Intermolecular reactions nucleophilic termination

Examples of palladium- and rhodium-catalyzed hydroaminations of alkynes are shown in Equations 16.90-16.92 and Table 16.9. The reaction in Equation 16.90 is one of many examples of intramolecular hydroaminations to form indoles that are catalyzed by palladium complexes. The reaction in Equation 16.91 shows earlier versions of this transformation to form pyrroles by the intramolecular hydroamination of amino-substituted propargyl alcohols. More recently, intramolecular hydroaminations of alkynes catalyzed by complexes of rhodium and iridium containing nitrogen donor ligands have been reported, and intermolecular hydroaminations of terminal alkynes at room temperature catalyzed by the combination of a cationic rhodium precursor and tricyclohexylphosphine are known. The latter reaction forms the Markovnikov addition product, as shown in Equation 16.92 and Table 16.9. These reactions catalyzed by rhodium and iridium complexes are presumed to occur by nucleophilic attack on a coordinated alkyne. 

Molecularity vs. Mechanism. Cyclization Reactions and Effective Molarity A useful illustration of the distinctions between mechanism, molecularity, and order arises in the analysis of intramolecular versions of typically intermolecular reactions. Consider a classic Sn2 reaction of an amine and an alkyl iodide. The reaction is second order (first order in both amine and alkyl iodide) and bimolecular (two molecules involved in the transition state that s what the "2" in "Sn2" Stands for). The mechanism involves the backside attack of the nucleophilic amine on the C, displacing the iodide in a single step. Now consider a long chain molecule i that terminates in an amine on one end and an alkyl iodide on the other. Now two types of Sn2 reactions are possible. If two different molecules react, we still have a second order, bimolecular, intermolecular reaction. The product would ultimately be a polymer, ii, and we will investigate this type of system further in Chapter 13. Alternatively, an intramolecular reaction could occur, in which the amine reacts with the iodide on the same molecule producing a cyclic product. Hi. This is still called an S 2 reaction, even though it will be first order and unimolecular. 

Intramolecular carbopalladations, which lead to five-, six-, and seven-membered rings very efficiently, have been combined with a subsequent intermolecular nucleophilic termination. In this case, rather unreactive nucleophiles such as acetates can be employed. This type of reaction has been termed an anion capture process by Grigg and co-workers implementing both ionic and non-ionic sources of the terminating agent. 

Chloroadenallene 45 gave, after refluxing with triethylphosphite for 30 min, g-2 -phosphonate 47 in 30% yield (Scheme 7). A routine dealkylation afforded phosphonic acid 48 (60%). Thus, the usual reaction at the reactive allylic terminal was suppressed in favor of a nucleophilic attack at the sp carbon atom. The mechanism may include an intramolecular dealkylation as indicated in formula 49, although an intermolecular reaction is also possible. 

The synthetic utility and generality of the reaction is demonstrated by an intramolecular/intermolecular double allylation using an oo-dienyl aldehyde 38 as a probe. The internal diene terminus selectively undergoes nucleophilic allylation intramolecularly to form a cyclopentanol structure. The terminal... 

An interesting intermolecular version of this reaction has likewise been put forward for the preparation of seven-, eight-, and nine-mem-bered carbocycle, as illustrated with a sole example in Scheme 3 [7]. In contrast to the above, these reactions begin with a carbonyl addition reaction of chloroiodoalkanes to cyclic or acyclic keto esters leading to the formation of an intermediate lactone. An intramolecular nucleophilic acyl substitution then terminates the sequence. The example in Scheme 3 represents a simple method for the construction of the 5 8 5 tricyclic ring system. 

The corresponding reaction of but-3-yn-l-ols or pent-4-yn-l-ols with primary or secondary alcohols in the presence of catalytic amounts of Ph3PAuBF4 and p-TsOH afforded tetrahydrofuranyl ethers (Scheme 4-76). This tandem 5-endo-cycloisomerization/hydroalkoxylation proceeds via 2,3-dihydrofurans, which then undergo an intermolecular Bronsted acid-catalyzed addition of the external alcohol. The transformation is not restricted to internal alkynols but can be applied to terminal acetylenes as well. Application of the method to the s thesis of bicyclic heterocycles with a P-lactam structure was reported recently.Under the same conditions, epoxyalkynes undergo a sequence of epoxide opening, 6-exo-cycloisomerization, and nucleophilic addition to afford tetrahydropyranyl ethers. In a closely related transformation, cyclic acetals were obtained from alk-2-ynoates bearing a hydroxy group in 6- or 7-position by treatment with AuCU and MeOH. ... 

For the step which limits the reaction rate (rate limiting step), three mechanisms have been proposed, two of which are intramolecular - denominated intramolecular, as such, and solvolytic - and the other intermolecular (Figure 2.1.18). The first of these implies a covalent bond between water and the atoms of carbon during the whole of the transposition. In the solvolytic mechanism there is an initial rupture from the O-C, bond, followed by a nucleophilic attack of the H2O on the C3. Whilst the intermolecular mechanism corresponds to a nucleophilic attack of H2O on the terminal carbon C3 and the loss of the hydroxyl group protonated of the C. ... 

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