Highly Diastereoselective Addition of the Lithium Enolate of α-Diazoacetoacetate to N-Sulfinyl Imines: Enantioselective Synthesis of 2-Oxo and 3-Oxo Pyrrolidines

英文原文与中文译文逐段对照 · English original with Chinese translation

Highly Diastereoselective Addition of the Lithium

锂的高度非对映选择性加成

Enolate of $\alpha$ -Diazoacetoacetate to $N$ -Sulfinyl Imines: Enantioselective Synthesis of 2-Oxo and 3-Oxo Pyrrolidines

$\alpha$-重氮乙酰乙酸酯的烯醇锂对$N$-亚磺酰亚胺的加成:2-氧代和3-氧代吡咯烷的对映选择性合成

Changqing Dong, Fanyang Mo, and Jianbo Wang*

董长青，莫凡洋，王剑波*

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

北京分子科学国家实验室(BNLMS)及教育部生物有机化学与分子工程重点实验室，北京大学化学与分子工程学院，北京100871，中国

Received October 24, 2007

2007年10月24日收到

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

通过将$\alpha$-重氮乙酰乙酸酯的烯醇锂非对映选择性加成到手性N-亚磺酰亚胺上，然后进行光诱导的沃尔夫重排或铑(II)催化的分子内N-H插入，实现了2-氧代和3-氧代吡咯烷的高度对映选择性合成。

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 methodologies have been developed for their synthesis over the years. ${}^{2}$ The most widely applied ways to synthesize 2-oxo pyrrolidines include ring expansion of $\beta$ -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.

2-氧代和3-氧代吡咯烷广泛存在于天然产物和生物活性分子中。${}^{1}$手性吡咯烷酮是合成大量含氮天然产物(如吡咯里西啶和吲哚里西啶)的优良结构单元。${}^{{1a} - c}$因此，多年来已经开发了许多用于其合成的方法。${}^{2}$合成2-氧代吡咯烷最广泛应用的方法包括$\beta$-内酰胺衍生物的扩环、${}^{3}$形式上的[3+2]环合、${}^{4}$以及金属卡宾分子内C-H插入。${}^{5,6}$与2-氧代吡咯烷相比，合成3-氧代吡咯烷的方法相对较少。

The common ways to obtain this type of compounds are intramolecular $\mathrm{N} - \mathrm{H}$ insertions through decomposition of dia-zocarbonyl compounds by Lewis acid or protic acid, ${}^{7}$ and radical carbonylation-reductive cyclizations. ${}^{8}$

获得这类化合物的常见方法是通过路易斯酸或质子酸分解重氮羰基化合物进行分子内$\mathrm{N} - \mathrm{H}$插入、${}^{7}$以及自由基羰基化-还原环化。${}^{8}$

Although the above-mentioned reactions provide diverse access to these compounds, there are only limited methods to synthesize them in an enantioselective manner. ${}^{{3a}, c,{6e}, h,{7e},9}$ Consequently, it is highly desirable to develop efficient methods that allow one to access substituted 2-oxo and 3-oxo pyrrolidines

尽管上述反应为这些化合物提供了多种合成途径，但以对映选择性方式合成它们的方法仍然有限。${}^{{3a}, c,{6e}, h,{7e},9}$因此，非常需要开发高效的方法来合成取代的2-氧代和3-氧代吡咯烷

(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.

(3) 关于通过扩环合成2-氧代吡咯烷的近期例子，见:(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.

(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.

(4) 关于2-氧代吡咯烷合成中[3 + 2]环合的例子，见:(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.

(5) 关于通过金属卡宾分子内C-H插入反应合成2-氧代吡咯烷的近期实例，见:(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.

(6) 关于合成2-氧代吡咯烷的其他方法的近期实例，见:(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.

(7) 关于在合成3-氧代吡咯烷衍生物中分子内N-H键插入反应，见:(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.

(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.; González-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. 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).

