Electrophilic cyclizations

Those syntheses of pyrido[3,2-d]pyrimidines in which pyrimidines are the starting materials are completed either by an intramolecular electrophilic cyclization of a pyrimidine with a vacant 4-position (route i) or by the addition of the C-5 and C-6 atoms to a 4-substituted-5-aminopyrimidinc (route ii). 

The most satisfactory method involving this type of intramolecular electrophilic cyclization was the thermal ring-closure of aminomethylenemalonates (e.g., 119, R = COOEt) to yield the pyrido[3,2-d]pyrimidine-2,4,8(l/7,3/f,5/f)-trione (120, R = COOEt). 

Electrophilic cyclizations of unsaturated amides to form 5- and 6-member lactams 98T13681. 

A novel approach to azabicyclic ring systems, based on an epoxide-initiated electrophilic cyclization of an alkyl azide, has been developed by Baskaran. A new stereo- and enantioselective synthesis of the 5-hydroxymethyl azabicyclic framework 91a, present in (+)- and (-)-indolizidines 167B and 209D, for example, was... 

Scheme 8.24 Epoxide-initiated electrophilic cyclization of azides.

TL9381, 96CC1395>. The reaction involves deprotonation of the Vilsmeier reagent, dimerization of the carbene formed and electrophilic cyclization of the dimer by bromonium ion action followed by aqueous hydrolysis. 

Electrophilic cyclizations are useful for closure of a variety of oxygen-, nitrogen-, and sulfur-containing rings. The product structure depends on the ring size and the exo-endo selectivity. The most common cases are formation of five- and six-membered... 

Internal nucleophilic capture of seleniranium ion is governed by general principles similar to those of other electrophilic cyclizations.96 The stereochemistry of cyclization can usually be predicted on the basis of a cyclic TS with favored pseudoequatorial orientation of the substituents. 

The electrophilic cyclization of 19-1 and 19-2 gives two isomers, but with the unsubstituted reactant 19-3, only a single stereoisomer is formed. Explain the origin of the isomers and the absence of isomer formation in the case of 19-3. 

One drawback to this alkyne annulation chemistry is that it requires either symmetrical alkynes or unsymmetrical alkynes in which the two substitutents on the internal alkyne are sterically quite different or else one obtains mixtures of regioisomers. One way to overcome this problem is to prepare the corresponding arylalkyne through catalytic Pd/Cu chemistry and then effect electrophilic cyclization using organic halides and a Pd catalyst (Scheme 8).9... 

Mesoxalates are highly reactive substrates because of their strongly polarized carbon-oxygen bond. They have been used in pericyclic processes (e.g. Diels-Alder reactions,8 ene reactions,9 [3+2]10 and [2+2]11 cycloadditions), in aldol12 and Wittig as well as Friedel-Crafts reactions.13 Further applications arise from the use of the corresponding imines in hetero Diels-Alder reactions14 and electrophilic cyclizations.15... 

Electrophilic cyclization of the precursors 8, which are available from 3-(methylthio)pyridine by regioselective lithiation, followed by introduction of CBr4, and a subsequent Sonogashira coupling, has resulted in a series of thieno[3,2-b]pyridines 9... 

At present, the chemisty of selenophenes and tellurophenes is a relatively scantily studied area. Nevertheless, a number of new valuable contributions dealing with their chemistry have emerged. Electrophilic cyclization of l-(l-alkynyl)-2-(methylseleno)arenes provides a route to a variety of 2,3-disubstituted benzo[fe]selenophenes, as illustrated by the preparation of the system 88. Other useful electrophiles for similar reactions are E or NBS <06JOC2307>. Similar chemistry has also been employed in preparation of 2,3-disubstituted benzo[f>]selenophenes on solid phase <06JCC163>. In addition, syntheses of 2,3-dihydroselenolo[2,3- >]pyridines have been achieved using radical chemistry <06OBC466>. 

The Yao group has made use of a Ic type intramolecular Heck reaction to prepare the C2-symmetric dimeric indole core of chloptosin <06OL4919>. A solvent-free variation of the Bischler indole synthesis, electrophilic cyclization of a-arylamino imine tautomers prepared from aniline derived a-arylamino ketones, has been used by Menendez and co-workers for the preparation of 2-arylindoles <06SL91>. 

In this approach, the cis-disubstituted tetrahydrofuranone 75 [accessible with high diastereoselectivity via radical cyclization of the acylselenide 74 with tris(tri-methylsilyl) silane and triethylborane] was transformed into the corresponding enyne 76 by reduction and Wittig olefination. The subsequent electrophilic cyclization was carried out in analogy with the biomimetic synthesis of panacene (Scheme... 

Scheme 18.25 Synthesis of laurallene (65) [84] formation of the side chains and electrophilic cyclization.

Similarly, electrophilic cyclizations of dienols and trienols, such as homogeraniol and homonerol, were carried out without addition of strong acid, using benzeneselenenyl triflate18,144 as the organoselenium reagent (equations 145 and 146). 

Although the chemistry of pentatetraenylidene complexes [M]=C(=C)3=CR R has not received as much attention as that of aUenylidenes, there is ample experimental evidence to confirm the electrophilic character of the C, Cy and carbons of the cumulenic chain [26-29, 31]. Thus, treatment of tra s-[RuCl(=C=C=C=C=CPh2) (dppe)2][PFg] (132) with alcohols or secondary amines resulted in addition of the nucleophilic solvent across the Cy=Cs double bond to give alkenyl-allenylidenes 138 (Scheme 48) [358]. In chloroform, electrophilic cyclization with one of the Ph groups occurred to give 139. This transformation is actually the parent of the later observed allenylidene to indenylidene intramolecular rearrangement (Scheme 15). 

This is a complicated series of reactions, but includes impressive examples of carbocation rearrangements. The electrophilic cyclization sequence is also quite striking, and this is discussed in more detail in Box 8.3. 

This problem covers a reaction sequence and a variety of different reactions, some easier than others. This one includes enolate anions, electrophilic cyclization, nucleophilic substitution, and simple carboxylic acid chemistry. 

The next transformation is an electrophilic cyclization. Protonation of the terminal alkene produces the more favourable tertiary carbocation, then ring formation occurs by electrophilic addition to the neighbouring alkene. 

Intramolecular electrophilic cyclization of methyl selenoate gives only a 12% yield of benzo[/]pyrrolo[2,l- ][l,3]thiazepin-9(10H)-one 285, while cyclization of an acetate derivative under a variety of the conditions failed (Scheme 61 (1998JMC3763)). An alternate route from pyrrole ketones 286 by oxidation and TFAA induced cyclization proved to be advantageous providing a 40% yield of 285. 

The formation of lactam 79b from amide 79a as recently published (09OBC3561) is placed first here it proceeds in two steps via acetal hydrolysis and electrophilic cyclization of the intermediate piperidinium salt. 

Armstrong RJ, Weiler L (1986) Synthesis of ( )-karahana ether and a ( )-labdadienoic acid by the electrophilic cyclization of epoxy allylsilanes. Can J Chem 64 584—596... 

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