Lactams carbene complex reactions

Silylketenes in formation of (3-lactones and (3-lactams 98JCS(P1)2105. Syntheses of (3-lactams, (3-lactones, and 1,3- and 1,4-diazetidinediones by pho-tochemically induced cycloaddition reactions of chromium carbene complexes with imines, aldehydes, and azo compounds 97T4105. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

The usefulness of this reaction for the preparation of heterocycles under mild conditions became apparent in 1978, when chemists from Merck, Sharp Dohme reported the synthesis of bicyclic 3-lactams by intramolecular carbene N-H insertion [1179]. Intramolecular N-alkylation of P-lactams by carbene complexes is one of the best methods for preparation of this important class of antibiotic and many P-lactam derivatives have been prepared using this methodology [1180 -1186] (Table 4.11). Intramolecular N-H insertion can also be used to alkylate amines [1187-1189], y-lactams [1190], and carbamates [1191-1193] (Table 4.11). 

Scheme 41. Reactions of heterocycles 25, 121 with Fischer carbene complexes as a synthetic approach to bicyclic j0-lactams 122-124 [26,33,59]...

The photochemical reaction of alkoxychromium(0)carbene complexes and ferrocene mono- and disubstituted imines have been reported to form 2-azetidinones having one or two ferrocene moieties in good yields [136]. The chromium(0) carbene complex reacted smoothly with ferrocene imines that allowed to place ferrocene substituents at the N-l, and the C-4, or simultaneously at the N-l and the C-4 positions of the (3-lactam ring, with cis stereoselectivity (Scheme 71). 

Pyridone is O-alkylated more readily than normal amides, because the resulting products are aromatic. With soft electrophiles, however, clean N-alkylations can be performed (Scheme 1.7). The Mitsunobu reaction, on the other hand, leads either to mixtures of N- and O-alkylated products or to O-alkylation exclusively, probably because of the hard, carbocation-like character of the intermediate alkoxyphosphonium cations. Electrophilic rhodium carbene complexes also preferentially alkylate the oxygen atom of 2-pyridone or other lactams [20] (Scheme 1.7). 

Besides the thermal reactions of Fischer car-benes, photochemical transformations of such complexes also deserve attention. Since the discovery of McGuire and Hegedus [4] in the early 1980s that irradiation of chromium carbene complexes (4) with visible light in the presence of N-substituted benzaldimines (5) leads to (racemic) )ff-lactams of type 6, photolytic reactions of Fischer carbene complexes have been intensively investigated by L.S. Hegedus and his group in Fort Collins, Colorado [5]. 

For complexes of type 10 (with a hydrogen at the carbene carbon) a synthesis was worked out in which a formamide is first reacted with K2[Cr(CO)j] followed by reaction with TMSCI [7]. This way, the non-racemic formamide 12 leads to the chirally modified amino carbene complex 13, which serves as starting material for the diastereoselective synthesis of various optically active yff-lactams [8]. An example is the (formal) total synthesis of 1-carbacephalothin 16, a carbon analog of the cephalosporins (Scheme 5) [8b]. In this case, the complex 13 is irradiated in the presence of in situ prepared imine 14 to afford the /(-lactam with high dia-stereoselectivity but only in modest yield. The product (15) could (in principle) be converted in to the target compound 16. 

McGuire and Hegedus 181) demonstrated the synthesis of a series of -lactams by the photolytic reactions of chromium-carbene complexes with imines [Eq. (142)]. The yields of the organic products were good... 

The carbene complex 21 (100 mg, 0.40 mmol), diphenylacetylene (81 mg, 0.45 mmol), and A7-/err-butylimine (38 mg, 0.45 mmol) were placed in a tube under argon. THE was transferred to the tube via a syringe, then the tube was sealed and heated to 80°C for 1.5 d. The reaction was monitored by TLC. The mixture was then air-oxidized in sunlight or under Vitalite, filtered through Celite, and purified on a Chromatotron (hexane/EtOAc 5 1) to yield the lactam as a white solid yield 77% mp 115-117"C. 

Phosphorylglycines are easily prepared, but in limited yield, by alkoxycarbonylation of the a-lithiated Schiff base of diethyl aminomethylphosphonate in THF at low temperature. The acylated Schiff base is converted in high yield (80%) to the corresponding p-lactam by photochemical reaction with the [(methoxy)(methyl)carbene]chromium complexes in CHjCF. ... 

Optically active thiazolines give rise to -lactams through the photolysis of chromium alkoxy-carbene complexes (Scheme 17). This reaction proceeds with very high stereoselectivity <94JOC496 >. 

A new synthetic route to j8-lactams has recently been reported " involving the photolytic reaction of chromium carbene complexes with imines. Detailed analysis now establishesa mechanism involving the initial photolytic formation of a ketene complex (24). This is followed by nucleophilic attack by the imine at the ketene carbonyl to produce a zwitterion intermediate, which undergoes a conrotatory ring closure to form the j8-lactam as shown in Scheme 15,... 

The synthesis of monocyclic 3-amino-P-lactams by the photolytic reaction of imines with pentacarbonyl[(dibenzylamino)carbene]chromium(0) was developed by Hegedus and co-workers [74]. These reactions are closely related to the previously described [2 -h 2]-cycloaddition reactions in that they are thought to involve attack of the imine nitrogen on a photogenerated, metal-bound ketene, followed by ring closure (Scheme 15). In a synthesis of a nocardicin precursor, optically active imine trimer 122 was photolyzed with carbene complex 123 providing a 46% yield of a 1 1 diastereomeric mixture of lactams... 

While no asymmetric induction was observed in the present instance, prior examples with more sterically biased imines had given high levels of induction. A solution to this problem for the monocyclic p-lactam case was provided by chiral carbene complex 125 [75]. A variety of other imine analogs with N-heteroatom bonds were examined in the reaction sequence without success, presumably due to insufficient nucleophilicity of the nitrogen atom for attack on the ketene complex or insufficient electrophilicity of the imine analog for the required ring closure. 

P-Lactams finm Fischer carbene complexes Scope, limitations, and reaction mechanism 13THC(30)65. 

---