(9) 关于2-氧代和3-氧代吡咯烷对映选择性合成的近期实例，见:(a) Escalante, J.; González-Tototzin, M. A. 《四面体:不对称性》2003年，第14卷，981 - 985页。(b) Fernandes, R. A.; Yamamoto, Y. 《有机化学杂志》2004年，第69卷，3562 - 3564页。(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. 《生物有机与药物化学快报》2004年，第14卷，5537 - 5542页。(d) Forzato, C.; Nitti, G.; Pitacco, E.; Valentin, S.; Morganti, E.; Rizzato, D.; Spinelli, C.; Dell’Erba, P.; Petrillo, G.; Tavani, C. 《四面体》2004年，第60卷，11011 - 11027页。(e) Ramachandran, P. V.; Burghardt, T. E. 《欧洲化学杂志》2005年，第11卷，4387 - 4395页。(f) Park, J.-H.; Ha, J.-R.; Oh, S.-J.; Kim, J.-A.; Shin, D.-S.; Won, T.-J.; Lam, Y.-F.; Ahn, C. 《四面体快报》‘2005年，第46卷，1755 - 1757页。(g) Raghavan, B.; Johnson, R. L. 《有机化学杂志》2006年，第71卷，2151 - 2154页。(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. 《四面体快报》2006年，第47卷，69 - 72页。(i) Davis, F. A.; Xu, H.; Wu, Y.; Zhang, J. 《有机快报》2006年，第8卷，2273 - 2276页。以对映体纯形式。我们最近基于烯醇钛对N - 甲苯磺酰亚胺的亲核加成开发了一种新的2 - 氧代吡咯烷合成方法。${}^{10}$ 在此我们报告该方法进一步扩展至2 - 氧代和3 - 氧代吡咯烷的对映选择性合成(方案1)。

(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.

(1) 关于选定的综述，见:(a) Daly, J. W.; Spande, T. F.; Garraffo, H. M. 《天然产物杂志》2005年，第68卷，1556 - 1575页。(b) O’Hagan, D. 《天然产物报告》’ ‘2000年，第17卷，435 - 442页。(c) Leclercq, S.; Braekman, J. C.; Daloze, D.; Pasteels, J. M. 《有机天然产物化学进展》2000年，第79卷，115 - 229页。(d) Corey, E. J.; Li, W.-D. Z. 《化学与药学通报》1999年，第47卷，1 - 10页。

(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.

(2) 有关2-氧代吡咯烷合成的近期综述，见:(a) Huang, P.-Q. 于《氮杂环的不对称合成新方法》；Research Signpost: 印度特里凡得琅，2005年；第197 - 222页。(b) Smith, M. B. 于《合成科学》；Weinreb, S. 编；Georg Thieme Verlag: 德国斯图加特，2005年；第21卷，第647 - 711页。(c) Renaud, P.; Giraud, L. 《合成》1996年，913 - 926页。(d) Fallis, A. G.; Brinza, I. M. 《四面体》1997年，53卷，17543 - 17594页。(e) Ley, S. V.; Cox, L. R.; Meek, G. 《化学评论》1996年，96卷，423 - 442页。

SCHEME 1. Enantioselective Synthesis of 2-Oxo and 3-Oxo Pyrrolidines

方案1. 2-氧代和3-氧代吡咯烷的对映选择性合成

SCHEME 2. Enantioselective Synthesis of 2-Oxo and 3-Oxo Pyrrolidines

方案2. 2-氧代和3-氧代吡咯烷的对映选择性合成

In the outset of this work, we attempted catalytic Mukaiyama strategy. Thus, the silyl enol ether of $\alpha$ -diazoacetoacetate was expected to add to N-(benzylidene)-p-toluene sulfinamide 1a under catalysis with Lewis acids, such as ${\mathrm{{Et}}}_{2}\mathrm{O} \cdot {\mathrm{{BF}}}_{3},{\mathrm{{TiCl}}}_{4},\mathrm{{Cu}}$ - ${\left( \mathrm{{OTf}}\right) }_{2},\mathrm{{La}}{\left( \mathrm{{OTf}}\right) }_{3}$ , 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 α-diazoacetoacetate could not be optimized (Scheme 2).

