl Compounds
TABLE 4. Effect of Lewis Acids on Rearrangement of
6-Membered N-Tosyl Cyclic Amine
SCHEME 3. Proposed Mechanism for the Rearrangement
of Activated 5-Membered Cyclic Amine
yield, %
entry
Lewis acid
time, h
6
7
1
2
3
Sn(OTf)2
Sc(OTf)3
In(OTf)3
48
48
5
35
12
8
46
75
78
SCHEME 5. Ring Opening of the Activated
Four-Membered Ring
TABLE 3. Rearrangement of r,r-Disubstituted Methyl Ether of
5-Membered N-Tosyl Cyclic Amine 4a
selectivity for the amino ketone 6 was very poor and an
elimination product 7 was predominantly formed.
After successful demonstration of the ring opening of five-
and six-membered N-activated cyclic amines, the reaction was
extended to a four-membered cyclic amine. Thus, compound 8
was treated with Sn(OTf)2 and, to our surprise, no hydride-
migrated product was obtained. Instead, an aryl-migrated ketone
10 was isolated along with an elimination product 9 in a ratio
of 1:1 (Scheme 5). To confirm that the reaction in the cases of
five- and six-membered rings (vide supra) proceeds via an
epoxide as proposed in the mechanism described in Scheme 3,
we thought of converting 8 into a similar epoxide 11 using aza-
Payne rearrangement. Ibuka and co-workers have reported the
aza-Payne rearrangement of a series of 2,3-disubstituted aziri-
dine-1-ols, as well as the reaction of rearranged product with
different nucleophiles, including organocuprates and amines.14
Although base-induced ring opening of activated 2,3-aziridine-
1-ol has been well-utilized in the synthesis of enantiomerically
pure nitrogen-containing compounds,15 to our knowledge, the
aza-Payne rearrangement of R,R-disubstituted azetidinemethanol
yield, %
entry
4 Å MS
time, h
2a
62
trace
3a
1
2
no
yes
3
7
92
SCHEME 4. Proposed Mechanism for the Rearrangement
of r,r-Disubstituted Methyl Ether of 5-Membered N-Tosyl
Cyclic Amine 4
(14) (a) Ibuka, T.; Nakai, K.; Akaji, M.; Tamamura, H.; Fujii, N.;
Yamamoto, Y. Tetrahedron 1996, 52, 11739-11752. (b) Nakai, K.; Ibuka,
T.; Otaka, A.; Tamamura, H.; Fujii, N.; Yamamoto, Y. Tetrahedron Lett.
1995, 36, 6247-6250. (c) Najime, R.; Pilard, S.; Vaultier, M. Tetrahedron
Lett. 1992, 33, 5351-5354. (d) Bouyacoub, A.; Volatron, F. Eur. J. Org.
Chem. 2002, 24, 4143-4150. (e) Moulines, J.; Charpentier, P.; Bats, J.-P.;
Nuhrich, A.; Lamidey, A.-M. Tetrahedron Lett. 1992, 33, 487-490. (f)
Atkinson, R. S.; Fawcett, J.; Russell, D. R.; Williams, P. J. Tetrahedron
Lett. 1995, 36, 3241-3244. (g) Ibuka, T.; Nakai, K.; Habashita, H.; Fujii,
N.; Garrido, F.; Mann, A. Tetrahedron Lett. 1993, 34, 7421-7424.
(15) (a) Ibuka, T.; Nakai, K.; Habashita, H.; Hotta, Y.; Otaka, A.;
Tamamura, H.; Fuji, N.; Mimura, N.; Miwa, Y.; Taga, T.; Chounan, Y.;
Yamamoto, Y. J. Org. Chem. 1995, 60, 2044-2058. (b) Ibuka, T. Chem.
Soc. ReV. 1998, 27, 145-154. (c) Schomaker, J. M.; Bhattacharjee, S.; Yan,
J.; Borhan, B. J. Am. Chem. Soc. 2007, 129, 1996-2003. (d) Rosser, C.
M.; Coote, S. C.; Kirby, J. P.; O’Brien, P.; Caine, D. Org, Lett. 2004, 6,
4817-4819. (e) Hudlicky, T.; Rinner, U.; Gonzalez, D.; Akgun, H.;
Schilling, S.; Siengalewicz, P.; Martinot, T. A.; Pettit, G. R. J. Org. Chem.
2002, 67, 8726-8743 and references cited therein.
entry 2), which indicated that the hydroxyl group is essential
for the opening of activated ring and the reaction proceeds via
an epoxide (Scheme 4).
To extend the scope of the method, the reaction of six-
membered cyclic amine has been investigated in the presence
of Lewis acids (Table 4). It was observed that in this case, the
J. Org. Chem, Vol. 72, No. 26, 2007 10143

Selvakumar et al.
