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DOI: 10.1055/s-2004-832832
Chiral Relay in Enantioselective Conjugate Radical Additions Using Pyrazolidinone Templates. How Does Metal Geometry Impact Selectivity?
Publication History
Publication Date:
24 September 2004 (online)
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Abstract
A novel class of achiral templates containing fluxional groups has been evaluated in conjugate radical additions. Magnesium and copper Lewis acids provide high enantioselectivity (>90% ee) for radical additions. The impact of the metal geometry on enantioselectivity using relay templates has also been assessed.
Key words
radical reactions - chiral Lewis acid - relay - conjugate additions - pyrazolidinones - enantioselectivity amplification
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1a
Catalytic Asymmetric Synthesis
Ojima I. Wiley-VCH; New York: 2000. -
1b
Comprehensive Asymmetric Catalysis
Jacobsen EN.Pfaltz A.Yamamoto H. Springer; New York: 1999. - For selected examples on the use of achiral templates in enantioselective transformations from other laboratories see:
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2a
Matsunaga S.Kinoshita T.Okada S.Harada S.Shibasaki M. J. Am. Chem. Soc. 2004, 126: 7559 -
2b
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Kanemasa S.Oderaotoshi Y.Sakaguchi S.-i.Yamamoto H.Tanaka J.Wada E.Curran DP. J. Am. Chem. Soc. 1998, 120: 3074 -
2d
Evans DA.Miller SJ.Lectka T.von Matt P. J. Am. Chem. Soc. 1999, 121: 7559 -
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Jensen KB.Gothelf KV.Hazell RG.Jørgensen KA. J. Org. Chem. 1997, 62: 2471 -
2f
Kanemasa S.Kanai T. J. Am. Chem. Soc. 2000, 122: 10710 -
2g
Palomo C.Oiarbide M.Garcia JM.Gonzalez A.Arceo E. J. Am. Chem. Soc. 2003, 125: 13942 -
2h For work from our laboratory see:
Sibi MP.Sausker JB. J. Am. Chem. Soc. 2002, 124: 984 -
2i
Sibi MP.Shay JJ.Ji J. Tetrahedron Lett. 1997, 38: 5955 -
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Sibi MP.Shay JJ.Liu M.Jasperse CP. J. Am. Chem. Soc. 1998, 120: 6615 -
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Sibi MP.Liu M. Org. Lett. 2000, 2: 3393 - 3
Sibi MP.Venkatraman L.Liu M.Jasperse CP. J. Am. Chem. Soc. 2001, 123: 8444 -
4a For a mini review on this subject see:
Corminboeuf O.Quaranta L.Renaud P.Liu M.Jasperse CP.Sibi MP. Chem.-Eur. J. 2003, 9: 28 -
4b Chiral relay in diastereoselective transformations see:
Bull SD.Davies SG.Fox DJ.Garner AC.Sellers TGR. Pure Appl. Chem. 1998, 70: 1501 -
4c Selected examples of chiral relay in enantioselective transformations:
Watanabe Y.Mase N.Furue R.Toru T. Tetrahedron Lett. 2001, 42: 2981 -
4d
Davis TJ.Balsells J.Carroll PJ.Walsh PJ. Org. Lett. 2001, 3: 2161 -
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Balsells J.Walsh PJ. J. Am. Chem. Soc. 2000, 122: 1802 -
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Evans DA.Campos KR.Tedrow JS.Michael FE.Gagné MR. J. Am. Chem. Soc. 2000, 122: 7905 -
4g
Hiroi K.Ishii M. Tetrahedron Lett. 2000, 41: 7071 -
4h
Wada E.Pei W.Kanemasa S. Chem. Lett. 1994, 2345 -
4i
Sibi MP.Zhang R.Manyem S. J. Am. Chem. Soc. 2003, 125: 9306 -
4j
Quaranta L.Corminboeuf O.Renaud P. Org. Lett. 2002, 4: 39 -
5a
Sibi MP.Ma Z.Jasperse CP. J. Am. Chem. Soc. 2004, 126: 718 -
5b
