Cross-coupling reactions propargylation

Palladium And/Or Copper-Mediated Cross-Coupling Reactions Between 1-Alkynes And Vinyl, Aryl, 1-Alkynyl, 1,2-Propadienyl, Propargyl And Allylic Halides Or Related Compounds. A Review, Rossi. R. Carpita, A. Beilina, F. Org. Prep. Proceed. Int., 1995, 27, 129... 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

Scheme 51 Cross-coupling reaction of Ar3Bi with propargyl bromide...

In Table 1 containing 72 (= 9 x 8) classes of cross-coupling reactions, 42 of them, nearly 60% of the total, involve the use of at least one allyl, benzyl or propargyl (or allenyl) reagent as a cross-coupling partner. They can be divided into five categories corresponding to the five blocks in Table 1, as shown below. 

A unique reaction of allenylindium reagents, prepared from propargyl bromides and indium, and haloazines gives rise to the appropriate allenyl-azines. Although the reaction is not a Heck coupling, but a cross-coupling reaction, the aryl moiety is formally attached to a carbon-carbon multiple bond, therefore we mention it here. 

The direct substitution of hydroxyl groups can also be extended towards propargylic alcohols. In the presence of FeCl3, a plethora of O-, N- or S-nudeophiles are able to react with substituted propargylic alcohols [17]. Amongst the variety of nucleophiles, allylsilanes occupy an important position since this example resembles a cross-coupling reaction between an organometallic compound and an alcohol (Scheme 7.12) [17]. 

The cyclopropyl effect has controlled the regioselectivity of the cross-coupling reactions of propargylic/allenylic metallic species with electrophiles afford alkynic cyclopropanes (Scheme 9).70 Cyclopropyl ring strain, which makes the formation of vinylidenecyclopropanes unfavourable, is believed to control the regioselectivity. 

Tsuji, J. and Mandai, T., Palladium-catalyzed Coupling Reactions of Propargylic Compounds , in Metal-catalyzed Cross-coupling Reactions, Wiley-VCH, Weinheim, 1998, pp. 455-489. 

E. Cross-coupling Reactions with Allyl and Propargyl Halides..1283... 

R. Rossi, A. Carpita, F. Beilina, Palladium- and/ or copper-mediated cross-coupling reactions between 1-alkynes and vinyl, aryl, 1-alkynyl, 1,2-propadienyl, propargyl and allylic halides or related compounds A review, Org. Prep. Proced. Int. 1995, 27, 127-160. 

As a consequence of the mild reaction conditions in the sequence to 3-halo furans 55 the palladium catalyst should be still intact to trigger another Pd-catalyzed coupling in the sense of a sequentially Pd-catalyzed process [31]. As a consequence, a sequential Sonogashira-deprotection-addition-cyclocondensation-Suzuki reaction, where the same catalyst system is applied in two consecutive significantly different cross-coupling reactions in the same reaction vessel should be feasible. Therefore, upon consecutive reactions of (hetero)aroyl chlorides 7 and THP-protected propargyl alcohols 54, Nal and PTSA, and finally, addition of 1.05 equiv of boronic acids 60 and sodium carbonate, the substituted 3-aryl furans 61 can be obtained in decent yields (Scheme 35). 

The cross-coupling reaction of organoboron compounds with organic halides or triflates proceeds selectively in the presence of a base, such as sodium or potassium carbonate, phosphate, hydroxide, and alkoxide [11, 45], The bases can be used in aqueous solution, or in suspension in dioxane or DMF. In contrast, the cross-coupling reaction with certain electrophiles, such as allylic acetates [45], 1,3-butadiene monoxide [49], and propargyl carbonates [50], occurs under neutral conditions without any assistance from a base. The transmetallation of organoboron compounds with palladium halides under basic or neutral conditions can be considered to involve three routes, 1, 2, and 3 (Schemes 2-18, 2-20, and 2-23, below). 

The reaction is completely regioselective in favor of the 8 2 product, and the cross-coupling of propargyl epoxides with organocuprates give nearly an exclusive anti-product when dimethyl sulfur is present, but give mixtures of syn- and anti-products in its absence. 

More recently, cross-coupling reactions between Grignard reagents and propargylic methyl ethers were studied by Alexakis [80], who found that the reaction was highly regioselective in favor of the Sn2 product and highly stereoselective [Eq. (77)]. 

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