Carbonylative lactonization

There appear to be few examples of the formation of azetidin-2-ones by closure of the C(2) —C(3) bond. One reaction which fits into this category involves reaction of the iron carbonyl lactone complexes (144) with an amine to give the allyl complexes (145) which on oxidation are converted in high yield to 3-vinyl-/3-lactams (146) (80CC297). 

Addition of diols to the carbonyl lactone group leads to the formation of cyclic orthoesters. Compounds containing a spiro, cyclic orthoester inter-linkage at the anomeric carbon atom are of interest, as this type of structure is found in the oligosaccharide antibiotics orthosomycins (91) (such as ever-ninomicin, flambamycin, and avilamycin). 

The required 4,7-dihydroxy coumarins were prepared from resorcinol using known methods [81]. Postulated structures of the newly synthesized compounds 39a-d, 40a-d, 41a-d and 42a-d were in agreement with their IR, 1H NMR spectral and elemental analysis data. In the IR spectrum of compound 39a, (R = 6-CH3) exhibited prominent bands around 1709, 1648 and 3042 cm-1 due to carbonyl lactone of coumarin, carbonyl of acetophenone... 

The bishydrazones are now known to be in the 1,4-lactone form, showing that no opening of the lactone ring in DHA occurred during the reaction. However, at one time (38) the 1,5-lactone was the preferred form, since the IR spectra of the bishydrazones showed a carbonyl lactone band at a frequency lower than that expected for a... 

It has been shown recently that homoallylic alcohols (309) undergo regiocontrolled carbonylation-lactonization to form (310) or (311) in good yield (equation 109). In the reaction of cis-3-hexenol, (315) is formed as a side product to (313), presumably via the isomerization of intermediate (312) to (314) (Scheme 11). 

Rearrangements. Allyl esters are directly converted to isocyanates when the modified Curtins rearrangement is carried out in the presence of (Ph,P)4Pd. A versatile construction of the core structure of antibiotic CP-263114 is highlighted in a reaction sequence consisting of carbonylation, lactonization, and siloxy-Cope rearrangement. "... 

Nystatin (Fungicidin) Carboxyl Carbonyl (lactone ) Hydroxyl groups (8) (175)... 

With specially structured alkenes, such as norbomadiene, it is feasible to observe the in-termolecular version of the carbopalladation-carbonylative lactonization tandem process, as shown in Scheme This also represents a rare example in which the termination step involves lactonization. Althongh a single example of termination by lartamiyatinn is shown in Eq. 6 of Scheme 13, there does not appear to be any example in which termination involves intermolecular amidation. 

Homopumiliotoxin and Pumiliotoxin were totally synthesized in the late twentieth century by Kibayashi s goup [73-75]. Intramolecular alkoxycarbonylation for the formation of lactone frames were taken as a fundamental step (Scheme 10.12). Negishi and Liao reported a palladium-catalyzed carbonylative lactonization of (Z)-cr-iodoalkenols and applied that in the total synthesis of (h-)-hamabiwalactone B [76]. 

Coumestrol was first isolated from alfalfa, strawberry, Lucerne, and Ladino clover by Bickoff et al. in the 1950s, and has been reported to inhibit bone resorption and stimulate bone mineralization. In 2005 Larock and colleagues reported the synthesis of coumestrol and coumestans by the iodocyclization of acetoxy-containing 2-(l-alkynyl)anisoles and subsequent direct palladium-catalyzed carbonylation/lactonization [114]. The naturally occurring products were produced in good to excellent yields (Scheme 10.29). 

Hydroxyalkenes possessing a nucleophilic group on C-5 cyclize, via palladium-catalysed addition of the nucleophile to the alkene and subsequent carbonylative lactonization to the 3-hydroxy-group, to give bicyclic [3-3-0] systems. This general process has been used to prepare bicyclic bis-lactones, cis-3-hydroxypyrrolidine-... 

VI.2.1.2 Intramolecular Cyclization Processes via Palladium-Catalyzed Carbonylative Lactonization and Lactamization... 

TABLE 2. Termination of Pd-Catalyzed Formation of Cyclic Ethers by Carbonylative Lactonization... 

VI Pd-CATALYZEDCARBONYLATION AND OTHER RELATED REACTIONS TABLE 5. Pd-Catalyzed Cyclic Amination-Carbonylative Lactonization Tandem Reaction... 

When the Pd-catalyzed carbonylation with diaryl dichalcogenides and CO is apphed to propargyl alcohols, carbonylative lactonization occurs under higher CO pressure giving /3-(arylchalcogeno)-a,/3-unsaturated y-lactones in good yields (Scheme... 

In 2005, Larock and co-workers reported a palladium-catalyzed carbony-lative synthesis of coumestans and coumestrols. The reaction involves iodocyclization of acetoxy-containing 2-(l-all nyl)anisoles and subsequent direct palladium-catalyzed carbonylation-lactonization. The desired coumestans and coumestrols and their related analogues were produced in low to excellent yields (Scheme 3.46a). In 2009, Willis s group demonstrated that... 

Carbonyls Lactones Carbonyls Monoterpenes Carbonyls Carbonyls... 

Termination of cyclic carbopalladation of alkynes via carbonylative lactonization/ lactamization has been achieved with alkenyl iodides containing an ca oxydryl or amido/amino moiety [85]. 

Only a limited number of metal-mediated approaches for the construction of the pyrone ring of coumestans have been reported to date in the literature. In this context, Larock and coworkers developed an efficient synthesis of coumestrol in which the pyrone ring is formed through a palladium-catalyzed carbonylation/lactonization of the 2-aryl-3-iodobenzofuran derivative 93, accessible by iodocyclization of the fxmctionalized diphenylacetylene 92 (Scheme 41) [140]. 

---