Heck reaction, intramolecular

Heck reaction, intramolecular, 60, 2 Helicenes, synthesis by photocyclization, 30, 1... 

Intramolecular reactions with alkenes. While the intermolecular reaction is limited to unhindered alkenes, the intramolecular version permits the participation of even hindered substituted alkenes, and various cyclic compounds are prepared by the intramolecular Heck reaction. Particularly the... 

In the synthesis of morphine, bis-cyclization of the octahydroisoqtiinolinc precursor 171 by the intramolecular Heck reaction proceeds using palladium trifluoroacetate and 1,2,2,6,6-pentamethylpiperidine (PMP). The insertion of the diene system forms the rr-allylpalladium intermediate 172, which attacks the phenol intramolecularly to form the benzofuran ring (see Section 1.1.1.3). Based on this method, elegant total syntheses of (-)- and (+ )-dihydrocodei-none and (-)- and ( + )-morphine (173) have been achieved[141]. 

Asymmetric cyclization using chiral ligands has been studied. After early attempts[142-144], satisfactory optical yields have been obtained. The hexahy-dropyrrolo[2,3-6]indole 176 has been constructed by the intramolecular Heck reaction and hydroaryiation[145]. The asymmetric cyclization of the enamide 174 using (S j-BINAP affords predominantly (98 2) the ( )-enoxysilane stereoisomer of the oxindole product, hydrolysis of which provides the ( l-oxindole aldehyde 175 in 84% yield and 95% ec. and total synthesis of (-)-physostig-mine (176) has been achieved[146]. 

The development of methods for aromatic substitution based on catalysis by transition metals, especially palladium, has led to several new methods for indole synthesis. One is based on an intramolecular Heck reaction in which an... 

Synthesis of heterocycles using the intramolecular Heck reaction involving a formal nnd-elimination process 99H(51)1957. 

This reaction also represents an example of the intramolecular Heck reaction, a variant that has gained some importance in recent years. Another instructive example of the potential of this reaction for the construction of ring systems has been reported by de Meijere and coworkers, taking advantage of a sequence of four consecutive intramolecular Heck reactions. The bromodiene-yne 18 reacts in a sequence of domino reactions within 3 d at 80 °C under Heck conditions to give the tetracyclic product 19 in 74% yield ... 

The intramolecular Heck reaction presented in Scheme 8 is also interesting and worthy of comment. Rawal s potentially general strategy for the stereocontrolled synthesis of the Strychnos alkaloids is predicated on the palladium-mediated intramolecular Heck reaction. In a concise synthesis of ( )-dehydrotubifoline [( )-40],22 Rawal et al. accomplished the conversion of compound 36 to the natural product under the conditions of Jeffery.23 In this ring-forming reaction, the a-alkenylpalladium(n) complex formed in the initial oxidative addition step engages the proximate cyclohexene double bond in a Heck cyclization, affording enamine 39 after syn /2-hydride elimination. The latter substance is a participant in a tautomeric equilibrium with imine ( )-40, which happens to be shifted substantially in favor of ( )-40. 

The Heck reaction has also been performed intramolecularly. An intramolecular version that couples vinyl bromide with a C=C unit leads to cyclic com-... 

The intramolecular Heck reaction of polymer bound aryl halides such as 84 affords indole analogs 85 after cleavage of the final product from the resin with TFA <96TL4189>, Other notable uses of the Heck cyclization include a synthesis of an antimigraine agent <96TL4289>, and thia-tryptophans <96T14975>. 

As an application of this methodology to the syntheses of natural products, Sannicolo et al. have reported the preparation of benzazepine and tetra-hydroisoquinoline derivatives by silane-terminated intramolecular Heck reactions. These workers argued that one main disadvantage of the Heck reaction... 

Scheme 7.4 Syntheses of benzazepines and tetrahydroisoquinolines by intramolecular silane-terminated Heck reactions with (T )-BITIANP and ( + )-TMBTP ligands.

Scheme 7.6 Intramolecular Heck reaction with thiophene-containing phosphinoox-azoline ligands.

There are numerous examples of intramolecular Heck reactions,151 such as in Entries 10 to 14. Entry 11 is part of a synthesis of the antitumor agent camptothecin. The Heck reaction gives an 11 1 endocyclic-exocyclic mixture. Entries 12-14 are also steps in syntheses of biologically active substances. Entry 12 is part of a synthesis of maritidine, an alkaloid with cytotoxic properties the reaction in Entry 13 is on a route to galanthamine, a potential candidate for treatment of Alzheimer s disease and Entry 14 is a key step in the synthesis of a potent antitumor agent isolated from a marine organism. 

Carbonylation can also be carried out as a tandem reaction in intramolecular Heck reactions. 

The intramolecular Heck reaction is an appropriate method for the synthesis of all types of cyclic compounds such as normal, medium, and large rings [29]. Using... 

Scheme 6/1.17. Influence of the substitution pattern on the enantioselectivity in intramolecular double Heck reaction.

HO Me Claisen-type condensation Intramolecular Heck reaction... 

Scheme 9.2 Prior approaches to the C3-C3 linked dimers, (a) Hendrickson s oxidative dimerization approach to chimonanthine. (b) Scott s oxidative dimerization of tryptamines. (c) Overman s intramolecular Heck reaction, (d) Overman s asymetric alkylation...

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