Carbene with rhodium compounds

There are several examples of intramolecular reactions of monocyclic /3-lactams with carbenes or carbenoids most of these involve formation of olivanic acid or clavulanic acid derivatives. Thus treatment of the diazo compound (106) with rhodium(II) acetate in benzene under reflux gives (107), an intermediate in the synthesis of thienamycin (80H(14)1305, 80TL2783). 

In addition to conventional generation of carbenes from nitrodiazo compounds (22) (79), target intermediates C can be prepared by oxidation of functionalized AN CH2XNO2 with phenyliodonium diacetate. The reactions of Rhodium intermediates with certain olefins afford the corresponding cyclopropanes (23). The cycloaddition reaction was performed in the presence of a catalyst. (The successful synthesis of nitrocyclopropanes from trinitromethane derivatives and nitroacetic ester was also documented (81)). 

One of the key steps in building the fused ring involves the reaction of the activated acetoacetate methylene group in that compound with toluenesulfonyl azide to give the diazo intemediate (12-1). Treatment of that product with rhodium acetate leads to a loss of nitrogen with the consequent formation of carbene (12-2) this inserts into the adjacent amide N—H bond to form a five-membered ring and thus the carbapenem (12-3) [15]. The first step in the incorporation of the thioenol function consists in the conversion of the ketone to the enol phosphate derivative... 

Carbene insertion into the O-H bond of alcohols is especially versatile for the formation of ethers. Diazomethane has been used, but other diazo compounds have also been used even those with fluorine in the carbene species. Rhodium acetate seems to be the catalyst of choice for the decomposition of a-diazo esters. Different alcohols 21 react with compound 22 to give fluorinated ethers 23 in good yield. ... 

Ylide generation from diazo compounds by reaction of carbenoids is a better method than photochemical or thermal dediazoniation in the presence of organic substrates containing heteroatoms, because these dediazoniations without metal catalysis yield, in most cases, not very selective carbenes. Here again, the copper-catalyzed route is in most cases inferior to that with rhodium catalysts. The diazoketo ester with a terminal thioalkyl group (8.145) can be obtained from the... 

Cyclopentanones and other five-membered ring-containing compounds can be prepared readily by intramolecular C—H insertion of carbenes derived from diazocarbonyl compounds and rhodium(n) acetate. Thus, treatment of the diazoketone 99 with rhodium(II) acetate gave the C—H insertion product 100, used in a synthesis of the toxin muscarine (4.78). 

The addition of a diazocarbonyl compound to an alkene with metal catalysis is an effective method for the formation of cyclopropanes, as discussed above. However, direct addition to aldehydes, ketones or imines is normally poor. Epoxide or aziridine formation can be promoted by trapping the carbene with a sulfide to give an intermediate sulfur ylide, which then adds to the aldehyde or imine. For example, addition of tetrahydrothiophene to the rhodium carbenoid generated from phenyldiazomethane gave the ylide 131, which adds to benzaldehyde to give the trans epoxide 132 in high yield (4.104). On formation of the epoxide, the sulfide is released and hence the sulfide (and the rhodium complex) can be used in substoichiometric amounts. 

By analogy with the rhodium carbene intermediate proposed in the C H insertion reaction with diazo compounds, C— H amination is believed to proceed via a rhodium nitrene species, although such an intermediate has never been characterized. However, as chiral dimeric rhodium complexes lead to the formation of enantioen-riched amination products, it suggests that the metal center is closely associated with the reactive nitrogen during the C—H insertion step. Both a rhodium nitrene or rhodium phenyliminoiodinane species may be involved (Figure 5.2). 

Diazoketones also undergo macrocyclic aromatic cycloaddition reactions. Decomposition of 108 with rhodium(II) prefluorobutyrate yields aromatic cycloaddition products 109 and 110 in 30% and 9% yield, respectively. When cycloheptatriene 109 is exposed to neutral alumina, isomerization to 111 occurs. It is interesting that the 1,4-isomer 110 is inert to rearrangement on both silica and alumina. The ability to formally connect a carbene to a remote aromatic ring provides new opportunities for the construction of macrocyclic compounds. 

Rhodium compounds easily react with diazomethane to afford the carbene complex as shown in eq. (18.28) [50-52]. 

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