在这项工作开始时，我们尝试了催化Mukaiyama策略。因此，预计$\alpha$-重氮乙酰乙酸酯的硅烯醇醚在路易斯酸(如${\mathrm{{Et}}}_{2}\mathrm{O} \cdot {\mathrm{{BF}}}_{3},{\mathrm{{TiCl}}}_{4},\mathrm{{Cu}}$-${\left( \mathrm{{OTf}}\right) }_{2},\mathrm{{La}}{\left( \mathrm{{OTf}}\right) }_{3}$和TBSOTf)催化下会加成到N-(亚苄基)-对甲苯亚磺酰胺1a上。${}^{13}$我们发现只有TBSOTf能提供低产率的预期加成产物。经过一些尝试，我们得出结论，α-重氮乙酰乙酸酯的硅烯醇醚的反应无法优化(方案2)。

We then turned to a straightforward way to generate the enolate by using a strong base (Table 1). When ${}^{t}\mathrm{{BuOK}}$ was added to the mixture of $\alpha$ -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 $\alpha$ proton of a carbonyl compound, we speculated that the byproduct ${}^{1}{\mathrm{{Pr}}}_{2}\mathrm{{NH}}$ might hamper the following nucleophilic 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 moderately high (entry 3). Since ‘BuLi is a very strong base 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 (LHMDS) was the most suitable base for this reaction. Further examination of solvent effects led to the following optimized reaction conditions: with ${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$ as solvent, LHMDS as base, at $- {100}{}^{ \circ }\mathrm{C}$ .

然后我们转向一种直接的方法，即使用强碱来生成烯醇盐(表1)。当将${}^{t}\mathrm{{BuOK}}$添加到$\alpha$-重氮乙酰乙酸酯和N-亚磺酰基亚胺的混合物中时，根本没有发生反应。用LDA也得到了类似的结果。由于LDA显然足够强，可以去除羰基化合物的$\alpha$质子，我们推测副产物${}^{1}{\mathrm{{Pr}}}_{2}\mathrm{{NH}}$可能会阻碍随后的亲核加成。然后研究了叔丁基锂。确实得到了预期的加成产物3a，尽管产率很低。令我们高兴的是，产物的非对映选择性中等偏高(第3项)。由于丁基锂是一种非常强的碱，可能会引起副反应，因此研究了其他碱。使用双(三甲基硅基)氨基钾(KHMDS)时，产率和非对映选择性都得到了提高(第4项)。然而，双(三甲基硅基)氨基钠(NaHMDS)导致了复杂的混合物。最终，我们发现双(三甲基硅基)氨基锂(LHMDS)是该反应最合适的碱。对溶剂效应的进一步研究导致了以下优化的反应条件:以${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}$为溶剂，LHMDS为碱，在$- {100}{}^{ \circ }\mathrm{C}$下。

TABLE 1. Optimization of Reaction Conditions with 1a

表1. 用1a优化反应条件

a Isolated yield after chromatography. ${}^{\mathrm{b}}$ Ratio was determined by ${}^{1}\mathrm{H}$ NMR (300 MHz) of the crude product. ${}^{\mathrm{c}}$ No reaction occurred. ${}^{\mathrm{d}}$ The reaction gave a complex mixture.

a 柱色谱分离后的产率。${}^{\mathrm{b}}$比例通过粗产物的${}^{1}\mathrm{H}$ NMR(300 MHz)测定。${}^{\mathrm{c}}$无反应发生。${}^{\mathrm{d}}$反应得到复杂混合物。

TABLE 2. The Reaction of 2 with N-sulfinylimine 1a-k

表2. 2与N - 亚磺酰基亚胺1a - k的反应

${}^{a}$ Isolated yield after chromatography. ${}^{b}$ Ratio was determined by ${}^{1}\mathrm{H}$ NMR (300 MHz) of the crude product.

${}^{a}$柱色谱分离后的产率。${}^{b}$比例通过粗产物的${}^{1}\mathrm{H}$ NMR(300 MHz)测定。

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 ${10}\mathrm{\;{min}}$ .

