Heterocycles Synthesis at Carbonylation of Acetylenic Compounds

The carbonylation of unsaturated hydrocarbons, alcohols, organic halides and other substrates catalyzed by transition metals, salts of transition metals and organometallic complexes is a wide used synthesis method of new carbonyl, carboxyl and alkoxy carbonyl containing compounds including creation or modificationt of heterocycles. The data about synthesis of heterocycles at carbonylation of acetylenic compounds have been appeared at last 20 years and are demonstrated in our review. Introduction of carbon monoxide in the catalytic reactions of acetylenic compounds permits to obtain in oneput process the diverse heterocycles, having carbonyl, carboxyl or alkoxycarbonyl substitutes or containing these fragments inside of heterocycles.


Introduction
The carbonylation of unsaturated hydrocarbons, alcohols, organic halides and other substrates catalyzed by transition metals, salts of transition metals and organometallic complexes is a wide used method of new carbonyl, carboxyl and alkoxycarbonyl containing compounds synthesis including creation or modification of heterocycles [1][2][3][4][5][6][7][8]. However the data about synthesis of heterocycles at carbonylation of acetylenic compounds in these books and reviews practically are absent because ones mainly have ap-peared at last 25 years. These data are given in our review.

The synthesis of alkoxycarbonyl derivatives of dimethylenepyrrolidines
It is found by Chiusoli G.P. et al. that α,α-tetraalkylsubstituted dipropargylamines react with carbon monoxide and alcohols or water in the presence of PdCl 2 -thiourea complex forming alkoxycarbonyl derivatives of dimethylenepyrrolidines (1, 2) [