SCHEME 6. Ring Opening of Chiral Aziridinol
Lewis acid chelates to the oxygens of the sulfonyl and the
hydroxyl group. After chelation, the antiperiplanar 1,2-aryl
migration and aziridine ring opening occurs simultaneously to
give â-amino ketone in a highly stereospecific manner via a
phenonium ion (Scheme 8).
Conclusion
SCHEME 7. Diastereoselective Ring Opening of Aziridinol
In conclusion, we have described an efficient method for the
synthesis of amino carbonyl compounds through cleavage of
activated cyclic amines. In the cases of activated pyrrolidine
and piperidine rings, reaction occurs via ring opening of the
cyclic amine followed by a 1,2-hydride shift leading to a gem-
diphenyl keto amine. However, in the case of aziridine and
azetidine ring, an aryl-migrated product is formed via a 1,2-
carbon-carbon bond migration in SN2 fashion.
SCHEME 8. Proposed Mechanism for the Formation of
Enantiomerically Pure â-Amino Ketone
Experimental Section
General Procedure for Preparation of N-Sulfonyl Derivatives
(1a-h). A solution of sulfonyl chloride (11 mmol) in dichlo-
romethane (10 mL) was added dropwise to a solution of amino
alcohol9 (9.3 mmol) in dichloromethane (15 mL) containing
triethylamine (20 mmol) and DMAP (1.1 mmol) at 0 °C. After the
reaction mixture was stirred for 10 h at rt, it was quenched with
water and extracted (3 times) with dichloromethane. The combined
organic extract was washed with brine and dried over anhydrous
Na2SO4. The solvent was removed and the residue was purified by
column chromatography to obtain the pure corresponding sulfonate
as a colorless solid.
(S)-[1-(4-Bromobenzenesulfonyl)pyrrolidin-2-yl]diphenyl-
methanol (1b): yield 56%; white solid; [R]25 -68.6 (c 1.0,
has not been studied. The reaction of 8 with 4 equiv of NaH in
10:1 THF/HMPA16 led to an epoxy amine 11 via an aza-Payne
rearrangement in 92% yield.17 The epoxide 11, in the presence
of Sn(OTf)2, rearranged to a â-amino ketone 12 in 77% yield
(Scheme 5). This study supports the intermediacy of an epoxide
in the cases of six- and five-membered activated amines.
Having studied the ring system from four- to six-membered
N-tosyl cyclic amines, it was interesting to study the reaction
of N-activated three-membered aziridines with a Lewis acid.
Thus, a chiral N-tosyl aziridine alcohol 1316 was treated with 1
equiv of Sn(OTf)2 at room temperature for 10 min. Gratifyingly,
the sole product 14 obtained was enantiomerically pure (>99%
ee) in high chemical yield (Scheme 6).18 The reaction proceeded
as in the case of a four-membered ring by the migration of a
phenyl group. There was no trace of elimination product. Other
Lewis acids such as Sc(OTf)3, Cu(OTf)2, Yb(OTf)3, Zn(OTf)2,
TiCl4, BF3‚OEt2, and SnCl4 also facilitated the reaction with
equal ease, but Sn(OTf)2 was found to be the best.
D
CHCl3); mp 160 °C; TLC Rf 0.80 (30%, EtOAc/petroleum ether);
1
IR (NaCl cell, CH2Cl2, cm-1) 3497, 3059, 1601; H NMR (400
MHz, CDCl3) δ 0.88 (m, 1H), 1.31 (m, 1H), 1.90 (m, 2H), 2.84
(m, 1H), 3.31 (m, 1H), 4.09 (s, 1H), 4.90 (m, 1H), 7.26-7.43 (m,
10H), 7.59-7.66 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 24, 29.5,
49.9, 67.4, 80, 127.3, 127.4, 127.7, 127.9, 128, 129, 132.4, 143.4,
145.3. Anal. Calcd for C23H22BrNO3S: C, 58.48; H, 4.69; N, 2.97.
Found: C, 58.32; H, 4.53; N, 3.04.
(S)-[1-(4-Fluorobenzenesulfonyl)pyrrolidin-2-yl]diphenylmeth-
anol (1c): yield 58%; white solid; [R]25 -70.2 (c 1.0, CHCl3);
D
mp 158 °C; TLC Rf 0.70 (30%, EtOAc/petroleum ether); IR (NaCl
cell, CH2Cl2, cm-1) 3491, 3060, 1591; 1H NMR (400 MHz, CDCl3)
δ 0.87 (m, 1H), 1.28 (m, 1H), 1.89 (m, 2H), 2.8 (m, 1H), 3.31 (m,
1H), 4.91 (m, 1H), 7.17-7.44 (m, 12H), 7.76-7.79 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 24, 29.5, 49.9, 67.3, 78, 116.2, 166.5,
127.3, 127.4, 127.9, 128, 130.2, 134.2, 143.4, 145.4, 163.9, 166.4.