然后将优化后的反应条件应用于一系列 N-亚磺酰基亚胺(表 2)。所有芳香族亚胺与烯丙基重氮乙酰乙酸酯反应顺利，得到了优异的非对映选择性和良好的产率。芳环上的取代基对反应影响不大。当脂肪族亚胺进行该反应时，产率有所下降，但非对映选择性仍然很高。值得注意的是，在所有情况下，加成反应进行得非常快，并且可以在${10}\mathrm{\;{min}}$内完成。

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).

通过对 3c 的单晶进行 X 射线分析确定了新生成的手性中心的绝对构型。当硫的手性中心具有 S 构型时，新形成的手性中心具有 R 构型(图 1)。

This stereochemical outcome is consistent with the previous reports of the addition of enolates derived from ester or ketones 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 ${\mathrm{{Li}}}^{ + }$ with the sulfinyl oxygen plays a vital role in controlling the attack of the enolate to the Re face of the imine. ${}^{14}$

这种立体化学结果与先前关于酯或酮衍生的烯醇盐加成到 N-亚磺酰基亚胺的报道一致。${}^{{12},{14}}$基于立体化学信息，我们得出结论，诱导方向可以通过调用六元 Zimmerman-Traxler 型过渡态来类似地预测，如先前对于乙酸烯醇盐加成到 N-亚磺酰基亚胺的类似反应所建议的那样(方案 3)。在这个过渡态中，${\mathrm{{Li}}}^{ + }$与亚磺酰基氧的螯合在控制烯醇盐对亚胺 Re 面的进攻中起着至关重要的作用。${}^{14}$

(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.

(10) (a) 邓，G.；姜，N.；马，Z.；王，J. 《Synlett》2002 年，第 1913 - 1915 页。(b) 董，C.；邓，G.；王，J. 《有机化学杂志》2006 年，第 71 卷，第 5560 - 5564 页。

(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.

(11) (a) 卡尔特，M. A.；苏加萨帕拉，P. M.；朱，C. 《四面体快报》1997 年，第 38 卷，第 3837 - 3840 页。(b) 卡尔特，M. A.；朱，C. 《有机化学杂志》1999 年，第 64 卷，第 1415 - 1419 页。(c) 邓，G.；田，X.；曲，Z.；王，J. 《德国应用化学》2002 年，第 41 卷，第 2773 - 2776 页。(d) 赵，Y.；王，J. 《Synlett》2005 年，第 2886 - 2892 页。(e) 廖，M.；董，S.；邓，G.；王،J. 《四面体快报》2006 年，第 47 卷，第 3927 - 3929 页。

(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.

(12) 有关综述，请参阅:(a) 埃尔曼，J. A.；欧文斯，T. D.；唐，T. P. 《化学研究述评》2002 年，第 35 卷，第 984 - 995 页。(b) 周，P.；陈，B.-C.；戴维斯，F. A. 《四面体》2004 年，第 60 卷，第 8003 - 8030 页。

(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.

(13) (a) 昆杜，K.；多伊尔，M. P. 《四面体:不对称性》2003 年，第 17 卷，第 574 - 577 页。(b) 多伊尔，M. P.；昆杜，K.；拉塞尔，A. E. 《有机快报》2005 年，第 7 卷，第 3131 - 3134 页。

FIGURE 1. X-ray structure of 3c.

图 1. 3c 的 X 射线结构。

SCHEME 3. Transition State of the Diastereoselective Addition Reaction

方案 3. 非对映选择性加成反应的过渡态

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 $3\mathrm{a}\left( {\mathrm{R} = \mathrm{{Ph}}}\right)$ was photolyzed with a high-pressure Hg lamp $\left( {\lambda > {300}\mathrm{\;{nm}}}\right)$ 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, ${}^{{10}\mathrm{\;b}}$ 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 reaction ${}^{17}$ and 5-substituted 2-oxo pyrrolidine 6a was obtained with ${98}\%$ ee. This reaction sequence was then applied to other diazo compounds $3\mathrm{\;b} - \mathrm{k}$ , and the corresponding 5-substituted 2-oxo pyrrolidines 6b-k were obtained in excellent overall yields with high enantiomeric selectivities (Table 3).

