Coupling allylic substitution

Yamano T, Taya N, Kawada M, Huang T, Imamoto T (1999) Tetrahedron Lett 40 2577 Brunner H, Nishiyama H, Itoh K (1993) Asymmetric hydrosilylation. In Ojima I (ed) Catalytic asymmetric synthesis. Wiley-VCH, New York, chap 6 Sawamura M, Kuwano R, Ito Y (1994) Angew Chem, Int Ed Engl 33 111 Kuwano R, Uemura T, Saitoh M, Ito Y (1999) Tetrahedron Lett 40 1327 Hayashi T (1993) Asymmetric allylic substitution and grignard cross-coupling. In Ojima I (ed) Catalytic asymmetric synthesis. WUey-VCH, New York, chap 7-1 Trost BM, Vranken DLV (1996) Chem Rev 96 395 Consiglio G,Waymouth RM (1989) Chem Rev 89 257... 

Keywords Allylic substitution Catalysis Cross-coupling Cycloaddition Cycloisomerisation DNIC Ferrate Hydrogenase Iron... 

Palladium(0)-catalyzed coupling reactions - i. e. the Heck and Sonogashira reactions, the carbonylative coupling reactions, the Suzuki and Stille cross-coupling reactions, and allylic substitutions (Fig. 11.1) - have enabled the formation of many kinds of carbon-carbon attachments that were previously very difficult to make. These reactions are usually robust and occur in the presence of a wide variety of functional groups. The reactions are, furthermore, autocatalytic (i.e. the substrate regenerates the required oxidation state of the palladium) and a vast number of different ligands can be used to fine-tune the reactivity and selectivity of the reactions. 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

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. 

Blechert reported a skillful method of cross-enyne metathesis. Solid-supported alkyne 139 is reacted with alkene in the presence of Ic to give 140. For cleavage of 1,3-diene from solid-supported product 140 having an allyl acetate moiety, palladium-catalyzed allylic substitution is used. Thus, 140 is treated with Pd(PPh3)4 in the presence of methyl malonate to afford three-component coupling product 141 in good yield ... 

Scheme 10.5 The stereospecific allylic substitution approach to a stereotetrad using a linchpin cross-coupling reaction.

Transition metal-catalyzed allylic substitution with phenols and alcohols represents a fundamentally important cross-coupling reaction for the construction of allylic ethers, which are ubiquitous in a variety of biologically important molecules [44, 45]. While phenols have proven efficient nucleophiles for a variety of intermolecular allylic etherification reactions, alcohols have proven much more challenging nucleophiles, primarily due to their hard, more basic character. This is exemphfied with secondary and tertiary alcohols, and has undoubtedly limited the synthetic utihty of this transformation. 

A polyethylene glycol-polystyrene graft copolymer palladium catalyst has been used in allylic substitution reactions of allyl acetates with various nucleophiles in aqueous media.58 Another polymer-bound palladium catalyst 40 was developed and used in a Heck coupling of allylic alcohols with hypervalent iodonium salts to afford the substituted allylic alcohols as the sole products under mild conditions with high catalytic efficiency.59 The same polymer-bound palladium catalyst has also been used for Suzuki cross-coupling reactions.60... 

Bremberg, U., Lutsenko, S., Kaiser, N.F., Larhed, M., Hallberg, A. et at, Rapid and stereoselective C—C, C—O, C—N andC—S couplings via microwave accelerated palladium-catalysed allylic substitutions, Synthesis, 2000, 1004-1008. 

In an effort to extend the use of the Pyrphos-derived dendrimers to asymmetric Pd-catalyzed coupling reactions, strongly positive selectivity effects were observed upon going to very large multi-site chiral dendrimer catalysts. This enhancement of the catalyst selectivity was observed in palladium-catalyzed allylic substitutions, such as that displayed in Scheme 3, which are known to be particularly sensitive to small changes in the chemical environment of the active catalyst sites [17]. 

The detachment of molecules with concomitant cross-coupling or allylic substitution is an elegant means of increasing diversity on cleavage. A common drawback of most methods is contamination with transition metal catalysts and organo-metallic by-products, although a variety of methods is available for the sequestering of transition metals from the cleaved products. The same applies to removal of other by-products. 

A tandem radical 5-exo cyclization/radical addition/allylic substitution reaction was subsequently described [292]. Allylic ot-bromo acetal 242b cyclized cobalt-catalyzed. Addition to diene 245 and subsequent coupling with coformed organocobalt(I) species generates an allylcobalt complex, which undergoes reductive elimination to cyclic product 246 in 93% yield (cf. Fig. 56). 

Allylindium reagents can be utilized in the Pd-catalyzed cross-coupling reaction with aryl halides. The Pd-catalyzed allylic substitution of allyl carbonate produces 1,5-dienes (Scheme 103).353-355... 

Keywords Allylic substitution CH activation Cross-coupling Cycloisomerization Domino reactions Metallation Multicomponent reactions Palladium catalysis... 

The categories of sequentially Pd-catalyzed processes in this chapter are based upon the initial process. These are Heck reactions, allylic substitutions, aminations, Sonogashira couplings, metallations, CH activations, cycloisomer izations and miscellaneous processes. 

In this sense Organ and coworkers [80] have developed intriguing syntheses of polysubstituted olefins based upon consecutive intermolecular reactions such as allylic and allylic-vinylic halide coupling sequences. Therefore, l-acetoxy-4-chloro but-2-ene can be readily submitted as a template for Pd-catalyzed allylic substitutions with two different carbon or nitrogen nucleophiles, leading to unsymmetrically substituted butene derivatives 66-70 in good yields (Scheme 22). Mechanistically, the chloro substituent is replaced... 

If 2,3-dibromo propene is used as an allylic substrate the substitution product 71 can be either isolated or, after addition of additives and adjustment of the reaction conditions, 71 can readily react in cross-coupling reactions with alkynes (Sonogashira coupling), stannanes (Stille coupling), or boronic acids and boronates (Suzuki coupling) to provide the sequential allylic substitution-cross-coupling products 72-78 in moderate to good yields (Scheme 23). 

Equally, a 1.5 1 mixture of cis- and frans- 1,3-dibromo propene reacts with sodium dimethyl methylmalonate to furnish the vinyl bromo derivative 79 in excellent yield, which in turn is transformed in a one-pot fashion to a 1.5 1 mixture of enyne 80 or the corresponding Suzuki products 81 and 82 (Scheme 24). Interestingly, (( )-3-bromo-propenyl)-tributylstannane furnishes the vinyl stannane 83 upon allylic substitution that instantaneously is subjected to the conditions of a Stille coupling with iodo benzene to give the sequence s product 84 in 68% yield (Scheme 25). 

Sequential allylic substitution-Stille coupling" Sequential allylic substitution-Suzuki coupling"... 

Scheme 23 Sequential allylic substitution-cross-coupling [80]...

Using this principle, Kibayashi and coworkers [147] have introduced a sequential cyclic carbopalladation-Stille vinylation of enyne compounds. Upon treating the enyne 196 and vinyl tributylstannane with catalytic amounts of Pd2(dba)3 CHCI3 in the presence of AcOH the allyl-substituted methylene cyclopentane 197 was formed in 53% yield (Scheme 80). The subsequent cross-coupling occurs with complete suppression of /M I-climinalion and the Alder-ene product 198 was not detected. Likewise, this sequence was extended to heteroatom-linked enynes and further vinyl tin compounds to provide the heterocyclic analogs 199 in moderate to excellent yields (Scheme 81). 

---