Anal. Calcd for C23H22FNO3S: C, 67.13; H, 5.39; N, 3.40. Found:
C, 66.92; H, 5.23; N, 3.33.
(S)-[1-(4-Methoxybenzenesulfonyl)pyrrolidin-2-yl]diphenyl-
methanol (1d): yield 48%; white solid; [R]25 -90.9 (c 1.0,
To confirm high stereoselectivity in the reaction, a chiral
aziridine compound 1516 with two stereogenic centers was
exposed to a Lewis acid under the optimized condition and only
one stereoisomer of the â-amino ketone 16 was isolated in high
yield (Scheme 7).
D
CHCl3); mp 134-136 °C; TLC Rf 0.50 (30%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3467, 3058, 1595; H NMR
(400 MHz, CDCl3) δ 0.73 (m, 1H), 1.26 (m, 1H), 1.65 (m, 1H),
1.84 (m, 1H), 2.77 (m, 1H), 3.26 (m, 1H), 3.89 (s, 3H), 4.6 (s,
1H), 4.8 (m, 1H), 7.0 (d, J ) 8.8 Hz, 2H), 7.26-7.43 (m, 10H),
7.76 (d, J ) 8.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 23.7,
29.7, 49.9, 55.6, 67.2, 79.7, 114.3, 127.2, 127.3, 127.5, 128, 128.3,
129.7, 143.6, 145.6, 163.1. Anal. Calcd for C24H25NO4S: C, 68.06;
H, 5.95; N, 3.31. Found: C, 67.92; H, 5.78; N, 3.44.
(S)- [1-(2-Nitrobenzenesulfonyl)pyrrolidin-2-yl]diphenylmeth-
anol (1e): yield 49%; yellow solid; [R]25D -127.2 (c 1.3, CHCl3);
mp 140 °C; TLC Rf 0.50 (30%, EtOAc/petroleum ether); IR (NaCl
cell, CH2Cl2, cm-1) 3528, 3028, 1542; 1H NMR (400 MHz, CDCl3)
δ 1.35 (m, 1H), 1.56 (m, 1H), 1.93 (m, 1H), 2.17 (m, 1H), 3.10
(m, 1H), 3.71 (m, 1H), 5.34 (m, 1H), 7.10-7.66 (m, 14H); 13C
NMR (100 MHz, CDCl3) δ 25.1, 29.7, 51.2, 53.4, 68.3, 80.3, 123.7,
The stereochemical outcome of the reaction was explained
on the basis of experimental results and literature reports.6a The
(16) Xichun, F.; Guofu, Q.; Shucai, L.; Hanbing, T.; Lamei, W.;
Xianming, H. Tetrahedron: Asymmetry 2006, 17, 1394-1401.
(17) The exposure of 1a to base NaH in THF/HMPA (10:1) did not affect
it even after 24 h.
(18) (a) Chiracel AD-H, UV detector 254 nm, 1 mL/min, 90:10 hexane/
propan-2-ol, retention time of 14 tR ) 42.97 min. (b) The reaction of epoxide
derived from aza-Payne rearrangement of 13, with Lewis acid under standard
condition afforded the hydride migrated product in 16% yield (Based on
recovered starting material) after 14 h.
10144 J. Org. Chem., Vol. 72, No. 26, 2007

Preparation of Amino Carbonyl Compounds
126.8, 126.9, 127.1, 127.3, 127.9, 128, 131, 131.5, 132.9, 133,
143.9, 145.2, 147.5. Anal. Calcd for C23H22N2O5S: C, 63.00; H,
5.06; N, 6.39. Found: C, 62.32; H, 4.86; N, 6.14.
General Procedure for Aza-Payne Rearrangement. To a
suspension of NaH (60% suspension in mineral oil, 24 mg, 1 mmol)
in a mixture of THF (2 mL) and HMPA (330 µL) was added a
solution of 8 (0.25 mmol) in THF (2 mL) at 0 °C. After the reaction
mixture was stirred for 3 h at rt, it was quenched with 2 mL of 5%
citric acid at 0 °C with stirring and extracted with diethyl ether.
The combined organic layer was washed (3 times) successively
with saturated citric acid (25 mL), brine (25 mL), 5% NaHCO3
(25 mL), and brine (25 mL), then dried over Na2SO4. The solvent
was removed and the residue was purified by column chromatog-
raphy to obtain the pure epoxyamine.
