Heterocycles alkenylation

Treatment of [IrCl(CO)2(/ -toluidene)] with azine phosphines of type Z, -PPh2CH2C( Bu) =N-N=C(Q)R, Q = H, Me, R = an organic group, activates aryl, heterocyclic, alkenyl, or aliphatic C—H bonds to give cyclometalated Ir111 hydrides.339... 

Heterocycles. Alkenyl and aryl boronates deliver their organic residues to the opposition of the nitrogen atom of cyclic carbinolamines to replace the hydroxyl group. Synthesis of 2,3,5-trisubstituted furans, from a catalyzed reaction of alkynyl borates and enones, is achieved in one step. 

Alkoxythiazoles are prepared by heterocyclization (274, 462). The Williamson method using catalytic amounts of KI and cupric oxide is also possible (278. 288, 306). 5-Acetoxy-4-alkenylthiazoles are obtained by treatment of 242 with acetyl chloride and triethylamine or with acetic anhydride and pyridine (450). Similarly, the reaction of diphenylketene with 242 affords 5-acyloxy-4-alkenylthiazoles (243) (Scheme 120) (450). The readiness of these o-acetylations suggests that 4-alkylidene thiazoline-5-one might be in equilibrium with 4-alkenyl-5-hydroxythiazoles (450). 

Crozet and coworkers have used Sp l reactions followed by elimination of HNO for the synthesis of various new heterocyclic compounds substituted with alkenyl groups These compounds are expected to be important for pharmaceutical nse fsee Eq 7 139)... 

In a similar way as described for the hydroformylation, the rhodium-catalyzed silaformylation can also be used in a domino process. The elementary step is the formation of an alkenyl-rhodium species by insertion of an alkyne into a Rh-Si bond (silylrhodation), which provides the trigger for a carbocyclization, followed by an insertion of CO. Thus, when Matsuda and coworkers [216] treated a solution of the 1,6-enyne 6/2-87 in benzene with the dimethylphenylsilane under CO pressure (36 kg cm"2) in the presence of catalytic amounts of Rh4(CO)12, the cyclopentane derivative 6/2-88 was obtained in 85 % yield. The procedure is not restricted to the formation of carbocycles rather, heterocycles can also be synthesized using 1,6-enynes as 6/2-89 and 6/2-90 with a heteroatom in the tether (Scheme 6/2.19). Interestingly, 6/2-91 did not lead to the domino product neither could 1,7-enynes be used as substrates, while the Thorpe-Ingold effect (geminal substitution) seems important in achieving good yields. 

The synthesis of (5 5 5) fused heterocycle 62 has been achieved via intramolecular Diels-Alder reaction involving a series of A-alkenyl-substituted furanyl amides 494 (Scheme 112) <2006JOC5432>. 

As the representative examples in Scheme 6.11 illustrate, similar stragies may be applied to the corresponding alkenyl ethers (vs. styrenyl ethers) [26], The Zr-catalyzed kinetic resolution/Ru-catalyzed metathesis protocol thus delivers optically pure 2-substituted di-hydrofurans that cannot be accessed by resolution of the five-membered ring heterocycles (see Scheme 6.8). It should be noted, however, that the efficiency of the Zr-catalyzed resolution is strongly dependent, and not in a predictable manner, not only on the presence but the substitution of the acyclic alkene site of the diene substrate. The examples shown in Scheme 6.11 clearly illustrate this issue. 

This hydroxycyclopropanation of a terminal double bond also works perfectly well in an intramolecular situation, e. g. with terminally alkenyl-substituted esters, to yield substituted l-hydroxybicyclo[n.l.O]alkanols [85a,85b,100], aminobicyclo[n.l.O]alkanols [85c], and heterocyclic analogues [99a,99b,100], in which five- and six-membered rings are formed (Table 11.7). 

This RCM has proven to be a useful synthetic method for the construction of a variety of heterocycles. Mono and bicyclic unsaturated ethers and sulfides are obtained from alkenyl thioacetals having an ether or sulfide linkage (Table 14.2) [30],... 

In addition, there are several Japanese patents on antibacterial pyridazine derivatives as represented by formulae (110, X = halogen R = substituted amino, AlkS) [320, 321], (111, R1 = substituted Ph R2 = alkyl, alkenyl, morpholinosulphonyl) [322] and (112, R1 = aryl, aminosubstituted heterocycle R2 = H, halogen, alkyl R3 = COOH R4 = aryl, aralkyl, etc.) [323]. 

A wide range of carbon-carbon double bonds undergo chain polymerization. Table 3-1 shows monomers with alkyl, alkenyl, aryl, halogen, alkoxy, ester, amide, nitrile, and heterocyclic substituents on the alkene double bond. 

When only one heteroatom of the dinucleophile possesses a hydrogen substituent, the reactions lead instead to alkenyl complexes rather than carbene compounds. Effectively, treatment of diphenylallenylidenes 1 and 6 with pyrazoles yields the heterocyclic derivatives 61 (Scheme 2.25) [76]. Interestingly, the dissymmetric 3-methylpyrazole (R=H, R = Me) provides only one regioisomer, in which the methyl group points towards the metal. This process, which formally corresponds to the addition of two nitrogen nuclei at C and Cy and a hydrogen atom at Cp, is assumed to take place through an initial nucleophilic attack at the Ca position. 

A -Benzyl groups on pyrimidinones and quinazolinones are removable by hydrogenolysis, although it is now more common to use a PMB substituent that can be removed with either TFA or CAN. Other N-protecting groups to be commonly used include benzyloxymethyl (BOM), removable by hydrogenation, ferZ-butoxycarbonyl (BOC), removable by anhydrous acid, and pivaloyloxymethyl (POM), which is removable by methanolic ammonia at room temperature. Alkenyl pyrimidinones have been employed in 1,3-dipolar cycloaddition reactions to prepare heterocyclic nucleotides. 

A [4-f2] cycloaddition was the key step in the synthesis of substituted dihydrothiopyrans from 2-alkenyl-l,3-oxathianes and an alkene. The reaction was mediated by a Lewis acid. It is assumed that the Lewis acid attacks the oxygen of the heterocycle which upon ring opening gives the highly reactive cationic heterodiene which reacts with alkenes to the thiopyrans in 31-88% yield (Scheme 75) <2000TL371>. 

A related reaction has been observed with alkenyl substituted 1,2-dihydroquinolines. Heating these compounds results in oxidation of the heterocycle with corresponding reduction of the double bond. A radical mechanism was also postulated to be operating in this reaction (equation 14) (75JOC2288). 

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