Cyclopropanations palladium acetate

It was demonstrated that palladium acetate catalyzed cyclopropanation of methyl-enecyclopropanes is an effective method of preparation of spiropentane derivatives (equation 8 see also equation 36 below)9. 

CYCLOPROPANATION Palladium(II) acetate. Rhodium(III) porphyrins. Simmons-Smith reagent. Zinc. 

The ring expansion of the benzoxepinones 134 to benzoxocinones 136 involved a cyclopropanation with diazomethane in the presence of palladium acetate and a catalytic hydrogenation. The cleavage of the more labile internal bond in the cyclopropyl derivatives 135 leads to the eight-membered ketones 136 exclusively in excellent yields (90-95%). Reduction of ketones 136 with sodium borohydride affords the hydroxy derivatives 137 in a stereo-controlled manner (Scheme 34) <2002CC634>. 

Methylene ( CH2) generated photochemically or thermally from diazomethane is highly reactive and is prone to incur side reactions to a substantial extent. In order to avoid these undesirable complexities, the cyclopropanation of multiple bonds with diazomethane has usually been carried out under catalytic conditions The catalysts most frequently employed are copper salts and copper complexes as well as palladium acetate. The intermediate produced in the copper salt-catalyzed reactions behaves as a weak electrophile and exhibits a preference to attack an electron-rich double bond. It is also reactive enough to attack aromatic nuclei. In contrast, the palladium acetate-catalyzed decomposition of diazomethane cyclopropanates a,a- or a,jS-disubstituted a,jS-unsaturated carbonyl compounds in high yields (equation 47). The trisubstituted derivatives, however, do not react. The palladium acetate-catalyzed reaction has been applied also for the cyclopropanations of some strained cyclic alkenesstyrene derivatives and terminal double bondsHowever, the cyclopropanation of non-activated, internal double bonds occurs only with difficulty. The difference, thereby. 

A chiral oxazolidine prepared from a,j6-unsaturated aldehydes and ( —)- or (-l-)-ephedrine efficiently induced asymmetric cyclopropanation with excess of diazomethane in the presence of palladium acetate, e.g. formation of 24 from ( —)-ephedrine and ( )-cinnamaldehyde 24 was cyclopropanated to give 25 and the auxiliary removed giving... 

Upon Simmons-Smith cyclopropanation (CH2I2, Zn/Ag " or Zn/Cu ) vinylidenecyclo-propane gave a mixture of bicyclopropylidene (7) and dispiro[2.1,2.0]heptane (8). - An analogous reaction took place when 7-methylenedispiroheptane (9) was reacted with diiodo-methane and zinc-silver couple to give the trispiro[2.0.2.0.2.0]nonane (10) in quantitative yield.Small quantities of dispiro[2.1.2.0]heptane were isolated from the palladium acetate catalyzed reaction of vinylidenecyclopropane and diazomethane together with a variety of methylene insertion products. 

Palladium-based catalysts also bring about cyclopropanations in high-yield. With palladium acetate/CHjNj, styrene , unactivated terminal olefins strained olefins , 1,3-dienesan enamine , as well as a,3-unsaturated carbonyl compounds have been cyclopropanated (Table 1). Contrary to an earlier report, the reaction also works well with cyclohexene if the conditions are chosen appropriately it seems that the notniyst is rapidly deactivated in the presence of this olefin >. Trisubstituted a,p-unsaturated carbonyl compounds were found to be unreactive, and the same is true for the double bonds in diethyl fumarate, maleic anhydride, coumarin and 1,3-dimethyluracil. Whereas the latter two were totally unreactive, [3-1-2] cycloaddition of diazomethane gave pyrazolines in the former two cases. The last entry of Table 1 shows that an allyl alcohol function can still be cyclopropanated, but methylene insertion into the O—H bond is a competing process. 

CYCLOPROPANATION Copper-lsonitrile complexes. Cupric chloride. Diethylzinc-Bromoform-Oxygen. Palladium acetate. Titanium(IV) chloride-Lithium aluminum hydride. 

Whereas diazoacetic ester reacts with acrylonitriles at room temperature to give 2-pyrazolines (136), above 100 °C the cyclopropanes (138) are formed quantitatively, the 1-pyrazoline (137) being an intermediate. When the reaction is catalysed by palladium acetate, the oxazoles (139) are formed. ... 

