Carbonylative cross-coupling reaction

Moderate yields of acids and ketones can be obtained by paHadium-cataly2ed carbonylation of boronic acids and by carbonylation cross-coupling reactions (272,320,321). In an alternative procedure for the carbonylation reaction, potassium trialkylborohydride ia the presence of a catalytic amount of the free borane is utilized (322). FiaaHy, various tertiary alcohols including hindered and polycycHc stmctures become readily available by oxidation of the organoborane iatermediate produced after migration of three alkyl groups (312,313,323). 

As described above, our synthetic strategy involves the convergent construction of the central cyclopentanone ring with a carbonylative cross-coupling reaction and a photo-Nazarov cyclization reaction (Chart 2.2). The electrophilic coupling component 51 was synthesized by an intramolecular Diels-Alder reaction [34] and the nucleophilic coupling component 52 by a vinyiogous Mukaiyama aldol reaction [35]. 

Carbonylative cross-coupling reaction between triarylbismuth(V) compounds and organostannanes is smoothly catalyzed by PdCl2 under 1 atm CO at room temperature (Scheme 48) [34]. Not only arylstannanes, but also heteroaryl-, alkynyl-, and vinyltributylstannanes were employed efficiently. 

Scheme 48 Carbonylative cross-coupling reaction of Ar3BiX2 with organostannanes...

The carbonylative cross-coupling reactions of haloazines are usually run under an ambient to moderate carbon monoxide pressure. Arylboronic acids or tetraarylborates are usually the reagent of choice due to their robustness and availability. The coupling of 2-iodopyridine and phenylboronic acid under ambient CO pressure, for example, led to the formation of 2-benzoylpyridine in good yield (7.66.),87... 

For the ketone synthesis via the present protocol, acid chlorides are useful precursors, in deed. Nevertheless, carbonylative cross coupling with organic halides is strategically the most simple and direct way to this purpose. The palladium-catalyzed carbonylative cross-coupling reaction with various organic halides has been extensively investigated, because of its merits from synthetic as well as phenomenal point of view. Acid chlorides are not always readily available, and their preparation is not always compatible with many sensitive functionalities. Therefore the development of this type of reaction widens the scope of the ketone synthesis in the present protocol because of the ready availability and storability of organic halides and pseudohalides. 

Castanet and co-workers have transformed a series of 2-halopyridines to 2-benzoylpyridines via a unique carbonylative cross-coupling reaction <03SL1874>. 

Scheme 7.5 Palladiumd-catalyzed carbonylative cross-coupling reactions of aryl iodides with alkynones to furans...

Scheme 11.2 Synthesis of N-benzylbenzamide via a gas-liquid carbonylative cross-coupling reaction.

The Pd-catalyzed carbonylative cross-coupling reaction of organic halides (or triflates) with organostannanes is an especially valuable and versatile synthetic method of un-symmetrical ketone. One serious drawback is the high toxicity of organostannanes. 

Arenediazonium salts, irrespective of the electronic nature and the position of the substituents on the aromatic ring, undergo a smooth carbonylative cross-coupling reaction with tetramethylstannane in the presence of 2% of Pd(OAc)2 under 9 atm of CO at room temperature (Scheme 9). Tetraethylstannane is less reactive and aryl ethyl ketones are obtained in less than 50% yields. Tetrabutylstannane does not react under these conditions. The reaction is successful for X = BF4 and PFg, but not for X = Cl. In this case, the yields drop to less than 10% and intractable tarry material results (Scheme 9). ... 

The carbonylative cross-coupling reaction of allyl chlorides with phenyl-, 3-furyl-, and vinylstannanes is more fruitful than the reaction with allylstannanes (Scheme 14)... 

Another important aspect of the triflate methodology is Ihe ready availability of both kinetic and thermodynamic triflates with high regioselectivity (more than 93%) and their carbonylative cross-coupling reaction with vinylstannane with more than 95% regioselectivity (Scheme 18)3 ... 

Organozinc halides undergo a Pd-catalyzed carbonylative cross-coupling reaction with allylic benzoates and phosphates to furnish allyl alkyl ketones under 1 atm of CO (Scheme 24).In Table 2 are summarized typical examples for the reaction with /3-... 

The Pd-catalyzed carbonylative cross-coupling reaction of trans-carvyl phosphates with y-zincioester proceeds nicely in the presence of 11.3 equiv of HMPA at room tan-perature under 1 atm of CO and yields the corresponding cii-ketone as a single isomer in 59% yield (Scheme 21)P Under similar conditions, cii-carvyl phosphate exclusively provides the trans-i omer. These stereochemical outcomes clearly indicate that the carbonylative coupling reaction proceeds stereospecifically with overall inversion of configuration at the ally lie stereocenters. 

Organoboranes have many advantages as the organometallic component (R M) for the Pd-catalyzed carbonylative cross-coupling reaction with organic halides (RX). They can be prepared in many ways and are compatible with a variety of functional groups of synthetic importance. Most boronic acids and esters are stable to air and moisture. 

Pd-catalyzed carbonylative cross-coupling reaction of 9-alkyl-9-BBN with 1-halo-l-alkenes is effectively promoted in the presence of K3PO4 at room temperature to provide alkyl vinyl ketones in good yields (Scheme 33). Zn(acac)2 is not effective for the present carbonylative coupling reaction (cf. Scheme 31). The ready availability of 9-alkyl-9-BBN... 

The carbonylative cross-coupling reaction with ethynylsilane has not been realized so far (Scheme 37). Even under 30 atm of CO, the direct cross-couphng product is obtained as the single product. This may be attributed to an extremely rapid alkynyl transfer from Si to ArPdl as compared with the CO insertion into the Ar— Pdl bond. 

Aryl iodides undergo carbonylative cross-coupling reaction with terminal alkynes under 20 atm of CO in the presence of 1% of PdCl2(dppf) in triethylaniine as the solvent (Scheme 41). The corresponding aryl bromides show the lower yields of the products. The direct cross-coupling prodncts (ArC=CR ) and homoconpling products (R C=CC=CR ) are produced in negligible amounts under the conditions. 

A similar reaction pattern has been observed for the carbonylative cross-coupling reaction of o-iodoaniline and terminal acetylenes, where 2-snbstituted l,4-dihydro-4-oxoquinolines are obtained in good yields (Scheme 43). " The reaction of aromatic acetylenes generally gives a better yield than that of aliphatic acetylenes. Fnnctional groups such as acetal, THP, and ester are compatible with the reaction conditions. Other authors have reported that PdCl2(dppf) is similarly effective and the yield depends on the amine nsed. " For example, 2-phenyl-l,4-dihydro-4-oxoquinoline is obtained in 83% (diethylamine), 70% (triethylamine), 60% (piperidine), and 61% (morpholine) yields under 20 atm of CO in the presence of 10% of the catalyst at 120 °C for 1 h. 

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