Cyclopropane ring diazo compounds

In the first edition (CHEC-I) <84CHEC-I(4)74i> it was mentioned that three types of products were identified in the reaction of thiophenes with carbenes generated from diazo compounds, cyclopropanes, 5,C-ylides, and 2-substituted thiophenes, corresponding to carbene attack at the 2,3-double bond, ring sulfur or at C-2, respectively. However, it now appears very likely that the... 

These results can be interpreted in terms of competition between recombination of the diradical intermediate and conformational equilibration, which would destroy the stereochemical relationships present in the azo compound. The main synthetic application of azo compound decomposition is in the synthesis of cyclopropanes and other strained-ring systems. Some of the required azo compounds can be made by 1,3-dipolar cycloadditions of diazo compounds (see Section 6.2). 

It should be noted, however, that the 1,3-dipolar cycloaddition chemistry of diazo compounds has been used much less frequently for the synthesis of natural products than that of other 1,3-dipoles. On the other hand, several recent syntheses of complex molecules using diazo substrates have utilized asymmetric induction in the cycloaddition step coupled with some known diazo transformation, such as the photochemical ring contraction of A -pyrazolines into cyclopropanes. This latter process often occurs with high retention of stereochemistry. Another useful transformation involves the conversion of A -pyrazolines into 1,3-diamines by reductive ring-opening. These and other results show that the 1,3-dipolar cycloaddition chemistry of diazo compounds can be extremely useful for stereoselective target-oriented syntheses and presumably we will see more applications of this type in the near future. 

The enol acetate moiety in diketene can be utilized for cyclopropane formation. Unfortunately, with most diazo compounds, yields are rather moderate 29), and therefore the synthetic value of methods developed on this basis is restricted. As exemplified by the ethyl diazoacetate adduct 44 (Scheme 4) the ring opening of this masked tricarbonyl compound can lead to different classes of acyclic or cyclic products. The outcome of these reactions depends on the conditions employed. They simultaneously transform the P-ketoester unit present in 44 29b). 

The catalytic cycle proposed for the rhodium-porphyrin-based catalyst is shown in Fig. 7.18. In the presence of alkene the rhodium-porphyrin precatalyst is converted to 7.69. Formations of 7.70 and 7.71 are inferred on the basis of NMR and other spectroscopic data. Reaction of alkene with 7.71 gives the cyclopropanated product and regenerates 7.69. As in metathesis reactions, the last step probably involves a metallocyclobutane intermediate that collapses to give the cyclopropane ring and free rhodium-porphyrin complex. This is assumed to be the case for all metal-catalyzed diazo compound-based cyclo-propanation reactions. 

Heating of 2//-l-benzothiete 697 and a diazo compound in the presence of Rh2(OAc)4 as a catalyst yields 2,3-dihydro-benzo[3]thiophene 700, which is oxidized to afford thiophene 701. The mechanism probably involves the initial formation of thiirane 698 or cyclopropane 699 followed by its ring enlargement with a [1.3] shift (Scheme 105) <1995TL6047>. 

Another cyclopropanation procedure that is quite general involves the use of Rh-carbene complexes, which can act catalytically to effect ring formation. Scheme 10.7 shows some of the details of this method. Ccaibene is derived from corresponding diazo compounds, which were traditionally used directly as sources of free carbenes. The scheme includes a catalytic cycle for conversion of the diazo compound to the Rh-carbene complex, which then delivers Ccarbene to the alkene. Transfer of Ccaibene regenerates an active catalyst that can react with another mole of diazo compound. The detailed mechanism of step c in the cycle resembles path b from Scheme 10.6. 

The rhodiumcarbene intermediate, which is believed to be the active species in rhodium acetate catalyzed cyclopropanations with diazo compounds, shows electrophilic reactivity. Thus, diazopropenes preferentially add to electron-rich alkenes, demonstrated by the reaction of 3-diazo-l,l-dichloropropene (15) with 2-trimethylsiloxybuta-l,3-diene (16) . A mixture of Z-configurated divinylcyclopropanes 17 and rearranged dienones 18 was obtained (see also Section 1. B.2.4.5.1. for further examples of the formation of seven-membered rings such as 18). 

Phenyl(trimethylsilyl)carbene can be generated by gas-phase pyrolysis of phenyl(trimethyl-silyl)diazomethane (1) at 500 °C (see Houben-Weyl Vol. El9b, p 1427). An attempt to trap this carbene with 2,3-dimethylbuta-l,3-diene furnished cyclopropane 3 only in trace amounts besides products 2, 4, and 5. Cyclopropane 3 can be prepared independently and in better yield by photolyzing the diazo compound in the presence of the butadiene. Thermally induced ring expansion of 3 provides cyclopentene 4, a fact that explains the low yield found under pyrolysis conditions. 

Substitution at the cyclopropane ring is also observed when diazocyclopropane reacts with d -20-oxosteroids. ° From pregna-4,16-diene-3,20-dione the major product (25%) was the corresponding dihydro[17a,16-c]pyrazole 3 which, however, reacted further to a significant extent and gave 4 (19%) and 5 (3%). When 3/J-acetoxypregna-5,16-dien-20-one was exposed to diazocyclopropane under the same conditions two products resulted the main product 6 was isolated in 64% yield, but in addition 7 was obtained in 15% yield. The latter product results when 6 is attacked by the diazo compound at the carbonyl group. 

Cyclopropanation of dienes 90 or 94 with 3,3-dichlorodiazopropene (91b) or the parent diazo compound 91 a (X = h) in the presence of dirhodium tetraacetate leads to a mixture of the rearranged fused eyeloheptadienes 93 and 96 and the stable tra .v-l,2-divinylcyclopropanes 92 and 95. The trans- 1,2-divinyl derivatives can be transformed to the seven-meinbered ring by heating to 110 °C854. 

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