Dicarbonyl(cycloheptadienyl)(triphenyl phosphite)iron Hexafluorophosphate

[85956-40-7]  · C27H24F6FeO5P2  · Dicarbonyl(cycloheptadienyl)(triphenyl phosphite)iron Hexafluorophosphate  · (MW 660.27)

(synthesis of functionalized cycloheptadienes)

Physical Data: obtained as an amorphous powder.

Solubility: sol CH2Cl2, MeCN, acetone.

Form Supplied in: not commercially available.

Analysis of Reagent Purity: IR (MeCN) 2067, 2028 cm-1; 1H NMR (CD3CN) d 7.49 (15H, m, P(OPh)3), 6.36 (1H, t, J = 6.5 Hz, 3-H), 6.03 (2H, m, 2-H, 4-H), 4.92 (2H, m, 1-H, 5-H), 2.65 (2H, m, endo-6-H, endo-7-H), 1.80 (2H, m, exo-6-H, exo-7-H).

Preparative Methods: Triphenylmethyl Hexafluorophosphate (124 g) is dissolved in the minimum volume of dry CH2Cl2 and to that solution, dicarbonyl(cycloheptadiene)(triphenyl phosphite)iron1 (150 g) is added. The mixture is swirled to dissolve the complex and set aside at rt for 2 h. The product is precipitated by pouring the mixture into wet ether, collected by filtration, and washed thoroughly with wet ether to afford pure (1) (190 g, 99%). The corresponding tetrafluoroborate salt is prepared from dicarbonyl(h4-cycloheptatriene)(triphenyl phosphite)iron and Tetrafluoroboric Acid.2

Regio- and Stereocontrolled Functionalization of Cycloheptadiene.1,3

By reacting the dienyl complex (1) with a range of nucleophiles, a variety of substituted cycloheptadienes are obtained. The addition of nucleophile is stereospecific, trans to the Fe(CO)2P(OPh)3 group. The regioselectivity of the addition to the complex (1) is strongly dependent on the nature of the nucleophile, soft nucleophiles attacking C-1 and hard nucleophiles attacking C-2 of the dienyl ligand. For example, hard nucleophiles such as lithium or magnesium alkyls give predominant C-2 addition to give complexes (2) in good to excellent yield (eq 1), while organocuprate reagents (soft nucleophiles) result in predominant, in many cases exclusive, C-1 addition to give diene complexes (3) (eq 2).

The dienyl complexes also undergo very clean, high-yielding addition of stabilized enolates, NaCH(CO2Me)2, NaCH(COMe)CO2Me, NaCH(SO2Ph)CO2Me, and NaCH(CN)CO2Me, to give diene complexes (4) as the exclusive products (eq 3).

To expand the synthetic utility, the monosubstituted diene complexes can be converted to the dienyl complexes (5) with the triphenylmethyl carbocation (eq 4) and reacted with nucleophiles to give disubstituted cycloheptadienes. The reactions with (5) are stereospecific, regiospecific, and give high yields. For example, reactions of (5) with alkyllithium, Grignard reagents, and cuprates give products (6) of C-1 addition, cis to the already present substituent (eq 4). As expected, the complex (5) also reacts with stabilized enolates to give stereochemically defined disubstituted complexes (6e-h) in very high yield (eq 4).

The complex (1) is a better reagent for preparing functionalized cycloheptadiene than its tricarbonyl analog, where yields of the products are very low with very poor regioselectivities.

Stereocontrolled Multiple Functionalization of Cycloheptadiene.4

The complex (1) is also used for the preparation of stereocontrolled trisubstituted cycloheptadiene complex (10) (eq 5). Deprotonation of complex (1) provides the h4-triene complex (7) in quantitative yield. Hydroboration of the complex (7) gives a single alcohol (8) in 92% yield. The alcohol is converted to the ketone (9) in 81% yield by Swern oxidation. The ketone is used for the stereospecific synthesis of multiply functionalized cycloheptadiene complex (10) in two steps (eq 5).

Asymmetric Synthesis of Cycloheptadienes.5

The complex (1) is also used in the preparation of optically active mono- and disubstituted cycloheptadiene iron complexes with sulfoximine chiral auxiliaries (eq 6). The treatment of the enolate anion of ester (11) with (1) gives the diene complex (12) as a mixture of diastereomers (98-99% yield). The desulfonylation of (12) gives up to 50% ee of monoester (13) in 80-83% yield. The optically active monoester (13) is used for the preparation of optically active disubstituted dienes (14) in good yield (eq 6).

Synthesis of Precursors of Biologically Active Compounds.

Dimethylcycloheptadiene complex (6a) serves as an intermediate for the synthesis of (+)-Prelog-Djerassi lactonic acid (15) (eq 7).6 This lactone is isolated as a degradative product of methymycin and related compounds, narbomycin, picromycin, and neomethymycin.7 The racemic monoester complex (14a) has been utilized as an intermediate for the synthesis of precursor (16) of the antibiotic carbomycin B (eq 8).8 The monoester (14a) has also been used as an intermediate for the synthesis of the lactone (17), a subunit of the antibiotic tylosin (eq 9).6

1. Pearson, A. J.; Kole, S. L.; Ray, T. JACS 1984, 106, 6060.
2. Pearson, A. J.; Chen, B. JOC 1985, 50, 2587.
3. Pearson, A. J.; Kole, S. L.; Chen, B. JACS 1983, 105, 4483.
4. Pearson, A. J.; Chang, K. CC 1991, 394; JOC 1993, 58, 1228.
5. (a) Pearson, A. J.; Yoon, J. CC 1986, 1467. (b) Pearson, A. J.; Blystone, S. L.; Nar, H.; Pinkerton, A. A.; Roden, B. A.; Yoon, J. JACS 1989, 111, 134.
6. Pearson, A. J.; Lai, Y-S.; Lu, W.; Pinkerton, A. A. JOC 1989, 54, 3882.
7. (a) Anliker, R.; Drovnik, D.; Gable, K.; Heusser, H.; Prelog, V. HCA 1956, 39, 1785. (b) Djerassi, C.; Zderic, J. A. JACS 1956, 78, 6390.
8. Pearson, A. J.; Ray, T. TL 1986, 27, 3111.

M. Mahmun Hossain & Anjan K. Saha

University of Wisconsin-Milwaukee, WI, USA

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