拿到加成产物后，我们按照之前报道的反应顺序，将这些手性重氮化合物转化为2-氧代和3-氧代吡咯烷。${}^{10b}$首先，重氮化合物$3\mathrm{a}\left( {\mathrm{R} = \mathrm{{Ph}}}\right)$在派热克斯玻璃管中用高压汞灯$\left( {\lambda > {300}\mathrm{\;{nm}}}\right)$进行光解。预期会发生沃尔夫重排以形成烯酮中间体，${}^{15}$随后氨基进行分子内亲核进攻，得到2-氧代吡咯烷。${}^{16}$然而，并未得到预期的2-氧代吡咯烷，相反，光解产生了一种深色的复杂混合物。考虑到我们之前对N-磺酰基重氮化合物的研究，其能以良好的产率得到相应的2-氧代吡咯烷，${}^{{10}\mathrm{\;b}}$我们得出结论，N-亚磺酰基与光化学条件不兼容。因此，N-亚磺酰基被叔丁氧羰基(Boc)取代，对N-Boc重氮化合物4a进行光解。令我们高兴的是，相应的2-氧代-3-烯丙氧羰基吡咯烷5a以优异的产率得到，但由于C3处容易发生差向异构化，该反应的非对映选择性较差。因此，通过钯(0)催化反应${}^{17}$除去烯丙氧羰基，得到了具有${98}\%$对映体过量(ee)的5-取代2-氧代吡咯烷6a。然后将该反应顺序应用于其他重氮化合物$3\mathrm{\;b} - \mathrm{k}$，并以优异的总产率和高对映选择性得到了相应的5-取代2-氧代吡咯烷6b - k(表3)。

TABLE 3. Reaction of 2a with Various Aromatic Compounds

表3. 2a与各种芳香化合物的反应

a Isolated yield after chromatography. ${}^{\mathrm{b}}$ Ee was determined by HPLC with chiral column. ${}^{\mathrm{c}}$ Under photochemical conditions, partial isomerization of the double bond occurred. ${}^{d}6\mathrm{\;g}$ 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.

a 柱色谱分离后的产率。${}^{\mathrm{b}}$ 对映体过量(ee)通过手性柱的高效液相色谱法测定。${}^{\mathrm{c}}$ 在光化学条件下，双键发生部分异构化。${}^{d}6\mathrm{\;g}$ 进行衍生化，衍生物作为${96}\%$ ee值进行测定。见支持信息。${}^{e}$ ee值在除去Boc基团后测定。见支持信息。

SCHEME 4. Conversion of 4a, h, k to 3-Oxa Pyrrolidines $8\mathrm{a} - \mathrm{c}$

方案4. 4a、h、k转化为3-氧杂吡咯烷$8\mathrm{a} - \mathrm{c}$

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 ${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}$ -catalyzed intramolecular $\mathrm{N} - \mathrm{H}$ insertion of $\delta$ -amino $\alpha$ -diazo $\beta$ -ketoesters to give 3-oxo pyrrolidines. ${}^{7\mathrm{e}}$ We found that reaction of $3\mathrm{a}$ with ${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}$ catalysis resulted in a complex mixture. When N-Boc protected $\delta$ -amino diazo compound $4\mathrm{a}$ was subjected to the same ${\mathrm{{Rh}}}_{2}$ - ${\left( \mathrm{{OAc}}\right) }_{4}$ catalysis, the expected intramolecular $\mathrm{N} - \mathrm{H}$ product was obtained as a mixture of diastereoisomers and tautomers. The mixture was further catalyzed with $\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$ 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 $\delta$ -amino $\alpha$ -diazo $\beta$ -ketoesters, both 2-oxo and 3-oxo 5-substituted pyrrolidines could be prepared efficiently.