(S)-(1-(Methylsulfonyl)pyrrolidin-2-yl)diphenylmethanol (1h):
yield 44%; yellow solid; [R]25 -33.4 (c 1.0, CHCl3); mp 142-
D
144 °C; TLC Rf 0.60 (30%, EtOAc/petroleum ether); IR (NaCl cell,
1
CH2Cl2, cm-1) 3482, 3026, 1598; H NMR (400 MHz, CDCl3) δ
1.19 (m, 1H), 1.65 (m, 1H), 1.94 (m, 1H), 2.19 (m, 1H), 2.6 (s,
3H), 2.94 (m, 1H), 3.37 (s, 1H), 3.62 (m, 1H), 5.1 (dd, J ) 9, 3.4
Hz, 1H), 7.24-7.49 (m, 10H); 13C NMR (100 MHz, CDCl3) δ 25.1,
29.4, 39.1, 49.8, 67, 80.7, 127.2, 127.4, 127.8, 128, 143.6, 145.6.
Anal. Calcd for C18H21NO3S: C, 65.23; H, 6.39; N, 4.23. Found:
C, 65.93; H, 6.14; N, 4.11.
N-(2-(3,3-Diphenyloxiran-2-yl)ethyl)-4-methylbenzenesulfona-
mide (11): yield 92%; viscous liquid; TLC Rf 0.80 (30%, EtOAc/
petroleum ether); IR (NaCl cell, CH2Cl2, cm-1) 3282, 2924, 1327;
1H NMR (400 MHz, CDCl3) δ 1.28 (m, 1H), 1.76 (m, 1H), 2.41
(s, 3H), 3.12 (m, 2H), 3.4 (dd, J ) 8.04, 4.12 Hz, 1H), 4.7 (t, J )
Preparation of Diphenyl(1-tosylpiperidin-2-yl)methanol (5).
A solution of amino alcohol19 (1 equiv) in pyridine (5 equiv) was
treated with sulfonyl chloride (1.2 equiv) at 0 °C in portions and
the reaction mixture was stirred at room temperature for 10 h. Water
was then added and the aqueous phase was extracted with
dichloromethane (3 times). The combined organic extract was
washed with brine and dried over anhydrous Na2SO4. The solvent
was removed and the residue was purified by column chromatog-
raphy to obtain the pure corresponding sulfonate 5: yield 45%;
white solid; mp 162-164 °C; TLC Rf 0.60 (20%, EtOAc/petroleum
5.12 Hz, 1H), 7.25-7.37 (m, 12H), 7.7 (d, J ) 8.28 Hz, 2H); 13
C
NMR (100 MHz, CDCl3) δ 21.5, 29.3, 40.8, 64, 65.9, 126.9, 127,
127.8, 127.9, 128.3, 129.7, 136.6, 136.9, 140.2, 143.4; HRMS
(TOF-ES+) calcd for C23H23NO3S 394.1478 [M + H]+, found
394.1472.
General Procedure for Preparation of Amino Carbonyl
Compound/Olefinic Compound. To a solution of activated amine
(0.18 mmol) in dry dichloromethane (2 mL) was added Lewis acid
(0.18 mmol) at rt. After completion of the reaction, as monitored
by TLC, the solvent was evaporated to give crude product.
Purification by column chromatography (20% EtOAc in petroleum
ether) yielded the desired amino carbonyl compound/olefinic
compound.
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3506, 2926, 1306; H NMR
(400 MHz, CDCl3) δ 1.39 (m, 3H), 1.77 (m, 2H), 1.9 (m, 1H),
2.36 (s, 3H), 2.9 (s, 1H), 3.39 (m, 2H), 5.1 (m, 1H), 7.09-7.54
(m, 14H); 13C NMR (100 MHz, CDCl3) δ 20.2, 21.4, 22.5, 24.9,
43, 56.8, 83.9, 126.4, 126.5, 126.8, 127.1, 127.5, 127.9, 128.3,
129.3, 137.3, 142.7, 245.4, 145.6; MS (ES+) 422 [M+ + 1].
