A-Diazoacetamides

Recently, Yu and co-workers developed an operationally simple catalytic system based on [RuCl2(/>-cymene)]2 for stereoselective cyclization of a-diazoacetamides by intramolecular carbenoid C-H insertion.192 /3-Lactams were produced in excellent yields and >99% m-stereoselectivity (Equation (53)). The Ru-catalyzed reactions can be performed without the need for slow addition of diazo compounds and inert atmosphere. With a-diazoanilide as a substrate, the carbenoid insertion was directed selectively to an aromatic C-H bond leading to y-lactam formation (Equation (54)). 

In 2005, the group of Choi has reported a catalytic system based on [RuC12 (p-cymene)2] that produced the stereoselective cyclization of a-diazoacetamides by intramolecular carbenoid C-H insertion and afforded [I-lactams in excellent yield (>97%) with m-stereoselectivity (>99%), (Scheme 110), [239]. 

Doyle et al.344 and Wee and Liu345 have reported the ring-closing transformation of a-diazoacetamides 108 and 109 to yield 2(3//)-indolinones over Nafion-H [Eq. (5.136)]. In the transformation of compounds 109 the electrophilic intramolecular substitution is followed by decarboxylation.345 Small amounts of 2-azetidinone derivatives (4—10%) formed through a carbene intermediate were also detected. The yield of products from compounds 108 are even higher than observed in the presence of Rh(OAc)2 often applied in the decomposition of diazo compounds.344... 

Ruthenium porphyrins are effective catalysts for the cyclization of A-tosylhydrazones via intramolecular carbenoid C-H insertion to afford azetidin-2-ones <2003OL2535, 2003TL1445>. A non-porphyrin-based ruthenium catalyst, [RuCl2(/>-cymene)]2, has been developed recently for catalytic carbenoid transformation <20050L1081>. A [RuCl2(/>-cymene)]2-catalyzed stereoselective cyclization of a-diazoacetamides 418 by intramolecular C-H insertion produced azetidin-2-ones 419 in excellent yields and excellent (>99%) air-stereoselectivity (Equation 168). 

The reaction of a-methoxycarbonyl-a-diazoacetamides is best catalyzed by Rh2(S-PTTL)4 or related catalysts [2,10]. Again, there is competition between /3-lac-tam and y-lactam formation. The chemistry has been applied to the synthesis of a variety of/3-lactam derivatives, as illustrated in Scheme 6 [11]. Rh2(S-PTTL)4-cata-... 

Scheme 6. Rh2(S-PTTL)4 catalyzed intramolecular C-H insertion of an a-methoxycarbonyl-a-diazoacetamide.

An intramolecular carbenoid addition onto a carbon-carbon double bond provides a possible synthetic route to the pyrrolidine ring. The rho-dium(II) acetate-catalyzed reaction of diazo amide 106 leads to a mixture of diastereomers 107 and 108 (6 1) in 43% yield (88TL1181). The decomposition of AjA-diallyl-a-diazoacetamide catalyzed by Rh2(55-MEPY)4 forms product 109 from an enantioselective intramolecular cyclopropanation (50% yield, 72% e.e.) (94T1665). Spiro-fused ring systems were produced by this route from quinonediazides 110 and 111 under irradiation (83TL4773 86TL2687). 

Stereo- and regiocontrol in the formation of lactams by rhodium-carbenoid C-H insertion of a-diazoacetamides 04EJO3773. 

Metal-catalyzed decomposition of a-diazocarbonyls followed by intramolecular carbenoid C-H insertion is an effective means to access important heterocyclic compounds [36, 221-223]. A variety of p- and y-lactams have been synthesized from a-diazoacetamides. Several dirhodium catalysts are used for this transformation [224—228]. Diruthenium catalysts with acetate (1), pyridonate (60), sacchari-nate (63), and triazenide (69) bridges were employed as potential catalysts for this reaction. A new class of compounds containing calix [4]arenedicarboxylate moiety (70-72) were also used (Scheme 42) [67]. The catalytic activity of all these diruthenium(I,I) complexes are compared with dirhodium(II,II) complexes 37 and 73 (Scheme 43). 

Hashimoto needed a step to remove the methoxycarbonyl group, Hu et al. proposed an alternative synthesis via the same approach. The a-diazoacetamide 5 prepared in four steps from the isovanillin 2 was treated in the presence of 1 mol% Rh2[(4/ )-MEOX]4 in methylene chloride to afford the expected lactam 6 in 64% yield albeit in lower enantiomeric excess (46% ee). After removal of the cumyl protecting group and two recrystallizations, 1 was isolated in 88% ee (Scheme 23.4). 

---