Insertion diazo

Rhodium-catalyzed diazo insertions, known since 1976, have been extensively reviewed39. The first report40 indicated that rhodium acetate efficiently catalyzes diazo insertion into an alkene, giving the cyclopropane. Rhodium-catalyzed intramolecular C-H insertion was first observed by workers at Beecham Pharmaceuticals, who reported that 1, on exposure to a catalytic amount of rhodium acetate, cyclizes cleanly to the /1-lactam41. This approach to thienamycin derivatives has been developed further by these workers42,43. 

An Gt-diazo ketone or ester such as (144) will, via metal-mediated nitrogen loss, insert into an alkene to make the corresponding cyclopropane (145 equation 58). As illustrated, alkene geometry is retained, as would be expected for a concerted process. Cyclopropane construction by diazo insertion is reviewed in detail elsewhere in these volumes. 

Hubert in 1976 reported that rhodium acetate efficiently catalyzes diazo insertion into an alkene, to give the cyclopropane. In 1979, Southgate and Ponsford reported that rhodium acetate also catalyzes diazo insertion into a C—H bond. Prompted by these studies, Wenkert then demonstrated that cyclization of (58) to (59) proceeded much more efficiently with the rhodium carboxylates than it had with copper salt catalysis (equation 23). ... 

Closely related to diazo insertions, the work of Lebel using TMS-N2 in the presence of [(IPr)CuCl] for ketone methylenation should also be mentioned. ... 

A more direct synthesis makes use of the L-serine hydroxamate (20) (18). Cyclisation of chloride (21) followed by removal of the iV-substituent afforded the P-lactam (22). Progression to (23) necessitated introduction of the protected phenylglycyl residue either by alkylation or diazo-insertion. Deprotection then led to 3-ANA in good overall yield. 

Phenyldiazonium salts react with malonaldioxime to produce a 2-isoxazoline (7 IGEPl 920245), and the diazo ketone (484) when photolyzed gave a mixture of 2-isoxazoline and an isoxazole by a 1,5 carbon-hydrogen insertion. A phenyl migration was apparently not involved (Scheme 124) (66CC689). 

A final method of /3-lactam 3,4-bond formation which has found fairly wide application is based on carbenlc insertion (78T1731 p. 1739). The carbenic centre can be generated by photolysis of a diazo compound as in the case of (158) (72JA1629, 79CC846) or from organometalllc precursors, for example (159) (71ACS1927). 

A melting point test has been described for diazo compounds. The first 1 mm of a melting-point tube filled with c. 10 mg of test compound is inserted in a melting-point apparatus heated at 270°C. Once decomposition starts, the tube is removed. The decomposition rapidly propagates through the entire mass for unstable diazo compounds no such propagation is reported for stable versions. 

The Bamford-Stevens decomposition of tosylhydrazones by base has been applied to steroids, although not extensively. It has been demonstrated that the reaction proceeds via a diazo compound which undergoes rapid decomposition. The course of this decomposition depends upon the conditions in proton-donating solvents the reaction has the characteristics of a process involving carbonium ions, and olefins are formed, often accompanied by Wagner-Meerwein-type rearrangement. In aprotic solvents the diazo compound appears to give carbene intermediates which form olefins and insertion products ... 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

The diazo function in compound 4 can be regarded as a latent carbene. Transition metal catalyzed decomposition of a diazo keto ester, such as 4, could conceivably lead to the formation of an electron-deficient carbene (see intermediate 3) which could then insert into the proximal N-H bond. If successful, this attractive transition metal induced ring closure would accomplish the formation of the targeted carbapenem bicyclic nucleus. Support for this idea came from a model study12 in which the Merck group found that rhodi-um(n) acetate is particularly well suited as a catalyst for the carbe-noid-mediated cyclization of a diazo azetidinone closely related to 4. Indeed, when a solution of intermediate 4 in either benzene or toluene is heated to 80 °C in the presence of a catalytic amount of rhodium(n) acetate (substrate catalyst, ca. 1000 1), the processes... 

Intermediate 37 can be transformed into ( )-thienamycin [( )-1)] through a sequence of reactions nearly identical to that presented in Scheme 3 (see 22— 1). Thus, exposure of /(-keto ester 37 to tosyl azide and triethylamine results in the facile formation of pure, crystalline diazo keto ester 4 in 65 % yield from 36 (see Scheme 5). Rhodium(n) acetate catalyzed decomposition of 4, followed by intramolecular insertion of the resultant carbene 3 into the proximal N-H bond, affords [3.2.0] bicyclic keto ester 2. Without purification, 2 is converted into enol phosphate 42 and thence into vinyl sulfide 23 (76% yield from 4).18 Finally, catalytic hydrogenation of 23 proceeds smoothly (90%) to afford ( )-thienamycin... 

Ring enlargement via an insertion of a carbene generated in the a-position to the ring is an established method and has also been applied to the synthesis of oxepins. The ()3-allylpalladium chloride catalyzed decomposition of substituted ethyl diazo(4/7-pyran-4-yl)acetates in benzene at room temperature gives ethyl oxepin-4-carboxylates 1 in excellent yield.190 The ester function can be replaced by the phosphonate group and other P = 0-functions (see Houben-Weyl,... 

The thermal decomposition of diazo(phenylsulfonyl)methane 223 under a nitrogen atmosphere generates phenylsulfonylcarbene which is trapped by olefin such as cyclohexene to give norcaranes 224 and 225 (equation 138)132. No cycloheptatriene derivative is isolated from the thermolysis of223 in benzene133. In contrast, intramolecular insertion of sulfonylcarbenes into a benzene ring is observed in the thermolysis of 226 (equation 139)134. 

Abstract The dirhodium(II) core is a template onto which both achiral and chiral ligands are placed so that four exist in a paddle wheel fashion around the core. The resulting structures are effective electrophilic catalysts for diazo decomposition in reactions that involve metal carbene intermediates. High selectivities are achieved in transformations ranging from addition to insertion and association. The syntheses of natural products and compounds of biological interest have employed these catalysts and methods with increasing frequency. 

Muller et al. have also examined the enantioselectivity and the stereochemical course of copper-catalyzed intramolecular CH insertions of phenyl-iodonium ylides [34]. The decomposition of diazo compounds in the presence of transition metals leads to typical reactions for metal-carbenoid intermediates, such as cyclopropanations, insertions into X - H bonds, and formation of ylides with heteroatoms that have available lone pairs. Since diazo compounds are potentially explosive, toxic, and carcinogenic, the number of industrial applications is limited. Phenyliodonium ylides are potential substitutes for diazo compounds in metal-carbenoid reactions. Their photochemical, thermal, and transition-metal-catalyzed decompositions exhibit some similarities to those of diazo compounds. 

McKervey and Ye have developed chiral sulfur-containing dirhodium car-boxylates that have been subsequently employed as catalysts for asymmetric intramolecular C-H insertion reactions of y-alkoxy-ot-diazo-p-keto esters. These reactions produced the corresponding ci -2,5-disubstituted-3(2H)-furanones with diastereoselectivities of up to 47% de. Moreover, when a chiral y-alkoxy-a-diazo-p-keto ester containing the menthyl group as a chiral auxiliary was combined with rhodium(II) benzenesulfoneprolinate catalyst, a considerable diastereoselectivity enhancement was achieved with the de value being more than 60% (Scheme 10.74). 

Scheme 10.74 Rh-catalysed intramolecular C-H insertions of y-alkoxy-a-diazo-P-keto esters with sulfonamide ligands.

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