Preparation of Diphenyl(1-tosylazetidin-2-yl)methanol (8). To
a suspension of magnesium turnings (23.4 mmol) in dry THF (25
mL) was added bromobenzene (23.4 mmol) dropwise and the
mixture was allowed to stir for 1 h. A solution of N-benzyl azetidine
ester20 (5.9 mmol) in dry THF (10 mL) was added to the above
mixture at 0 °C. After the reaction mixture was stirred overnight
at rt, it was quenched with saturated NH4Cl solution (10 mL) and
extracted with diethyl ether. The organic phase was washed with
brine and dried over anhydrous Na2SO4. The solvent was removed
in vacuo, and the crude compound was purified by column
chromatography to obtain pure (1-benzylazetidin-2-yl)diphenyl-
methanol as a white solid: yield 80%; mp 116 °C; TLC Rf 0.70
(10%, EtOAc/petroleum ether); IR (NaCl cell, CH2Cl2, cm-1) 3256,
2962; 1H NMR (400 MHz, CDCl3) δ 1.94 (m, 1H), 2.11 (m, 1H),
2.84 (m, 1H), 3.04-3.20 (m, 3H), 4.38 (t, J ) 7.8 Hz, 1H), 5.19
(s, 1H), 7.05-7.30 (m, 11H), 7.45 (d, J ) 8.28 Hz, 2H), 7.62 (d,
J ) 8.08 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 19.4, 50.3, 61.3,
72, 75.8, 125.7, 125.8, 126.6, 126.7, 126.9, 128.1, 128.2, 128.4,
137.7, 144, 147.
Then to a solution of this N-benzyl compound (4.7 mmol) in
dry MeOH (24 mL) was added Pd(OH)2/C (500 mg) under argon
atmosphere. The reaction mixture was hydrogenated at 55 psi for
12 h at rt. Then the reaction mixture was filtered through a pad of
celite and washed with MeOH. The solvent was removed and the
residue was purified by column chromatography to obtain the pure
amino alcohol, which was converted into the corresponding
sulfonate by following the same procedure as for 1a: yield (2 steps)
57%; mp 132 °C; TLC Rf 0.50 (30%, EtOAc/petroleum ether); IR
(NaCl cell, CH2Cl2, cm-1) 3461, 3058, 1335; 1H NMR (400 MHz,
CDCl3) δ 2.04-2.14 (m, 2H), 2.44 (s, 3H), 3.52 (m, 1H), 3.76 (m,
1H), 4.24 (s, 1H), 4.95 (m, 1H), 7.21-7.39 (m, 12H), 7.52 (d, J )
8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 19, 21.5, 47.5, 70.5,
77.8, 126, 126.7, 127, 127.2, 127.9, 128.1, 129.7, 132.4, 142.8,
144, 144.1. Anal. Calcd for C23H23NO3S: C, 70.20; H, 5.89; N,
3.56. Found: C, 69.89; H, 5.72; N, 3.70.
4-Methyl-N-(3-oxo-4,4-diphenylbutyl)benzenesulfonamide (2a):
yield 72%; viscous liquid; TLC Rf 0.20 (20%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3284, 3028, 1713; H NMR
(400 MHz, CDCl3) δ 1.72 (m, 2H), 2.41 (s, 3H), 2.61 (t, J ) 6.8
Hz, 2H), 2.88 (m, 2H), 4.59 (t, J ) 6.4 Hz, 1H), 5.1 (s, 1H), 7.19-
7.33 (m, 12H), 7.68 (d, J ) 8.3 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 21.5, 23.5, 39.4, 42.4, 64.2, 126.9, 127.3, 128.7, 129.7,
136.7, 138, 143.3, 208.2; HRMS (TOF-ES+) calcd for C24H25NO3S
[M + H]+ 408.1634, found 408.1631.
2-(Diphenylmethylene)-1-tosylpyrrolidine (3a): yield 72%;
white solid; mp 144 °C; TLC Rf 0.70 (20%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 2958, 1634, 1358; H NMR
(400 MHz, CDCl3) δ 1.65 (m, 2H), 2.05 (t, J ) 7.32 Hz, 2H), 2.43
(s, 3H), 3.62 (t, J ) 7.32 Hz, 2H), 7.08 (m, 2H), 7.19-7.29 (m,
10H), 7.59 (d, J ) 8.32 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
21.5, 22.2, 30.1, 49.3, 126.6, 127.5, 127.7, 127.9, 129.3, 129.9,
130.2, 135.3, 136.6, 142.2, 143.5.; HRMS (TOF-ES+) calcd for
C24H23NO2S [M + H]+ 390.1528, found 390.1521.
4-Bromo-N-(3-oxo-4,4-diphenylbutyl)benzenesulfonamide (2b):
yield 77%; viscous liquid; TLC Rf 0.30 (20%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3286, 2926, 1713; H NMR
(400 MHz, CDCl3) δ 1.75 (m, 2H), 2.61 (t, J ) 6.6 Hz, 2H), 2.89
(m, 2H), 4.68 (t, J ) 6.1 Hz, 1H), 5.1 (s, 1H), 7.18-7.34 (m, 10H),
7.60-7.66 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 23.4, 39.4,
42.5, 64.3, 127.3, 127.4, 127.5, 128.4, 128.6, 128.7, 128.9, 129,
132.3, 132.4, 138, 138.8, 208.4; MS (FAB) 472 [M+ + 1].
