Aldehydes converting from alkynes

Oxidation of the vinylborane (using basic hydrogen peroxide) gives a vinyl alcohol (end), resulting from anti-Markovnikov addition of water across the triple bond. This end quickly tautomerizes to its more stable carbonyl (keto) form. In the case of a terminal alkyne, the keto product is an aldehyde. This sequence is an excellent method for converting terminal alkynes to aldehydes. 

Allylic alcohols. Alkenylzirconocenes derived from alkynes are converted into the zinc reagents (with Me2Zn at —65°), which react with aldehydes. 

Aliphatic and aromatic aldehydes react with carbon tetrabromide and triphenylphosphine to yield 1,1-dibromoalkenes 156, which are converted into alkynes 157 by the action of butyllithium or lithium amalgam. A convenient modification of the second step is the use of magnesium metal in boiling THF. 1-Chloro-l-alkynes 159 (R = Bu, hexyl, heptyl etc.) are produced from aldehydes and carbon tetrachloride/triphenylphosphine/magnesium, followed by dehydrochlorination of the products 158 with potassium hydroxide in the presence of the phase-transfer agent Aliquat 336. ... 

The aldehyde was then converted to a carboxylic acid via a Pinnick oxidation. Further elaboration to generate acyl telluride 185 was achieved by initial activation of the acid as a mixed anhydride using isobutyl chloro-formate under basic conditions. Nucleophilic displacement with sodium phenyl telluride, generated in situ from borohydride reduction of diphenyl ditelluride, completed the transformation. With acyl telluride 185 in hand, nitrogen deprotection employing TFA, followed by a reductive amination with aldehyde 186 furnished alkyne 187, which was envisioned to be a substrate for radical cyclization (Scheme 19). 

We see from these examples that many of the carbon nucleophiles we encountered in Chapter 10 are also nucleophiles toward aldehydes and ketones (cf. Reactions 10-104-10-108 and 10-110). As we saw in Chapter 10, the initial products in many of these cases can be converted by relatively simple procedures (hydrolysis, reduction, decarboxylation, etc.) to various other products. In the reaction with terminal acetylenes, sodium acetylides are the most common reagents (when they are used, the reaction is often called the Nef reaction), but lithium, magnesium, and other metallic acetylides have also been used. A particularly convenient reagent is lithium acetylide-ethylenediamine complex, a stable, free-flowing powder that is commercially available. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. This procedure is called the Favorskii reaction, not to be confused with the Favorskii rearrangement (18-7). ... 

Pyranopyrrolothiazoles can be prepared in a similar way to certain pyrano- and thiopyrano-pyrrolizines and pyrrolizinopyridines as discussed earlier. Thus, thiazolidine-4-carboxylic acid reacts with the aldehyde 179 to give a 2 1 mixture of 180 and 181 (Equation 16). This reaction is a 1,3-dipolar cycloaddition of the alkene to the 1,3-dipole formed from reaction of the amino acid amine with the aldehyde <1988T4953, 1990T2213>. The alkyne analogue of 179 is similarly converted into 182 (Equation 17). 

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

The reaction of alkenes (and alkynes) with synthesis gas (CO + H2) to produce aldehydes, catalyzed by a number of transition metal complexes, is most often referred to as a hydroformylation reaction or the oxo process. The discovery was made using a cobalt catalyst, and although rhodium-based catalysts have received increased attention because of their increased selectivity under mild reaction conditions, cobalt is still the most used catalyst on an industrial basis. The most industrially important hydrocarbonylation reaction is the synthesis of n-butanal from propene (equation 3). Some of the butanal is hydrogenated to butanol, but most is converted to 2-ethylhexanol via aldol and hydrogenation sequences. 

Allyl cyanides can be added across alkynes in the presence of a nickel catalyst prepared from (COD)2Ni and (4-CF3CeH4)3P in situ to give functionalized di- or tri-substituted acrylonitriles in a highly stereoselective manner, presumably via n-allylnickel intermediates. a-Siloxyallyl cyanides also react at the y -position of a cyano group with both internal and terminal alkynes to give silyl enol ethers, which can be converted into the corresponding aldehydes or ketones upon hydrolysis.70... 

One of the characteristic reactions of the Ti reagent is the intramolecular nucleophilic acylation of the titanacycle with esters, and 2,7- and 2,8-enyne esters afford interesting mono- and bicyclic skeletons [125], Titanacycle 297, formed from a, /i-unsaturated ester 296, is converted to the alkenyltitanium 300 by protonation, and the cyclopentenone 301 is formed by intramolecular acylation [126], As 297 is a tautomeric form of the Ti enolate, it reacts with electrophiles such as aldehydes to give 298, which cyclizes to 299. The a,/i-alkynic ester 302 generates the titanacycle 303 and is converted to the bicyclo[3.1.0]hexane system 305 via 304 [126]. The titanacycle... 

On the basis of the same principle, we developed a three-component synthesis of macrocycles starting from azido amide (46), aldehyde (47) and a-isocyanoaceta-mide (48) (the cx-isocyanoacetamides are easily available, see [84—86]) bearing a terminal triple bond (Scheme 11) [87]. The sequence is initiated by a nucleophilic addition of isonitrile carbon to the in situ generated imine 50 led to the nitrilium intermediate 51, which was in turn trapped by the amide oxygen to afford oxazole 52 (selected examples [88-94]). The oxazole 52, although isolable, was in situ converted to macrocycle 51 by an intramolecular [3+2] cycloaddition upon addition of Cul and diisopropylethylamine (DIPEA). In this MCR, the azido and alkyne functions were not directly involved in the three-component construction of oxazole, but reacted intramolecularly leading to macrocycle once the oxazole (52) was built up. The reaction created five chemical bonds with concurrent formation of one macrocycle, one oxazole and one triazole (Scheme 15). 

Thus, for example, the direct conversion of an ether into an acetal or ketal is difficult to achieve whereas the oxidation of an alcohol to an aldehyde or ketone (or the reverse process) is a trivial transformation. Similarly, the transition from an oxidation level of 2 to level 1 is problematic in the case when one tries to convert dihalides into monohalides while the transformation of alkynes into alkenes may be safely considered a viable route to carry out this transition. 

Propargylic halides are converted to allenyl and propargylic tin halides upon exposure to SnCl2 in a mixture of A(,A(-dimethylformamide (DMF) and l,3-dimethyl-2-imidazo-lidinone (DMI) [87]. Subsequent addition of aldehydes leads to homopropargylic and/or allenic carbinols (Table 47). The ratio of the two regioisomeric adducts depends on the nature of and R. Alkyl substitution on the alkyne (R = Me) strongly favors the allenic adduct. On the other hand, the ratio of adducts from the TMS substituted alkyne (R = TMS) is dependent on the aldehyde substituent. 

The alcohols that we have learned to make can be converted into other kinds of compounds having the same carbon skeleton from complicated alcohols we can make complicated aldehydes, ketones, acids, halides, alkenes, alkynes, alkanes, etc. 

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