Highly diastereoselective addition of the lithium enolate of α-diazoacetoacetate to N-sulfinyl imines: Enantioselective synthesis of 2-oxo and 3-oxo pyrrolidines

Article abstract of DOI:10.1021/jo702275a

(Chemical Equation Presented) The highly enantioselective synthesis of 2-oxo and 3-oxo pyrrolidines has been achieved by diastereoselective addition of the lithium enolate of α-diazoacetoacetate to chiral N-sulfinyl imines, followed by photoinduced Wolff rearrangement or Rh(II)-catalyzed intramolecular N-H insertion.

Full text of DOI:10.1021/jo702275a

The common ways to obtain this type of compounds are
intramolecular N-H insertions through decomposition of dia-
zocarbonyl compounds by Lewis acid or protic acid,7 and radical
carbonylation-reductive cyclizations.8
Although the above-mentioned reactions provide diverse
access to these compounds, there are only limited methods to
synthesize them in an enantioselective manner.3a,c,6e,h,7e,9 Con-
sequently, it is highly desirable to develop efficient methods
that allow one to access substituted 2-oxo and 3-oxo pyrrolidines
Highly Diastereoselective Addition of the Lithium
Enolate of r-Diazoacetoacetate to N-Sulfinyl
Imines: Enantioselective Synthesis of 2-Oxo and
3-Oxo Pyrrolidines
Changqing Dong, Fanyang Mo, and Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS)
and Key Laboratory of Bioorganic Chemistry and Molecular
Engineering of Ministry of Education, College of Chemistry,
Peking UniVersity, Beijing 100871, China
(3) For recent examples of the synthesis of 2-oxo pyrrolidines through
ring expansions, see: (a) Alcaide, B.; Almendros, P.; Alonso, J. M. J. Org.
Chem. 2004, 69, 993-996. (b) Park, J.-H.; Ha, J.-R.; Oh, S.-J.; Kim, J.-A.;
Shin, D.-S.; Won, T.-J.; Lam, Y.-F.; Ahn, C. Tetrahedron Lett. 2005, 46,
1755-1757. (c) Alcaide, B.; Almendros, P.; Cabrero, G.; Ruiz, M. P. Org.
Lett. 2005, 7, 3981-3984. (d) Van Brabandt, W.; De Kimpe, N. J. Org.
Chem. 2005, 70, 3369-3374. (e) Scott, M. E.; Schwarz, C. A.; Lautens,
M. Org. Lett. 2006, 8, 5521-5524.
wangjb@pku.edu.cn
ReceiVed October 24, 2007
(4) For examples of [3 + 2] annulations in 2-oxo pyrrolidine synthesis,
see: (a) Roberson, C. W.; Woerpel, K. A. J. Org. Chem. 1999, 64, 1434-
1435. (b) Sun, P.-P.; Chang, M.-Y.; Chiang, M. Y.; Chang, N.-C. Org.
Lett. 2003, 5, 1761-1763. (c) Romero, A.; Woerpel, K. A. Org. Lett. 2006,
8, 2127-2130.
(5) For recent examples of 2-oxo pyrrolidine synthesis by metal carbene
intramolecular C-H insertions, see: (a) Yoon, C. H.; Zaworotko, M. J.;
Moulton, B.; Jung, K. W. Org. Lett. 2001, 3, 3539-3542. (b) Wee, A. G.
H.; Duncan, S. C. Tetrahedron Lett. 2002, 43, 6173-6179. (c) Yoon, C.
H.; Nagle, A.; Chen, C.; Gandhi, D.; Jung, K. W. Org. Lett. 2003, 5, 2259-
2262. (d) Choi, M. K.-W.; Yu, W.-Y.; Che, C.-M. Org. Lett. 2005, 7, 1081-
1084. (e) Wee, A. G. H.; Duncan, S. C.; Fan, G. J. Tetrahedron: Asymmetry
2006, 17, 297-307.
(6) For recent examples of other methods to synthesize 2-oxo pyrro-
lidines, see: (a) Ryu, I.; Matsu, K.; Minakata, S.; Komatsu, M. J. Am. Chem.
Soc. 1998, 120, 5838-5839. (b) Benati, L.; Leardini, R.; Minozzi, M.;
Nanni, D.; Spagnolo, P.; Strazzari, S.; Zanardi, G. Org. Lett. 2002, 4, 3079-
3081. (c) Vergnon, A. L.; Pottorf, R. S.; Winters, M. P.; Player, M. R. J.