4-Fluoro-N-(3-oxo-4,4-diphenylbutyl)benzenesulfonamide (2c):
yield 88%; viscous liquid; TLC Rf 0.20 (20%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3286, 2925, 1713, 1330; H
NMR (400 MHz, CDCl3) δ 1.72 (m, 2H), 2.62 (t, J ) 6.5 Hz,
2H), 2.89 (m, 2H), 4.59 (m, 1H), 5.1 (s, 1H), 7.13-7.34 (m, 12H),
7.79-7.82 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 23.5, 29.7,
39.4, 64.3, 116.2, 116.7, 128.7, 128.9, 129.6, 135.9, 137.9, 208.3;
MS (FAB) 412 [M+ + 1].
4-Methoxy-N-(3-oxo-4,4-diphenylbutyl)benzenesulfonamide
(2d): yield 32%; viscous liquid; TLC Rf 0.20 (20%, EtOAc/
petroleum ether); IR (NaCl cell, CH2Cl2, cm-1) 3283, 3027, 1713;
1H NMR (400 MHz, CDCl3) δ 1.75 (m, 2H), 2.62 (t, J ) 6.8 Hz,
2H), 2.89 (m, 2H), 3.86 (s, 3H), 4.4 (t, J ) 6.3 Hz, 1H), 5.1 (s,
1H), 6.9 (dd, J ) 6.8, 1.9 Hz, 2H), 7.1-7.3 (m, 10H), 7.7 (dd, J
(19) Rama Rao, A. V.; Gurjar, M. K.; Sharma, P. A.; Kumar, V.
Tetrahedron Lett. 1990, 31, 2341-2344.
(20) Wasserman, H. H.; Lipshutz, B. H.; Tremper, A. W.; Wu, J. S. J.
Org. Chem. 1981, 46, 2991-2999.
J. Org. Chem, Vol. 72, No. 26, 2007 10145

Selvakumar et al.
) 6.8, 1.9 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 23.5, 29.6,
39.4, 42.4, 64.2, 114.2, 127.3, 128.7, 128.9, 129.1, 131.3, 138,
162.8, 208.2; MS (FAB) 424 [M+ + 1].
cell, CH2Cl2, cm-1) 2926, 1598, 1324; 1H NMR (400 MHz, CDCl3)
δ 1.57 (m, 2H), 1.87 (m, 2H), 2.26 (m, 1H), 2.31 (s, 3H), 2.5 (m,
1H), 3.12 (m, 1H), 3.94 (m, 1H), 6.97-7.32 (m, 14H); 13C NMR
(100 MHz, CDCl3) δ 21.4, 24.1, 26.2, 29.5, 49.5, 126.5, 127.2,
127.6, 127.7, 128, 129, 129.5, 134.1, 136.7, 141, 141.3, 141.4,
142.6; HRMS (TOF-ES+) calcd for C25H25NO2S [M + H]+
404.1685, found 404.1680.
2-Nitro-N-(3-oxo-4,4-diphenylbutyl)benzenesulfonamide (2e):
yield 44%; viscous liquid; TLC Rf 0.20 (20%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3333, 2923, 1714, 1362; H
NMR (400 MHz, CDCl3) δ 1.80 (m, 2H), 2.67 (t, J ) 6.8 Hz,
2H), 3.05 (m, 2H), 5.11 (s, 1H), 5.28 (m, 1H), 7.20-7.34 (m, 10H),
7.72 (m, 2H), 7.82 (m, 1H), 8.07 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 23.8, 39, 42.9, 64.3, 125.3, 127.3, 128.7, 128.9, 131.1,
132.7, 133.5, 133.7, 138.1, 207.6; MS (FAB) 439 [M+ + 1].
4-Nitro-N-(3-oxo-4,4-diphenylbutyl)benzenesulfonamide (2f):
yield 48%; viscous liquid; TLC Rf 0.20 (20%, EtOAc/petroleum
2-(Diphenylmethylene)-1-tosylazetidine (9): yield 49%; viscous
liquid; TLC Rf 0.60 (30%, EtOAc/petroleum ether); IR (NaCl cell,
1
CH2Cl2, cm-1) 2922, 1596, 1354; H NMR (400 MHz, CDCl3) δ
2.45 (s, 3H), 2.49 (t, J ) 8.3 Hz, 2H), 4.1 (t, J ) 8.32 Hz, 2H),
6.82 (m, 2H), 7.10 (m, 3H), 7.32 (m, 7H), 7.59 (d, J ) 8.28 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ 21.6, 33.6, 49.7, 126.7, 127,
127.7, 127.9, 128, 128.6, 129.4, 130.1, 135, 135.5, 143,7; MS (ES+)
375.13 (M+ + 1).
