Cycloaddition-Elimination mechanism

The 1,2,4-thiadiazolidine (369) and the 1,2,4-dithiazolidine (370) are interconvertible in the presence of electrophilic nitriles and give the l,2,4-thiadiazoline-5-ones (371) as products (Scheme 61) (91JOC3268). It is suggested that the reaction goes by a consecutive cycloaddition - elimination mechanism via hypervalent sulfur intermediates in which the nitrile approaches in the plane of the heterocycle. 

Electron-poor nitriles react with compound 87 and its derivatives to form the 5-amino-l,2,4-thiadiazole derivatives 104 <1985JOC1295>. Therefore, the formation of product 94 (see Scheme 21) may be explained alternatively by the addition of amidonitrile 93 to compound 90. The mechanism of the formation of product 104 was discussed in detail in CHEC-II(1996) <1996CHEC-II(4)691> but most probably the steps involved are (1) reaction of the electrophilic nitrile with the exocyclic nitrogen of compound 87 or its derivatives (2) loss of nitrogen similarly to the previous reactions and formation of an imine 103 (3) masked 1,3-dipolar cycloaddition/elimination reaction of the nitrile to the imine 103. Since the same nitrile is expelled in the elimination step, only 1 equiv of reagent is needed (Scheme 24). 

In addition to isolation and characterization of the ruthenacycle complexes 18 or 32, the detailed reaction mechanism of the [2 + 2 + 2] cyclotrimerization of acetylene was analyzed by means of density functional calculations with the Becke s three-parameter hybrid density functional method (B3LYP) [25, 33]. As shown in Scheme 4.12, the acetylene cyclotrimerization is expected to proceed with formal insertion/reductive elimination mechanism. The acetylene insertion starts with the formal [2 + 2] cycloaddition of the ruthenacycle 35 and acetylene via 36 with almost no activation barrier, leading to the bicydic intermediate 37. The subsequent ring-... 

In the case of the attacks of neutral molecules on alkynes, nucleophilic attack is often difficult to distinguish from molecular cycloaddition or electrophilic initiation. Reaction (7) is typical of many which could equally as well be formulated as beginning with a dipolar cycloaddition or an acyclic zwitterion Detailed mechanism of these cycloaddition-elimination reactions remains to be explored... 3 . 

A related approach for the synthesis of spirocyclopenteneoxindoles was developed by Barbas and coworkers. Chiral diphosphines catalyzed the [3+2] cycloaddition between the A-protected methyleneindolin-2-ones 17b and the Morita-Baylis-Hillman (MBH) carbonates 37 [18]. This reaction was initiated by the displacement of the carbonate moiety by the phosphine VI, an addition-elimination mechanism, which was followed by the deprotonation to afford ylide 39. A regioselective nucleophilic addition on 17 by 39, followed by an intramolecular conjugate addition, afforded intermediate 40 that, after elimination of PR3, delivered the corresponding spirocycle 41 (Scheme 10.11). 

The coupling of alkynes and iminocarbene complexes (e.g., 4, Scheme 17.2) affords pyrrole ring systems (e.g., 6) in a formal [3-1-2]-cycloaddition process [2,3]. The pyrroles obtained are analogous to those obtained from nitrile ylide cycloadditions. A mechanism was proposed involving a net metalla-[4- -2] cycloaddition to afford azametallacycle 7 followed by reductive elimination and alkene isomerization. The regiochemistry arises through a nonconcerted addition to the triple bond via... 

The formation of the tricarbonylchromium-complexed fulvene 81 from the 3-dimethylamino-3-(2 -trimethylsilyloxy-2 -propyl)propenylidene complex 80 and 1-pentyne also constitutes a formal [3+2] cycloaddition, although the mechanism is still obscure (Scheme 17) [76]. The rf-complex 81 must arise after an initial alkyne insertion, followed by cyclization, 1,2-shift of the dimethylamino group, and subsequent elimination of the trimethylsilyloxy moiety. Particularly conspicuous here are the alkyne insertion with opposite regioselectivity as compared to that in the Dotz reaction, and the migration of the dimethylamino functionality, which must occur by an intra- or intermo-lecular process. The mode of formation of the cyclopenta[Z ]pyran by-product 82 will be discussed in the next section. 

The [3S+1C] cycloaddition reaction with Fischer carbene complexes is a very unusual reaction pathway. In fact, only one example has been reported. This process involves the insertion of alkyl-derived chromium carbene complexes into the carbon-carbon a-bond of diphenylcyclopropenone to generate cyclobutenone derivatives [41] (Scheme 13). The mechanism of this transformation involves a CO dissociation followed by oxidative addition into the cyclopropenone carbon-carbon a-bond, affording a metalacyclopentenone derivative which undergoes reductive elimination to produce the final cyclobutenone derivatives. 

The reaction of methyl acrylate and acrylonitrile with pentacarbonyl[(iV,iV -di-methylamino)methylene] chromium generates trisubstituted cyclopentanes through a formal [2S+2S+1C] cycloaddition reaction, where two molecules of the olefin and one molecule of the carbene complex have been incorporated into the structure of the cyclopentane [17b] (Scheme 73). The mechanism of this reaction implies a double insertion of two molecules of the olefin into the carbene complex followed by a reductive elimination. 

A plausible mechanism for the [2+2+2] cycloaddition reactions between diynes and heterocumnlenes (or nitriles) is shown in Scheme 5.16. Initially [2+2] oxidative addition of one alkyne and the heterocnmnlene (or nitrile) forms the five-mem-bered intermediate 54 compound 55 is formed after the insertion of the second alkyne and finally the seven-membered compound 55 undergoes reductive elimination to afford the prodnct 56 and regenerate the Ni(0) catalyst. 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

An allenylaldehyde can be transformed efficiently into an a-methylene-y-butyro-lactone by a ruthenium-catalyzed carbonylative cycloaddition process (Scheme 16.34) [37]. The reaction mechanism may involve a metallacyclopentene, which undergoes insertion of CO and reductive elimination leading to the product. 

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