Comb. Chem. 2004, 6, 903-910. (d) Hu, T.; Li, C. Org. Lett. 2005, 7,
2035-2038. (e) He, M.; Bode, J. W. Org. Lett. 2005, 7, 3131-3134. (f)
Ramachandran, P. V.; Burghardt, T. E. Chem. Eur. J. 2005, 11, 4387-
4395. (g) Masse, C. E.; Ng, P. Y.; Fukase, Y.; Sanchez-Rosello, M.; Shaw,
J. T. J. Comb. Chem. 2006, 8, 293-296. (h) Gheorghe, A.; Schulte, M.;
Reiser, O. J. Org. Chem. 2006, 71, 2173-2176. (i) Zhou, C.-Y.; Che, C.-
M. J. Am. Chem. Soc. 2007, 129, 5828-5829.
(7) For intramolecular N-H bond insertion in the synthesis of 3-oxo
pyrrolidine derivatives, see: (a) Moyer, M. P.; Feldman, P. L.; Rapoport,
H. J. Org. Chem. 1985, 50, 5223-5230. (b) Clark, J. S.; Hodgson, P. B. J.
Chem. Soc., Chem. Commun. 1994, 2701-2702. (c) Wang, J.; Hou, Y.;
Wu, P. J. Chem. Soc., Perkin Trans. 1 1999, 2277-2280. (d) Yang, H.;
Jurkauskas, V.; Mackintosh, N.; Mogren, T.; Stephenson, C. R. J.; Foster,
K.; Brown, W.; Roberts, E. Can. J. Chem. 2000, 78. 800-808. (e) Davis,
F. A.; Fang, F.; Goswami, R. Org. Lett. 2002, 4, 1599-1602.
(8) Berlin, S.; Ericsson, C.; Engman, L. J. Org. Chem. 2003, 68. 8386-
8396.
(9) For recent examples of enantioselective synthesis of 2-oxo and 3-oxo
pyrrolidines, see: (a) Escalante, J.; Gonza´lez-Tototzin, M. A. Tetrahedron:
Asymmetry 2003, 14, 981-985. (b) Fernandes, R. A.; Yamamoto, Y. J.
Org. Chem. 2004, 69, 3562-3564. (c) Newhouse, B.; Allen, S.; Fauber,
B.; Anderson, A. S.; Eary, C. T.; Hansen, J. D.; Schiro, J.; Gaudino, J. J.;
Laird, E.; Chantry, D.; Eberhardt, C.; Burgess, L. E. Bioorg. Med. Chem.
Lett. 2004, 14, 5537-5542. (d) Forzato, C.; Nitti, G.; Pitacco, E.; Valentin,
S.; Morganti, E.; Rizzato, D.; Spinelli, C.; Dell’Erba, P.; Petrillo, G.; Tavani,
C. Tetrahedron 2004, 60, 11011-11027. (e) Ramachandran, P. V.;
Burghardt, T. E. Chem. Eur. J. 2005, 11, 4387-4395. (f) Park, J.-H.; Ha,
J.-R.; Oh, S.-J.; Kim, J.-A.; Shin, D.-S.; Won, T.-J.; Lam, Y.-F.; Ahn, C.
Tetrahedron Lett. 2005, 46, 1755-1757. (g) Raghavan, B.; Johnson, R. L.
J. Org. Chem. 2006, 71, 2151-2154. (h) Hansen, J. D.; Newhouse, B. J.;
Allen, S.; Anderson, A.; Eary, T.; Schiro, J.; Gaudino, J.; Laird, E.; Allen,
A. C.; Chantry, D.; Eberhardt, C.; Burgess, L. E. Tetrahedron Lett. 2006,
47, 69-72. (i) Davis, F. A.; Xu, H.; Wu, Y.; Zhang, J. Org. Lett. 2006, 8,
2273-2276.
The highly enantioselective synthesis of 2-oxo and 3-oxo
pyrrolidines has been achieved by diastereoselective addition
of the lithium enolate of R-diazoacetoacetate to chiral
N-sulfinyl imines, followed by photoinduced Wolff rear-
rangement or Rh(II)-catalyzed intramolecular N-H insertion.
