Subscribe to RSS
DOI: 10.1055/s-2006-926276
Highly Diastereoselective Sequential Michael-Aldol Reactions of Methyl 2-Chloro-2-cyclopropylideneacetate with Grignard Reagents and Aldehydes [1]
Publication History
Publication Date:
11 January 2006 (online)
![](https://www.thieme-connect.de/media/synthesis/200603/lookinside/thumbnails/10.1055-s-2006-926276-1.jpg)
Abstract
Grignard reagents, especially isopropylmagnesium chloride, smoothly undergo Michael addition onto methyl 2-bromo- and 2-chloro-2-cyclopropylideneacetate (1-Cl), and the thus formed magnesium enolates are particularly efficiently trapped with aromatic aldehydes. This one-pot reaction provides highly substituted chlorohydrines, mostly in high yields (10 out of 18 examples with 72-92%) and as pure (2S*,3R*)-diastereomers (anti-aldols). These chlorohydrines can be transformed to Darzens-type α,β-epoxyesters in good yields, as demonstrated for one example.
Key words
small ring systems - Michael additions - aldol reactions - domino reactions - diastereoselectivity - synthetic methods
-
1a
Part 119 in the series ‘Cyclopropyl Building Blocks for Organic Synthesis’.
-
1b
For part 118 see: Yucel, B.; Arve, L.; de Meijere, A. Tetrahedron 2005, 61, 11355.
-
1c
Part 117: Bräse, A.; Nüske, H.; Frank, D.; de Meijere, A. Eur. J. Org. Chem. 2005, 4167.
-
2a
Liese T.Splettstösser G.de Meijere A. Angew. Chem., Int. Ed. Engl. 1982, 21: 790 ; Angew. Chem. 1982, 94, 799 -
2b
Liese T.Seyed-Mahdavi F.de Meijere A. Org. Synth. 1990, 69: 148 -
2c For an advanced synthesis of 1-Br and 1-Cl see:
Limbach M.Dalai S.de Meijere A. Adv. Synth. Catal. 2004, 346: 760 - For reviews see:
-
3a
de Meijere A. Bull. Soc. Chim. Belg. 1984, 93: 241 -
3b
de Meijere A.Wessjohann L. Synlett 1990, 20 -
3c
de Meijere A. In New Aspects of Organic Chemistry II, Proceedings of the Fifth International Kyoto Conference on New Aspects of Organic Chemistry (IKCOC 5, Kyoto, Nov. 11-15, 1991)Oshiro Y. Kodansha; Tokyo: 1992. p.181 -
3d
de Meijere A.Kozhushkov SI.Hadjiarapoglou L. Top. Curr. Chem. 1999, 207: 149 -
4a
Brandi A.Cicchi S.Cordero FM.Goti A. Chem. Rev. 2003, 103: 1213 -
4b
Nakamura I.Yamamoto Y. Adv. Synth. Catal. 2002, 344: 111 -
5a
Liese T.Teichmann S.de Meijere A. Synthesis 1988, 25 -
5b
Seyed-Mahdavi F.Teichmann S.de Meijere A. Tetrahedron Lett. 1986, 27: 6185 -
6a
Spitzner D.Engler A.Liese T.Splettstößer G.de Meijere A. Angew. Chem., Int. Ed. Engl. 1982, 21: 791 ; Angew. Chem. 1982, 94, 799 -
6b
Spitzner D.Engler A.Wagner P.de Meijere A.Bengtson G.Simon A.Peters K.Peters E.-M. Tetrahedron 1987, 43: 3213 -
6c
Hadjiarapoglou L.Klein I.Spitzner D.de Meijere A. Synthesis 1996, 525 -
6d
de Meijere A.Teichmann S.Seyed-Mahdavi F.Kohlstruk S. Liebigs Ann. 1996, 1989 -
6e
Wessjohann L.Giller K.Zuck B.Skattebøl L.de Meijere A. J. Org. Chem. 1993, 58: 6442 -
6f
Hadjiarapoglou L.de Meijere A.Seitz H.-J.Klein I.Spitzner D. Tetrahedron Lett. 1994, 35: 3269 -
6g
de Meijere A.Hadjiarapoglou LP.Noltemeyer M.Gutke H.-J.Klein I.Spitzner D. Eur. J. Org. Chem. 1998, 441 -
7a
de Meijere A.Teichmann S.Yu D.Kopf J.Oly M.von Thienen N. Tetrahedron 1989, 45: 2957 -
7b
Wessjohann L.Skattebøl L.de Meijere A. J. Chem. Soc., Chem. Commun. 1990, 574 -
7c
Giller K.Baird MS.de Meijere A. Synlett 1992, 524 -
7d
Es-Sayed M.Heiner T.de Meijere A. Synlett 1993, 57 -
7e
Zorn C.Goti A.Brandi A.Johnsen K.Kozhushkov SI.de Meijere A. Chem. Commun. 1998, 903 -
