Easy Access to (n+3)-Dimethylamino-1-ethenylbicyclo[n.1.0]alkanes and their Facile Conversion to Ring-annelated Cyclopentadienes [1]

Abstract

Aminocyclopropanation of 1-ethenylcycloalkenes 2a-d with N,N-dibenzyl- and N,N-dimethylformamide, respectively, by treatment with cyclohexylmagnesium bromide in the presence of methyltitanium triisopropoxide yielded the exo-(n+3)-N,N-dime­thylamino-1-ethenylbicyclo[n.1.0]alkanes 3a-d (58-72%). Compounds 7b-d could be transformed by thermal vinylcyclopropane to cyclopentene rearrangement to the corresponding exo-4-dimethyl­aminobicyclo[n.3.0]alk-1-enes 7b-d (84-90%). Elimination of the dimethylamino group led to the cyclopentadienes 11b-d and 12b-d (72-82%). The 5-dimethylamino-1-ethenylbicyclo[2.1.0]pentane did not undergo the typical vinylcyclopropane rearrangement, but ring-opening at the bridgehead-bridgehead bond to form 1-ethenyl-2-dimethylaminocyclopentene 8.

cyclopentadiene derivatives - cyclopropane derivatives - organometallics - rearrangement - titanium chemistry

References

1a

Part 82 in the series ‘Cyclopropyl Building Blocks for Organic Synthesis’. Part 81 see: Frank, D.; Kozhushkov, S. I.; Labahn, T.; de Meijere, A. Tetrahedron 2002, in press.

1b

Part 80: von Seebach, M.; de Meijere, A.; Grigg, R. Eur. J. Org. Chem. 2002, in press.

For reviews on substituted cyclopentadienyl ligands and their complexes see:

2a Okuda J. Top. Curr. Chem.  1992,  160:  97 

2b Janiak C. Schumann H. Adv. Organomet. Chem.  1991,  33:  291 

2c Okuda J. Eberle T. In Metallocenes   Togni A. Halterman RL. Wiley; New York: 1998.  p.415 

3 Winterfeldt E. Chem. Rev.  1993,  93:  827 

4 Halterman RL. Chem. Rev.  1992,  92:  965 

5 Williams CM. Chaplinski V. Schreiner PR. de Meijere A. Tetrahedron Lett.  1998,  39:  7695 

1-Ethenylcyclobutene (2a):

6a Markgraf JH. Greeno EW. Miller DM. Zaks WJ. Lee GA. Tetrahedron Lett.  1983,  24:  241 

6b Thummel RP. Nutakul W. J. Org. Chem.  1977,  42:  300 

1-Ethenylcycloalkenes 2b-d and NMR spectroscopic data:

7a Mason TJ. Harrison MJ. Hall JA. Sargent GD. J. Am. Chem. Soc.  1973,  95:  1849 

7b Rodriguez J. Brun P. Waegell B. J. Organomet. Chem.  1989,  359:  343 

7c Biela R. Bilas W. Ihsan U. Pritzkow W. Schmidt-Renner W. J. Prakt. Chem.  1983,  325:  893 

7d Thummel RP. Rickburn B. J. Org. Chem.  1971,  36:  1365 

7e Meier H. Schmitt M. Tetrahedron Lett.  1989,  30:  5873 

7f Maciagiewicz I. Dybowski P. Skowronñska A. Tetrahedron Lett.  1999,  40:  3791 

7g Salomon RG. Sinka A. Salomon MF. J. Am. Chem. Soc.  1987,  100:  520 

8

Alternatively, 1-ethenylcycloalkenes 2a-d may be prepared from the corresponding cycloalkanones via the enol triflates by Stille cross coupling with tri-n-butylvinylstannane. Cf. ref. [6]

