Synthesis of 1,3,n-Oligo-enes, 1,3,n-Oligo-en-ones, 1,3,n-Oligo-en-ynes

dienes

dienes_table

X-ray structure of 9m:


(to see the X-ray structure you need MDL Chemscape Chime plug-in)

The allyl ironcarbene complexes 1 readily react with lithium enolates or potassium enoxyborates of ketones or esters to give the corresponding 4-substituted (3E)–1,3-diene complexes 9[5], [6]. The reaction is likely to start with an attack of the enolate on the C-6 terminus of 1 to give a neutral, fairly unstable (eta2-alkene)–ironcarbene complex 10. Due to its geometrical and electronic properties, 10 does not undergo cyclopropanation but – as a formal ferravinyl allyl ether – an intramolecular Claisen–type rearrangement to the cationic allyl–tetracarbonyliron compound 11. Deprotonation by the methoxide anion from the side opposite to the central metal, loss of carbon monoxide and recomplexation yields the eta4-(3E)–1,3-diene complex 9.

As to the diene moiety, the initial C–C coupling step takes place highly regio– and stereoselectively with both types of carbon nucleophiles. The starting metallacycles 1 are chiral, so products 9 derived from (pro)chiral enolates or enoxyborates are formed as mixtures of diastereoisomers in a ratio depending chiefly on the bulkiness of the nucleophile. Ratios of up to 90:10 in the case of the lithium enolates derived from indanone or cyclohexanone reveal a distinct inductive ability of the chiral metallacyclic plane in 1. With unsymmetric carbonyl compounds the additional problem of ketone–regioselectivity arises. Lithium enolates quite often give mixtures of regioisomers derived from both the "kinetic" and the "thermodynamic" enolates, whereas potassium enoxy borates of unsymmetric methyl–alkyl ketones mostly give only products derived from the "kinetic" isomer, i. e. products with substituents R2 = R3 = H. With ketones bearing a phenyl group in alpha- or beta-position to the carbonyl group on the other hand, the corresponding "thermodynamic" products result, either exclusively (9l) or predominantly (9m), due to formation of particularly stabilized conjugated enoxy borates.

It was only for complex 9m that we got exclusive formation of one (racemic) diastereomer, the X-ray structure of it is shown above. The acetyl group at the newly generated stereocentre is oriented "inwards" (i.e. gauche to 4-H), but also points "upwards", so that the methyl group lies along the hiatus between two of the terminal carbonyl ligands, what is probably due to the great steric demand of the benzyl group.

Phosphanes react in a similar manner to furnish cationic (3E)–1,3-diene complexes, which can be further converted to vinylallenes


functionalized diene komplexes

functionalized diene komplexes - table

Demetalation of 9 with ceric ammonium nitrate (CAN) leads to (3E)-6-oxo-
1,3-dienes 12.

Prior to decomplexation of the diene ligand, various transformations of the carbonyl group
of 9 can be performed, thus making use of the protective and/or stereodirecting properties of the tricarbonyliron moiety.

For instance, hotrienol 13, a (3E)-1,3,7-triene-6-ol, naturally occurring in the leaf oil of the japanese Ho tree, can be prepared in 5 steps (beginning from 1-methyl-1-vinyl oxirane) in 45% overall yield. Grignardation of 9h with vinylmagnesiumbromide in THF at 0 °C and decomplexation – preferrably with H2O2/NaOH in this case – sets free the unrearranged organic ligand 13.
Wittig or Horner-Wittig olefination of 9 gives the (3E)-1,3,6-triene complexes optionally with additional functionalities like alkynyl-, aldehyde-, keto-, ester- or nitril-groups. Demetalation under mild conditions (CAN) leaves 14.
Alternatively, the carbonyl group in "formyl-terminated" complexes 9 can be directly converted to a 1-alkyne unit by reaction with 1-diazo-2-oxo-propyldimethylphosphonate under slightly basic conditions.


