Diazoester cyclopropanation intramolecular

The use of chiral additives with a rhodium complex also leads to cyclopropanes enantioselectively. An important chiral rhodium species is Rh2(5-DOSP)4, which leads to cyclopropanes with excellent enantioselectivity in carbene cyclopro-panation reactions. Asymmetric, intramolecular cyclopropanation reactions have been reported. The copper catalyzed diazoester cyclopropanation was reported in an ionic liquid. ° It is noted that the reaction of a diazoester with a chiral dirhodium catalyst leads to p-lactones with modest enantioselectivity Phosphonate esters have been incorporated into the diazo compound... 

Intramolecular cyclopropanation using diazoesters is a powerful synthetic tool. Diazoesters are readily prepared from the corresponding alcohol via House s methods56-57. Numerous examples using the application of this transformation in synthesis have been reported. These include the potent synthetic pyrethroid NRDC 182 (22)58, (1 R)-( )-cis-chrysanthemic acid (23)59, the highly strained bicyclic system 2460, antheridic acid 2561,62 and cycloheptadiene 26 (equations 33-37). 

In intramolecular cyclopropanation, Doyle s catalysts (159) show outstanding capabilities for enantiocontrol in the cyclization of allyl and homoallyl diazoesters to bicyclic y-and <5-lactones, respectively (equations 137 and 138)198 205. The data also reveal that intramolecular cyclopropanation of Z-alkenes is generally more enantioselective than that of E-alkenes in bicyclic y-lactone formation198. Both Rh(II)-MEPY enantiomers are available and, through their use, enantiomeric products are accessible. In a few selected cases, the Pfaltz catalyst 156 also results in high-level enandoselectivity in intramolecular cyclopropanation (equation 139)194. On the other hand, the Aratani catalyst is less effective than the Doyle catalyst (159) or Pfaltz catalyst (156) in asymmetric intramolecular cyclo-propanations201. In addition, the bis-oxazoline-derived copper catalyst 157b shows lower enantioselectivity in the intramolecular cyclopropanation of allyl diazomalonate (equation 140)206. 

The allylsilyl-substituted diazoester 1, while stable thermally up to 140 C and towards Rh2(pfb)4, undergoes a photochemically induced intramolecular cyclopropanation reaction leading to the rather strained 2-silabicyclo[2.1.0]butane 17 in surprisingly good yield [9]. 

Cyclopropanation of olefins with diazoesters can be performed intramolecularly as in the formation of a cyclopropyllactone (129) from a cyclohexenyl diazoester in the presence of bis-(iV-r-butylsalicylaldiminato) copper(II) (equation 31) Next to diazoesters other... 

The most significant breakthrough in this area was Doyle s introduction of chiral rhodium (II) carboxamidates (Fig. 4). These catalysts show an exceptional ability to direct highly enantioselective intramolecular cyclopropanation of al-lylic and homoallylic diazoesters, Eq. (19), and diazoamides, Eq. (20). 

The work of Martin and co-workers [49] has shown that excellent diastereo-control can be achieved in cyclopropanation of single enantiomers of chiral secondary diazoesters by catalyst matching. Thus, while Rh2(5R-MEPY)4 and the (S)-diazoester in Eq. (27) react to afford a 37 63, endo exo mixture of diastereoi-someric cyclopropanes, the 5S-MEPY catalyst affords a >95 <5 ratio of the same products. A final illustrative example of the versatility of this methodology is shown in Eq. (28). Here diazoacetates of prochiral divinyl carbinols undergo intramolecular cyclopropanation catalysed by Rh2(5S-MEPY)4 with exceptional enantiocontrol [49]. 

Enantiocontrol in intramolecular cyclopropanation reactions of diazoacetamides has been developed to levels comparable with those now accessible with diazoesters. Several substituent variations in Eq. (20) are summarized in Table 3, which reveals examples where ee s exceed 90%. In general diazoamides have a conformational feature which differs from their diazoester counterparts, namely, the relatively slow syn-anti isomerization by rotation about the N-CO bond. If the interconversion of (18) and (19) or their respective metal carbenes is slow relative to the reaction timescale [50], only isomer (18) can lead to intramolecular cyclopropanation. However, an alternative process to which (18) is prone un-... 

Rhodium complexes generated from A-functionalized (S)-proline 3.60 [933, 934, 935] or from methyl 2-pyrrolidone-5-carboxylates 3.61 [936, 937, 938] catalyze the cyclopropanation of alkenes by diazoesters or -ketones. Diastereoisomeric mixtures of Z- and E-cydopropylesters or -ketones are usually formed, but only the Z-esters exhibit an interesting enantioselectivity. However, if intramolecular cyclopropanation of allyl diazoacetates is performed with ligand 3.61, a single isomer is formed with an excellent enantiomeric excess [936,937], The same catalyst also provides satisfactory results in the cyclopropanation of alkynes by menthyl diazoacetate [937, 939] or in the intramolecular insertion of diazoesters into C-H bonds [940]. 

---