Scheme 1
On using of PdCl 2 as catalyst in the presence of oxygen apart from carbon monoxide (CO/O 2 = 90: 10) in methanol dimethoxycarbonyl dimethylenepyrrolidines (3 and 4) mainly are forming besides of monomethoxycarbonyl derivatives 1 and 2. Similar pic-ture is at catalysis by Pd 0 /C in the presence of KI and oxygen (CO/O 2 = 94: 6). At that the third stereo isomer of methoxycarbonyl dimethylenepyrrolidine (5) is formed in a small amount [11] (Scheme 2).
Methoxycarbonylation of dipropargylmethylamine at catalysis by PdCl 2 -thiourea complex leads to both mono-and dimethoxycarbonyldimethylene pyrrolidines forming but with smaller yields [11].
At the oxidative alkoxycarbonylation of dipropargylamines and amides by mixture of CO/air at 4 bar pressure in the alcohole at Pd 0 /C catalysis in the pres-ence of KI the mixture of 3,4-bis(alkoxycarbonylmethylene)pyrrolidines 6 has been obtained. An isomerization of those in the various conditions leads to the forming of pyrrols 7 and free pyrrolo-3,4-diacetic acids 8 [12]
Reaction proceeds at the room temperature and atmospheric pressure of carbon monoxide. Polycyclic compounds 11 are formed at dimerization of cyclopentadienone 10. When the reaction is carried out in a base -alcohol medium (at X = NH, NMe, R = alkyl) the cyclopentadienone 10 "is catched" by alkoxyl group with the forming of corresponding alkoxycyclopentenones 12. Application of various alkenes and alkynes as dienophiles, using for "catching" of cyclopentadienones 10, allows to extend the number of obtaining heteropolycyclic compounds 13-15 (Scheme 5) [14].
Palladium on charcoal (10%), complexes of Pd°s uch as Pd 2 (dba) 3 (dba -dibenzyledenacetone) or palladium salts lightly reducing in reaction conditions up to metallic Pd are used as catalysts. The using of alkynes as dienophiles leads to obtaining of products those are spontaneously aromatizated at the heating.
The better yields of polycyclic compounds 13 and 15 (up to 98%) are observed in reaction of alkenes and alkynes with terminal double and triple bonds. In the absence of CO in the same reaction conditions any reactions not proceed. But at the using of Ni and Co complexes as catalysts the cycloaromatization reaction of dialkynes 9 has proceeded [15].
The mechanism of process includes the formation of intermediate bicyclic Pd complex, carbonylating by CO into acylpalladium complex, giving in reaction with methanol the final product and Pd 0 species. Catalyst regeneration happens in result of Pd 0 into Pd 2+ oxidation with participation of CuCl 2 [20].
Lately the sphere of reaction application has extended and the series of 2-substituted 3-methoxycarbonylindoles and benzofurans 26 has been obtained. Only lactams 27 have formed from 2-alkynylforma- nilides in these conditions [21] (Scheme 9).
The palladium-catalyzed reaction of readily accessible 2-alkynyltrifluoroacetanilides with aryl halides and vinyl triflates under a carbon monoxide atmosphere (1 or 7 atm) in the presence of potassium carbonate produces 2-substituted-3-acyl indoles in fair to good yield. The acidity of the nitrogen-hydrogen bond proved to be primary importance for the success of the reaction. The methodology has been applied to the synthesis of pravadole 30, a drug that shows analgesic activity against postoperative pain in man. Pravadole 30 was prepared from acylindole 29, wich was obtained by palladium-catalyzed carbony-
The alteration of pressure, amines, solvents and catalysts allows to find the best conditions those are given at the Scheme 12. The best catalyst is PdCl 2 (dppf) complex (dppf is 1,1'-bis(diphenylphosphino)ferrocene.
Reaction carrying out in the secondary amine (the best one -is Et 2 NH) at 20 atm CO and catalysis by 2 mol % PdCl 2 (dppf) leads to flavone 36 (scheme 13) [26]. Selective formation of aurone or flavone at carbonylation of o-iodophenole and phenylacetylene depends on reaction conditions (temperature, CO pressure) and used bases. The influence of the nature of a solvent, amine, catalyst, carbon monoxide pressure, and temperature on the yield of the flavone was studied [26,27].
The influence of various solvents, catalysts and additives on the yields of benzopyrans 39 was studied. The best reaction conditions were (i) for obtaining benzopyran 39a (79% yield) and (ii) for benzopyran 39b (79% yield).
The same authors have shown for the first time that on simaltaneously interaction of the propargylalkylamines with a carbon monoxide and a carbon dioxide catalyzed by PdI 2 or Pd 0 /C in the presence of KI consistent carboxylation and alkoxycarbonylation reactions proceed leading to Z-and E-[(alkoxycarbonyl)methylene]oxazolidin-2-ones 45 a and 45 b [31,32] (Scheme 17).
In the absence of carbon monoxide only oxazolidinone 46 has been formed (Scheme 18).
Among other synthetic methods for such structural inits catalytic cyclocarbonylation of acetylene alcohols at first had not great importance, because of it gave low yields of α-methylene-γ-butyrolactone 47 by reaction of 3-butyn-1-ol with stoichiometric amount of nickel tetracarbonyl [35]    Comparative study of the ability of the various catalytic systems to cyclocarbonylate of acyclic and cyclic alcohols has shown that system PdCl 2 , anhydrous SnCl 2 and 2 equiv. of tertiary phosphine in acetonitrile is the best one. At that not only α-methylene γ-lactones, but δ-lactones of various structure in cis-and trans-fused rings can be made with rather high yields, if the substrate concentration is kept sufficiently low (0.1-1М), to direct the reaction into intramolecular cyclization way. Study of cyclocarbonylation mechanism shows at first carboalkoxy intermediate species is formed from Pd(II), CO and acetylene alcohol, followed by intramolecular cis addition to the triple bond [37,38] (Scheme 21).
Competitive intermolecular insertion of the triple bond in another substrate can occur, leading to obtaining of dimeric and, eventually, polymeric products. Cleavage of the vinyl-palladium bond by the proton generated in the first reaction removes the product and regenerates the initial Pd(II) complex. In the course of mechanism studies the authors design a much more efficient Pd(II) catalyst system with SnCl 2 as a cocatalyst, that of role is in labilizing of palladium coordination sphere. As at use of PdI 2 /Bu 3 P/MeCN catalyst system the rate-determining step evidently being the uptake of CO by Pd, then for second catalyst system case (PdCl 2 /2Ph 3 P/SnCl 2 /MeCN) the rate-determining step is coordination of the substrate, followed by   2 Br, (CH 2 ) 2 CH=CH 2 , (CH 2 ) 3 , (CH 2 ) 4 , (CH 2 ) 5 i PdCl 2 (0.07 equiv.), SnCl 2 (0.07 equiv.), PPh 3 (or PBu 3 ) (0.14 equiv.), CO (to 7.8 atm.), MeCN, 65-75°C.
The presence of alkyl substituents α to the triple bond is essential in order to achieve good selectivi-excellent yields. Where there was dialkyl substitution α to the triple bond as in 51c, the reaction was slower, and the product yield of the γ-lactone 52 lower. When cyclization is disfavoured by molecular geometry, as in the case of trans-2-ethynylcyclopentan-1-ol 51, product distribution changes in favour of maleate, the γ-lactone 52e being obtained as byproduct [39].
Formation of α α α α α-(triorganosilyl)methylene β β β β β -, γ γ γ γ γ -, and δ δ δ δ δ-lactones Cyclocarbonylation of acetylenic alcohols 60, 63, γ-Lactone 65 is derived from homopropargyl type alcohols 63 by a similar operation even more easily than 61 already with employment of Me 2 PhSiH and Et 3 N. This operation is also applicable to the synthesis of six-membered α-silylmethylene lactones 66, although a combined use of t-BuMe 2 SiH and Et 3 N is required for the selective formation of δ-lactone 66.  Intermediate A may be proposed as the common intermediate to give lactone and propenal derivatives.
The general method of selective synthesis of fu-ran-2(5H)-ones 76 and 77 from acetylenes has been proposed, being in elaboration of lasts by water gas and carbon monoxide (100 atm) in THF containing triethylamine at 100°С in the presence of rhodium carbonyl cluster catalyst [47,48]