2-Oxo and 3-oxo pyrrolidines are widespread among natural
products and biologically active molecules.1 Chiral pyrrolidi-
nones are used as excellent building blocks for the synthesis of
a plethora of nitrogen-containing natural products, such as
pyrrolizidines and indolizidines.1a-c Consequently, many meth-
odologies have been developed for their synthesis over the
years.2 The most widely applied ways to synthesize 2-oxo
pyrrolidines include ring expansion of â-lactam derivatives,3
formal [3+2] annulations,4 and metal carbene intramolecular
C-H insertions.5,6 Compared to 2-oxo pyrrolidines, there are
relatively fewer methods for the synthesis of 3-oxo pyrrolidines.
(1) For selected reviews, see: (a) Daly, J. W.; Spande, T. F.; Garraffo,
H. M. J. Nat. Prod. 2005, 68, 1556-1575. (b) O’ Hagan, D. Nat. Prod.
Rep. 2000, 17, 435-442. (c) Leclercq, S.; Braekman, J. C.; Daloze, D.;
Pasteels, J. M. Prog. Chem. Org. Nat. Prod. 2000, 79, 115-229. (d) Corey,
E. J.; Li, W.-D. Z. Chem. Pharm. Bull. 1999, 47, 1-10.
(2) For recent reviews on 2-oxo pyrrolidine syntheses, see: (a) Huang,
P.-Q. In New Methods for the Asymmetric Synthesis of Nitrogen Hetero-
cycles; Research Signpost: Trivandrum, India, 2005; pp 197-222. (b)
Smith, M. B. In Science of Synthesis; Weinreb, S., Ed.; Georg Thieme
Verlag: Stuttgart, Germany, 2005; Vol 21, pp 647-711. (c) Renaud, P.;
Giraud, L. Synthesis 1996, 913-926. (d) Fallis, A. G.; Brinza, I. M.
Tetrahedron 1997, 53, 17543-17594. (e) Ley, S. V.; Cox, L. R.; Meek, G.
Chem. ReV. 1996, 96, 423-442.
10.1021/jo702275a CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/12/2008
J. Org. Chem. 2008, 73, 1971-1974
1971

TABLE 1. Optimization of Reaction Conditions with 1a
SCHEME 1. Enantioselective Synthesis of 2-Oxo and 3-Oxo
Pyrrolidines
entry
base
solvent
yield (%)a
drb
1
2
3
4
5
6
7
8
9
tBuOK
THF
THF
THF
THF
THF
THF
Et2O
PhCH3
CH2Cl2
N.R.c
N.R.c
25
44
d
55
81
59
78
LDA
tBuLi
91:9
>95:5
KHMDS
NaHMDS
LHMDS
LHMDS
LHMDS
LHMDS
SCHEME 2. Enantioselective Synthesis of 2-Oxo and 3-Oxo
Pyrrolidines
>95:5
91:9
94:6
>95:5
a Isolated yield after chromatography. b Ratio was determined by 1H
NMR (300 MHz) of the crude product. c No reaction occurred. d The
reaction gave a complex mixture.
TABLE 2. The Reaction of 2 with N-sulfinylimine 1a-k
in enantiomerically pure form. We have recently developed a
new synthesis of 2-oxo pyrrolidines based on the nucleophilic
addition of Ti(IV) enolate to N-tosylimines.10 Here we report
the further extension of this method to the enantioselective
synthesis of 2-oxo and 3-oxo pyrrolidines (Scheme 1).
In the outset of this work, we attempted catalytic Mukaiyama
strategy. Thus, the silyl enol ether of R-diazoacetoacetate was
expected to add to N-(benzylidene)-p-toluene sulfinamide 1a
under catalysis with Lewis acids, such as Et2O‚BF3, TiCl4, Cu-
(OTf)2, La(OTf)3, and TBSOTf.13 We found that only TBSOTf
could provide a low yield of the expected addition product. After
some attempts, we reached the conclusion that the reaction with
the silyl enol ether of R-diazoacetoacetate could not be
optimized (Scheme 2).
entry
imine (1a-k, R)
1a, R ) Ph
yield (%)a
drb
1
2
3
4
5
6
7
8
9
3a, 78
3b, 78
3c, 66
3d, 74
3e, 70
3f, 84
3g, 63
3h, 69
3i, 45
3j, 53
3k, 56
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
1b, R ) p-FC6H4
1c, R ) p-CH3OC6H4
1d, R ) o,p-Cl2C6H3
1e, R ) piperonyl
1f, R) o-CH3C6H4
1g, R ) trans-C6H5CHdCH
1h, R) 2-furyl
1i, R ) cyclohexyl
1j, R ) hexyl
1k, R ) isobutyl
We then turned to a straightforward way to generate the
t
10
11
enolate by using a strong base (Table 1). When BuOK was
added to the mixture of R-diazoacetoacetate and N-sulfinyl
imine, no reaction occurred at all. A similar result was obtained
with LDA. Since LDA is obviously strong enough to remove
the R proton of a carbonyl compound, we speculated that the
a Isolated yield after chromatography. b Ratio was determined by 1H
NMR (300 MHz) of the crude product.
