Carbonylation esterification

A spectacular example of application of the cyclic carbopalladation-carbonylative esterification tandem process is the synthesis of a possible intermediate for the synthesis of perophoramidine [121] (Scheme 39). 

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...

The catalytic cyclic carbopalladation of alkynes can proceed to produce five- and six-membered rings at 1.0-1.1 atm of CO without premature incorporation of CO, and in situ regeneration of Pd-phosphine catalysts can be achieved in high yields by termination of the cyclic carbopalladation via deferred carbonylative esterification and lactonization, as suggested by the results shown in Scheme 1. One key to observing the formation of the desired products in high yields is to employ 1.0-1.0 atm of CO. Some representative examples are summarized in Scheme 3. 

Cyclic carbopalladation producing five- and six-membered rings can proceed in good yields despite the fact that the expected carbonylative esterification does take... 

A detailed investigation with 10 summarized in Table 2 indicates that premature esterification and cyclopropanation (Type HI C— Pd process in Scheme 2) can occur as dominant side reactions but that, under the optimized conditions (entry 7), both can be suppressed to insignificant levels (<3%). It is also important to note that, in marked contrast with the cyclic acylpalladation (Type n Ac—Pd) discussed in Sect. VI.4.1.1, monosubstituted alkenes that can readily participate in dehydropalladation (e.g., 11) cannot undergo the cyclic carbopalladation-carbonylative esterification tandem process (Type II C-Pd) since they merely undergo the cyclic Heck reaction (Type I C— Pd process in Scheme 14). The contrasting behavior mentioned above may be attributable to a chelation effect exerted by the carbonyl group in the acylpalladation (Scheme 15), which is lacking in the carbopalladation shown in Scheme 14. 

C.ii. Diastereoselective Cyclic Carbopalladation of 1,1-Disubstituted Alkenes Terminated by Carbonylative Esterification... 

The synthesis of polycyclic compounds can also be accomplished by a palladium(O)-catalysed transformation of enediynes [75]. In a process described by Negishi and coworkers, enetetraynes of type 132 undergo a tetracyclization followed by a carbonylative esterification to form the fifth ring leading to 133 in 66% yield. In this case, the initial alkenyl-palladium species is obtained by an oxidative addition of palladium(0) to the alkenyliodide moiety in 132 [76] (Scheme 8.34). 

Cop6ret, C. and Negishi, E.-i. (1999) Palladium-catalyzed highly diastereoselective cyclic carbopalladation-carbonylative esterification tandem reaction of iododienes and iodoary-lalkenes. Org. Lett., 1,165-7. 

Sugihara, T., Coperet, C., Owczarczyk, Z. et al. (1994) Deferred carbonylative esterification in the Pd-catalyzed cyclic carbometalation-carbonylation cascade. J. Am. Chem. Soc., 116, 7923-4. 

VI.2.1.3 Tandem and Cascade Processes Terminated by Carbonylative Esterification, Amidation, and Related Reactions... 

TABLE 1. Pd-Catalyzed Cyclization-Carbonylative Esterification Tandem Process Giving Tetrahydropyrans... 

VI.2.1.3 TANDEM AND CASCADE PROCESSES TERMINATED BY CARBONYLATIVE 2391 TABLE 4. Pd-Catalyzed Cyclic Amidation-Carbonylative Esterification Tandem Reaction... 

The cyclic acylpalladation process can be terminated by carbonylative esterification, that is, Type II AcPd process, as discussed in Sect. VL4.1. In some cases, however, this process can be overshadowed by premature esterification This difficulty can be circumvented by a two-step alternative consisting of Type III AcPd process followed by methanolysis (Schemes 21 and 22). The results shown in Scheme 23 suggest that further optimization of the reaction conditions for the Type III AcPd process appears to be promising and highly desirable. 

In fact, the preferential cyclic carbopalladation even in the presence of large excesses of CO and MeOH has been exploited in developing cyclic carbopalladation cascades terminated by carbonylative esterification, as discussed in Sect. IV.3.3. More recent attempts... 

FruUanolide and its epimer, arbusculin B, were synthesized by using the Type II Ac-Pd reaction, as summarized in Scheme 33 Interestingly, the thermodynamically less stable epimer of the desired bicyclic ketone was obtained as the predominant product along with minor amounts of the desired epimer and the cyclic carbometallation— carbonylative esterification products, but epimerization with 10% NaOMe in MeOH produced the desired cts-isomer, which was >98% isomerically pure. 

Hi) Alkyl Electrophiles. Even some alkyl halides undergo Pd-catalyzed carbonylative esterification. The reaction shown in eq 56 is presumably an-chimerically assisted by the preexisting C02Et group. 

Schmalz HG, Geis O. Tandem and cascade processes terminated by carbonylative esterification, amidation, and related reactions. In Negishi E-i, editor. Handbook of organopalla-dium chemistry for organic syntheses. New York John Wiley 2002. Volume 2, p 2377 2397. 

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