9

General Procedure (GP) for the Preparation of 1-ethenyl- exo -( n +3)-dialkylaminobicyclo[ n .1.0]alkanes 3: To a well-stirred solution of the corresponding 1-ethenylcycloalkene 2a-d (10 mmol), MeTi(i-PrO)₃ (12 mmol) and N,N-dialkylformamide (10-20 mmol) in 30 mL of THF was added cyclohexylmagnesium bromide (13.3-24 mL, 20-36 mmol) as a 1.50 M solution in diethyl ether) over a period of 2 h, and the mixture was stirred at ambient temperature overnight. The reaction was quenched by carefully adding 5 mL of water, the mixture was exposed to air until it had turned light yellow or colorless and then filtered. The solids on the filter were washed with diethyl ether (3 × 20 mL). The combined filtrates were concentrated in vacuo, and the light yellow residue was subjected to column chromatography (column 2 × 25 cm, 40 g of silica gel) eluting with pentane/diethyl ether/triethylamine 90:9.5:0.5.
exo -5-Dibenzylaminobicyclo[2.1.0]pentane (3a): According to GP, 962 mg (12 mmol) of 1-ethenylcyclo-butene (2a) with N,N-dibenzylformamide (5.63 g, 25 mmol), methyltitanium triisopropoxide (2.88 g, 12 mmol) and 15.8 mL (30 mmol) of cyclohexylmagnesium bromide solution (1.90 M in diethyl ether) gave 2.20 g (63%) of 3a as a
light yellow oil. ¹H NMR (250 MHz, CDCl₃): δ = 1.42
(ddd, ² J = 11.0, ³ J = 6.5, ³ J = 3.9 Hz, 1 H, 3-H _endo ), 1.55 (ddd, ² J = 11.0, ³ J = 6.5, ³ J = 4.6 Hz, 1 H, 2-H _endo ), 1.79
(d, ³ J = 4.6 Hz, 1 H, 4-H), 2.01 (dddd, ² J = 11.0, ³ J = 11.0, ³ J = 4.6, ³ J = 4.6 Hz, 1 H, 3-H _exo ), 2.31 (ddd, ² J = 11.0, ³ J = 11.0, ³ J = 3.9 Hz, 1 H, 2-H _exo ), 2.36 (s, 1 H, 5-H),
3.61 (AB, d, ² J = 14.0 Hz, 2 H, NCH₂Ph), 3.80 (AB, d, ² J = 14.0 Hz, 2 H, NCH₂Ph), 5.09 (dd, ² J = 1.9, ³ J _trans = 17.5 Hz, 1 H, 7-H), 5.17 (dd, ² J = 1.9, ³ J _cis = 10.8 Hz, 1 H, 7-H), 6.20 (dd, ³ J _trans = 17.5, ³ J _cis = 10.8 Hz, 1 H, 6-H), 7.25-7.47 (m, 10 H, Ph-H).
¹³C NMR (62.9 MHz, CDCl₃, additionally DEPT): δ = 19.2 (-, C-3), 22.9 (-, C-2), 31.3 (+, C-4), 36.0 (C_quat, C-1), 56.9 (-, 2 C, NCH₂Ph), 57.7 (+, C-5), 112.3 (-, C-7), 126.9 (+, 2 C, Ph-C), 128.1 (+, 4 C, Ph-C), 129.3 (+, 4 C, Ph-C), 137.4 (+, C-6), 137.9 (C_quat, 2 C, Ph-C). MS (70 eV): m/z (%) = 289(16) [M⁺], 288(12) [M⁺ - H], 262(3) [M⁺ - C₂H₃], 224(11), 198(29) [M⁺ - C₇H₇], 170(5) [M⁺ - C₇H₇ - C₂H₄], 144(20) [M⁺ - C₇H₇ - C₄H₆], 106(8) [HNC₇H₇ ⁺], 91(100) [C₇H₇ ⁺]. C₂₁H₂₃N: 289.1830 (correct HRMS). Anal. Calcd for C₂₀H₂₃N (289.4): C, 87.15; H, 8.01; N, 4.84. Found; C, 86.88; H, 7.90; N, 4.97.

