Efficient Syntheses of Angularly Fused Triquinanes via β-Amino-Substituted α,β-Unsaturated Fischer-Carbene Complexes

Jelena Milic; Heiko Schirmer; Bernard L. Flynn; Mathias Noltemeyer; Armin de Meijere

doi:10.1055/s-2002-31910

LETTER

Efficient Syntheses of Angularly Fused Triquinanes via β-Amino-Substituted α,β-Unsaturated Fischer-Carbene Complexes

Jelena Milic^a, Heiko Schirmer^a, Bernard L. Flynn^b, Mathias Noltemeyer^c, Armin de Meijere*^a
^a Institute für Organische Chemie der Georg-August-Universität Göttingen, Tammannstrasse 2-4, 37077 Göttingen, Germany
Fax: +49(551)399475; e-Mail: Armin.deMeijere@chemie.uni-goettingen.de;
^b Department of Chemistry, Australian National University, Canberra ACT 0200, Australia
^c Institute für Anorganische Chemie der Georg-August-Universität Göttingen, Tamannstrasse 2-4, 37077 Göttingen, Germany

Abstract

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Abstract

Formal [3+2] cycloadditions of the carbene ligand in the new (3-dimethylamino-1-alkoxyalkenylidene)pentacarbonylchromium complexes 5 and 14 both with cyclopropyl substituents in the 3-position, onto alkynes give 5-dimethylamino-3-ethoxycyclopentadienes 6 and 15a-f, the latter along with regioisomers 16a-d, in good yields (55-72%). Treatment of these with hydrochloric acid liberates two carbonyl groups in each of them, and the resulting 5-dimethylaminocyclopent-1-en-3-ones 7 and 17a-c/18a-c, under basic conditions, undergo a cascade of two cyclizations, to yield angularly fused triquinanes 10 (68%) and 23a-c (30-97%). The overall procedure consists of four operational steps and produces cyclopropane-annelated tricyclo[6.3.0.0 [1] [5] ]undecane skeletons from two different alkynes each in 22-47% overall yield.

Key words

carbenechromium complexes - cycloadditions - cyclopentadienones - cascade reactions - spiro[4.4]nonenones - triquinanes

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References

References and Notes

Reviews see:

1a Paquette LA. Top. Curr. Chem. 1979, 79: 41

1b Paquette LA. Top. Curr. Chem. 1984, 119: 1

1c Paquette LA. Doherty AM. Polyquinane Chemistry Springer; Berlin: 1987.

2 de Meijere A. Pure Appl. Chem. 1996, 68: 61

3 de Meijere A. Schirmer H. Duetsch M. Angew. Chem. Int. Ed. 2000, 39: 3964 ; Angew. Chem. 2000, 112, 4124

4 Flynn BL. Funke FJ. Silveira CC. de Meijere A. Synlett 1995, 1007

5 Schirmer H. Funke FJ. Müller S. Noltemeyer M. Flynn BL. de Meijere A. Eur. J. Org. Chem. 1999, 2025

6 Review: Metha G. Srikrishna A. Chem. Rev. 1997, 97: 671

The alkyne 4 has been prepared from (+)-carene previously:

7a Donkervoort JG. Gordon AR. Johnstone C. Kerr WJ. Lange U. Tetrahedron 1996, 52: 7391

7b

Better yields of 4, however, were obtained by modifying the reported procedure in two steps. Firstly, the cyclopropane-carboxylic acid 2 was converted to the cyclopropyl methyl ketone according to the protocol of House et al., [8] and secondly the protocol of Negishi et al. [9] was applied to convert the methyl ketone to the terminal alkyne via the enol phosphate.

