Cyclization transmetalation

Termination occurs by transmetallation with organometallic compounds of B and Sn, followed by reductive elimination. The aryl iodide 172 underwent 5-exo cyclization. Transmetallation of the alkylpalladium with vinyltin reagent, followed by reductive elimination, afforded 173 [85]. The anion trap is not limited to the... 

The allylstannane 474 is prepared by the reaction of allylic acetates or phosphates with tributyltin chloride and Sml2[286,308] or electroreduction[309]. Bu-iSnAlEt2 prepared in situ is used for the preparation of the allylstannane 475. These reactions correspond to inversion of an allyl cation to an allyl anion[3l0. 311], The reaction has been applied to the reductive cyclization of the alkenyl bromide in 476 with the allylic acetate to yield 477[312]. Intramolecular coupling of the allylic acetate in 478 with aryl bromide proceeds using BuiSnAlEti (479) by in situ formation of the allylstannane 480 and its reaction with the aryl bromide via transmetallation. (Another mechanistic possibility is the formation of an arylstannane and its coupling with allylic... 

An enantioselective variant of the diene cydization reaction has been developed by application of chiral zirconocene derivatives, such as Brintzinger s catalyst (12) [10]. Mori and co-workers demonstrated that substituted dial-lylbenzylamine 25 could be cyclized to pyrrolidines 26 and 27 in a 2 1 ratio using chiral complex 12 in up to 79% yield with up to 95% ee (Eq. 4) [ 17,18]. This reaction was similarly applied to 2-substituted 1,6-dienes, which provided the analogous cyclopentane derivatives in up to 99% ee with similar diastereoselectivities [19]. When cyclic, internal olefins were used, spirocyclic compounds were isolated. The enantioselection in these reactions is thought to derive from either the ate or the transmetallation step. The stereoselectivity of this reaction has been extended to the selective reaction of enantiotopic olefin compounds to form bicyclic products such as 28, in 24% yield and 59% ee after deprotection (Eq. 5) [20]. 

A copper-mediated cyclization of metallated thiophenes has been utilized to prepare polycyclic thiophenes and thiophene cyclophanes. Treatment of dibromide 106 in succession with M-butyllithium (halogen-metal exchange), zinc chloride (transmetallation), and copper chloride gave 7//-cyclopcnta[ 1,2-fc 4,3-6 dithiophene (107) <00H(52)761>. This conversion has also been achieved using a palladium-mediated cyclization performed in the presence of hexamethylditin . Copper-mediated cyclizations have also been applied to the syntheses of cyclopenta[2,l-6 3,4-A ]dithiophen-4-one (108) (three steps from 73) <00S1253> and cyclophane 109 <00CC2329>. 

The reaction of CO2 with 1,3-butadienes in the presence of Ni catalysts usually gave an isomeric mixture of carboxylic acids 89 and 90 after hydrolysis (Scheme 32).47,48 The oxa-7r-allylnickel complexes 87 and 88 might be the reaction intermediates, which could be formed through oxidative cyclization of Ni(0) with C02 and the dienes. When Me2Zn was used as a transmetallation agent to react with the oxa-7r-allylnickel intermediates under a C02 atmosphere, further carboxylation took place at the 7r-allylnickel unit. Thus, the 1,4-diesters 95 were obtained after acidic hydrolysis and treatment with diazomethane as shown in Scheme 32.47... 

A novel Ni(cod)2-catalyzed allene/alkene cyclization has been utilized in the synthesis of (-)-a-kainic acid (Scheme 16.88) [96], A stereocontrolled metallacycle would be generated via coordination of Ni(0) species to both an alkene of the enone and a proximal allenyl double bond followed by oxidative cyclization of the Ni(0) complex. The metallacycle would be transformed into the product through transmetallation of Me2Zn and ensuing reductive elimination. 

Transmetalations of alkenylstannanes with copper salts are reversible if they are performed with CuCl in polar solvents [101]. This has found application in cyclization reactions (Scheme 2.49) [102]. 

It has been found that enantio-enriched a-(homoallyloxy)alkyllithiums (84), formed from the corresponding stannanes (83) by stereoretentive transmetallation, cyclize with complete retention of configuration at the lithium-bearing -carbon to yield enantio-enriched Q ,jS-disubsfituted tetrahydrofurans (85 and 86). This is consistent with earlier theoretical calculations which suggested that the lithium might coordinate with the olefinic bond in the transition state. 

The mechanism was proposed to involve the formation of a nickel metallacycle by the oxidative cyclization of Ni(0) with the aldehyde and alkyne, followed by conversion of the metallacycle to product by a transmetalation/reductive elimination sequence. If R possesses a P-hydrogen, then P-hydride elimination after the transmetalation step generates the product with R = H in some instances. The mechanism was shown to be ligand dependent, and the mechanism depicted below is undoubtedly oversimplified. ... 

Ortholithiated oxazoline 62 is best transmetallated to its magnesium analogue before reaction with aldehydes. As with the equivalent amide reaction, treatment with 4.5 M HCl then cyclizes the products to lactones (Scheme 31) °. ... 

The availabihty of enantioenriched 2-tribntylstannylpyrrolidines ° can be used to advantage in these reactions. Conversion to a snbstrate snitable for cyclization allows, after transmetalation, the determination of the stereoselectivity on intramolecnlar carbolithia-tion. Treatment of the enantioenriched stannane shown in Scheme 23 with bntyllithinm resnlted in the formation of the pyrrolizidine alkaloid psendoheliotridane. The prodnct was formed as a single diastereomer and with no loss of optical pnrity, occnrring with overall retention of confignration at the carbanion center. Related cychzation reactions... 

Pd(II)-cataIyzed cyclization of the siloxyhexatriene 34 offers a cyclohexe-none annulation method. The Pd enolate 35, formed by transmetallation of the silyl enol ether with Pd(II), is an intermediate which undergoes intramolecular endo-alkene insertion. Then Pd(II) is regenerated to give 36, and finally cyclohexenone is formed[38]. 

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