Carbonylation/cyclization

Scheme 5.24. Light-Pd°-induced cyclization/carbonylation sequence.

An interesting Pd-induced diyne cyclization-carbonylation sequence has been discovered by Chiusoli [117]. Thus, diyne 162 is transformed as shown into a mixture of ( )- and (Z)-bis(alkylidene)pyrrolidines 163 and 164. 

In an analogous approach explored by Dixneuf et al., a conjugated enynyl carbonate is converted into an oxolenone or a bicyclic lactone in significant yields via double carbonylation in the presence of methanol (Scheme 22) [128]. When a neighboring carbonyl group is present in the substrate, it can also participate in palladium-catalyzed cyclization-carbonylation. Indeed, 4-yn-l-ones lead to cyclic ketals that can be easily converted into 2-cyclopentenone carboxylates in an acidic medium (Scheme 22) [129]. 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

This chapter covers the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions from 1993 to early 2005. In addition, technical development in carbonylation processes with the use of microwave irradiation as well as new reaction media such as supercritical carbon dioxide and ionic liquids are also discussed. These carbonylation reactions provide efficient and powerful methods for the syntheses of a variety of carbonyl compounds, amino acids, heterocycles, and carbocycles. 

In this chapter, the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions are reviewed and the scope and mechanisms of these reactions are discussed. It is clear that these carbonylation reactions play important roles in synthetic organic chemistry as well as organometallic chemistry. Some of the reactions have already been used in industrial processes and many others have high potential to become commercial processes in the future. The use of microwave irradiation and substitutes of carbon monoxide has made carbonylation processes suitable for combinatorial chemistry and laboratory syntheses without using carbon monoxide gas. The use of non-conventional reaction media such as SCCO2 and ionic liquids makes product separation and catalyst recovery/reuse easier. Thus, these processes can be operated in an environmentally friendly manner. Judging from the innovative developments in various carbonylations in the last decade, it is easy to anticipate that newer and creative advances will be made in the next decade in carbonylation reactions and processes. 

The substrates 69, 73, 76 and 79 were chosen16 17) to test the possibility of forming five and six-membered rings and of cyclizing carbonyls onto alkene, alkyne and benzenoid moieties. Reductions were carried out with DMP+ as the catalyst and without it, and the results are shown in Table 10. In the absence of DMP+ reduction... 

Fig. 46 Light-stimulated palladium-catalyzed tandem radical cyclization/carbonylation/ Suzuki-Miyaura coupling reactions...

A Pd(ll) catalyst system with an oxazoline ligand 44 has been described that allows the desymmetrization of meso-Z-alkyl-2-propargylcyclohexane-l,3-diols in an asymmetric cyclization-carbonylation reaction. The products which contain a chiral quaternary carbon were obtained in excellent yields with high ee s (Scheme 56) <2006T9988>. 7-Hydroxy terminal <2005JOC3099> and internal <2006TL2793> alkenes can be converted to tetrahydrofurans by Pd(0)-catalyzed carboetherification reactions combined with a coupling of aryl or vinyl halides. 

Many unaccomplished and yet highly necessary tasks remain. The scope and limitations as well as mechanistic details of most of the reactions discussed above need to be further delineated. More extensive and challenging applications of the newly developed reactions to the synthesis of natural products and other complex organic molecules must also be carried out. In addition, other less routine but highly desirable aspects should also be explored. These include asymmetric cyclization and catalytic procedures for cyclization-carbonylation. 

The key step for the conversion of open-chained a,3-unsaturated aldehydes to their corresponding cyclized carbonyl compounds involves the regioselective alkylation of (39) with dihalides. 

Oppolzer, W., Robyr, C. Synthesis of ( )-hirsutene by a catalytic allylpalladium-alkyne cyclization/carbonylation cascade. Tetrahedron 1994, 50, 415 24. 

Cyclization-carbonylation-anion capture processes involving in situ generated vinylstannanes as terminating agents (as in Section 5.6.2) afford a variety of complex heterocyclic a, (3-unsaturated ketones in good yield. Typical examples are shown in Table 5.6.4. °... 

Table 5.6.4 Cascade hydrostannylation-cyclization-carbonylation-anion-capture processes ...

Scheme 5.6.19 One-pot sequential process interfacing oxypyridinium betaine cycloaddition with cyclization-carbonylation-organostannane capture...

Scheme 57. Heterocyclization of Alkenylamines and Alcohols via (a) Cyclization—/ -Hydride Elimination, (b) Cyclization—/ -Hydroxy Elimination, (c) Cyclization—Acetalization, (d) Cyclocarbonylation, and (e) Cyclization—Carbonylative Esterification...

Kato et al. reported that palladium(II)-mediated cyclization—carbonylation of the 4-yn-l-ones 305 gave the cyclic acetals 306 (Scheme 97).164 This reaction proceeds through nucleophilic attack of the carbonyl oxygen on the alkynyl moiety coordinated to palla-... 

Substituted 3-Oxobicyclo 3.3.0 oct-4-ene-2-acetates 19, 3-Oxobicyclo 3.3.0]octanc-2-acctates and Their 7-Aza Analogs 16 General Procedure for Cyclization/Carbonylation of Substituted ( )-8-Iodo-6-oeten-l-ynes 17, ( )-8-Iodo-1,6-octadienes and Their 4-Aza Analogs 14 ... 

Ketyls generated by the reaction of SmE with aldehydes and ketones have been incorporated into numerous sequential processes in which a radical reaction is involved. Sequential radical processes, radical cyclization/carbonyl additions, radical cyclization/substitution reactions, nucleophilic acyl substitution/radical cyclizations, cyclization/elimination processes, and others have all been realized. Because these types of reactions have been extensively reviewed [2b, 25], further details will not be given here. Needless to say, new sequential processes based on SmE-promoted ketyl/olefin coupling reactions are still being developed (Eq. 75) [88]. 

Cyclizative Carbonylations 29 Table 2. Tin hydride-mediated radical carbonylations Part 2... 

The second example in Table 5 shows the cyclization-carbonylation-allylation sequence, in which 5-hexenyl radical cyclization precedes CO trapping. Because of the nucleophilic nature of acyl radicals, in a mixed alkene system comprised of an electron deficient alkene and allyltin, they favor the electron deficient alkene first and the resulting product radical, which have an electrophilic character, and then smoothly add to allyltributyltin. This four-component coupling reaction provides a powerful radical cascade approach leading to y -functionalized, -unsaturated ketones, which are not readily accessible by other methods [52]. 

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