8 Bare TM. House HO. Org. Synth. 1969, 49: 81

9 Negishi E.-I. King AO. Tour JM. Org. Synth. 1985, 64: 44

10

All new compounds were fully characterized by IR, NMR (¹H, ¹³C) mass spectra as well as correct elemental analyses. Spectroscopic data of representative examples are as follows:
Pentacarbonyl[(2 E / Z )-3-dimethylamino-3-{(1′ S ,3′ R )- cis -2′,2′-dimethyl-3′-[2′′-(2′′′-methyl-[1′′′,3′′′]-dioxolan-2′′′-yl)ethyl]cyclopropyl}-1-ethoxy-2-propen-1-yliden]-chromium(5): R_f = 0.56 (Z-isomer), R_f = 0.39 (E-isomer), Et₂O (10:1)], yellow crystals, mp 75 °C. IR (KBr): 2980 cm^-1 (C-H), 2912 (C-H), 2769 (C-H), 2044 (C=O), 1969 (C=O), 1889 (C=O), 1527 (C=C), 1431, 1376, 1317, 1254, 1148, 1094, 1069, 1038, 982, 923, 869, 782, 671. ¹H NMR (250 MHz, CDCl₃): δ = 0.96 (s, 3 H, CH₃), 1.01 (m_c, 1 H, 3′-H), 1.24 (s, 3 H, CH₃), 1.29 (s, 3 H, CH₃), 1.35 (m_c, 1 H, 1′-H), 1.44 (t, ³ J = 7.0 Hz, 3 H, OCH₂CH ₃), 1.44-1.73 (m, 4 H, 4′′-H, 5′′-H), 3.13 [bs, 6 H, N(CH₃)₂], 3.92 (m_c, 4 H, OCH₂CH₂O), 4.65 (q, ³ J = 7.0 Hz, 2 H, OCH ₂CH₃), 6.25 (s, 1 H, 2H). ¹³C NMR (62.9 MHz, CDCl₃, plus DEPT): δ = 15.2 (+, C-3′), 15.5 (+, OCH₂ CH₃), 20.8 (-, C-1′′), 23.2 (C_quat., C-2′), 23.6 (+, CH₃), 28.5 (+, CH₃), 30.1 (+, C-1′), 32.3 (+, CH₃), 38.8 (-, C-2′′), 41.5 [+, N(CH₃)₂], 64.4 (-, OCH₂CH₂O), 72.9 (-, OCH₂CH₃), 109.4 (C_quat, C-2′′′), 119.8 (+, C-2), 159.7 (C_quat, C-3), 219.3, 224.4 (C_quat, C=O), 279.9 (C_quat, C-1). - MS (70 eV), m/z (%): 501(3) [M⁺], 473(13) [M⁺ - CO], 445(5) [M⁺ - 2CO], 417(6) [M⁺ - 3 CO], 389(2) [M⁺ - 4 CO], 361(100) [M⁺ - 5 CO], 220(21), 204(29), 191(64), 95(25), 87(28), 52(47) [Cr⁺], 43(34).
4,5,11,11-Tetramethyltetracyclo[6.4.0.0 [1] [5] .0 [10] [12] ]-dodec-an-3,7-dione(10): R_f = 0.25 in Pentane-Et₂O (3:1, colorless crystals, mp 101 °C. IR (KBr): 3010 cm^-1 (C-H), 2957 (C-H), 2938 (C-H), 2877 (C-H), 1732 (C=O), 1456, 1390, 1376, 1339, 1266, 1206, 1191, 1124, 1100, 1083, 1008, 931, 895, 841, 647, 542, 465. ¹H NMR (500 MHz, CDCl₃): δ = 0.99 (s, 3 H, CH₃), 1.01 (s, 3 H, CH₃), 1.02 (d, ³ J = 7.0 Hz, 3 H, CH₃), 1.17 (s, 3 H, CH₃), 1.23 (dd, ³ J = 6.4, ³ J = 6.4 Hz, 1 H, 10-H), 1.29 (d, ³ J = 6.4 Hz, 1 H, 12-H), 1.88 (ddd, ² J = 13.8, ³ J = 8.0, ³ J = 6.4 Hz, 1 H, 9-H), 2.01 (AB, d, ² J = 18.1 Hz, 1 H, 6-H), 2.08 (AB, d, ² J = 18.1 Hz, 1 H, 6-H), 2.16 (dd, ² J = 13.8, ³ J = 10.7 Hz, 1 H, 9-H), 2.38 (dq, ³ J = 7.0, ⁴ J = 1.7 Hz, 1 H, 4-H), 2.40 (AB, d, ² J = 19.9 Hz, 1 H, 2-H), 2.42 (dd, ³ J = 10.7, ³ J = 8.0 Hz, 1 H, 8-H), 2.78 (dd, ² J = 19.9, ⁴ J = 1.7 Hz, 1 H, 2-H). ¹³C NMR (62.9 MHz, CDCl₃, plus DEPT): δ = 9.2 (+, CH₃), 16.3 (+, CH₃), 19.3 (C_quat, C-11), 21.5 (+, CH₃), 27.9 (+, CH₃), 29.6 (-, C-9), 30.8 (+, C-10), 37.6 (+, C-12), 48.0 (-, C-2), 49.0 (-, C-6), 50.0 (C_quat, C-5), 53.2 (+, C-4), 56.3 (C_quart, C-1), 60.9 (+, C-8), 217.9, 218.7 (C_quat, C-3, C-7). MS (70 eV), m/z (%): 246(24) [M⁺], 218(31) [M⁺ - CO], 203(11), 190(8), 175(17), 161(8), 148(56), 133(9), 121(100), 105(55).
4,7-Dimethylspiro{cyclopropane-1,11-tricyclo-[6.4.0.0 [1] [5] ]undeca-4,6-dien-3-one}(23a): R_f = 0.75 in Et₂O, colorless oil. IR(film): 3066 cm^-1 (C-H), 2948 (C-H), 2915 (C-H), 2854 (C-H), 1695 (C=O), 1641 (C=O), 1587, 1436, 1336, 1246, 1014, 971, 843, 728, 668, 592. ¹H NMR (500 MHz, CDCl₃): δ = -0.65 to -0.25 (m, 1 H, cPr-H), 0.08-0.13 (m, 1 H, cPr-H) 0.16-0.20 (m, 1 H, cPr-H) 0.33-0.38 (m, 1 H, cPr-H), 1.20-1.30 (m, 1 H, 10-H), 1.65 (s, 3 H, CH₃) 1.63-1.73 (m, 1 H, 10-H), 1.92 (s, 3 H, CH₃), 1.96-2.08 (m, 2 H, 9-H), 2.32 (AB, d, ² J = 16 Hz, 1 H, 2-H), 2.48 (AB, d, ² J = 16 Hz, 1 H, 2-H), 3.00-3.07 (m, 1 H, 8-H), 6.10 (s, 1 H, 6-H). ¹³C NMR (62.9 MHz, CDCl₃, plus, DEPT): 4.9 (-, cPr-C), 8.7 (+, CH₃), 14.1 (-, cPr-C), 16.5 (+, CH₃), 26.5 (-, C-10), 31.8 (C_quat, C-11), 36.9 (& ndash;, C-9), 48.7 (-, C-2), 58.1 (+, C-8), 60.0 (C_quat, C-1), 120.9 (+, C-6), 124.8 (C_quat, C-5), 162.8 (C_quat, C-7), 179.5 (C_quat, C-4), 209.6 (C_quat, C-3). MS (70 eV), m/z (%): 214(100) [M⁺], 199(19) [M⁺ - CH₃], 185(16) [M⁺ - C₂H₅O], 171(35) [M⁺ - C₃H₇O], 159(38), 143(21), 132(18), 115(17), 91(16), 77(10), 65(4), 53(4), 41(4).

11

Milic, J.; Schirmer, H.; de Meijere, A. unpublished results.

12

Crystallographic data for the angular triquinanes 10 and 23c have been deposited with the Cambridge Crystallographic Data Centre as supplementary publications no. CCDC-180879(10) and CCDC-180718(23c). Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk).

13 A 1,1-disubstituted cyclopropane moiety can actually also serve as a masked gem-dimethyl group, which can be unmasked by catalytic hydrogenation. Cf.: Piers E. Karunaratne V. Tetrahedron 1989, 45: 1089

14 Militzer H.-C. Schömenauer S. Otte C. Puls C. Hain J. Bräse S. de Meijere A. Synthesis 1993, 998

15 Schizuri Y. Shojiro M. Ohkubo M. Yamamura S. Tetrahedron Lett. 1990, 7167