i
byproduct Pr2NH might hamper the following nucleophilic
(LHMDS) was the most suitable base for this reaction. Further
examination of solvent effects led to the following optimized
reaction conditions: with CH2Cl2 as solvent, LHMDS as base,
at -100 °C.
addition. tert-Butyllithium was then examined. The expected
addition product 3a was indeed obtained, albeit in low yield.
To our delight, the diastereoselectivity of the product was
t
moderately high (entry 3). Since BuLi is a very strong base
The optimized reaction condition was then applied to a series
of N-sulfinyl imines (Table 2). All aromatic imines reacted
smoothly with allyl diazoacetoacetate and afforded excellent
diastereoselectivities and good yields. The substituents on the
aromatic ring had little influence on the reaction. When aliphatic
imines were subjected to the reaction, the yields somewhat
decreased but diastereoselectivities remained high. It was worth
noting that in all cases the addition reaction proceeded very
fast and could complete within 10 min.
that may cause side reactions, other bases were examined. With
potassium bis(trimethylsilyl)amide (KHMDS), both yield and
diastereoselectivity were improved (entry 4). However, sodium
bis(trimethylsilyl)amide (NaHMDS) resulted in a complex
mixture. Eventually, we found lithium bis(trimethylsilyl)amide
(10) (a) Deng, G.; Jiang, N.; Ma, Z.; Wang, J. Synlett 2002, 1913-1915.
(b) Dong, C.; Deng, G.; Wang, J. J. Org. Chem. 2006, 71, 5560-5564.
(11) (a) Calter, M. A.; Sugathapala, P. M.; Zhu, C. Tetrahedron Lett.
1997, 38, 3837-3840. (b) Calter, M. A.; Zhu, C. J. Org. Chem. 1999, 64,
1415-1419. (c) Deng, G.; Tian, X.; Qu, Z.; Wang, J. Angew. Chem., Int.
Ed. 2002, 41, 2773-2776. (d) Zhao, Y.; Wang, J. Synlett 2005, 2886-
2892. (e) Liao, M.; Dong, S.; Deng, G.; Wang, J. Tetrahedron Lett. 2006,
47, 3927-3929.
(12) For reviews, see: (a) Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc.
Chem. Res. 2002, 35, 984-995. (b) Zhou, P.; Chen, B.-C.; Davis, F. A.
Tetrahedron 2004, 60, 8003-8030.
(13) (a) Kundu, K.; Doyle, M. P. Tetrahedron: Asymmetry 2003, 17,
574-577. (b) Doyle, M. P.; Kundu, K.; Russell, A. E. Org. Lett. 2005, 7,
3131-3134.
The absolute configuration of the newly generated chiral
center was established by X-ray analysis of a single crystal of
3c. When the chiral center of sulfur has the S configuration,
the newly formed chiral center has the R configuration
(Figure 1).
This stereochemical outcome is consistent with the previous
reports of the addition of enolates derived from ester or ketones
1972 J. Org. Chem., Vol. 73, No. 5, 2008

TABLE 3. Reaction of 2a with Various Aromatic Compounds
FIGURE 1. X-ray structure of 3c.
4, yield 5, yield 6, yield
ee
entry
imine (3a-k, R)
3a, R ) Ph
(%)a
(%)
(%)
(%)b
SCHEME 3. Transition State of the Diastereoselective
Addition Reaction
1
2
3
4
5
6
7
8
9
98
96
98
97
96
98
99
98
92
92
91
77
66
60
60
51
75
84c
53
94
92
89
87
87
93
87
85
88
86
74
99
96
93
98
99
96
98
96
3b, R ) p-FC6H4
3c, R ) p-CH3OC6H4
3d, R ) o,p-Cl2C6H3
3e, R ) piperonyl
3f, R) o-MeC6H4
3g, R ) trans-C6H5CHdCH
3h, R) 2-furyl
3i, R ) cyclohexyl
3j, R ) hexyl
3k, R ) isobutyl
94
95d
96
95
10
11
94e
94e
a Isolated yield after chromatography. b Ee was determined by HPLC
with chiral column. c Under photochemical conditions, partial isomerization
of the double bond occurred. d 6g was derivatized and the derivative was
measured as the 96% ee value. See the Supporting Information. e The ee
value was determined after removing the Boc group. See the Supporting
Information.
