Exploration of Aryllithium-Derived Copper Reagents for Quaternary-Stereogenic-Center-Forming Allylic Substitution of γ,γ-Disubstituted Secondary Allylic Picolinates

Takuri Ozaki; Yuichi Kobayashi

doi:10.1055/s-0035-1560907

Synlett, Table of Contents

Synlett 2016; 27(04): 611-615
DOI: 10.1055/s-0035-1560907

letter

Exploration of Aryllithium-Derived Copper Reagents for Quaternary-Stereogenic-Center-Forming Allylic Substitution of γ,γ-Disubstituted Secondary Allylic Picolinates

Takuri Ozaki

Department of Bioengineering, Tokyo Institute of Technology, Box B-52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan Email: ykobayas@bio.titech.ac.jp

,

Yuichi Kobayashi*

Department of Bioengineering, Tokyo Institute of Technology, Box B-52, Nagatsuta-cho 4259, Midori-ku, Yokohama 226-8501, Japan Email: ykobayas@bio.titech.ac.jp

› Author Affiliations

Abstract

All articles of this category

Abstract

The allylic substitution of γ,γ-disubstituted secondary allylic picolinates (esters of 2-PyCO₂H) with aryllithium-based copper reagents was carried out in order to construct quaternary carbons. Initially, 2-methyl-7-phenylhept-2-en-4-yl picolinate was reacted with phenyl copper reagents derived from phenyllithium with Cu(acac)₂, Cu(OMe)₂, CuBr·Me₂S, and CuCN in 1–3:1 ratios in the presence of excess magnesium bromide. Although the S_N2′ product with a quaternary carbon was formed, the regioselectivity was 90% at most. Instead, phenyllithium/copper(I) thiophene-2-carboxylate/magnesium bromide (Ph/Cu = 1.5–2:1, Mg/Li = >1) was found to produce >98% regioselectivity and sufficient reactivity. This system was successful with eight aryllithium based copper reagents possessing sterically congested, electron-donating, or electron-withdrawing substituents. The anti stereochemical course was established by using an enantiomerically enriched geranaldehyde-derived picolinate.

Key words

allylic substitution - aryl lithium - anti S_N2′ - copper reagents - picolinate - quaternary carbon

Full Text

References

References and Notes

1a Das JP, Marek I. Chem. Commun. 2011; 47: 4593
1b Shimizu M. Angew. Chem. Int. Ed. 2011; 50: 5998
1c Hawner C, Alexakis A. Chem. Commun. 2010; 46: 7295
1d Marek I, Sklute G. Chem. Commun. 2007; 1683
1e Trost BM, Jiang C. Synthesis 2006; 369
1f Christoffers J, Baro A. Angew. Chem. Int. Ed. 2003; 42: 1688
1g Corey EJ, Guzman-Perez A. Angew. Chem. Int. Ed. 1998; 37: 388

2a Fañanás-Mastral M, Vitale R, Pérez M, Feringa BL. Chem. Eur. J. 2015; 21: 4209
2b Hojoh K, Shido Y, Ohmiya H, Sawamura M. Angew. Chem. Int. Ed. 2014; 53: 4954
2c Magrez M, Guen YL, Baslé O, Crévisy C, Mauduit M. Chem. Eur. J. 2013; 19: 1199
2d Fañanás-Mastral M, Pérez M, Bos PH, Rudolph A, Harutyunyan SR, Feringa BL. Angew. Chem. Int. Ed. 2012; 51: 1922
2e Jung B, Hoveyda AH. J. Am. Chem. Soc. 2012; 134: 1490
2f Gao F, Carr JL, Hoveyda AH. Angew. Chem. Int. Ed. 2012; 51: 6613
2g Zhang P, Le H, Kyne RE, Morken JP. J. Am. Chem. Soc. 2011; 133: 9716
2h Dabrowski JA, Gao F, Hoveyda AH. J. Am. Chem. Soc. 2011; 133: 4778
2i Gao F, McGrath KP, Lee Y, Hoveyda AH. J. Am. Chem. Soc. 2010; 132: 14315
2j Gao F, Lee Y, Mandai K, Hoveyda AH. Angew. Chem. Int. Ed. 2010; 49: 8370
2k Lee Y, Li B, Hoveyda AH. J. Am. Chem. Soc. 2009; 131: 11625
2l Lee Y, Hoveyda AH. J. Am. Chem. Soc. 2006; 128: 15604
2m Van Veldhuizen JJ, Campbell JE, Giudici RE, Hoveyda AH. J. Am. Chem. Soc. 2005; 127: 6877
2n Okamoto S, Tominaga S, Saino N, Kase K, Shimoda K. J. Organomet. Chem. 2005; 690: 6001
2o Murphy KE, Hoveyda AH. Org. Lett. 2005; 7: 1255
2p Kacprzynski MA, Hoveyda AH. J. Am. Chem. Soc. 2004; 126: 10676
2q Kimura M, Yamazaki T, Kitazume T, Kubota T. Org. Lett. 2004; 6: 4651
2r Larsen AO, Leu W, Oberhuber CN, Campbell JE, Hoveyda AH. J. Am. Chem. Soc. 2004; 126: 11130
2s Luchaco-Cullis CA, Mizutani H, Murphy KE, Hoveyda AH. Angew. Chem. Int. Ed. 2001; 40: 1456

