Stille coupling with enols

Scheme 32. Stille couplings of regioselectively generated enol triflates with a vinylstannane.

Stille has employed the Pd-catalyzed coupling that bears his name in syntheses of anthramycin and analogues [79, 80]. Thus, enol triflate 112 is smoothly coupled with acrylates to provide 113-115. 

An application of Stille couplings to the solid phase using a traceless A-glycerol linker with 2-stannylindoles has been developed [177]. Only a few examples of the use of 3-stannylindoles in Stille reactions have been described. Ortar and co-workers prepared 169 and 170 and effected Pd-catalyzed cross coupling reactions with several aryl, heteroaryl, and vinyl substrates (bromides, iodides, triflates) to give the expected products 171 in high yields [178]. Enol triflates behave exceptionally well under the Ortar conditions, e.g., 172 to 173. 

The introduction of the allylic silane moiety required for the intermolec-ular Hosomi-Sakurai reaction is depicted in Scheme 16. Following the formation of the enol triflate 97, a Stille coupling provided excess to the allylic alcohol 98 [51]. The allylic alcohol (98) was endowed with a phosphate leaving group for the subsequent allylic substitution. Utilizing a trimethylsilyl cuprate as nucleophile for the 5 2 reaction, the allylic phosphate was converted into the allylic silane 89. A useful substrate-induced diastereoselectivity in favour of (14i )-89 was encountered at small scale but decreased significantly upon up-scaling. 

Vinyl triflates (C=C-0S02CF3) react with vinyl tin derivatives in the presence of palladium catalysts to form dienes, in what is known as the Stille coupling. Vinyl triflates can be prepared from the enolate by reaction with Al-phenyl trifli-... 

Hong, F.-T., Paquette, L. A. Olefin metathesis in cyclic ether formation. Direct conversion of olefinic esters to cyclic enol ethers with Tebbe-type reagents. Copper(l)-promoted Stille cross-coupling of stannyl enol ethers with enol triflates construction of complex polyether frameworks. Chemtracts t997, 10,14-19. 

Arylquinones, arylallenes, dienyl sul more unusual molecules whose assembly 1 cross coupling with a-alkoxyalkenylstana proach to enol ethers of defined configurat A technical modification of the Stille c polymer support. ... 

Stille coupling of 2-carboxyethyl enol triflates with organostannanes. ° In the presence of Pd(OAc)2/P(C6H5)3 (1 2) or Pd[P(C6Hs)3]4, the enol triflates of -keto esters couple with vinyl-, allyl-, and alkynyl(tributyl)stannanes, but not with phenyltributyltin. 

AUcynylstannanes can cross-couple with a variety of other functional groups employing the Stille protocol. Couphng to acyl chlorides is a well-known procedure that affords aUcynylketones in respectable yields. Other reports include alkynyltin cross-couplings with a-haloethers and a-halocarbonyls, enol phosphinates and phosphonates, alkenyl(phenyl)iodonium salts, alkynyl halides, and allyl hahdes (Table 9.18). Alkynylstannanes have also been shown to cross-couple with iron halides under the Stille conditions to effectively form iron-carbon bonds. 

The installation of the pharmacologically important isoquinoline group was achieved by a Stille coupling. Reduction by diimide yielded the trans-fused perhydroindane subunit in 329. An oxidation, enol triflation and reduction sequence converted 329 to enone 331. Enol triflation and deprotection afforded 332. Palladium-catalyzed vinylation, followed by a Parikh-Doering oxidation gave 333. The final and rather splendid step consisted of dimethyl imine-formation and vinysilane cyclization to furnish cortistatin J in high yield and with the correct dimethylamine stereochemistry (Scheme 18.66). 

Still s synthesis of monensin (1) is based on the assembly and union of three advanced, optically active intermediates 2, 7, and 8. It was anticipated that substrate-stereocontrolled processes could secure vicinal stereochemical relationships and that the coupling of the above intermediates would establish remote stereorelationships. Scheme 3 describes Still s synthesis of the left wing of monensin, intermediate 2. This construction commences with an aldol reaction between the (Z) magnesium bromide enolate derived from 2-methyl-2-trimethylsilyloxy-3-pentanone (21) and benzyloxymethyl-protected (/ )-/ -hydroxyisobutyraldehyde (10).2° The use of intermediate 21 in aldol reactions was first reported by Heathcock21 and, in this particular application, a 5 1 mixture of syn aldol diastereoisomers is formed in favor of the desired aldol adduct 22 (85% yield). The action of lithium diisopropylamide (LDA) and magnesium(n) bromide on 21 affords a (Z) magnesium enolate that... 

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