to N-sulfinyl imines.12,14 On the basis of the stereochemical
information, we conclude that the sense of induction can be
similarly predicted by invoking a six-membered Zimmerman-
Traxler-type transition state as previously suggested for the
similar addition of acetate enolates to N-sulfinyl imines (Scheme
3). In this transition state, the chelation of the Li+ with the
sulfinyl oxygen plays a vital role in controlling the attack of
the enolate to the Re face of the imine.14
SCHEME 4. Conversion of 4a,h,k to 3-Oxa Pyrrolidines
8a-c
With the addition products in hand, we proceeded to convert
these chiral diazo compounds to 2-oxo and 3-oxo pyrrolidines
by the reaction sequence that we have reported previously.10b
First, the diazo compound 3a (R ) Ph) was photolyzed with a
high-pressure Hg lamp (λ > 300 nm) in a Pyrex tube. The Wolff
rearrangement was expected to occur to form the ketene
intermediate,15 followed by intramolecular nucleophilic attack
by the amino group to afford 2-oxo pyrrolidines.16 However,
the expected 2-oxo pyrrolidines were not obtained, instead, the
photolysis resulted in a dark complex mixture. Considering our
previous study with N-sulfonyl diazo compounds, which gave
the corresponding 2-oxo pyrrolidines in good yield,10b we
concluded that the N-sulfinyl group was not compatible with
the photochemical condition. So the N-sulfinyl group was
replaced by tert-butyloxycarbonyl (Boc), and the N-Boc diazo
compound 4a was subjected to the photolysis. To our delight,
the corresponding 2-oxo-3-allyloxycarbonyl pyrrolidine 5a was
obtained in excellent yield, but the diastereoselectivity of this
reaction was poor due to the easy epimerization at C3.
Consequently, the allyloxycarbonyl was removed by Pd(0)-
catalyzed reaction17 and 5-substituted 2-oxo pyrrolidine 6a was
obtained with 98% ee. This reaction sequence was then applied
to other diazo compounds 3b-k, and the corresponding
5-substituted 2-oxo pyrrolidines 6b-k were obtained in excel-
lent overall yields with high enantiomeric selectivities
(Table 3).
Next, we conceived that intramolecular N-H insertion of
metal carbene generated from diazo compound 3 or 4 would
afford 3-oxo pyrrolidine derivatives.7 Davis and co-workers have
previously reported the Rh2(OAc)4-catalyzed intramolecular
N-H insertion of δ-amino R-diazo â-ketoesters to give 3-oxo
pyrrolidines.7e We found that reaction of 3a with Rh2(OAc)4
catalysis resulted in a complex mixture. When N-Boc protected
δ-amino diazo compound 4a was subjected to the same Rh2-
(OAc)4 catalysis, the expected intramolecular N-H product was
obtained as a mixture of diastereoisomers and tautomers. The
mixture was further catalyzed with Pd(PPh3)4 to remove the
alloxycarbonyl group. 5-Phenyl-substituted 3-oxo pyrrolidine
8a was thus obtained with 98% ee and in 83% overall yield
from 4a. This transformation was also applied to 4h and 4k,
and similar results were obtained (Scheme 4). Therefore, starting
from chiral N-Boc protected δ-amino R-diazo â-ketoesters, both
2-oxo and 3-oxo 5-substituted pyrrolidines could be prepared
efficiently.
(14) (a) Davis, F. A.; Reddy, R. E.; Szewczyk, J. M. J. Org. Chem. 1995,
60, 7037-7039. (b) Davis, F. A.; Yang, B. J. Am. Chem. Soc. 2005, 127,
8398-8407.
(15) For a recent review on Wolff rearrangement, see: Kirmse, W. Eur.
J. Org. Chem. 2002, 2193-2256.
(16) (a) Wang, J.; Hou, Y. J. Chem. Soc. Perkin Trans. 1 1998, 1919-
1924. (b) Wang, J.; Hou, Y.; Wu, P.; Qu, Z.; Chan, A. S. C. Tetrahedron:
Asymmetry 1999, 10, 4553-4561. (c) Lee, D. J.; Kim, K.; Park, Y. J. Org.
Lett. 2002, 4, 873-876.
(17) Jeffrey, P. D.; McCombie, S. W. J. Org. Chem. 1982, 47, 587-
590.