Sibi MP.Itoh K.Jasperse CP. J. Am. Chem. Soc. 2004, 126: 5366 -
5c
Sibi MP.Liu M. Org. Lett. 2001, 3: 4181 - For reviews on stereoselective radical chemistry see:
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6a
Renaud P.Gèrster M. Angew. Chem. Int. Ed. 1998, 37: 2563 -
6b
Sibi MP.Porter NA. Acc. Chem. Res. 1999, 32: 163 -
6c
Sibi MP.Manyem S.Zimmerman J. Chem. Rev. 2003, 103: 3263 -
6d
Bar G.Parsons AF. Chem. Soc. Rev. 2003, 32: 251 -
6e
Sibi MP.Manyem S. Tetrahedron 2000, 56: 8303 -
6f See also:
Radicals in Organic Synthesis
Vol. 1:
Renaud P.Sibi MP. Wiley-VCH; Weinheim: 2001. -
6g
Radicals in Organic Synthesis
Vol. 2:
Renaud P.Sibi MP. Wiley-VCH; Weinheim: 2001. - Enantioselective conjugate radical reactions:
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7a
Sibi MP.Ji J.Wu JH.Gurtler S.Porter NA. J. Am. Chem. Soc. 1996, 118: 9200 -
7b
Sibi MP.Ji J. J. Org. Chem. 1997, 62: 3800 -
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Sibi MP.Shay JJ.Ji J. Tetrahedron Lett. 1997, 38: 5955 -
7d
Sibi MP.Chen J. J. Am. Chem. Soc. 2001, 123: 9472 -
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Sibi MP.Manyem S. Org. Lett. 2002, 4: 2929 -
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Sibi MP.Petrovic G. Tetrahedron: Asymmetry 2003, 15: 2879 -
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Sibi MP.Zimmerman J.Rheault TR. Angew. Chem. Int. Ed. 2003, 42: 4521 -
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Iserloh U.Curran DP.Kanemasa S. Tetrahedron: Asymmetry 1999, 10: 2417 -
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Murakata M.Tsutsui H.Hoshino O. Org. Lett. 2001, 3: 299 -
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Sibi MP.He L. Org. Lett. 2004, 6: 1749 -
11a For a review on stereochemical reversal see:
Sibi MP.Liu M. Curr. Org. Chem. 2000, 5: 735 -
11b
Evans DA.Johnson JS.Bergey CS.Campos KR. Tetrahedron Lett. 1999, 40: 2879
References
For the synthesis of pyrazolidinone templates see details in ref. [3] and ref. [5]
9
Typical Reaction Conditions: The chiral ligand (0.031 mmol) and Lewis acid (0.03 mmol) were dissolved in CH2Cl2 at r.t. under nitrogen and stirred for 30 min. The substrate (0.1 mmol) was added and the mixture was stirred for an additional 30 min. The reaction mixture was cooled to -78 °C and after 15 min, the reaction was initiated by sequential addition of 2-iodopropane (0.5 mmol), tributyltin hydride (0.2 mmol), triethyl borane (0.3 mmol) and oxygen (10 mL). After 2 h, the reaction was quenched with silica gel (5 g), evaporated, washed with hexane (50 mL) and extracted with EtOAc. The product was purified by column chromatography over silica gel.
Compound 5a (entry 1, Table
[1]
): 1H NMR (500 MHz, CDCl3): d = 0.74 (d, 3 H, J = 6.5 Hz,), 0.79 (t, 3 H, J = 7.0 Hz,), 0.98 (s, 3 H), 0.99 (d, 3 H, J = 6.5 Hz), 1.13 (m, 4 H), 1.19 (s, 3 H), 1.89 (m, 1 H), 2.48 (m, 2 H), 2.67 (m, 2 H), 3.05 (m, 2 H), 3.58 (m, 1 H), 7.21 (m, 5 H). 13C NMR (125 MHz, CDCl3): d = 20.7, 21.0, 21.2, 21.3, 25.8, 26.1, 27.1, 33.5, 39.8, 43.7, 48.9, 60.6, 61.9, 126.3, 128.1, 128.8, 143.2, 170.2, 175.7. HRMS: m/z calcd for C21H32N2O2Na+: 367.2356; found: 367.2360. [a]D
25 -7.03 (c 1.18, CHCl3) ee 52% (Chiralcel AD, hexanes-i-PrOH 99:1, flow rate 0.5 mL/min; t
R major enantiomer: 17.7 min, minor enantiomer: 21.2 min).