3a Soorukram D, Knochel P. Org. Lett. 2007; 9: 1021
3b Breit B, Demel P, Grauer D, Studte C. Chem. Asian J. 2006; 1: 586
3c Leuser H, Perrone S, Liron F, Kneisel FF, Knochel P. Angew. Chem. Int. Ed. 2005; 44: 4627
3d Breit B, Demel P, Studte C. Angew. Chem. Int. Ed. 2004; 43: 3786
3e Harrington-Frost N, Leuser H, Calaza MI, Kneisel FF, Knochel P. Org. Lett. 2003; 5: 2111
3f Spino C, Beaulieu C. Angew. Chem. Int. Ed. 2000; 39: 1930
3g Ibuka T, Akimoto N, Tanaka M, Nishii S, Yamamoto Y. J. Org. Chem. 1989; 54: 4055

4a Kaneko Y, Kiyotsuka Y, Acharya HP, Kobayashi Y. Chem. Commun. 2010; 46: 5482
4b Feng C, Kobayashi Y. J. Org. Chem. 2013; 78: 3755
4c Feng C, Kaneko Y, Kobayashi Y. Tetrahedron Lett. 2013; 54: 4629
4d Kawashima H, Kaneko Y, Sakai M, Kobayashi Y. Chem. Eur. J. 2014; 20: 272
4e Ozaki T, Kobayashi Y. Org. Chem. Front. 2015; 2: 328
4f Ozaki T, Kobayashi Y. Synlett 2015; 26: 1085

5 Substitution of secondary allylic 4-Ph₂PC₆H₄ esters with PhMgBr produces mixture of regioisomers (ref. 3b and 3d), whereas that of primary allylic phosphates with ArAlEt₂ proceeds with high regioselectivity and with somewhat low enantioselectivity (ref. 2j). Pd-catalyzed substitution of allylic acetates and PhB(OH)₂ gives S_N2′ products. However, stereoselectivity was not studied: Ohmiya H, Makida Y, Li D, Tanabe M, Sawamura M. J. Am. Chem. Soc. 2010; 132: 879

6a Kiyotsuka Y, Kobayashi Y. Tetrahedron Lett. 2008; 49: 7256
6b Kiyotsuka Y, Kobayashi Y. J. Org. Chem. 2009; 74: 7489
6c Kiyotsuka Y, Kobayashi Y. Tetrahedron 2010; 66: 676

Although being Cu(II) species, Cu(acac)₂ is likely reduced to Cu⁺ species by ArMgBr; see:

7a House HO, Respess WL, Whitesides GM. J. Org. Chem. 1966; 31: 3128
7b Fujii N, Nakai K, Habashita H, Yoshizawa H, Ibuka T, Garrido F, Mann A, Chounan Y, Yamamoto Y. Tetrahedron Lett. 1993; 34: 4227

8 Prepared according to the procedure in: Enev VS, Felzmann W, Gromov A, Marchart S, Mulzer J. Chem. Eur. J. 2012; 18: 9651
9 Seyferth D. Organometallics 2006; 25: 2
10 Snieckus V. Chem. Rev. 1990; 90: 879
11 Reuman M, Meyers AI. Tetrahedron 1985; 41: 837
12 Strick BF, Mundal DA, Thomson RJ. J. Am. Chem. Soc. 2011; 133: 14252
13 Gao Y, Hanson RM, Klunder JM, Ko SY, Masamune H, Sharpless KB. J. Am. Chem. Soc. 1987; 109: 5765
14 The kinetic resolution was repeated several times and the alcohol with 98% ee was used for the next reaction.
15 Defined as (% ee of product)·100/[% ee of (R)-8].

16a Ozonolysis of (R)-9e derived from (R)-8 (87% ee) gave the aldehyde with [α]_D ²² +23 (c 1.03, CHCl₃); cf. [α]_D ²⁰ –65.2 (c 1.45, CHCl₃).^16b The lower value is attributed to contamination of unidentified compound (s) that was eluted with the aldehyde during chromatography.
16b Kita Y, Furukawa A, Futamura J, Ueda K, Sawama Y, Hamamoto H, Fujioka H. J. Org. Chem. 2001; 66: 8779

Supplementary Material

Supporting Information