Lactam synthesis carbonylation

Using a strategy of lactam synthesis with a combination of carbonylation and nitrogenation, 2-methyl- and 2-benzylquinazolin-4(3i/)-one 17 are obtained in 54 and 40% yield, respectively, on treatment of corresponding 2-bromoacetanilides 16 with tetrakis(triphenylphosphane)-palladium [Pd(Ph3P)J, potassium carbonate, and a titanium isocyanate complex in A-methyl-pyrrolidone under a carbon monoxide atmosphere. ... 

The examples outlined in this chapter show that carbohydrates are efficient stereodifferentiating auxiliaries, which offer possibilities for stereochemical discrimination in a wide variety of chemical reactions. Interesting chiral products are accessible, including chiral carbo- and heterocycles, a- and 3-amino acid derivatives, 3-lactams, branched carbonyl compounds and amines. Owing to the immense material published since the time of the earlier review articles on carbohydrates in asymmetric synthesis [9,10], the examples discussed in this chapter necessarily focused on the use of carbohydrates as auxiliaries covalently linked to and cleavable from the substrate. Given the scope of this chapter, a discussion of other interesting asymmetric reactions has not been permitted — for example, reactions in which carbohydrate-derived Lewis acids, such as cyclopentadienyl titanium carbohydrate complexes, exhibit stereocontrol in aldol reactions [180]. Similarly, processes in which in situ glycosylation induces reactivity and stereodifferentiation — for example, in Mannich reactions of imines [181] — have also been excluded from this discussion. 

Uozumi Y, Kawasaki N, Mori E, Mori M, Shibasaki M (1989) Incorporation of molecular nitrogen into (nganic compounds. 2. Novel lactam synthesis by use of a combination system of carbonylation and nitrogenation. J Am Chem Soc lll(10) 3725-3727... 

Carbonylation of halides in the presence of primary and secondary amines at I atm affords amides[351j. The intramolecular carbonylation of an aryl bromide which has amino group affords a lactam and has been used for the synthesis of the isoquinoline alkaloid 498(352], The naturally occurring seven-membered lactam 499 (tomaymycin, neothramycin) is prepared by this method(353]. The a-methylene-d-lactam 500 is formed by the intramolecular carbonylation of 2-bromo-3-alkylamino-l-propene(354]. 

Schemes 15 and 16 summarize the syntheses of intermediates that represent rings A and D of vitamin Bi2 by the Eschenmoser group. Treatment of lactam/lactone 51, the precursor to B-ring intermediate 8 (whose synthesis has already been described, see Scheme 8), with potassium cyanide in methanol induces cleavage of the y-lac-tone ring and furnishes intermediate 76 after esterification of the newly formed acetic acid chain with diazomethane. Intermediate 76 is produced as a mixture of diastereomers, epimeric at the newly formed stereocenter, in a yield exceeding 95%. Selective conversion of the lactam carbonyl in 76 into the corresponding thiolactam...

Treatment of the 1,2-oxazines 52 with carbon monoxide at 1000 psi in the presence of cobalt carbonyl brings about insertion of carbon monoxide to form the 1,3-oxazepines S3 <96TL2713>. A convenient route to P-lactams fused to oxepines is made available by alkene metathesis. Thus reaction of 4-acetoxyazetidin-2-one with ally alcohol in the presence of zinc acetate, followed by iV-allylation of the nitrogen affords the derivative 54 which cyclises by RCM to form the oxazepinone 55 <96CC2231>. The same communication describes a similar synthesis of 1,3-dioxepines. 

The synthesis of medium-sized lactams 100 has been attempted by means of amine-directed carbonylation of 5-iST-benzylamino-l-pentene 97. In presence of... 