J. Org. Chem, Vol. 73, No. 5, 2008 1973

in a Pyrex tube was irradiated with a 300-W Hg lamp with a water-
cooled tube inserted in the solvent. The reaction temperature was
kept at about 35 °C. The reaction was complete in about 30 min.
The solution was concentrated under reduced pressure to give the
crude product, which was purified by flash silica gel column
chromatography to yield the diastereomeric mixture of the corre-
sponding 3-allyloxycarbonyl-2-oxo pyrrolidines 5a-k. The dia-
stereomeric mixture could not be separated by column chromatog-
raphy because of the isomerization of the products on silica gel.
General Procedure for the Removal of Allyloxycarbonyl
Group of 5 with Pd(PPh3)4. 5a-k (0.2 mmol) was dissolved in
THF (5 mL) and Pd(PPh3)4 (5 mol %) and morpholine (1.5 equiv)
were added at room temperature. When the reaction was complete
as monitored by TLC, the solution was concentrated under reduced
pressure and purified by flash column chromatography with silica
gel to afford the pyrrolidine derivative 6a-k.
General Procedure for the Rh2(OAc)4-Catalyzed Reaction of
Diazo Compound 4a,h,k, Followed by Pd(PPh3)4-Catalyzed
Removal of the Allyloxycarbonyl Group. A solution of 4a,h,k
(0.5 mmol) and Rh2(OAc)4 (0.005 mmol) in benzene (15 mL) was
heated to reflux. The reflux was continued for about 10 min and
then the solution was cooled to room temperature. Pd(PPh3)4 (5
mol %) and morpholine (1.5 equiv) were added and the mixture
was stirred for about 1 h under argon. When the reaction was
complete as monitored by TLC, the solution was concentrated under
reduced pressure and purified by flash column chromatography with
silica gel to afford the 3-oxo pyrrolidines 8a,b,c.
In summary, the highly diastereoselective addition of the
lithium enolate of R-diazoacetoacetate to N-sulfinylimines has
been achieved to afford δ-N-sulfinylamino R-diazo â-ketoesters.
The chiral δ-N-sulfinylamino R-diazo â-ketoesters can be easily
converted into 5-substituted 2-oxo and 3-oxo pyrrolidines. This
transformation represents a new route to 5-substituted 2-oxo
and 3-oxo pyrrolidines with high enantiomeric purity.
Experimental Section
Caution: Diazo compounds are generally toxic and potentially
explosive. They should be handled with care in a well-ventilated
fume hood.
General Procedure for the Diastereoselective Addition of Allyl
R-Diazoacetoacetate 2 with N-Sulfinylimine 1. To a solution of
1 (1 mmol) in dichloromethane (12 mL) was added LHMDS (2
mmol of 1.0 M in hexane) at -100 °C and then 2 (1.5 mmol) in
dichloromethane (8 mL) was dropped into the solution. After being
stirred for approximate 5-10 min, the reaction was quenched with
saturated aqueous NH4Cl at -100 °C and then warmed quickly to
room temperature. The organic layer was separated and the aqueous
layer was extracted with CH2Cl2 (2 × 15 mL). The organic layers
were then combined and dried over Na2SO4. The crude product
was purified by flash silica gel column chromatography to yield
the addition products 3a-k.
General Procedure for the Replacement of the Sulfinyl Group
in 3 by the Boc Group. The addition product 3a-k (0.5 mmol)
was treated by TFA (5.0 equiv) in MeOH (5 mL) and the sulfinyl
group in 3 was removed in 1 h to give the corresponding amine
salt. The solution was concentrated, and then was dissolved in THF.
The solution was treated at 0 °C with Boc2O (1.2 equiv)/Et3N (6
equiv) and a catalytic amount of DMAP. After being stirred for
about 2 h, the solution was concentrated and purified by silica gel.
The N-Boc protected product 4a-k was obtained nearly quantita-
tively for the two steps.
Acknowledgment. The project is generously supported by
the Natural Science Foundation of China (Grant Nos. 20572002,
20521202, and 20772003) and the Ministry of Education of
China.
Supporting Information Available: Characterization data, CIF
for 3c, and 1H and 13C NMR spectra for all new compounds. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
General Procedure for the Irradiation of the Diazo Com-
pound 4a-k. A solution of 4a-k (0.5 mmol) in benzene (25 mL)
JO702275A
1974 J. Org. Chem., Vol. 73, No. 5, 2008