From diazo esters

Doyle s rhodium(n) carboxamidate complexes are undisputedly the best catalysts for enantioselective cyclizations of acceptor-substituted carbenoids derived from diazo esters and diazoacetamides, displaying outstanding regio- and stereocontrol.4 These carboxamidate catalysts consist of four classes of complexes pyrrolidinones... 

The intramolecular reaction of the carbene from diazo ester 280, which contains a 1,3-diene moiety in the ester group and a double bond adjacent to the carbene center, leads to the formation of a substituted 1,2-divinyl-cyclopropane, whose CIS isomer then undergoes a Cope rearrangement to give substituted cycloheptadiene. In such a way, bicyclic 281 and tricyclic 282 y-lactones with a neighboring seven-membered carbocycle have been obtained (89JOC930). 

The oxepino[2,3-d]isoxazol system 408 was prepared in 77% yield from diazo ester 409 and DMAD with a rhodium(II) acetate catalyst. The transient furoisoxazole 410 undergoes 1,5-electrocyclization to a carbene, which yields the final products via reaction with DMAD followed by a series of consecutive transformations (91TL1161). 

Prepared in this manner was ethyl cis-4-methyl-3-[(E)-2-phenylvinyl]cyclohepta-1,5-diene-I-carboxylate (22, = r2 = r3 = = H R5 = Me R = CH = CHPh), from diazo ester 21 (R = CH = CHPh ... 

The use of silyl ethers also provided a good glimpse into the steric effects of the C-H insertion [98], Relative rates were obtained for insertion a to the oxygen atom in silyl protected n-butanol. It was found that the reaction rate increased dramatically as the size of the silyl protecting group decreased, with a 100-fold rate difference between TBDPS and TMS. Complementary steric and electronic effects were observed with the tetralkoxy silane substrates [97,98], hi competition experiments, it was found that the carbenoid derived from diazo ester 99 reacted solely with tetraethoxy silane 123 to form product 126, and not the corresponding tetramethoxy or tetraisopropoxy derivatives 124 or 125 (Scheme 28). Thus, the secondary C-H bonds appear to possess the right balance between steric and electronic requirements for the insertion. 

From Diazo Compounds via 1,3-Dipolar Cycloaddition. This method has been utilized widely in heterocychc chemistry. Pyrazohne (57) has been synthesized by reaction of ethyl diazoacetate (58) with a,P-unsaturated ester in the presence of pyridine (eq. 12) (42). 

The BF3 Et20-catalyzed aziridination of compounds 47 (Scheme 3.15) with a diazo ester derived from (R)-pantolacetone gave aziridine-2-carboxylates 48 [59]. The reaction exhibited both high cis selectivity (>95 <5) and excellent diastereose-lectivity. Treatment of a-amino nitrile 49 (Scheme 3.16) with ethyl diazoacetate in the presence of 0.5 equivalent of SnCl4 afforded aziridines 50 and 51 in 39% yield in a ratio of 75 25 [60]. 

The starting diazo esters 110 were prepared by diazo transfer from the corresponding malonate esters 109. A selection of chiral Hgands in conjunction with 2mol% (with respect to the diazo compound) of [Cu(OTf)2] in (CH2C1)2 was then examined at 65 °C (Scheme 31). All of the Hgands tested were sufficiently reactive to produce diazo decomposition at 65 °C, although the yields of cyclopropanation products were quite variable. Even tertiary... 

The insertion reaction can be used to form lactones from -diazo-(J-keto esters. 

The combined ether solutions are then subjected to distillation at 20° or below under the vacuum obtainable from a water pump until all the ether is removed. Prolonged distillation results in decomposition of the diazo ester and in a decreased yield. The yellow residual oil is practically pure ethyl diazoacetate and is satisfactory for most synthetic purposes (Note 3). The yield is about 98 g. (85%) (Notes 4 and 5). 

From ref. 64 b Reaction conditions 22 °C molar ratio 3000 (olefin)/l(catalyst)/200 (diazo ester) c 54% isolated yield reported in reference 70. Reaction conditions room temp. molar ratio 7400 (olefin)/l(catalyst)/1020(diazo ester). 

It has been pointed out earlier that the anti/syn ratio of ethyl bicyclo[4.1,0]heptane-7-carboxylate, which arises from cyclohexene and ethyl diazoacetate, in the presence of Cul P(OMe)3 depends on the concentration of the catalyst57). Doyle reported, however, that for most combinations of alkene and catalyst (see Tables 2 and 7) neither concentration of the catalyst (G.5-4.0 mol- %) nor the rate of addition of the diazo ester nor the molar ratio of olefin to diazo ester affected the stereoselectivity. Thus, cyclopropanation of cyclohexene in the presence of copper catalysts seems to be a particular case, and it has been stated that the most appreciable variations of the anti/syn ratio occur in the presence of air, when allylic oxidation of cyclohexene becomes a competing process S9). As the yields for cyclohexene cyclopropanation with copper catalysts [except Cu(OTf)2] are low (Table 2), such variations in stereoselectivity are not very significant in terms of absolute yields anyway. 

Baldwin et al. have used the same catalyst/diazo ester combination for the synthesis of optically active deuterated phenylcyclopropanes (Scheme 28) 197). From cis-1,2-dideuteriostyrene, d/-menthyl a-deuteriodiazoacetate and (+)-195d, the cis- and mnw-cyclopropanes 196 were obtained, both with 90% optical purity. The dominant enantiomer of trans-196 had (+)-(15, IS, 35) configuration. Analogously, the cyclopropanes c -198 and trans-198, obtained from styrene, d/-menthyl a-deuteriodiazoacetate and (+)-195d with subsequent transesterification of cisjtrans-197, had optical purities of 86 and 89%, respectively. The major optical isomer of cis-198 had (IS, 2R) configuration, that of trans-198 (IS, 2S) configuration. 

Use of a chiral diazo ester proved less rewarding in terms of enantioselective cyclopropanation. Only very low enantiomeric excesses were obtained when styrene was cyclopropanated with the carbenoid derived from diazoacetic esters 219 bearing a chiral ester residue 214). 

Reactions of carbenoids with 4-thio-substituted 2-azetidinones have attracted much interest recently. Insertion of the carbene unit derived from diazomalonic esters 297-34°> or ethyl diazo(diethoxyphosphoryl)acetate 340 into the C4—S bond of simple P-lactams 353 and 354 took place irrespective of whether a N—H or a N—R... 

---