Compound 5b (entry 2, Table
[1]
): 1H NMR (500 MHz, CDCl3): d = 0.74 (d, 3 H, J = 7.0 Hz,), 0.77 (d, 3 H, J = 2.0 Hz), 0.79 (d, 3 H, J = 2.0 Hz), 0.98 (d, 3 H, J = 7.0 Hz), 0.99 (s, 3 H), 1.17 (s, 3 H), 1.60 (m, 1 H), 1.88 (m, 1 H), 2.31 (m, 2 H), 2.48 (m, 2 H), 3.04 (m, 2 H), 3.52 (m, 1 H), 7.17 (m, 5 H). 13C NMR (125 MHz, CDCl3): d = 14.0, 20.7, 20.8, 21.0, 25.7, 29.5, 33.5, 39.5, 44.3, 48.9, 53.1, 60.2, 126.4, 128.1, 128.8, 143.2, 170.3, 175.5. HRMS: m/z calcd for C21H32N2O2Na+: 367.2356; found: 367.2359. [a]D
25 -6.4 (c 1.66, CHCl3) ee 58% (Chiralcel AS, hexanes-i-PrOH 99:1, flow rate 0.5 mL/min; t
R minor enantiomer: 11.3 min, major enantiomer: 21.1 min).
Compound 5c (entry 1, Table
[2]
): 1H NMR (500 MHz, CDCl3): d = 0.71 (d, 3 H, J = 6.5 Hz,), 0.93 (d, 3 H, J = 6.5 Hz), 1.00 (s, 3 H), 1.14 (s, 3 H), 1.85 (m, 1 H), 2.43 (m, 2 H), 2.89 (m, 1 H), 2.98 (m, 1 H), 3.42 (m, 1 H), 3.85 (s, 2 H), 7.24 (m, 10 H). 13C NMR (125 MHz, CDCl3): d = 20.6, 21.0, 26.1, 26.2, 33.4, 39.5, 44.0, 48.7, 56.7, 60.7, 126.4, 127.7, 128.2, 128.6, 128.8, 129.5, 137.7, 143.4, 169.9, 174.6. HRMS: m/z calcd for C24H30N2O2Na+: 401.2200; found: 401.2222. [a]D
25 -13.4 (c 1.0, CHCl3) ee 98% (Chiralcel AS, hexanes-i-PrOH 98:2, flow rate 0.5 mL/min; t
R minor enantiomer: 25.3 min, major enantiomer: 31.0 min).
Compound 5d (entry 4, Table
[1]
): 1H NMR (500 MHz, CDCl3): d = 0.47 (d, 3 H, J = 8.0 Hz,), 0.59 (d, 3 H, J = 8.0 Hz), 1.14 (s, 3 H), 1.19 (s, 3 H), 1.52 (m, 1 H), 2.65 (m, 5 H), 4.16 (d, 1 H, J = 16.0 Hz), 4.35 (d, 1 H, J = 16.0 Hz), 6.86 (d, 2 H, J = 9.0 Hz), 7.08 (m, 3 H), 7.36 (m, 1 H), 7.48 (m, 1 H), 7.55 (m, 2 H), 7.75 (d, 1 H, J = 10.5 Hz), 7.83 (d, 1 H, J = 10.5 Hz), 8.14 (d, 1 H, J = 11.0 Hz). 13C NMR (125 MHz, CDCl3): d = 20.2, 20.6, 25.8, 26.3, 32.9, 38.9, 43.4, 47.9, 54.9, 61.3, 123.5, 125.7, 125.9, 126.1, 126.5, 128.1, 128.7, 129.1, 132.1, 132.6, 133.8, 143.2, 170.8, 174.3. HRMS: m/z calcd for C28H32N2O2Na+: 451.2355; found: 451.2347. [a]D
25 -30.24 (c 1.64, CHCl3) ee 90% (Chiralcel AD, hexanes-i-PrOH 97:3, flow rate 1.0 mL/min; t
R minor enantiomer: 14.4 min, major enantiomer: 19.0 min).
The absolute stereochemistry of the products 5a-d were determined by hydrolysis to the acid and comparison of their rotation with 3-phenyl-4-methyl-pentanoic acid.
12Although the proximity will vary, the ligand will be orthogonal to the substrate so long as one of the ligand nitrogen occupies an apical position, whether that is in an octahedral, trigonal bipyramidal, square pyramidal, or tetrahedral complex.
13The molecular graphics images in Figure [2] were produced using the UCSF Chimera package from the Computer Graphics Laboratory, University of California-San Francisco.
14In cycloadditions the bulk of the pyrazolidinone templates can also influence regioselectivity (ref. [5b] ) or exo/endo diastereoselectivity (ref. [5a] ).
15Magnesium iodide and magnesium triflimide both provide nearly identical results when used in combination with ligand 8; for example see entry 14 in Table [2] and entry 1 in Table [4] . The cheaper magnesium iodide was used for experiments in Table [4] .