Scheme 29
The isomer ratio of the formed furanones 76 and 77 depends on electronic and steric nature of the substituents. As catalysts, rhodium carbonyl clusters such as Rh 4 (CO) 12 and Rh 6 (CO) 16 are the best among the tested transition metal complexes. Ruthenium carbonyls showed a very low activity, but cobalt and iron carbonyls were almost inactive for the present rection. The presence of amines such as diethylamine or triethylamine is essential for the selective synthe-sis of furanones. The absence of amines resulted in a marked decrease in both catalytic activity and product selectivity.
Carbonylation of 2-methylbut-3-yn-2-ol catalyzed by Co 2 (CO) 8 in benzene proceeds with low yield, but 100% selectivily giving 5,5-dimethylfuran-2(5H)one 78 (Scheme 30) [49]. was formed, due to the fast hydrolysis of the acylcobalt intermediate prior to the alkyne complexation. Thus phenylacetic acid was the only product obtained. This inconvenience was circumvented by performing the reaction in the abcence of water in a solid-liquid system using a new kind of chelating agent, N[(CH 2 ) 2 O(CH 2 ) 2 OCH 3 ] 3 (TDA), wich has the same properties as a crown ether but without the toxicity and the work-up difficulties encountered with the macrocyclic catalysts [52]

Synthesis of but-2-enolide
Alkynes 79 react smoothly with CO and CH 3 J in a liquid-liquid two-phase system to yield regioselectivly the corresponding but-2-enolide 80, most probably via the intermediate formation of acylcobalt complex (Scheme 31) [50,51].
The catalyst is [CO 2 (CO) 8 ], and the reaction has been run at temperatures around 100°C and CO pressures of 100-300 and up to 1000 bar. Polar aprotic solvents as MeCN, MeNO 2 , acetone, N,N,N',N'tetramethylurea, esters and ethers appear to be most suitable. The yields in acetone as the solvent have been improved by adding phosphines or phosphates [57]. In 1975, it was shown that Co complexes are i Co 2 (CO) 8
The reaction of alkynes 94 with CO/O 2 in diox-