Subscribe to RSS
DOI: 10.1055/s-2007-990845
Synthesis of Unnatural α-Amino Acid Derivatives via a Three-Component Coupling Method Utilizing an Allylpalladium Umpolung
Publication History
Publication Date:
29 October 2007 (online)
![](https://www.thieme-connect.de/media/synthesis/200722/lookinside/thumbnails/10.1055-s-2007-990845-1.jpg)
Abstract
Highly substituted unnatural α-amino esters, for example, ethyl 3-alkyl-4-(aryl or vinyl)-2-(N-4-methoxyphenylamine)pent-4-enoates were prepared in a regiocontrolled and diastereoselective manner via Pd(II)-catalyzed three-component coupling of boronic acids and allenes with ethyl iminoacetate relying on the umpolung of the traditional electrophilicity of mono-π-allylpalladium complexes. The 2-aminopent-4-enoates were subjected to N-allylation and intramolecular ring-closing metathesis to afford tetrahydropyridines featuring an α-amino ester group.
Key words
amino acids - allyl complexes - multicomponent reactions - umpolung - palladium
-
1a
Monaghan DT.Bridges RJ.Cotman CW. Annu. Rev. Pharmacol. Toxicol. 1989, 29: 365 -
1b
Moloney MG. Nat. Prod. Rep. 1999, 16: 484 -
1c
Di Fabio Alvaro G.Bertani B.Donati D.Giacobbe S.Marchioro C.Palma C.Lynn SM. J. Org. Chem. 2002, 67: 7319 - 2
Perdih A.Dolenc MS. Curr. Org. Chem. 2007, 11: 801 -
3a
Zanda M. Lett. Org. Chem. 2006, 3: 328 -
3b
Kong J.-R.Cho C.-W.Krische MJ. J. Am. Chem. Soc. 2005, 127: 11269 -
3c
Ji J.-X.Wu J.Chan ASC. Proc. Natl. Acad. Sci. U.S.A. 2005, 102: 11196 -
3d
Knudtsen KR.Risgaard T.Nishiwaki N.Gothelf KV.Jorgensens KA. J. Am. Chem. Soc. 2001, 123: 5843 -
4a
Kabalka GW.Venkataiah B. Tetrahedron Lett. 2005, 46: 7325 -
4b
Marshall JA. Chem. Rev. 2000, 100: 3163 -
4c
Panek JS.Yang M.Solomon JS. J. Org. Chem. 1993, 58: 1003 -
5a
Hopkins CD.Guan L.Malinakova HC. J. Org. Chem. 2005, 70: 6848 -
5b
Hopkins CD.Malinakova HC. Org. Lett. 2004, 6: 2221 - 6
Hopkins CD.Malinakova HC. Org. Lett. 2006, 8: 5971 -
7a
Trost BM.Crawley ML. Chem. Rev. 2003, 103: 2921 -
7b
Trost BM.Van Vranken DL. Chem. Rev. 1996, 96: 395 -
8a
Fernandes RA.Stimac A.Yamamoto Y. J. Am. Chem. Soc. 2003, 125: 14133 -
8b
Nakamura H.Nakamura K.Yamamoto Y. J. Am. Chem. Soc. 1998, 120: 4242 -
8c
Nakamura H.Iwama H.Yamamoto Y. J. Am. Chem. Soc. 1996, 118: 6641 -
9a
Szabo KJ. Chem. Eur. J. 2004, 10: 5268 -
9b
Sebelius S.Wallner OA.Szabo KJ. Org. Lett. 2003, 5: 3065 -
9c
Wallner OA.Szabo KJ. J. Org. Chem. 2003, 68: 2934 - 10
Jolly PW. Angew. Chem., Int. Ed. Engl. 1985, 24: 283 -
11a
Solin N.Wallner OA.Szabo KJ. Org. Lett. 2005, 7: 689 -
11b
Solin N.Kjellgren J.Szabo KJ. J. Am. Chem. Soc. 2004, 126: 7026 -
11c
Solin N.Kjellgren J.Szabo KJ. Angew. Chem. Int. Ed. 2003, 42: 3656 - 12
Kurosawa H.Urabe A. Chem. Lett. 1985, 1839 - 13
Hosokawa T.Uno T.Inui S.Murahashi S.-I. J. Am. Chem. Soc. 1981, 103: 2318 - 14
Manhas MS.Ghosh M.Bose AK. J. Org. Chem. 1990, 55: 575 - In the η1,η3-coordinated bis-allylpalladium complexes, the preference for the bonding of the less-substituted terminus to the palladium center was established, directing the attack of the electrophile at the more substituted allyl terminus, see:
-
17a
Wallner OA.Szabo KJ. Chem. Eur. J. 2003, 9: 4025 -
17b
Szabo KJ. Chem. Eur. J. 2000, 6: 4413 - 19
Moreau J.-L.Gaudemar M. J. Organomet. Chem. 1976, 108: 159 -
20a
Sherrod SA.Bergman RG. J. Am. Chem. Soc. 1971, 93: 1925 -
20b
Jiang S.Liu Z.-H.Sheng G.Zeng B.-B.Cheng X.-G.Wu Y.-L.Yao Z.-J. J. Org. Chem. 2002, 67: 3404 -
21a
Pandey MK.Bisai A.Panday A.Singh VK. Tetrahedron Lett. 2005, 46: 5039 -
21b
Gebauer J.Dewi P.Blechert S. Tetrahedron Lett. 2005, 46: 43 - 22
Donohoe TJ.Orr AJ.Gosby K.Bingham M. Eur. J. Org. Chem. 2005, 1969
References
For a brief discussion of the effects of the nature of the N-protecting group in the imines on the three-component coupling reaction, see reference 6.
16An X-ray crystallographic analysis of the single crystal of a homoallylic amine arising from the coupling of an N-PMP-protected imine derived from 3-pyridinecarboxaldehyde, nona-1,2-diene, and 4-methoxycarbonylphenylboronic acid indicated that anti-diastereomer was generated with 50:1 diastereoselectivity (see reference 6). However, the preference for the formation of anti-products could not be unequivocally established for reactions with ethyl imino-acetates.
18This uncertainty regarding the relative stereochemistry in the major diastereomer of amino esters 1a-g precludes a detailed discussion of the structures of the transition states for the allyl transfer (e.g., open or closed transition states).
23Computational analyses performed on tetrahydropyridine 3a revealed that the correlations observed by NOE analyses on 3a would be present in both cis- and trans-isomers (see reference 6).