7f
Nötzel MW.Tamm M.Labahn T.Noltemeyer M.Es-Sayed M.de Meijere A. J. Org. Chem. 2000, 65: 3850 -
7g
Nötzel MW.Labahn T.Es-Sayed M.de Meijere A. Eur. J. Org. Chem. 2001, 3025 -
7h
Nötzel MW.Rauch K.Labahn T.de Meijere A. Org. Lett. 2002, 4: 839 -
7i
Zorn C.Goti A.Brandi A.Johnsen K.Noltemeyer M.Kozhushkov SI.de Meijere A. J. Org. Chem. 1999, 64: 755 -
8a
Wessjohann L.McGaffin G.de Meijere A. Synthesis 1989, 359 -
8b
Wessjohann L.Krass N.Yu D.de Meijere A. Chem. Ber. 1992, 125: 867 -
8c
Es-Sayed M.Gratkowski C.Krass N.Meyers AI.de Meijere A. Synlett 1992, 962 -
8d
Es-Sayed M.G ratkowski C.Krass N.Meyers AI.de Meijere A. Tetrahedron Lett. 1993, 34: 289 -
8e
Tamm M.Thutewohl M.Ricker CB.Bes MT.de Meijere A. Eur. J. Org. Chem. 1999, 2017 -
9a
Belov VN.Funke C.Labahn T.Es-Sayed M.de Meijere A. Eur. J. Org. Chem. 1999, 1345 -
9b
Funke C.Es-Sayed M.de Meijere A. Org. Lett. 2000, 2: 4249 -
9c
Limbach M.Dalai S.Janssen A.Es-Sayed M.Magull J.de Meijere A. Eur. J. Org. Chem. 2005, 610 - Reviews see:
-
10a
Gawley RE. Synthesis 1976, 777 -
10b
Notz W.Tanaka F.Barbas CF. Acc. Chem. Res. 2004, 37: 580 -
11a
Posner GH. Chem. Rev. 1986, 86: 831 -
11b
Tietze LF.Beifuss U. Angew. Chem., Int. Ed. Engl. 1993, 32: 131 ; Angew. Chem. 1993, 105, 137 -
11c
Tietze LF. Chem. Rev. 1996, 96: 115 - Recent examples:
-
12a
Barrett AGM.Kamimura A. J. Chem. Soc., Chem. Commun. 1995, 17: 1755 -
12b
Tsukada N.Nishimura TK.Tsubouchi H.Ono M.Hayama T.Nagaoka Y.Tomioka K. Tetrahedron Lett. 2003, 44: 2323 -
12c
Tsukada N.Shimida T.Gyoung YS.Asao N.Yamamoto Y. J. Org. Chem. 1995, 60: 143 - Recent examples:
-
13a
Hara O.Sugimoto K.Makino K.Hamada Y. Synlett 2004, 1625 -
13b
Rao HSP.Senthilkumar SP. J. Org. Chem. 2004, 69: 2591 -
13c
Makino K.Hara O.Takiguchi Y.Katano T.Asakawa Y.Hatano K.Hamada Y. Tetrahedron Lett. 2003, 44: 8925 -
13d
Huang X.Xiong Z.-C. Chem. Commun. 2003, 14: 1714 -
13e
Yamamoto Y.Momiyama N.Yamamoto H. J. Am. Chem. Soc. 2004, 126: 5962 - Recent examples:
-
14a
Paulsen H.Antons S.Brandes A.Lögers M.Müller SN.Naab P.Schmeck C.Schneider S.Stoltefuß J. Angew. Chem. Int. Ed. 1999, 38: 3373 ; Angew. Chem. 1999, 111, 3574 -
14b
Schneider C.Reese O. Angew. Chem. Int. Ed. 2000, 39: 2948 ; Angew. Chem. 2000, 112, 3074 -
14c
Kamimura A.Mitsudera H.Omata Y.Matsuura K.Shirai M.Kakehi A. Tetrahedron 2002, 58: 9817 -
14d
Huang X.Xie MH. Org. Lett. 2002, 4: 1331 -
14e
Huang X.Xie MH. J. Org. Chem. 2002, 67: 8895 -
14f
Arai T.Sasai H.Aoe K.-I.Okamura K.Date T.Shibasaki M. Angew. Chem., Int. Ed. Engl. 1996, 35: 104 ; Angew. Chem. 1996, 108, 103 -
14g
Halland N.Aburel PS.Jørgensen KA. Angew. Chem. Int. Ed. 2004, 43: 1272 ; Angew. Chem. 2004, 116, 1292 -
15a
Satoh T.Kitoh Y.Onda K.-I.Takana K.Yamakawa K. Tetrahedron 1994, 50: 4957 -
15b
Evans DA.Tedrow JS.Shaw JT.Downey CW. J. Am. Chem. Soc. 2002, 124: 392 -
16a
Thibonnet J.Knochel P. Tetrahedron Lett. 2000, 41: 3319 -
16b
Thibonnet J.Vu VA.Berillon L.Knochel P. Tetrahedron 2002, 58: 4787 - 18
Chandrasekhar S.Narsihmulu C.Reddy MR.Reddy MS. Tetrahedron Lett. 2003, 44: 2583 - 19
Sokolov V.V.Es-Sayed M.De Meijere A. unpublished results
References
Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited as supplementary publication no. CCDC-268832 with the Cambridge Crystallographic Data Centre. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: +44 (1223)336033; E-mail: deposit@ccdc.cam.ac.uk].