Anion capture, termination

Grigg and coworkers also pioneered the work on cyclization-anion capture reactions using hydride-, [45] carbonyl- [46] or cyanide- [47] capture (Scheme 6.10). The terminating anion capture is, however, not limited to these three examples in fact, the organopalladium(n) intermediate can be captured by a wide variety of anionic, neutral and organometallic agents [47]. 

In these cydizations, the reaction can be terminated in other ways than elimination of /3-hydrogen. Typically the reaction ends by an anion capture process[154]. The following anion transfer agents are known H, OAc , CN, S02Ph, CH(C02R)2, NHRj, CO/ROH, and RM [M = Sn(IV), B(lll), Zn(II)]. Trapping with an amine after alkene insertion to give 189 and 190 is an example. A-Acetyl protection is important in this reaction[155]. 

Terminal alkynes undergo the above-mentioned substitution reaction with aryl and alkenyl groups to form arylalkynes and enynes in the presence of Cul as described in Section 1.1.2.1. In addition, the insertion of terminal alkynes also takes place in the absence of Cul, and the alkenylpalladium complex 362 is formed as an intermediate, which cannot terminate by itself and must undergo further reactions such as alkene insertion or anion capture. These reactions of terminal alkynes are also treated in this section. 

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],... 

The alkyne insertion reaction is terminated by anion capture. As examples of the termination by the anion capture, the alkenylpalladium intermediate 189, formed by the intramolecular insertion of 188, is terminated by hydrogenolysis with formic acid to give the terminal alkene 192. Palladium formate 190 is formed, and decarboxylated to give the hydridopalladium 191, reductive elimination of which gives the alkene 192 [81]. Similarly the intramolecular insertion of 193 is terminated by transmetallation of 194 with the tin acetylide 195 (or alkynyl anion capture) to give the dienyne 196 [82], Various heterocyclic compounds are prepared by heteroannulation using aryl iodides 68 and 69, and internal alkynes. Although the mechanism is not clear, alkenylpalladiums, formed by insertion of alkynes, are trapped by nucleophiles... 

Z-tamoxifen 403 tandem cyclization 290, 295 tandem Heck reaction-anion capture 253-4 tandem Heck reaction-phenoxide capture 253 tandem Heck reactions 251, 252-4 tandem intramolecular Heck-intermolecular Stille cross-coupling 255 taxol 140, 143,243,245 ( )-tazettine 146,234 telomerization 352 telomerization products 343, 345 template effect 140 teraconic anhydride 468 terminal acetylenes, synthesis of 216-20 terminal alkynes 6, 213 terminal 2,2-diorgano-l-aIkcnylboronates 51 terminal diynes 207 ternary complex 444 ternary coupling 177... 

Carbamyl 1,2 and oxycarbonyl 5 chlorides have proven effective starter species although their cyclization-anion capture processes have been only briefly explored (Scheme 5.6.1)." The terminating species in Scheme 5.6.1 are alkynyl (1,5) and alkenyl (3) with pre-formed Sn(IV) capmre agents. These processes, as expected, are regio-and stereoselective and their full potential remains to be explored, but reference to Table 5.6.1 indicates the substantial leverage available from alternative terminating and anion capture species. 

Propargylic carbonates are valuable substrates in Pd(0)-catalyzed processes. Their chemistry differs mechanistically from that of simple alkynes in that they form allenyl palladium species. We and others have shown these versatile intermediates can serve a double function as both starter and terminating species in bis-cyclization-anion capture cascades A typical example is the process 45 46, which generates azabicyclo [3.1.0] hexanes (Scheme 5.6.12) in good yield. ... 

Cyclization-carbonylation-anion capture processes involving in situ generated vinylstannanes as terminating agents (as in Section 5.6.2) afford a variety of complex heterocyclic a, (3-unsaturated ketones in good yield. Typical examples are shown in Table 5.6.4. °... 

Grigg and coworkers have used 2-tributylstannylfuran to terminate a variety of interesting tandem cyclization-anion capture reactions. In one example, aryl iodide 105 reacts via a 5-exo-trig process to provide dihydroindolone 106 [105-107]. 

Another of Grigg s approaches to heterocyclic synthesis involves the anion-capture termination of the palladium cascade (91TL2545). In a typical example, a 1 1-mixture of benzyl halide 649 was reacted with sodium tetraphenylborate in the presence of Pd(0) to give compound 650 in 69% yield. Likewise, allyl acetate 651 reacted under similar conditions to afford 652 in 80% yield. 

Grigg has extended his cyclization-anion capture protocol for a variety of mono- and bis-cyclizations in which organoboron derivatives function as anion capture agents <97T11803>. Thus, as an example of a 5-exo trig monocyclization utilizing an alkene as the terminating species, the iodide 68 afforded the arylated indoline 69. 

Some examples of termination by anion capture are as follows. Reactions are terminated by carbonylation. Domino carbopalladation and carbonylation of the iododiene 163 under 1 atm of CO via a neopentylpalladium intermediate gave the cyclized ester 164 with high yield and diastereoselectivity [82], The iodide 165 underwent 5-exo cyclization to generate the neopentylpalladium 166 and its carbonylation gave the acylpalladium 167. Intramolecular attack by malonate anion affords 168 [83]. 

Intramolecular carbopalladations, which lead to five-, six-, and seven-membered rings very efficiently, have been combined with a subsequent intermolecular nncleophilic termination. In this case, rather unreactive nucleophiles such as acetates can be employed. This type of reaction has been termed an anion capture process by Grigg and co-workers implementing both ionic and non-ionic sources of the terminating agent. 

However, in the queuing processes terminating with stannanes orborane, as anion capture agents, the desired molecular queuing to 57 can be achieved only increasing... 

The chain grows by repetition of the last step each new C-C bond-forming step produces a new anion stabilized by the nitrile group. Termination probably occurs most frequently by proton capture from the solvent. The result is poly (acrylonitrile). 

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