Experimental data

1. Synthesis of 9a-g (general procedure method A):
n-BuLi (0.48 ml of a 2.5 M solution in hexane; 1.2 mmol) was added to a solution of N-isopropylcyclohexylamine (170 mg; 1.2 mmol) in THF (5 ml) at 0 °C. The mixture was stirred for 30 min, then cooled to -78 °C and treated with the carbonyl compound (1.2 mmol). After 1 h the resulting solution was transferred by means of a cannula to a slurry of 1a (354 mg; 1.0 mmol) in THF, chilled to -78 °C (or -40 °C in the case of cyclic ketones). Instantaneous deepening of the yellow shade indicated a swift reaction. Any volatile components were evaporated after another hour and the residue was repeatedly extracted with ether/hexane (2:1). The crude product thus obtained was subsequently purified by CC (silica; ether/petroleum ether, 1:1).
(5E)-Tricarbonyl[(5-8-hapto4)-2,4,4,7-tetramethyl-5,7-octadien-3-one]iron(0) (9d): IR (neat): 2975, 2930, 2875, 2040, 1975, 1960, 1705, 1465 cm-1. - 1H NMR (CDCl3, 400 MHz): 0.32 [d, 2J (8-Hen/8-Hex) = 1.65 Hz, 1H, 8-Hen], 0.91 [d, 3J (5-H/6-H) = 9.35 Hz, 1H, 5-H], 1.01 [d, 3J (1-H/2-H) = 6.6 Hz, 3H, 1-H],1.03 [d, 3J (2-H/CH3) = 6.6 Hz, 3H, 2-CH3], 1.15 [s, 3H, 4-CH3], 1.29 [s, 3H, 4-CH3], 1.80 [d, 2J (8-Hen/8-Hex) = 1.65 Hz, 1H, 8-Hex], 3.13 [qq, 3J (1-H/2-H) = 6.6 Hz, 1H, 2-H], 5.34 [d, 3J (5-H/6-H) = 9.35 Hz, 1H, 6-H]. - 13C NMR (CDCl3, 100.5 MHz): 20.65 (C-1, 2-CH3), 21.30 (7-CH3), 22.98 (4-CH3), 27.66 (4-CH3), 34.55 (C-2), 43.39 (C-8), 49.89 (C-4), 69.00 (C-5), 85.61 (C-6), 96.83 (C-7), 211.77 (Fe=CO), 216.43 (C-3). - MS (70) eV; m/z (%): 292 (10) [M+ - CO], 264 (38) [M+ - 2CO], 236 (100) [M+ - 3CO], 166 (73), 109 (48), 43 (64). - C15H20FeO4 (320.2): calcd. C 56.27, H 6.29; found C 55.98, H 6.39.

2. Synthesis of 9h-p (general procedure method B):
Solutions of the potassium enolates were prepared by dropwise addition of the respective carbonyl compound (0.78 mmol) to a suspension of potassium hydride (38 mg, 0.94 mmol) in THF (3 mL) at room temperature. After stirring vigorously for 10 min the solution was separated from excess potassium hydride by filtration over a glass sinter funnel. The resulting clear colourless to yellow filtrate was treated with triethylborane (0.98 mL of a 1 M solution in THF, 0.98 mmol) to give the corresponding enoxyborate. This solution was slowly transferred by means of cannula to a slurry of 1a (200 mg, 0.57 mmol) in THF (5 mL), kept at -78 °C. After one hour the reaction mixture was warmed to ambient temperature (25 °C) and any volatile components were evaporated in vacuo. The residue thus obtained was redissolved in the minimum amount of ether/pentane (1:1) and subsequently purified by column chromatography.
()-(4E)-Tricarbonyl [(4-7-h4)-3-benzyl-6-methyl-4,6-heptadien-2-one] iron (0) (9m): IR (neat): 2940, 2860, 2040, 1960, 1700, 1450, 1360, 1310, 750, 700 cm-1. 1H NMR (CDCl3/TMS): 0.43 (s, 1H, 7-Hen), 0.720.77 (m, 1H, 4-H), 1.79 (s, 1H, 7-Hex), 2.02 and 2.15 (s each, 6H, 1-H, 6-CH3), 2.643.02 (m, 3H, 3-H, 3-CH2C6H5), 4.78 (d, 1H, 3J (4-H/5-H) = 8.3 Hz, 5-H), 7.117.32 (m, 5H, Harom). 13C NMR (CDCl3/TMS): 22.7 (6-CH3), 30.3 (C-1), 42.9, 43.7 (3-CH2C6H5, C-7), 57.6, 59.7 (C-3, C-4), 86.8 (C-5), 100.2 (C-6), 126.7, 128.6, 129.2 (CHarom), 138.2 (Cipso), 208.9 (C-2), 211.5 (Fe=CO). MS: m/z (%) = 354 (M+, 1), 326 [M+ (CO), 8], 298 [M+ 2(CO), 22], 270 [M+ 3(CO), 100], 91 (C6H5CH2+, 23), 56 (Fe+, 18). Anal. C18H18FeO4 (354.1): Calcd C, 61.05; H, 5.12. Found C, 61.10; H, 5.13. Crystal structure:19 triclinic, P1, a = 6.4647(5) Å, b = 11.1092(9) Å, c = 12.4643(11) Å, a = 80.026(7)°, b = 82.014(7)°, g = 77.519(7)°, dcalc = 1.374 mg/m3, Z = 2.

