Aldehydes terminal alkynes

Scheme 17 Iron-catalyzed three-component coupling reactions of aldehydes, terminal alkynes, and amines...

Intermolecular couplings involving aldehydes, terminal alkynes, and organoz-incs also proceeded with high levels of chemo- and regioselectivity (Scheme 8.15). However, unlike intramolecular couplings, direct addition of more reactive... 

Finally, as noted in the last example in Table 6.7, triple bonds can undergo mono-hydroboration to produce vinylic boranes (both regiochemical adducts) and the latter oxidized with basic hydrogen peroxide to aldehydes (terminal alkynes) or ketones (nonterminal alkynes) or reduced, with acetic acid, to Z-alkenes (Scheme 6.72). 

P. Li, Y Zhang, L. Wang, Chem.-Eur. J. 2009, 15, 2045-2049. Iron-catalyzed ligand-free three-component coupling reactions of aldehydes, terminal alkynes and amines. 

CH3CH=CH CH3CH2CH an aldehyde terminal alkyne forms an aldehyde. 

Both copper- and silver-catalyzed three-component reactions between an aldehyde, terminal alkyne, and secondary amine have been used to generate propargylamines [17, 18] The copper-catalyzed hydroamination between hydroxylamine esters and unactivated aUcenes generates amines with the desired regiochemistry for a wide range of diverse substrates [20]... 

The cascade three-component coupling of aldehydes, terminal alkynes, and amines is one of the most convenient methods for the synthesis of propargylic amines with water as the only theoretical by-product. A recent example is the three-component couphng of aldehydes, alkynes, and carbamates with copper(II) triflate as catalyst, which furnished a diverse range of propargylcarbamates 103 in moderate to high yields, and no other cocatalyst or ligand is required in this transformation (Scheme 5.68) [71],... 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

The hydroboration/oxidation sequence is complementary to the direct, mercury(ll)-catalyzed hydration reaction of a terminal alkyne because different products result. Direct hydration with aqueous acid and mercury(IJ) sulfate leads to a methyl ketone, whereas hydroboration/oxidation of the same terminal alkyne leads to an aldehyde. 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

Terminal alkynes can be converted by a process of hydrosilylation followed by oxidative cleavage into carboxylic acids (10). An alternative basic" cleavage yields the corresponding aldehydes. 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

The hydration of triple bonds is generally carried out with mercuric ion salts (often the sulfate or acetate) as catalysts. Mercuric oxide in the presence of an acid is also a common reagent. Since the addition follows Markovnikov s rule, only acetylene gives an aldehyde. All other triple-bond compounds give ketones (for a method of reversing the orientation for terminal alkynes, see 15-16). With allqmes of the form RC=CH methyl ketones are formed almost exclusively, but with RC=CR both possible products are usually obtained. The reaction can be conveniently carried out with a catalyst prepared by impregnating mercuric oxide onto Nafion-H (a superacidic perfluorinated resinsulfonic acid). ... 

Triple bonds can be monohydroborated to give vinylic boranes, which can be reduced with carboxylic acids to cis alkenes or oxidized and hydrolyzed to aldehydes or ketones. Terminal alkynes give aldehydes by this method, in contrast to the mercuric or acid-catalyzed addition of water discussed at 15-4. However, terminal alkynes give vinylic boranes (and hence aldehydes) only when treated with a hindered borane such as 47, 48, or catecholborane (p. 798)," or with BHBr2—SMe2. The reaction between terminal alkynes and BH3 produces 1,1-... 

Both aliphatic and aromatic terminal alkynes reacted with aliphatic aldehydes giving exclusively a mixture of ( ,Z)-1,5-dihalo-1,4-dienes and disubstituted ( )-a,p-unsaturated ketones, the former being the major products in all cases. When nonterminal aromatic acetylenes were used, the trisubstituted ( )-a,p-unsat-urated ketones were the exclusive compounds obtained. The procedure was not valid for ahphatic and unsaturated alkymes. However, the catalytic system was found to be compatible with alcohols and their corresponding acetates although limited yields were obtained. 

To check the scope of this coupling reaction, a study with different combinations of aldehydes, amines, and terminal alkynes was performed. Aromatic alkynes turned out to be more reactive than aliphatic ones. This study included aliphatic... 

There are several procedures for synthesis of terminal alkenyl stannanes that involve addition to aldehydes. A well-established three-step sequence culminates in a radical addition to a terminal alkyne.150... 

The combination of Ni(COD)2/NHC complexes with EtaSiH as the reducing agent has also proved to be effective in inter molecular couplings of aldehydes and alkynes (Scheme 9) [21]. A broad range of substrates underwent couplings, including aromatic, non-aromatic, and terminal alkynes as well as branched, unbranched, and aromatic aldehydes. The regioselectivity with... 

The same authors have also reported the application of green solvents in additions of terminal alkynes to aldehydes in the presence of Zn(OTf)2 and l,8-diazabicyclo[5,4,0]-7-undecene (DBU, Scheme 109).287 The reactions proceeded very slowly, but afforded desirable alcohols 195 in moderate to good yields. 

The group of Leadbeater reported a different type of Mannich reaction, which involved condensation of an aldehyde (1.5 equivalents) with a secondary amine and a terminal alkyne, in the presence of copper(I) chloride (10 mol%) to activate the... 

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