Vinylation stannanes

Tributyltin hydride-mediated hydrodebromination of bromoarenes is selectively carried out. However, removal of the tin residue should be carefully carried out. The 10% w/w anhydrous potassium carbonate-silica repeatedly reduces organotin impurity levels below 15 ppm in this system (Table 3-12). In addition, organotin reagents such as tributyltin hydride, allyl stannanes, vinyl stannanes, arylstannanes, and distannanes can be purified by the K2CO3 and silica column chromatography. On the contraiy, halostannanes and sulfonated stannanes are trapped through this process (Table 3-13). 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

C Vinyl stannane coupling 9 3-Bromo-l-(methanesulfonyl)indole Pd(OAc)2, chloranil Z-(2-Etho,xy vinyl)tri-n-butylstannane, Pd(PPh3)2Cl2 83 [9]... 

Vinylation can also be done by Pd-catalysed cross-coupling in which one component is used as a halide or triflate and the other as a stannane (Stille reaction) or boronic acid (Suzuki reaction). Entry 9, Table 11.3, is an example of the use of a vinylstannane with a haloindole. lndole-3-boronic acids, which can be prepared by mcrcuration/boration, undergo coupling with vinyl triflates (Entry 10). 

The Suzuki coupling of arylboronic acids and aryl halides has proven to be a useful method for preparing C-aryl indoles. The indole can be used either as the halide component or as the boronic acid. 6-Bromo and 7-bromoindolc were coupled with arylboronic acids using Pd(PPh3)4[5]. No protection of the indole NH was necessary. 4-Thallated indoles couple with aryl and vinyl boronic acides in the presence of Pd(OAc)j[6]. Stille coupling between an aryl stannane and a haloindole is another option (Entry 5, Table 14.3). 

In related work, 3-chloromethylcephems were coupled with tributyl(tnfluoro-vinyl)stannane catalyzed by tri(2-furyl)phosphine palladium(O) [7S, 19] (equation 13). 

The above procedure was used for the preparation of all compounds except 104p, which was obtained from 104r by palladium-catalyzed coupling with tributylvinyl-stannane followed by palladium-catalyzed cyclopropanation of the resulting vinyl intermediate with diazomethane (Scheme 32) (99BMC3187). 

Legros et al. (2001T2507) carried out the synthesis of acetylquinolines (e.g. 130) via Heck reaction of 3-bromoquinoline (70) and -butyl vinyl ether (Scheme 16) employing either Pd(dba)2 or Pd(OAc)a as the catalyst. In each case it was found that the Heck reaction for this synthesis gave better overall yields than using the Stille reaction (see Section IV.C). Another advantageous point in favor of the Heck is that it avoids the use of toxic stannane. 

Stannyl cuprates couple widi vinyl halides or trlGales [16c-d, 85], and a vinyl stannane produced diis way has been used in die syntliesis of 7-[f )-alkylidetie]-cepbalosporlns [117]. Vinyl substitution reactions slariing Grom ddiydrofciraiis are... 

A number of StHle coupling reactions have been reported by Handy et al. [95]. With PdCl2(PhCN)2/Ph3As/Cul in [BMlM][Bp4], good yields and good catalyst recyclability (up to five times) were reported for the reaction between a-iodenones and vinyl and aryl stannanes (Scheme 5.2-19). However, the reported reaction rates were significantly lower than those obtained in NMP. 

Scheme 5.2-19 Pd-catalyzed Stille coupling of a-iodoenones with vinyl and aryl stannanes in...

Stannane 6a underwent facile transmetalation in tetrahydrofuran at — 78 °C on treatment with butyllithium to afford 6b. Addition of the lithium reagent 6b to a solution of 1.1 equivalents of copper(I) bromide-dimethyl sulfide in 1 1 diisopropyl sulfide/tetrahydrofuran at — 78 °C gave the copper reagent 6c, which reacted with methyl vinyl ketone at —78 "C in the presence of boron trifluoride-diethyl ether65, producing 7 in 55% yield65. 

Treatment of a-isomer 8, which was prepared from the corresponding stannane in a similar way with methyl vinyl ketone under identical conditions, afforded 9 in 75% yield. 

Very recently, the coupling of tributyl(phenyl) and tributyl(vinyl) stannanes with cyclohexene derivatives was successfully carried out using a similar catalytic cocktail prepared from Pdj(dba)3 CHCl, IPr HCl and Cs CO as base. Outstanding results... 

Scheme 6.38 CoupUng between cyclic aUyl chlorides and phenyl/vinyl stannanes...

The Stille reaction has been successfully applied to a number of macrocyclic ring closures.207 In a synthesis of amphidinolide A, the two major fragments were coupled via a selective Stille reaction, presumably governed by steric factors. After deprotection the ring was closed by coupling the second vinyl stannane group with an allylic acetate.208... 

Alkenyl silanes and stannanes have the potential for nucleophilic delivery of vinyl groups to a variety of electrophiles. Demetallation also occurs in these reactions, so the net effect is substitution for the silyl or the stannyl group. 

RajanBabu et al. have described an addition-elimination sequence employing vinyl stannanes for the preparation of homoallylic alcohols containing 5-membered rings [104],... 

The natural product panepophenanthrin (6/1-170), isolated in 2002 from the fermented broth of the mushroom strain Panus radus IFO 8994 [90], is the first example of an inhibitor of the ubiquitin-activating enzyme [91]. Retrosynthetic analysis based on a biomimetic analysis led to the conjugated diene 6/1-172 by a retro-Diels-Alder reaction via the hemiacetal 6/1-171. Further disconnections of 6/1-172 produces the vinyl stannane 6/1-173 and the vinyl bromide 6/1-174 [92]. 

Intramolecular nucleophilic assistance is another distinct possibility for providing activation, and can be realized by coordination of the metal center by a heteroatom (O, N, etc.) within the ligand which transiently forms a chelate-like attachment to the metal. Such a mode of activation was supposed to account for the ease of reaction of vinyl triflates with (zp-isomers of alkenyl-stannanes bearing OH groups in the proximity of the reaction center (71).2 5... 

The following two schemes exemplify the synthesis of piperidines via 1,4-addition of amines. In the first scheme below, a one-pot Stille coupling/double Michael addition, starting from readily available vinyl stannanes, is used to generate piperidinones 174 <06SL547>. An example of the reduction of piperidinone 174 to piperidine 175 is also highlighted. 

Pyran-2-ones are formed in high yield through the Pd-catalysed annulation of allenyl stannanes by P-iodo vinylic acids. The reaction, which probably involves a Stille cyclisation sequence, exhibits good selectivity (Scheme 36) <00CC1987>. 

Stannanes bearing aliphatic groups with unsaturation in the carbon chain are grouped in Table 3, including both open-chain and cyclic vinyl-, allyl- and alkynylstannanes. 

Reaction 39 shows the condensation of acylstannanes with primary amines. The only isomer produced was tentatively ascribed the Z-configuration291. Acylstannanes undergo Wittig-type processes with organophosphorus compounds to yield vinyl stannanes, as illustrated in reactions 40 and 41. In the latter reaction products are preferably of Z-configuration292. 

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