Carbonyl intramolecular

Benzodiazocines 182 and 183 were obtained through a sequence of Ugi-depro-tection-carbonylation/intramolecular amidation using ort/io-iodobenzaldehyde and a bifunctional acid or amine [146] (Fig. 36). This cyclocarbonylation was carefully optimized and succeeded in affording 8-membered lactams, which are typically difficult to obtain, in good yields. 

Vasudevan A, Verzal MK (2005) A post-Ugi carbonylation/intramolecular amidation approach toward the synthesis of macrolactams. Tetrahedron Lett 46 1697-1701... 

Carbonylative intramolecular Stille coupling to form macrocyclic molecules was investigated with a palladium complex of the polymer-bound ferrocenyl phosphine 21. One of the major problems encountered in the intramolecular... 

Nitro groups can be added to organic molecules through an aldol reaction between the anion of a nitroalkane and an aldehyde or ketone carbonyl. Intramolecular aldol reactions can be used to create five- or six-membered rings from dicarbonyl compounds (either aldehydes or ketones), which form in preference to smaller or larger rings that may be possible. 

Quinolones unsubstituted in the hetero ring result from a Pd-catalyzed domino alkenyl amino-carbonylation/intramolecular aryl amidation of 2-(2-halogenoalkenyl)aryl bromides with CO and primary amines (via the aminocarbonylation intermediates 119) [183] ... 

An economical mechanistic proposal assumes initial coordination of the carbene to the amide carbonyl. Intramolecular transfer of a proton from the positively charged nitrogen to the negatively charged carbon of the zwitterion constitutes the second step. The final step is base catalyzed removal of the imine proton with concurrent... 

Crisp, G.T. and Meyer, A.G. (1992) Palladium-catalyzed, carbonylative intramolecular coupling of hydroxyl vinyl... 

A closely allied reductive linking of carbonyl groups is an intramolecular version with esters, called the ac doin reaction, which again gives a 1,2-diox rgenated skeleton ... 

Intramolecular reactions between donor and acceptor centres in fused ring systems provide a general route to bridged polycyclic systems. The cts-decalone mesylate given below contains two d -centres adjacent to the carbonyl function and one a -centre. Treatment of this compound with base leads to reversible enolate formation, and the C-3 carbanion substitutes the mesylate on C-7 (J. Gauthier, 1967 A. Belanger, 1968). 

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

The catalytic oxidative carbonylation of allene with PdCb and CuCh in MeOH affords methyl a-methoxymethacrylate (559)[499]. The intramolecular oxidative aminocarbonylation of the 6-aminoallene 560 affords the unsaturated J-amino ester 561. The reaction has been applied to the enantioselective synthesis of pumiliotoxin (562)[500]. A similar intramolecular oxycarbonyla-tion of 6-hydroxyallenes affords 2-(2-tetrahydrofuranyl)acrylates[501]. 

Carbonylation of halides in the presence of primary and secondary amines at I atm affords amides[351j. The intramolecular carbonylation of an aryl bromide which has amino group affords a lactam and has been used for the synthesis of the isoquinoline alkaloid 498(352], The naturally occurring seven-membered lactam 499 (tomaymycin, neothramycin) is prepared by this method(353]. The a-methylene-d-lactam 500 is formed by the intramolecular carbonylation of 2-bromo-3-alkylamino-l-propene(354]. 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Various organotin reagents react with acyl and aroyl halides under mild conditions without decarbonylation to give carbonyl compounds[390,39l]. Alkyl- or alkenyltin reagents react with acyl and aroyl chlorides to give ketones[548.733,734]. One example is the preparation of the a,/3-dnsaturated 7-keto esters 860 and 861, carried out under a CO atmosphere[735]. The reaction has been applied intramolecularly to the synthesis of the macrocyclic keto... 

Similarly to alkenes. alkynes also insert. In the reaction of 775 carried out under a CO atmosphere in AcOH, sequential insertions of alkyne, CO. alkene. and CO take place in this order, yielding the keto ester 776[483]. However, the same reaction carried out in THF in the presence of LiCl affords the ketone 777, but not the keto ester[484]. The tricyclic terpenoid hirsutene (779) has been synthesized via the Pd-catalyzed metallo-ene carbonylation reaction of 778 with 85% diastereoselectivity as the key reaction[485], Kainic acid and allo-kainic acid (783) have been synthesized by the intramolecular insertion ol an alkene in 780, followed by carbonylation to give 781 and 782[486],... 

The allenyl moiety (2,3-aikadienyl system) in the carbonylation products is a reactive system and further reactions such as intramolecular Diels-Alder and ene reactions are possible by introducing another double bond at suitable positions of the starting 2-alkynyl carbonates. For example, the propargylic carbonate 33 which has l,8(or 1.9)-diene-3-yne system undergoes tandem carbonylation and intramolecular Diels-Alder reaction to afford the polycyclic compound 34 under mild conditions (60 C, 1 atm). The use of dppp as ligand is important. One of the double bonds of the allenyl ester behaves as part of the dieneflSj. 

The ring nitrogen can be involved in intramolecular reactions on carbonyl carbon as exemplified by the preparation of 6,7-dimethoxy-4-methyl-10,ll-thiopega-2,9-diene (72) (Scheme 51) (228). 

Intramolecular hydrogen bond between the —OH group and the carbonyl oxygen... 

Both enols have their carbon-carbon double bonds conjugated to a carbonyl group and can form an intramolecular hydrogen bond They are of comparable stability... 

Conjugation is more important 1 3 Cyclohexanedione exists mainly in its enol form in spite of the fact that intramolecular hydrogen bonding is impossible due to the distance between the carbonyl group and the enohc —OH group... 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

In the reaction of aHyl alcohol with carbon monoxide using cobalt carbonyl, Co(CO)g as the catalyst, in the presence of a small amount of hydrogen and carbon monoxide under pressure, 9.8 MPa (1420 psi), at 100°C, intramolecular hydroesterification takes place, yielding y-butyrolactone [96-48-0] (16). 

---