Apart from routine applications to cyclopropane synthesis,the application of new catalysts to the decomposition of diazo-compounds has received considerable attention. The use of palladium acetate, originally reported in 1972 by Paulissen et o/., has been extended and applied to diazomethane and ethyl diazoacetate in the presence of aP-unsaturated carbonyl compounds. With a- and a-substituted aP-unsaturated ketones, stereospecific cis-addition occurs in excellent yields, but the catalyst proves to be ineffective with analogous trisubstituted olefins, as illustrated for the formation of (110) with diazomethane. The use of palladium chloride with the... 

Cyclopropanes and their derivatives are versatile building blocks in organic synthesis. They are also present in many natural products and frequently included as substituents in the structure of new biologically active substances. While cydopropylbo-ranes have long been described [34], it is only since an efficient access to the boronic esters was reported that they really attracted chemist s interest. In 1989, the first additions of carbenes, generated from diazo compounds and palladium acetate, to pina-col alkenylboronic esters were reported to give racemic mixtures of cyclopropyl-boronates (Scheme 9.15) [35]. 

More recendy, the reaction of dienylboronates with diazoalkanes in the presence of palladium acetate was described to afford regio-, chemo- and diastereoselectively the corresponding trisubstituted cyclopropanes (Scheme 9.18) [45]. 

Scheme 9.18 Cyclopropanation of dienylboronate using diazoalkanes in the presence of palladium acetate.

A convenient one-step preparation of monobromocyclopropanes (476) from olefins is lacking. These can now be obtained by reaction of the olefin with dibromomethane and sodium bis(trimethylsilyl)amide in pentane. Transition-metal-catalysed cyclopropanation of olefins can be effected with ethyl diazoacetate and palladium acetate under mild thermal conditions. 

By Cyclopropanation. Alkenes undergo a cyclopropanation reaction with diazo compounds (caution) such as diazomethane or ethyl diazoacetate in the presence of a catalytic amount of palladium acetate. With diazomethane, a selective cyclopropanation of terminal double bonds can be obtained (eq 52). ... 

Palladium acetate catalyzes cyclopropanation with diazomethane and aryldiazoacetate (Scheme 1.138) [203]. 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

The transition metal-catalyzed reaction of diazoalkanes with acceptor-substituted alkenes is far more intricate than reaction with simple alkenes. With acceptor-substituted alkenes the diazoalkane can undergo (transition metal-catalyzed) 1,3-dipolar cycloaddition to the olefin [651-654]. The resulting 3//-pyrazolines can either be stable or can isomerize to l//-pyrazolines. 3//-Pyrazolines can also eliminate nitrogen and collapse to cyclopropanes, even at low temperatures. Despite these potential side-reactions, several examples of catalyzed cyclopropanations of acceptor-substituted alkenes with diazoalkanes have been reported [648,655]. Substituted 2-cyclohexenones or cinnamates [642,656] have been cyclopropanated in excellent yields by treatment with diazomethane/palladium(II) acetate. Maleates, fumarates, or acrylates [642,657], on the other hand, cannot, however, be cyclopropanated under these conditions. 

The addition of different types of carbenes onto bicyclopropylidene (1) is a common method for the preparation of [3]triangulane derivatives as well as branched trianguianes and normally proceeds without complications (for a review see [77]). Thus, the cyclopropanation under Gaspar-Roth [60] or modified Simmons-Smith [111] conditions gave dispiro[2.0.2.1]heptane ([3]triangulane, 97) in 80 [105] and 15% yield [5], respectively (Scheme 23). The palladium(II) acetate-catalyzed cycloprop anation of 1 with diazomethane, however, gave a number of products resulting from insertion of one or more than one methylene units into an initially formed palladacyclobutane 115 [112,113] (Scheme 23). 

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. 

The rhodium(II) catalysts and the chelated copper catalysts are considered to coordinate only to the carbenoid, while copper triflate and tetrafluoioborate coordinate to both the carbenoid and alkene and thus enhance cyclopropanation reactions through a template effect.14 Palladium-based catalysts, such as palladium(II) acetate and bis(benzonitrile)palladium(II) chloride,l6e are also believed to be able to coordinate with the alkene. Some chiral complexes based on cobalt have also been developed,21 but these have not been extensively used. 

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