Aldehydes reaction with acetylides

Now let s draw the forward scheme. 1,1-Dibromopentane is converted to 1-pentyne by reaction with excess sodium amide (to afford double elimination followed by deprotonation of the resulting alkyne), followed by aqueous woikup to protonate the terminal aUcynide. 1-Pentyne is converted to the aldehyde via hydroboration/oxidation. Subsequent reaction with sodium acetylide, followed by aqueous woikup, produces an alcohol. Reduction with H2 and Lindlar s catalyst converts the alkyne group to an alkene group. Ozonolysis converts the alkene to an aldehyde. Reaction with concentrated acid allows for elimination of the alcohol, producing the target compound. 

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

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). ... 

The substance is stable at ordinary temperatures and up to 100°C. Like cupric acetylide it decomposes on being heated in hydrochloric acid (Berthelot [102], Sabaneyev [107]). A solution of potassium cyanide also causes decomposition with the loss of acetylene. Makowka [108] showed that aldehyde-like compounds are formed from cuprous acetylide on reaction with a 30% solution of hydrogen peroxide. 

Given the structure or name of an aldehyde or ketone, write an equation for its reaction with the following nucleophiles alcohol, cyanide ion, Grignard reagent or acetylide, hydroxylamine, hydrazine, phenylhydrazine, 2,4-dinitrophenylhydrazine, primary amine, lithium aluminum hydride, and sodium borohydride. 

Diazo compounds have also been used as precursors in the preparation of pyrazoles and indazoles. The copper-promoted cycloaddition reaction of lithium acetylides 18 with diazocarbonyl compounds 19 provided a direct and efficient approach to the synthesis of pyrazoles 20 <07AG(I)3242>. A facile, efficient, and general method for the synthesis of 1-arylated indazoles 22 and A-unsubstituted indazoles 23 by the 1,3-dipolar cycloaddition of benzynes, generated from 21, with diazomethane derivatives has been reported <07AG(I)3323>. Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate <07S3371>. 

Titanium acetylides react with 3-benzyl-tetrahydro-l,3-oxazines and 1,3-oxazolidines to give the corresponding / -aminoacetylenes in modest to good yield.296 Vinyl Ti(iv) species prepared by the alkylation of vinylcarbene complexes with BTCl react with aldehydes to give allylic alcohols. Reaction with terminal alkynes produces conjugated dienes, in which a vinyl group regioselectively bonds to the unsubstituted side of carbon-carbon triple bond.297... 

The synthesis of the fragment C3-C13 was achieved in five steps from 169. Treatment of the tosylated stereotetrad 169 with 5 equivalents of lithium acetylide in DMSO led an acetylenic compound which was treated with ra-Buli and methyl iodide, and then reduced by Na/NH3 to produce the E-geometry of the C12-C13 double bond with concomitant removal of the PMB group at C5, giving the primary alcohol 170 (49% yield for the three-step sequence). Swern oxidation of 170 gave the corresponding aldehyde which was involved in an Evans-type asymmetric aldol reaction with the boron enolate A to produce the adduct 171 (dr > 95/5, 90% yield). (Scheme 33). 

A reaction with an acetylide was applied by Isler [40] for the first synthesis of vitamin A (29), which is still practised industrially. The Cao-skeleton is built up by addition of the Ci4-aldehyde 30 to an ethereal solution of the acetylide 31 to give the diol 32 which is aften/vards transformed to vitamin A (29) Scheme 7). 

The conjugate base of an alkyne is an alkyne anion (older literature refers to them as acetylides), and it is generated by reaction with a strong base and is a carbanion. It funetions as a nucleophile (a source of nucleophilic carbon) in Sn2 reactions with halides and sulfonate esters. Acetylides react with ketones, with aldehydes via nucleophilic acyl addition and with acid derivatives via nucleophilic acyl substitution. Acetylides are, therefore, important carbanion synthons for the creation of new carbon-carbon bonds. Some of the chemistry presented in this section will deal with the synthesis of alkynes and properly belongs in Chapter 2. It is presented here, however, to give some continuity to the discussion of acetylides. 

The other major synthetic use of alkyne anions is their reaction with ketones and aldehydes to give an alkynyl alcohol via nucleophilic acyl addition. The lithium salt of 1-propyne, for example, reacted with aldehyde 40 to give alcohol 41 as part of Smith s synthesis of (+)-acutiphycin.50 The reaction is selective for ketones and aldehydes in the presence of acid derivatives, if the acetylide is not present in large excess. l... 

Favorskii Reaction The reaction of aldehydes with terminal acetylenes is known as Favorskii reaction. Sodinm acetylides ate the most common reagents, bnt lithium, magnesium and other metallic acetylides have also been used. A particularly convenient reagent is lithimn acetylide-ethylene diamine complex. Alternatively, the substrate may be treated with the alkyne itself in the presence of a base, so that the acetylide is generated in situ. 1,4-Diols can be prepared by treatment of aldehyde with dimetalloacetylenes. 

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