接下来，我们设想由重氮化合物3或4生成的金属卡宾的分子内N-H插入反应能够得到3-氧代吡咯烷衍生物。 ${}^{7}$ 戴维斯及其同事之前报道了 ${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}$ 催化的分子内 $\mathrm{N} - \mathrm{H}$ 插入反应，该反应是将 $\delta$ -氨基 $\alpha$ -重氮 $\beta$ -酮酯转化为3-氧代吡咯烷。 ${}^{7\mathrm{e}}$ 我们发现， $3\mathrm{a}$ 与 ${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}$ 催化反应会生成复杂的混合物。当N-Boc保护的 $\delta$ -氨基重氮化合物 $4\mathrm{a}$ 进行相同的 ${\mathrm{{Rh}}}_{2}$ - ${\left( \mathrm{{OAc}}\right) }_{4}$ 催化反应时，预期的分子内 $\mathrm{N} - \mathrm{H}$ 产物以非对映异构体和互变异构体的混合物形式得到。该混合物进一步用 $\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$ 催化以去除异丁氧羰基。由此，以 ${98}\%$ 的对映体过量值和从4a开始计算的 ${83}\%$ 的总收率得到了5-苯基取代的3-氧代吡咯烷8a。该转化反应也应用于4h和4k，并得到了类似的结果(方案4)。因此，从手性N-Boc保护的 $\delta$ -氨基 $\alpha$ -重氮 $\beta$ -酮酯出发，可以高效地制备2-氧代和3-氧代5-取代的吡咯烷。

(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.

(14) (a) 戴维斯，F. A.；雷迪，R. E.；谢维茨克，J. M. 《有机化学杂志》1995年，60卷，7037 - 7039页。(b) 戴维斯，F. A.；杨，B. 《美国化学会志》2005年，127卷，8398 - 8407页。

(15) For a recent review on Wolff rearrangement, see: Kirmse, W. Eur. J. Org. Chem. 2002, 2193-2256.

(15) 关于沃尔夫重排的近期综述，见:基尔姆泽，W. 《欧洲有机化学杂志》2002年，2193 - 2256页。

(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.

(16) (a) 王，J.；侯，Y. 《化学会志:珀金 Transactions 1》1998年，1919 - 1924页。(b) 王，J.；侯，Y.；吴，P.；曲，Z.；陈，A. S. C. 《四面体:不对称性》1999年，10卷，4553 - 4561页。(c) 李，D. J.；金，K.；朴，Y. 《有机快报》2002年，4卷，873 - 876页。

(17) Jeffrey, P. D.; McCombie, S. W. J. Org. Chem. 1982, 47, 587- 590.

(17) 杰弗里，P. D.；麦康比，S. W. 《有机化学杂志》1982年，47卷，587 - 590页。

JOCNote

有机化学通讯笔记

In summary, the highly diastereoselective addition of the lithium enolate of $\alpha$ -diazoacetoacetate to N-sulfinylimines has been achieved to afford $\delta$ -N-sulfinylamino $\alpha$ -diazo $\beta$ -ketoesters. The chiral $\delta$ -N-sulfinylamino $\alpha$ -diazo $\beta$ -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.

总之，已实现将$\alpha$ -重氮乙酰乙酸的烯醇锂对N-亚磺酰亚胺进行高度非对映选择性加成，以得到$\delta$ -N-亚磺酰氨基$\alpha$ -重氮$\beta$ -酮酯。手性$\delta$ -N-亚磺酰氨基$\alpha$ -重氮$\beta$ -酮酯可轻松转化为5-取代的2-氧代和3-氧代吡咯烷。这种转化代表了一种获得高对映体纯度的5-取代2-氧代和3-氧代吡咯烷的新途径。

Experimental Section

实验部分

Caution: Diazo compounds are generally toxic and potentially explosive. They should be handled with care in a well-ventilated fume hood.