10

All new compounds were fully characterized by spectroscopic techniques (¹H and ¹³C NMR, MS), and bulk purities - except for the quaternary ammonium salts 9 and N-oxides 10 - were established by elemental analyses. Spectroscopic data of representative examples: exo-N , N -Dimethyl-(1-ethenylbicyclo[4.1.0]hept-7-yl)amine (3c): ¹H NMR (500 MHz, CDCl₃): δ = 1.03 (ddd, ³ J = 1.8, ³ J = 8.0 Hz, ³ J _trans = 4.3 Hz, 1 H, 6-H), 1.08-1.24 (m, 3 H, 3-H*, 4-H), 1.27-1.37 (m, 1 H, 4-H), 1.45 (d, ³ J _trans = 4.3 Hz, 1 H, 7-H), 1.52-1.63 (m, 2 H, 2-H, 5-H), 1.87-1.98 (m, 2 H, 2-H, 5-H), 2.20 (s, 6 H, CH₃), 4.99 (dd, ² J = 1.6, ³ J = 10.8 Hz, 1 H, 2′-H), 5.03 (dd, ² J = 1.6, ³ J = 17.6 Hz, 1 H, 2′-H), 5.82 (dd, ³ J = 10.8, ³ J = 17.6 Hz, 1 H, 1′-H). ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 21.1 (-, C-3*), 22.7 (-, C-4*), 22.1 (-, C-5**), 25.8 (-, C-2**), 27.7 (+, C-6), 28.5 (C_quat, C-1), 45.0 (+, 2 C, CH₃), 58.4 (+, C-7), 110.4 (-, C-2′), 143.7 (+, C-1′). MS (70 eV, EI):
m/z (%) = 165 (100) [M⁺], 150 (42), 136 (62), 122 (30), 108 (23), 84 (57), 70 (38), 58 (30), 42 (48). Anal. Calcd for C₁₁H₁₉N (165.3): C, 79.94; H, 11.59; N, 8.47. Found: C, 79.66; H, 11.35; N, 8.53.
exo-N , N -Dimethyl-(1-ethenylbicyclo[5.1.0]oct-8-yl)amine (3d): ¹H NMR (500 MHz, CDCl₃): δ = 0.89-1.14 (m, 4 H, 2-H*, 6-H, 7-H), 1.20-1.31 (m, 1 H, 3-H*), 1.40 (d, ³ J _trans = 3.8 Hz, 1 H, 8-H), 1.48-1.56 (m, 1 H, 3-H*), 1.58-1.72 (m, 2 H, 4-H*), 1.74-1.83 (m, 1 H, 5-H*), 2.19 (s, 6 H, CH₃), 2.14-2.27 (m, 1 H, 6-H), 2.30-2.37 (m, 1 H, 5-H*), 5.01 (dd, ² J = 1.6 Hz, ³ J = 17.4 Hz, 1 H, 2′-H), 5.02 (dd, ² J = 1.6 Hz, ³ J = 11.1 Hz, 1 H, 2′-H), 5.67 (dd, ³ J = 11.1 Hz, ³ J = 17.4 Hz, 1 H, 1′-H). ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 27.0 (-, C-2*), 29.4 (-,
C-3*), 30.8 (-, C-6), 32.4 (-, C-4*), 32.5 (-, C-5*), 33.8 (+, C-7), 34.7 (C_quat, C-1), 45.2 (+, 2 C, CH₃), 64.8 (+, C-8), 111.1 (-, C-2′), 142.4 (+, C-1′). MS (70 eV, EI): m/z (%) = 179 (30) [M⁺], 164 (21), 150 (18), 136(100), 122 (39) [M⁺ - C₄H₉], 108 (80) [M⁺ - C₅H₁₁], 84 (62), 71(45), 42 (100), 41 (49). Anal. Calcd for C₁₂H₂₁N (179.3): C, 80.38; H, 11.81; N, 7.81. Found: C,80.18; H, 11.74; N, 7.74.
(2,4,5,6,7,7a-Hexahydro-1 H -inden-1-yl)dimethylamine (7c): ¹H NMR (250 MHz, CDCl₃): δ = 0.93-1.38 (m, 3 H, 4-H*, 5-H*), 1.69-1.80 (m, 2 H, 6-H*), 1.80-1.98 (m, 1 H, 7-H*), 1.98-2.17 (m, 1 H, 7-H*), 2.17-2.45 (m, 4 H, 1-H, 2-H, 4-H), 2.23 (s, 6 H, CH₃), 2.55-2.64 (m, 1 H, 7a-H), 5.15 (m_c, 1 H, 3-H). ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 26.1 (-, C-6), 26.9 (-, C-5), 29.2 (-, C-4), 35.4 (-,
C-2), 35.5 (-, C-7), 43.3 (+, 2 C, CH₃), 48.5 (+, C-7a), 73.2 (+, C-1), 118.3 (+, C-3), 144.8 (C_quat, C-3a). MS (70 eV, EI): m/z (%) = 165 (100) [M⁺], 150 (42), 136 (51), 122 (23), 108 (15), 91 (24), 84 (41), 70 (33), 58 (19), 42 (26). Anal. Calcd for C₁₁H₁₉N (165.3): C, 79.94; H, 11.59; N, 8.47. Found: C, 79.85; H, 11.57; N, 8.35.
4,5,6,7-Tetrahydro-1 H -indene(11c) and 4,5,6,7-Tetrahydro-2 H -indene (12c): 11c: ¹H NMR see ref.¹¹.
¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 23.1 (-, C-4*), 23.3 (-, C-5*), 24.4 (-, C-6*), 25.3 (-, C-7*), 34.1 (-, C-1), 129.8 (+, C-2), 134.5 (+, C-3), 137.9 (C_quat, C-3a*), 139.2 (C_quat, C-7a*). 12c: ¹H NMR (250 MHz, CDCl₃): δ = 1.58-1.80 [m, 4 H, 5(6)-H], 2.47-2.58 [m, 4 H, 4(7)-H], 2.72-2.80 (m, 2 H, 2-H), 5.97 [m_c, 2 H, 1(3)-H]. ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 24.4 [-, C-4(7)], 25.7 [-,
C-5(6)], 39.7 (-, C-2), 125.1 [+, C-1(3)]. The signals of the quaternary carbon atoms C-3a and C-7a were not visible because of the low concentration of 12c.