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3295, 2925, 1713; H NMR
(400 MHz, CDCl3) δ 1.74 (m, 2H), 2.64 (t, J ) 6.6 Hz, 2H), 2.95
(m, 2H), 4.92 (t, J ) 6.08 Hz, 1H), 5.1 (s, 1H), 7.2-7.35 (m, 10H),
7.96 (d, J ) 8.5 Hz, 2H), 8.30 (d, J ) 8.8 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 23.4, 39.4, 42.7, 64.3, 124.3, 124.4, 127.3, 127.5,
128.1, 128.3, 128.7, 128.9, 137.8, 145.7, 149.9, 208.5; MS (FAB)
439 [M+ + 1].
4-Methyl-N-(4-oxo-3,4-diphenylbutyl)benzenesulfonamide (10):
yield 47%; viscous liquid; TLC Rf 0.40 (30%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3288, 2921, 1676, 1323; H
NMR (400 MHz, CDCl3) δ 1.97 (m, 2H), 2.35 (m, 1H), 2.38 (s,
3H), 2.93 (m, 2H), 4.67 (m, 2H), 7.16-7.37 (m, 9H), 7.46 (m,
1H), 7.68 (d, J ) 8.32 Hz, 2H), 7.89 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 21.5, 29.7, 33.2, 41.6, 50.4, 127, 127.3, 128.1, 128.4,
128.8, 129.2, 129.6, 133, 136, 136.5, 138.5, 143.4, 199.2; HRMS
(TOF-ES+) calcd for C23H23NO3S [M + H]+ 394.1478, found
394.1473.
N-(3-Oxo-4,4-diphenylbutyl)benzenesulfonamide (2g): yield
84%; viscous liquid; TLC Rf 0.20 (20%, EtOAc/petroleum ether);
1
IR (NaCl cell, CH2Cl2, cm-1) 3282, 2926, 1714, 1326; H NMR
(400 MHz, CDCl3) δ 1.73 (m, 2H), 2.61 (t, J ) 6.84 Hz, 2H), 2.90
(m, 2H), 4.64 (t, J ) 6.08 Hz, 1H), 5.1 (s, 1H), 7.19-7.33 (m,
10H), 7.46-7.58 (m, 3H), 7.8 (d, J ) 7.5 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 23.6, 39.4, 42.5, 64.2, 126.9, 127.3, 128.7, 128.9,
129, 132.6, 138, 208.2; MS (FAB) 394 [M+ + 1].
4-Methyl-N-(3-oxo-4,4-diphenylbutyl)benzenesulfonamide (12):
yield 77%; viscous liquid; TLC Rf 0.70 (30%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3291, 3028, 1713, 1327; H
N-(3-Oxo-4,4-diphenylbutyl)methanesulfonamide (2h): yield
80%; viscous liquid; TLC Rf 0.20 (20%, EtOAc/petroleum ether);
NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 2.78 (t, J ) 5.6 Hz, 2H),
3.12 (m, 2H), 5.06 (m, 2H), 7.15-7.34 (m, 12H), 7.69 (d, J )
8.28 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.4, 29.6, 38.3,
41.9, 64.2, 126.9, 127.4, 128.8, 129.7, 136.9, 137.6, 143.4, 208.2;
HRMS (TOF-ES+) calcd for C23H23NO3S [M + H]+ 394.1471,
found 394.1476.
(R)-4-Methyl-N-(3-oxo-2,3-diphenylpropyl)benzenesulfona-
mide (14): yield 95%; white solid; [R]25D +153.2 (c 1.06, CHCl3);
mp 104-106 °C; TLC Rf 0.60 (30%, EtOAc/petroleum ether); IR
(NaCl cell, CH2Cl2, cm-1) 3290, 3061, 1675; 1H NMR (400 MHz,
CDCl3) δ 2.38 (s, 3H), 3.38 (m, 1H), 3.54 (m, 1H), 4.8 (dd, J )
8.8, 5.2, Hz, 1H), 7.17-7.49 (m, 12H), 7.71 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 21.4, 46, 54.3, 126.9, 127.8, 128.1, 128.4,
128.8, 129.3, 129.7, 133.3, 135.5, 136.1, 137.1, 143.3, 198.6; MS
(ES+) 381 (M+ + 1).