注意:重氮化合物一般有毒且有潜在爆炸性。应在通风良好的通风橱中小心处理。

General Procedure for the Diastereoselective Addition of Allyl $\alpha$ -Diazoacetoacetate 2 with N-Sulfinylimine 1. To a solution of 1 (1 mmol) in dichloromethane (12 mL) was added LHMDS (2 mmol of ${1.0}\mathrm{M}$ in hexane) at $- {100}^{ \circ }\mathrm{C}$ and then 2 (1.5 mmol) in dichloromethane $\left( {8\mathrm{\;{mL}}}\right)$ was dropped into the solution. After being stirred for approximate $5 - {10}\mathrm{\;{min}}$ , the reaction was quenched with saturated aqueous ${\mathrm{{NH}}}_{4}\mathrm{{Cl}}$ at $- {100}{}^{ \circ }\mathrm{C}$ and then warmed quickly to room temperature. The organic layer was separated and the aqueous layer was extracted with ${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}\left( {2 \times {15}\mathrm{\;{mL}}}\right)$ . The organic layers were then combined and dried over ${\mathrm{{Na}}}_{2}{\mathrm{{SO}}}_{4}$ . The crude product was purified by flash silica gel column chromatography to yield the addition products $3\mathrm{a} - \mathrm{k}$ .

烯丙基$\alpha$ -重氮乙酰乙酸酯2与N-亚磺酰亚胺1的非对映选择性加成的一般步骤。在二氯甲烷(12 mL)中加入1(1 mmol)的溶液，于$- {100}^{ \circ }\mathrm{C}$加入LHMDS(2 mmol的${1.0}\mathrm{M}$于己烷中)，然后将二氯甲烷$\left( {8\mathrm{\;{mL}}}\right)$中的2(1.5 mmol)滴入溶液中。搅拌约$5 - {10}\mathrm{\;{min}}$后，于$- {100}{}^{ \circ }\mathrm{C}$用饱和${\mathrm{{NH}}}_{4}\mathrm{{Cl}}$水溶液淬灭反应，然后迅速升温至室温。分离有机层，水层用${\mathrm{{CH}}}_{2}{\mathrm{{Cl}}}_{2}\left( {2 \times {15}\mathrm{\;{mL}}}\right)$萃取。然后合并有机层，用${\mathrm{{Na}}}_{2}{\mathrm{{SO}}}_{4}$干燥。粗产物通过快速硅胶柱色谱纯化，得到加成产物$3\mathrm{a} - \mathrm{k}$。

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 $\mathrm{{MeOH}}\left( {5\mathrm{\;{mL}}}\right)$ and the sulfinyl group in 3 was removed in $1\mathrm{\;h}$ to give the corresponding amine salt. The solution was concentrated, and then was dissolved in THF. The solution was treated at $0{}^{ \circ }\mathrm{C}$ with ${\mathrm{{Boc}}}_{2}\mathrm{O}$ (1.2 equiv) $/{\mathrm{{Et}}}_{3}\mathrm{\;N}$ (6 equiv) and a catalytic amount of DMAP. After being stirred for about $2\mathrm{\;h}$ , the solution was concentrated and purified by silica gel. The N-Boc protected product $4\mathrm{a} - \mathrm{k}$ was obtained nearly quantitatively for the two steps.

用Boc基团取代3中亚磺酰基的一般步骤。加成产物3a - k(0.5 mmol)在$\mathrm{{MeOH}}\left( {5\mathrm{\;{mL}}}\right)$中用TFA(5.0当量)处理，3中的亚磺酰基在$1\mathrm{\;h}$中被除去，得到相应的胺盐。溶液浓缩，然后溶解在THF中。该溶液于$0{}^{ \circ }\mathrm{C}$用${\mathrm{{Boc}}}_{2}\mathrm{O}$(1.2当量)$/{\mathrm{{Et}}}_{3}\mathrm{\;N}$(6当量)和催化量的DMAP处理。搅拌约$2\mathrm{\;h}$后，溶液浓缩并用硅胶纯化。两步反应几乎定量得到N - Boc保护产物$4\mathrm{a} - \mathrm{k}$。

General Procedure for the Irradiation of the Diazo Compound $4\mathrm{a} - \mathrm{k}$ . A solution of $4\mathrm{a} - \mathrm{k}\left( {{0.5}\mathrm{{mmol}}}\right)$ in benzene $\left( {{25}\mathrm{\;{mL}}}\right)$ 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 ${35}^{ \circ }\mathrm{C}$ . The reaction was complete in about ${30}\mathrm{\;{min}}$ . 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 corresponding 3-allyloxycarbonyl-2-oxo pyrrolidines 5a-k. The dia-stereomeric mixture could not be separated by column chromatography because of the isomerization of the products on silica gel.

