Alkynes propargylic compound reactions

Propargylic (or 2-alkynyl) compounds are derivatives of alkynes. However, Pd-catalyzed reactions of propargylic derivatives, particularly esters and halides, are very different mechanistically from those of simple alkynes, except in a few cases. Therefore, the reactions of propargylic esters and halides are treated in this section separately from those of other alkynes. However, some reactions of propargylic alcohols, which behave similarly to simple alkynes, are treated in Section 6. 

Reactions of Propargylic Compounds Catalyzed by Pd(Q) 5.2 Reactions with Alkenes and Terminal Alkynes... 

Acylzirconocene chlorides 78, which are easily available through the hydrozirco-nation of alkenes or alkynes with Cp2Zr(H)Cl and subsequent CO insertion, can be used as acyl anion equivalents Cu(I)-catalyzed reactions with propargyl compounds 77 afford allenyl ketones 79 (Scheme 3.40) [86]. The use of an excess of 77 (2 equiv. to 78) is important for the selective preparation of 79, which prevents an undesirable side reaction of the allenic products 79 with 78. 

Propargylic compounds (2-alkynyl compounds) are derivatives of alkynes and they undergo several types of transformations in the presence of transition metal catalysts. However, catalytic reactions of propargylic compounds, particularly their esters and halides, clearly differ mechanistically from those of simple alkynes, except in a few cases. Therefore, the catalytic reactions of propargylic compounds are treated independently from those of simple alkynes. The most extensive studies have been carried out using Pd catalysts, and mainly Pd-catalysed reactions are treated in this chapter [1],... 

From a mechanistic viewpoint, the Pd(0)-eatalysed reactions of propargylic compounds so far discovered can be classified into four types I IV The allenyl complexes 5 undergo three types of transformations depending on reactants. Type I reactions proceed by insertion of unsaturated bonds to the n-bond between Pd and the sp2 carbon in 5. Type la is the insertion of alkenes to the palladium-carbon n-bond, and the 1,2,4-alkatrienes are formed by /f-elimination. Alkynes insert to form the alkenylpalladium 6, which undergoes various transformations such as insertion of unsaturated bonds and anion captures. 

Reduction of propargylic compounds with Sml2 is possible in the presence of Pd catalysts. Propargylic acetates 233 are converted mainly to the allene 236 by Pd-catalysed reaction with Sml2 in the presence of a proton source [51]. In this reaction, the allenylpalladium 234 is reduced with Sm(II) to the allenyl anion 235, which is protonated to give allene 236. The alkyne 237 is a byproduct. 2,3-Naphthoquinodi-methane (240) as a reactive intermediate, can be generated by applying this reaction. 

Soon afterwards, the same group developed methodologies for the oxidative carbonylation of 4-yn-l-ones and propargylic esters (Scheme 8.22). While 2-cyclopentenone carboxylates were obtained from appropriate carbonyl-substituted alkynes [96], cyclic orthoesters and furanones were successfully synthesized starting from corresponding propargylic compounds [97]. More recently, they also realized the asymmetric version of this reaction [98], which has also been applied in the total synthesis of (—)-AL-2 by Mukai and Miyakoshi [99]. 

This concept was refined by the research group of Li, who employed the thiol-yne reaction instead of the olefin cross-metathesis reaction as key step [60]. In this case, the carboxylic acid component served as anchor, whereby terminal alkynes were introduced by the remaining components (5-hexyn-l-al and propargyl isocyanoacetamide). Interestingly, thiol-yne addition of 3-mercaptopropionic acid to the pendant alkynes enabled not only the incorporation of further carboxylic acids, but also resulted in additional branching. Therefore, the second generation dendrimer, synthesized in three steps, exhibited 16 peripheral triple bonds. Moreover, this concept offers the opportunity to introduce structural diversity into the dendrimer architecture because the use of only one alkyne-functionalized compound in the Passerini-3CR still results in branching due to the thiol-yne reaction. Here, a structural sequence of employed phenylacetaldehyde and 2-nitrobenzaldehyde was demonstrated. 

In 2007, Guo et al. developed an efficient protocol to fused polycycles 172 from propargylic compounds 171 and alkynes via a palladium-catalyzed tandem biscyclization reaction involving C—H bond activation-initiated oxidative addition of propargylic esters, followed by cyclization and a l,n-palladium shift via C—H activation [69] (Scheme 6.47). 

Among several propargylic derivatives, the propargylic carbonates 3 were found to be the most reactive and they have been used most extensively because of their high reactivity[2,2a]. The allenylpalladium methoxide 4, formed as an intermediate in catalytic reactions of the methyl propargylic carbonate 3, undergoes two types of transformations. One is substitution of cr-bonded Pd. which proceeds by either insertion or transmetallation. The insertion of an alkene, for example, into the Pd—C cr-bond and elimination of/i-hydrogen affords the allenyl compound 5 (1.2,4-triene). Alkene and CO insertions are typical. The substitution of Pd methoxide with hard carbon nucleophiles or terminal alkynes in the presence of Cul takes place via transmetallation to yield the allenyl compound 6. By these reactions, various allenyl derivatives can be prepared. 

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... 

Extension of this reaction to electrophiles other than aldehydes was unsuccessful [22, 23], However, propargylic boronates were found to react with allylic halides and various carbonyl compounds [23], The boronates were prepared by lithiation of a methyl-substituted alkyne with t-butyllithium followed by treatment with a trialkylborane. The propargylic boronate preferentially reacts with the electrophile at the y-position to yield propargylic products (Eq. 9.20). The methodology has also been applied to alanates with comparable results. 

Some synthetically important allenylmetallics, such as allenylzinc and allenylin-dium reagents, are prepared from allenylpalladium intermediates. These reactions are discussed in appropriate sections of this chapter. This section covers the reactions of allenylpalladium compounds without further transmetallation. Allenylpalladium complexes can be prepared from propargylic halides, acetates, carbonates, mesylates, alcohols and certain alkynes [83-87], The allenylpalladium compound prepared from 3-chloro-3-methyl-l-butyne has been isolated and characterized spectroscopically (Eq. 9.106) [83], It was found to couple with organozinc chlorides to produce homologated allenes quantitatively (Eq. 9.107). 

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