Palladium steroid preparation

Use of DMF as a solvent for the oxidation of l-o1efins has been reported by Clement and Selwitz. The method requires only a catalytic amount of PdCl2 and gives satisfactory yields under mild conditions. A small amount of olefin migration product is the only noticeable contaminant in the cases reported. The procedure can be applied satisfactorily to various 1-olefins with other functional groups. This useful synthetic method for the preparation of methyl ketones has been applied extensively in the syntheses of natural products such as steroids,macrolides, dihydrojasmone, and muscone. " A comprehensive review article on the palladium-catalyzed oxidation of olefins has... 

An early example of this strategy is the palladium black catalyzed conversion of (Z)-2-buten-l,4-diol with primary amines (cyclohexyl amine, 2-aminoethanol, -hexyl amine, aniline) at 120 °C to give A-substituted pyrroles in 46-93% yield [119]. Trost extended this animation to the synthesis of a series of AT-benzyl amines 169 from the readily available a-acetoxy-a-vinylketones 168 [120]. This methodology allowed for the facile preparation of pyrrolo-fused steroids. 

Intermolecular cyclopropanation of diazoketones is an effective method in organic synthesis. Wenkert and coworkers have applied this methodology to the synthesis of a substantial number of cyclopropane adducts 2868, 2969 and 307° which are synthetic intermediates in the preparation of natural products (equations 41—43). Copper catalysts were chosen for these transformations. Another interesting application of intermolecular cyclopropanation is to be found in Daniewski s total synthesis of an aromatic steroid. Palladium(II) acetate catalysed decomposition of 4-bromo-l-diazo-2-butanone in the presence of m-methoxystyrene was used to give the cyclopropyl ketone 31 which was a key intermediate in the total synthesis (equation 44)71. 

Several tr-allyl palladium chloride complexes have been prepared from steroidal olefins. Reaction of cholest-4-ene (65), for example, with bis(benzonitrile)palladium dichloride produced dimeric complexes of structures (66) and (67) (76). 

A new synthetic method for steroids has been developed using a butadiene dimer (66) as a building block and the palladium-catalyzed oxidation as the key reaction. 3-Acetoxy-l,7-octadiene (66), prepared by the palladium-catalyzed reaction of butadiene with acetic acid, is hydrolyzed and oxidized to... 

A new synthetic method for steroids has been developed using a butadiene dimer (66) as a building block and the palladium-catalyzed oxidation as the key reaction.3-Acetoxy-l,7-octadiene (66), prepared by the palladium-catalyzed reaction of butadiene with acetic acid, is hydrolyzed and oxidized to l,7-octadien-3-one (67) in high yield. The enone (67) is a very useful reagent for bisanellation because its termiiud double bond can be regarded as a masked ketone which can be readily unmasked by the palladium catalyst to form the l,S-diketone (68) after Michael addition at the enone moiety of (67 Scheme 20). Thus, the enone (67) is the cheapest and most readily available bisanellation reagent, permitting a simple total synthesis of steroids. 

Miscellaneous Methods of Preparing Phosphines. Palladium-catalysed formation of phosphorus-carbon bonds continues to be developed as a useful route to organophosphines. The reactions of primary or secondary phosphines with aryl- or vinyl-halides in the presence of a palladium catalyst, usually palladium acetate or a zerovalent palladium-phosphine complex, have been used in the synthesis of steroidal phosphines, e.g., (128), the cationic diphosphine system... 

Asymmetric hydrocarboxylation of styrene and aliphatic alkenes with palladium(II) chloride in the presence of the steroidal phosphanes (+)-DICOL and (—)-DIOCOL (prepared from cholesterol) show remarkable catalytic activity and very high regioselectivity, but only poor stereoselectivities21, 22. Optical yields of up to 12.5% ee are obtained in asymmetric hydrocar-boxylations using DIOCOL. The results obtained with DICOL and DIOCOL have been compared with the inductions obtained with Diop. 

As vinyl triflates can be easily prepared from the corresponding ketones or aldehydes, which are abundant and wildly available, the use of vinyl triflates as starting materials in total synthesis has attracted a lot of attention [27—39]. Murai s group synthesized glycinoeclepin A by palladium-catalyzed carbonylation, using vinyl triflate as the key intermediate [40, 41]. Holt and colleagues prepared bioactive steroids [42, 43], whUe McDonald s team prepared cephalosporins [44]. 

Tietze and his co-workers prepared estradiol and a number of other steroid derivatives using a compact sequential Heck reaction approach. Compound 51 was obtained from the known Hajos-Wiechert ketone derivative 50 in 3 steps. Heck reaction with palladium(II) acetate in the presence of triphenylphosphine gave intermediate 52, the precursor of the second Heck reaction. Additional steps converted steroid analog 53 into estradiol (54). 

N,N-DimethylformamidelDimethyl Sulfate is another mild acetalization catalyst. Metal catalysts, such as Rh complexes and Palladium on Carbon have also been used effectively (eqs 9 and 10). Ion-exchange resins offer significant advantages for the preparation of sensitive steroid acetals (eq 11). An especially convenient method involves running a solution of the ketone and ethylene glycol through a column of Amberlyst. Zeolites have also been used to prepare acetals. ... 

Palladium-mediated cross-coupling of 2-pyrone-5-boronate (63), prepared by coupling of 5-bromo-2-pyrone with pinacol borane (30), with a range of androster-one-derived alkenyl triflates 64 affords bufadienolide type steroids 65 in high yields (Scheme 3.29) [47]. 

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