重氮化合物$4\mathrm{a} - \mathrm{k}$的辐照一般步骤。将$4\mathrm{a} - \mathrm{k}\left( {{0.5}\mathrm{{mmol}}}\right)$在苯$\left( {{25}\mathrm{\;{mL}}}\right)$中的溶液置于派热克斯管中，用插入溶剂中的水冷管的300 W汞灯照射。反应温度保持在约${35}^{ \circ }\mathrm{C}$。反应在约${30}\mathrm{\;{min}}$完成。溶液在减压下浓缩得到粗产物，通过快速硅胶柱色谱纯化，得到相应的3 - 烯丙氧基羰基 - 2 - 氧代吡咯烷5a - k的非对映异构体混合物。由于产物在硅胶上异构化，该非对映异构体混合物无法通过柱色谱分离。

General Procedure for the Removal of Allyloxycarbonyl Group of 5 with $\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}{.5}\mathrm{a} - \mathrm{k}\left( {{0.2}\mathrm{{mmol}}}\right)$ was dissolved in THF ( $5\mathrm{\;{mL}}$ ) and $\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$ ( $5\mathrm{\;{mol}}\%$ ) 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.

用$\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}{.5}\mathrm{a} - \mathrm{k}\left( {{0.2}\mathrm{{mmol}}}\right)$脱除5的烯丙氧羰基的通用步骤:将5溶于四氢呋喃($5\mathrm{\;{mL}}$)，在室温下加入$\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$($5\mathrm{\;{mol}}\%$)和吗啉(1.5当量)。通过薄层层析监测反应完成后，将溶液减压浓缩，并用硅胶柱快速层析纯化，得到吡咯烷衍生物6a - k。

General Procedure for the ${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}$ -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 $\left( {{0.5}\mathrm{{mmol}}}\right)$ and ${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}\left( {{0.005}\mathrm{{mmol}}}\right)$ in benzene $\left( {{15}\mathrm{\;{mL}}}\right)$ was heated to reflux. The reflux was continued for about ${10}\mathrm{\;{min}}$ and then the solution was cooled to room temperature. $\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$ (5 mol %) and morpholine (1.5 equiv) were added and the mixture was stirred for about $1\mathrm{\;h}$ 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.

${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}$催化重氮化合物4a、h、k反应，随后用四(三苯基膦)钯催化脱除烯丙氧羰基的通用步骤。4a、h、k$\left( {{0.5}\mathrm{{mmol}}}\right)$和${\mathrm{{Rh}}}_{2}{\left( \mathrm{{OAc}}\right) }_{4}\left( {{0.005}\mathrm{{mmol}}}\right)$在苯$\left( {{15}\mathrm{\;{mL}}}\right)$中的溶液加热至回流。回流约${10}\mathrm{\;{min}}$后，将溶液冷却至室温。加入$\mathrm{{Pd}}{\left( {\mathrm{{PPh}}}_{3}\right) }_{4}$(5摩尔%)和吗啉(1.5当量)，混合物在氩气下搅拌约$1\mathrm{\;h}$。通过薄层层析监测反应完成后，将溶液减压浓缩，并用硅胶柱快速层析纯化，得到3 - 氧代吡咯烷8a、b、c。

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.

致谢。本项目得到了中国国家自然科学基金(批准号20572002、20521202和20772003)以及中国教育部的慷慨支持。

Supporting Information Available: Characterization data, CIF for $3\mathrm{c}$ , and ${}^{1}\mathrm{H}$ and ${}^{13}\mathrm{C}$ NMR spectra for all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org.

可获得的支持信息:表征数据、$3\mathrm{c}$的晶体学信息文件以及所有新化合物的${}^{1}\mathrm{H}$和${}^{13}\mathrm{C}$核磁共振谱。此材料可通过互联网免费获取，网址为http://pubs.acs.org。

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