Internal alkynes, cross-coupling with

The reaction of certain palladium-heteroatom complexes to alkenes and alkynes is a versatile tool for the synthesis of alkanes and alkene having heteroatoms attached. In particular, the various B-B, B-Si, and B-Sn compounds can be used for palladium-catalyzed borylation of alkenes and alkynes (Scheme 5-2). Borostannylation takes place at ambient temperature, whereas silylboration " only proceeds at a temperature above 80 °C due to the slow oxidative addition of a B-Si bond to a palladium(O) catalyst. Both reactions selectively provide cz j-products via addition of silicone or tin to the internal carbon and boron. The reactions are compatible with various functional groups for both terminal and internal alkynes. Cross-coupling reaction of boranes with organic halides selectively occurs at the terminal C-B bonds to provide regiodefined and stereodefined alkenylboron, alkenylsilicon, and alkenyltin compounds. 

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

Silylacetylenes were reported to undergo cross-coupling with internal alkynes (Eq. 65) [109]. 

This method can be exploited as part of a one-pot hydroalkylation of an internal alkyne. Thus, titanium-catalyzed syn hydrozincation [24], followed by Negishi cross-coupling with an alkyl halide, stereospecifically generates a trisubstituted olefin (Eq. 8). 

In this section, Pd-catalyzed homocoupling of tenninal alkynes, cross-coupling of terminal alkynes with internal alkynes, and cross-coupling of terminal alkynes with allenes will be discussed. All three types of reactions involve (i) activation of the C—bond of a terminal alkyne, (ii) alkynylpalladation of another molecule of alkyne or allene, and (iii) reductive elimination or protonation to produce a conjugated enyne. For alkynylpallada-tions of allenes followed by trapping with nucleophiles, see Sect. IV.7. 

TMS-alkynes are oxidized at the terminal carbon to carboxylic acids by hydroboration/oxidation (dicyclohexylborane/NaOH, H2O2). This does not work with TIPS-alkynes. Instead, TIPS-alkynes are cleanly monohydroborated at the internal carbon by 9-borabicyclo[3.3.1]nonane dimer to give (Z)- -borylvinyl-silanes. These can be oxidized in high yields to a-silyl ketones, or cross coupled with a bromide R Br (R = aryl, benzyl, dimethyl-vinyl) in the presence of NaOH and tetrakis(triphenylphos-phine)palladium(0) to give /3,/3-disubstituted vinylsilanes (Suzuki reaction eq 14). The same nucleophilic substituted vinylsilane can be added to an aromatic aldehyde to provide access to ( )-3-silyl allyl alcohols. ... 

Denmark pursued intramolecular alkyne hydrosilylation in the context of generating stereodefined vinylsilanes for cross-coupling chemistry (Scheme 21). Cyclic siloxanes from platinum-catalyzed hydrosilylation were used in a coupling reaction, affording good yields with a variety of aryl iodides.84 The three steps are mutually compatible and can be carried out as a one-pot hydro-arylation of propargylic alcohols. The isomeric trans-exo-dig addition was also achieved. Despite the fact that many catalysts for terminal alkyne hydrosilylation react poorly with internal alkynes, the group found that ruthenium(n) chloride arene complexes—which provide complete selectivity for trans-... 

Protti, S., Fagnoni, M. and Albini, A. (2005) Photo-cross-coupling reaction of electron-rich aryl chlorides and aryl esters with alkynes a metal-free alkynylation. Angewandte Chemie, International Edition, 44, 5675-5678. 

In the presence of a base (Et3N) the ruthenium vinylidene complex RuCl(Cp )(PPh3)(=C=CHPh) promotes the selective cross-coupling of a bulky terminal alkyne with internal alkynes at room temperature to yield functionalized enynes (Eq. 10) [77]. 

The addition of diboron compounds to alkynes is an excellent method for the synthesis of c -diboryl alkenes (Scheme 2-11) [34], The reaction is catalyzed by Pt(PPh3)4 at 80 and works well not only with terminal but also with internal alkynes. The addition of the Si-B [35] or Sn-B [36] bonds to alkynes gives mixed-metal alkenylboron reagents which have potential ability for use in the stepwise double cross-coupling reaction at both metallated carbons. 

T.F. Walsh and co-workers synthesized two (S)- 3-methyl-2-aryltryptamine based gonadotropin hormone antagonists via a consecutive Larock indole synthesis and Suzuki cross-coupling. The required (S)-P-methyltryptophol derivatives were prepared by coupling 4-substituted o-iodoanilines with optically active internal alkynes under standard conditions. The resulting 2-trialkylsilyl substituted indoles were then subjected to a silver-assisted iododesilylation reaction to afford the 2-iodo-substituted indoles that served as coupling partners for the Suzuki cross-coupling step. 

This cross coupling can also be used with alkenylzirconium compounds derived from internal alkynes if metal salts of Zn or Cd, such as ZnCl2, are added in catalytic amounts. For example, the reaction of 1 with 2 under the above conditions fails, but in the presence of 0.2 equiv. of ZnCl2 it results in formation of 3 in 72% yield (2 hours). ... 

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