Extended Scope of Dirhodium(II)-Catalysed Enantioselective Intramolecular 1,3-Dipolar Cycloadditions of Carbonyl Ylides with Alkene and Alkyne Dipolarophiles

Abstract

Catalytic enantioselective tandem carbonyl ylide formation-intramolecular 1,3-dipolar cycloaddition reactions of 2-diazo-3,6-diketoesters show promising scope in terms of asymmetric induction as the tethered alkene/alkyne dipolarophile component is varied.

asymmetric catalysis - rhodium - ylides - cycloadditions - diazo compounds

References

1 Cycloaddition Reactions in Organic Synthesis   Kobayashi S. Jørgensen KA. Wiley-VCH; Weinheim: 2002. 

2 Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products   Padwa A. Pearson WH. John Wiley and Sons; New York: 2002. 

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3b Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds   John Wiley and Sons; New York: 1998.  Chap. 7.

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3d Mehta G. Muthusamy S. Tetrahedron  2002,  58:  9477 

3e For a recent application, see: Hodgson DM. Avery TD. Donohue AC. Org. Lett.  2002,  4:  1809 

4 Hodgson DM. Stupple PA. Johnstone C. Tetrahedron Lett.  1997,  38:  6471 

5a Hodgson DM. Stupple PA. Johnstone C. Chem. Commun.  1999,  2185 

5b Hodgson DM. Stupple PA. Pierard FYTM. Labande AH. Johnstone C. Chem.-Eur. J.  2001,  7:  4465 

6a Kitagaki S. Masahiro A. Kataoka O. Matsuno K. Umeda C. Watanabe N. Hashimoto S. J. Am. Chem. Soc.  1999,  121:  1417 

6b Kitagaki S. Yasugahira M. Anada M. Nakajima M. Hashimoto S. Tetrahedron Lett.  2000,  41:  5931 

7a Hodgson DM. Pierard FYTM. Stupple PA. Chem. Soc. Rev.  2001,  30:  50 

7b Hodgson DM. Stupple PA. Forbes DC. In Rodd’s Chemistry of Carbon Compounds, Topical Volume, Asymmetric Catalysis   Sainsbury M. Elsevier; Oxford: 2001.  p.65 

7c Kitagaki S. Hashimoto S. J. Synth. Org. Chem. Jpn.  2001,  59:  1157 

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8b Hodgson DM. Glen R. Grant GH. Redgrave AJ. J. Org. Chem.  2002, in press

9

A significant erosion in ee (and yield) has been observed for one (oxidopyrylium) substrate as the dipolarophile was even varied from DMAD (74% ee) to the corresponding diethyl ester (46% ee); 25% ee was observed with the di-tert-butyl ester. [6b]

10

Results in CH₂Cl₂ for all the substrates examined in the current paper are not given here; as previously found with 1, [5] the ees were uniformly lower than in hexane.

11

Hashimoto’s optimized catalyst-solvent combination [6] was not studied, since it had previously been shown with 1 to generate only racemic cycloadduct 3. [5]

12

Ees were determined directly on the cycloadducts by GC analysis and comparison with racemic samples prepared using Rh₂(OAc)₄ (chiral gas chromatography was carried out using a CE Instruments Trace GC (Thermoquest) machine with a CP Chirasil Dex-CD column).

13

NOE experiments support the relative stereochemistry of the cycloadducts shown in Scheme [3] . The absolute configurations of the predominant cycloadduct enantiomers are tentatively assigned as those shown, by analogy with cycloadduct (+)-3 of known absolute configuration. [5] Selected specific rotation values (c 1.0, CHCl₃): for (+)-14, using 5 at 0 °C: [α]_D ²⁴ +38.0; for (-)-15, using 5 at -15 °C: [α]_D ²⁵ -29.7; for (-)-16, using 5 at 0 °C: [α]_D ²⁵ -8.2; for (+)-17, using 5 at 0 °C: [α]_D ²⁴ +23.2.

14 Padwa A. Hornbuckle SF. Fryxell GE. Zhang ZJ. J. Org. Chem.  1992,  57:  5747 

15 For a recent example, see: Graening T. Friedrichsen W. Lex J. Schmalz H.-G. Angew. Chem. Int. Ed.  2002,  41:  1524 

16

Typical Procedure for Cycloadduct (+)-18: To a stirred, degassed solution tert-butyl 2-diazo-3,6-dioxoundec-10-ynoate (100 mg, 0.34 mmol) in hexane (5 mL) at 25 °C was added Rh₂[(R)-DDBNP]₄ (10 mg, 0.0034 mmol). After 30 min, the reaction mixture was concentrated in vacuo. The residue was purified by flash chromatography (SiO₂, light petroleum-Et₂O 8:2; R_f = 0.11) to afford a white solid (70 mg, 77%). IR(neat): ν_max = 2974, 2923, 1743, 1720, 1368, 1306, 1158, 1057 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 5.86 (t, 1 H, J ⁴ = 2.0 Hz), 2.89-2.80 (m, 1 H), 2.52-2.24 (m, 4 H), 2.16-2.00 (m, 3 H), 1.97-1.90 (m, 1 H), 1.77-1.69 (m, 1 H), 1.50 (s, 9 H). ¹³C NMR (100 MHz; CDCl₃): δ = 198.8, 165.1, 157.4, 119.2, 100.2, 96.5, 82.8, 33.0, 32.8, 29.6, 28.0, 26.2, 22.6. MS: m/z (%) [CI + (NH₃)] = 282(46) [M + NH₄ ⁺], 265(10) [M + H⁺), 226(100) {M - [CH₂C(CH₃)₂] + NH₄ ⁺}. HRMS (ES, [M + H]⁺) calcd 265.1440, measured 265.1449. GC analysis for ee determination: (CP Chirasil Dex-CD,
80° C/1 min/5° Cmin^{- 1}/170° C/100 min, 0.5 mLmin^{- 1}, 2 mgmL^-1), t _Rmn = 27.2 min; t _Rmj = 27.9 min.

17 Davies HML. Eur. J. Org. Chem.  1999,  2459 

18

Selected specific rotation values (c 1.0, CHCl₃): for (+)-19, using 5 at -15 °C: [α]_D ²⁵ +305.4; (+)-20, using 5 at 0 °C: [α]_D ²⁵ +283.9; (+)-21, using 5 at 0 °C: [α]_D ²⁴ +231.2.