3. Synthesis of 14e
14e was synthesized via Wittig-reaction with Methoxy-carbonyl triphenylphosphorane in pentane in the presence of silica gel [7].
(2E)(5E)-Tricarbonyl[(5-8-eta4)-1-methoxy-1-oxo-4,4,7-trimethyl-2,5,7-octatriene]iron (0)
IR (neat) : 2970, 2900, 2045, 1970, 1725, 1650 cm-1. 1H NMR : 0.00-0.01 [m, 1H, 8-Hen], 0.57 [d, 3J (5-H/6-H) = 9.4 Hz, 1H, 5-H], 0.99, 1.01 [je s, 6H, 4-CH3], 1.48-1.49 [m, 1H, 8-Hex], 1.76 [s, 3H, 7-CH3], 3.55 [s, 3H, O-CH3], 4.90 [d, 3J (5-H/6-H) = 9.4 Hz, 1H, 6-H], 5.86 [d, 3J (2-H/3-H) = 16.0 Hz, 1H, 2-H], 7.13 [d, 3J (2-H/3-H) = 16.0 Hz, 1H, 3-H]. 13C NMR : 22.4 (7-CH3), 27.2, 28.9 (4-CH3), 38.6 (C-4), 43.1 (C-8), 51.1 (O-CH3), 73.3 (C-5), 84.5 (C-6), 97.1 (C-7), 118.1 (C-2), 155.5 (C-3), 166.7 (C-1), 212.2 (Fe=CO). MS ( 70 eV) : m/e (%) = 334 (12) [M+], 306 (2) [M+-(CO)], 278 (8) [M+-2(CO)], 250 (100) [M+-3(CO)], 194 (50).

4. Synthesis of 14a-d*,f (general procedure):
A suspension of KH (1.2 mmol)in THF (5 mL) was treated with the phosphonate (1.2 mmol) under vigorous stirring at room temperature. After 5 min the solution was cooled to -78°C and slowly transferred by means of cannula to a solution of 9 (1.1 mmol) mmol) in THF (5 mL), kept at -78 °C. After one hour at this temperature the solution was allowed to warm to room temperature and quenched with saturated NH4Cl solution. After removal of the solvent the crude product was subjected to column chromatography (ether/petroleum ether).
(* For the synthesis of 14c diethyl cyclohexylvinylamino phosphonate was used. The imine formed hydrolyzes during chromatography to leave the aldehyde.)
(3E)(6E)-Tricarbonyl[(6-9-eta4)-5,5,8-trimethyl-3,6,8-nonatrien-2-one]iron (0)(14f) IR (neat) : 2970, 2900, 2860, 2040, 1970, 1730, 1680, 1620 cm-1. 1H NMR : 0.29 [s, 1H, 9-Hen], 0.78 [d, 3J (6-H/7-H) = 8.0 Hz, 1H, 6-H], 1.21 [s, 6H, 5-CH3], 1.79 [s, 1H, 9-Hex], 2.18 and 2.28 [s each, 6H, 8-CH3 and 1-H], 5.20 [d, 3J (6-H/7-H) = 8.0 Hz, 1H, 7-H], 6.99 [d, 3J (3-H/4-H) = 16.4 Hz, 1H, 3-H], 6.74 [d, 3J (3-H/4-H) = 16.4 Hz, 1H, 4-H]. 13C NMR : 22.9 (8-CH3), 26.9 (C-1), 28.2, 28.4 (5-CH3), 38.8 (C-5), 43.4 (C-9), 72.8 (C-6), 84.5 (C-7), 97.2 (C-8), 127.4 (C-3), 154.7 (C-4), 206.0 (C-2), 211.9 (Fe=CO). MS ( 70 eV) : m/e (%) = 318 (7) [M+], 262 (12) [M+-2(CO)], 234 (100) [M+-3(CO)], 162 (44).


[5] J. Böhmer, W. Förtsch, F. Hampel and R. Schobert Chem. Ber. 1996, 129, 427.
[6] J. Böhmer, F. Hampel and R. Schobert Synthesis 1997, 661.
[7]V. J. Patil, U. Mävers Tetrahedron Letters 1996, 37, 1281.


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