1
IR (NaCl cell, CH2Cl2, cm-1) 3293, 2926, 1713, 1320; H NMR
(400 MHz, CDCl3) δ 1.83 (m, 2H), 2.68 (t, J ) 6.8 Hz, 2H), 2.8
(s, 3H), 3.07 (m, 2H), 4.36 (s, 1H), 5.14 (s, 1H), 7.22-7.35 (m,
10H); 13C NMR (100 MHz, CDCl3) δ 24, 39.2, 40.1, 42.4, 64.3,
127.3, 128.8, 128.9, 138, 208.2; MS (FAB) 332 [M+ + 1].
Preparation of (S)-2-(Methoxydiphenylmethyl)-1-tosylpyr-
rolidine (4a). To a suspension of NaH (60% suspension in mineral
oil, 36 mg, 3 mmol) in dry DMF (1 mL) was added a solution of
1a (0.5 mmol) in DMF (1 mL) at 0 °C. This was followed by a
dropwise addition of MeI (94 µL, 1.5 mmol). After the reaction
mixture was stirred for 7 h at rt, it was carefully quenched with
saturated NH4Cl solution and extracted (two times) with ethyl
acetate. The combined organic extract was washed with brine and
dried over anhydrous Na2SO4. The solvent was removed and the
residue was purified by column chromatography to obtain the pure
(S)-2-(methoxydiphenylmethyl)-1-tosylpyrrolidine 4a as a white
solid: yield 93%; [R]25D -88.29 (c 1.35, CHCl3); mp 136 °C; TLC
Rf 0.70 (20%, EtOAc/petroleum ether); IR (NaCl cell, CH2Cl2,
4-Methyl-N-((2S,3R)-4-oxo-3,4-diphenylbutan-2-yl)benzene-
sulfonamide (16): yield 96%; white solid; [R]25D +75.73 (c 1.36,
CHCl3); mp 192-194 °C; TLC Rf 0.60 (30%, EtOAc/petroleum
1
ether); IR (NaCl cell, CH2Cl2, cm-1) 3299, 3029, 1665; H NMR
1
cm-1) 3053, 2929, 1323; H NMR (400 MHz, CDCl3) δ 0.89 (m,
(400 MHz, CDCl3) δ 1.24 (d, J ) 5.12 Hz, 3H), 2.38 (s, 3H), 3.91
(d, J ) 6.32 Hz, 1H), 4.63 (m, 2H), 7.07-7.55 (m, 12H), 7.78 (d,
J ) 8.04 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 19.5, 21.4, 52.7,
58.6, 126.9, 127.7, 128.5, 128.6, 128.8, 129.1, 129.6, 133.2, 135.5,
136.2, 137.3, 143, 198.3; HRMS (TOF-ES+) calcd for C23H23NO3S
[M + H]+ 394.1477, found 394.1477.
1H), 1.27 (m, 1H), 1.84 (m, 2H), 1.97 (m, 1H), 2.44 (s, 3H), 2.9
(s, 3H), 3.41 (m, 1H), 5.26 (dd, J ) 3.92, 9.28 Hz, 1H), 7.2-7.4
(m, 12H), 7.73 (d, J ) 8.28 Hz, 2H); 13C NMR (100 MHz, CDCl3)
δ 21.4, 24.3, 28.2, 49.3, 51.6, 64.9, 86.3, 127.1, 127.3, 127.6, 129.1,
129.9, 130, 138.2, 139.1, 139.8, 142.6.
4-Methyl-N-(4-oxo-5,5-diphenylpentyl)benzenesulfonamide (6):
yield 35%; viscous liquid; TLC Rf 0.20 (20%, EtOAc/petroleum
Acknowledgment. We thank CSIR (Government of India)
for financial support. S.S. thanks the Council of Scientific and
Industrial Research for a research fellowship.
1
ether); H NMR (400 MHz, CDCl3) δ 1.39-1.58 (m, 4H), 2.4 (s,
3H), 2.53 (t, J ) 6.8 Hz, 2H), 2.84 (m, 2H), 4.44 (t, J ) 6 Hz,
1H), 5.07 (s, 1H), 7.18-7.35 (m, 12H), 7.7 (d, J ) 8 Hz, 2H); 13
C
NMR (100 MHz, CDCl3) δ 20.4, 21.5, 28.8, 41.8, 42.7, 64, 127,
127.2, 128.7, 128.8, 129.7, 136.8, 138.1, 143.3, 208.2; HRMS
(TOF-ES+) calcd for C25H27NO3S [M + H]+ 422.1791, found
422.1792.
2-(Diphenylmethylene)-1-tosylpiperidine (7): yield 46%; vis-
cous liquid; TLC Rf 0.70 (20%, EtOAc/petroleum ether); IR (NaCl
Supporting Information Available: Characterization data for
1
some of the compounds, copy of H and 13C NMR spectra for
important compounds, and HPLC spectra for compound 14. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
JO702044K
10146 J. Org. Chem., Vol. 72, No. 26, 2007