Anion chemistry indole

H. Juwarker, J.-m. Suk, and K.-S. Jeong, Anion recognition in supramolecular chemistry—indoles and related heterocycles, in Topics in Heterocyclic Chemistry, eds P. A. Gale and W. Dehaen, Springer, New York, Heidelberg, 2010, pp. 177-204. 

Whereas Hegedus [335] and Danishefsky [336] were the first to discover a tandem Heck reaction from o-allyl-A -acryloylanilines leading to tricyclic pyrrolo[l,2-a]indoles or pyridino[l,2-a]indoles [336], it has been the fantastic work of Grigg to unleash the enormous potential of this chemistry. Grigg and his co-workers parlayed their Pd-catalyzed tandem polycyclization-anion capture sequence into a treasure trove of syntheses starting with IV-allyl-o-haloanilines [337-345], Diels-Alder and olefin metathesis reactions can be interwoven into the sequence or can serve as the culmination step, as can a wide variety of nucleophiles. An example of the transformation of 289 to 290 is shown below in which indole is the terminating nucleophile [340],... 

Several classes of carbon nucleophiles have been successfully used in these systems, reflecting the utility of Reissert chemistry for derivatizing azines via carbon-carbon bond formation. Apart from cyanide anion, other classes of carbon nucleophiles have been explored. For instance, addition of indole (51) to A-acyla-zinium salts proceeds selectively at the a-position (Scheme 9). Pyrrole, quinolines and isoquinolines all behave similarly [73-76]. A related reaction, yielding adduct 70 (Scheme 12b) has also been described. In this case, azine activation is promoted by Vilsmeier reagents (generated by reaction of amides with POCI3) [77]. p-Dicarbonyls are reactive inputs in this chemistry, and dialkyl malonates 53... 

Another important aspect of indole chemistry is the ability to achieve regioselectivity for the N-1 position. The formation of the anion usually results in this position being the most nucleophilic site. For example, deprotonation and subsequent reaction with an aUcyl halide or sulfonate is a standard method for introduction of a nitrogen substituent. However, this reactivity can also be exploited in catalytic systems. We will encounter several cases where N-1 or C-3 selectivity can be achieved by the choice and strength of a base. 

Wender and White published a very simple indole ring synthesis that involves the generation of a bis-lithio anion 1 and its reaction with an a-halo carbonyl compound 2, followed by acid- or base-catalyzed dehydration [1,2], The overall transformation is shown in Scheme 1, along with three examples. This chemistry illustrates yet another indole ring synthesis that uses a-halo carbonyl compounds [3]. We will encounter these compounds again with the venerable Bischler indole synthesis in Chapter 23. A summary of several Wender indole ring syntheses is tabulated in Table 1 [1, 2, 4-7], Entry 5 features a directed lithiation method to the bis-lithio nucleophile [5], a modification also described by Wender and White [2], Sainsbury and... 

Because the reactions of related in -cyclohexadienyl complexes are synthetically valuable, the reactions of this ligand have been studied extensively. An outline of how this chemistry can be conducted on the Fe(CO)j fragment is shown in Equation 11.51. A variety of cyclohexadienes are readily available from Birch reduction of substituted aromatics. Coordination and abstraction of a hydride, typically by trityl cation, leads to cationic cyclohexadienyl complexes. These cyclohexadienyl complexes are reactive toward organolithium, -copper, -cadmium, and -zinc reagents, ketone enolates, nitroal-kyl anions, amines, phthalimide, and even nucleophilic aromatic compounds such as indole and trimethoxybenzene. Attack occurs exclusively from the face opposite the metal, and exclusively at a terminal position of the dienyl system. This combination of hydride abstraction and nucleophilic addition has been repeated to generate cyclohexa-diene complexes containing two cis vicinal substituents. The free cyclohexadiene is ttien released from the metal by oxidation with amine oxides. ... 

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