11 Dané LM. de Haan JW. Klosterziel H. Tetrahedron Lett.  1970,  9:  2755 

12a Hudlicky T. Becker DA. Fan RL. Kozhushkov SI. Methods in Organic Chemistry (Houben-Weyl)   Vol. E 17c:  de Meijere A. Thieme; Stuttgart: 1997.  p.2538 

12b Hudlicky T. Reed JW. In Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.899 

13a Richey HG. Shull DW. Tetrahedron Lett.  1976,  575 

13b Williams CM. de Meijere A. J. Chem. Soc., Perkin Trans. 1  1998,  3699 

14

The structure of the by-products could not unambiguously be determined.

15a

The necessity of relatively high temperatures for the rearrangement of 3b-d is consistent with the fact that the dimethylamino and the ethenyl group in each of them are cis-oriented with respect to each other. It is known that the direct ring enlargement of a cis-2-donor-substituted ethenylcyclopropane to a cyclopentene is much slower than that of the trans isomer, and the cis to trans isomerization of 3b-d, which would correspond to an exo to endo isomerization, is retarded due to the bulk of the dimethylamino group.

15b Cf. ref. and ref. and see also: McGaffin G. Grimm B. Heinecke U. Michaelsen H. de Meijere A. Walsh R. Eur. J. Org. Chem.  2001,  3559 

16 Pauli A. Meier H. Chem. Ber.  1987,  120:  1617