Among the anionic/reduchve domino transformations, one of the most often encountered is the reductive amination of a carbonyl compound being followed by the formation of a lactam. As did many others before, Abdel-Magid and coworkers used this approach for the synthesis of y- and 6-lactams as 2-949 from either ketone 2-944 and amine 2-945 or amine 2-946 and ketone 2-947 via 2-948, employing sodium triacetoxyborane (Scheme 2.212) [484]. 

A 1992 patent describes the carbonylation of EO to yield /3-propiolactone using a mixture of Co2(CO)8 and 3-hydroxypyridine.982 A recent re-investigation of this system has indicated that the major product is the alternating copolymer, a polyester, catalyzed by the [Co(CO)4] anion (Scheme 24).983 The synthesis of lactones via this methodology has successfully been achieved using Lewis acidic counter-cations (Scheme 25) 984,985 a similar strategy allows /3-lactams to be... 

The insertion of carbon monoxide into readily available 2-bromo-3-aminopropene derivatives can be effected by catalytic quantities of palladium acetate and triphenylphosphine high CO pressures are not required (Scheme 16).38 The /Mactam products presumably arise by palladation,carbonylation, and cyclization as depicted in Scheme 17.38 An extension of this approach to the synthesis of biologically interesting condensed /(-lactams can be expected. 

The palladium-catalysed decarboxylative carbonylation of 5-vinyloxazolidin-2-ones 218 caused, unexpectedly, a ring enlargement process to 5-lactams 219 <00JA2944>. The conjugate addition of 4-phenyloxazolidin-2-one to a nitroalkene was used for the synthesis of diastereoisomers of dethiobiotin <00EJO3575>. Attempted deprotection of the O-TBDMS... 

Carbonylations involving catalytic amounts of Pd(n) and substoichiometric Cu(n) have been developed for the synthesis of lactams. This Wacker-type process is assumed to proceed via C-H functionalization involving a palladacycle intermediate such a hypothesis is backed by the high degree of regioselectivity attained, when using a bis-chelating substrate (Equation (114)).104... 

Zirconium enolates of various carbonyl compounds have also been investigated for Mannich-type reactions with different electrophiles. According to Shibasaki s method,148 the coupling reaction between a 3-acetoxy-4-alkyl-/3-lactam and the in r(/ -generated zirconium enolate 96 of a cyclohexanone derivative was realized as a key step during the total synthesis of an anitibiotic (Scheme 42).117,149... 

In the search of new methodologies for the asymmetric synthesis of nonproteinogenic amino acids, 8-methyl-4,8a-diphenyltetrahydro-17/-pyrrolo[2.1 -r l, 4 oxazinc-l, 6(7//)-dionc 62, obtained as described in Scheme 24 (Section 11.11.7.3), was selectively reduced at the lactam carbonyl with BH3 and further opened by hydrogenolysis to give syn-disubstituted proline derivative 64 in 95% yield <1997SL935> (Scheme 6). It is noteworthy that hydrogenolysis did not affect the benzylic position of bicyclic compound 63. 

Carbonylation is one of the most important reactions leading to C-C bond formation. Direct synthesis of carbonyl compounds with CO gives rise to carboxylic acids and their derivatives, such as esters, amides, lactones, lactams etc. The process can be represented by the simple reactions of Scheme 5.1. 

The synthesis of thieno[3,2-c]benzazepine derivative 106b has been reported by Friedel-Crafts intramolecular cyclization of isocyanates 105 (Equation (15) (2002S355)). Noteworthy, lactam 106b is formed in 51% yield, while dione 106a can not be obtained due to the electron-withdrawing effect of the carbonyl group. 

Bicyclic ester 100 forms in analogy to isomeric ester 65 (Section 2.4.1.1) (07JOC5608). /l-Phenylethylamine 101 undergoes palladium-catalyzed direct aromatic carbonylation, thus providing another synthesis of benzo-lactam 78b (06JOC5951). A stereoselective nitro-Mannich/lactamization cascade of y-nitro ester and cyclic imine affords polysubstituted lactam 102 (08OL4267). 

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