Nucleophilic addition of acetylide

Thus, we discovered the first asymmetric nucleophilic addition of acetylides to kehmines. The reaction mechanism was unfortunately not clear during this study but we felt that aggregation of lithium species might play an important role. 

Ethynyl carbinols (propargylic alcohols) such as 134 (Scheme 2.58) represent another important group of oxidation level 3 compounds. Their preparation involves nucleophilic addition of acetylides to the carbonyl group, a reaction that is nearly universal in its scope. Elimination of water from 134 followed by hydration of the triple bond is used as a convenient protocol for the preparation of various conjugated enones 135. Easily prepared O-acylated derivatives are extremely useful electrophiles in reactions with organocuprates, which proceed with propargyl-allenyl rearrangements to furnish allene derivatives 136. 

The metal vinylidene intermediates discussed elsewhere in this chapter are limited to a single carbon-substituent on account of the 1,2-migration process by which they form from terminal alkynes. Alkenylidenes—vinylidenes bearing two carbon-substituents—are formed by nucleophilic addition of the (i-carbon of a metal acetylide to an electrophile (Scheme 9.16) [30]. 

Interestingly, the first catalytic version of such nucleophilic additions of alkynyl silvers to aldehydes has been described." Indeed, silver chloride in the presence of tricyclohexylphosphine and mild bases such as ethyldiisopropylamine catalyzed the addition of terminal alkynes to aldehydes in good to high yields (Table 10.5). The reaction proved to be almost insensitive to electronic effects however, alkyla-cetylenes were less reactive than arylacetylenes. The solvent had a dramatic effect on the reaction course. Control experiments with preformed phenylethynylsilver showed that both phosphine and water activated the silver acetylide. 

The nucleophilic addition of an acetylide to form an ethynyl alcohol and the addition of organometallic reagents such as Grignard reagents to carbonyl compounds are important methods for C-C bond formation. 

Many syntheses of useful compounds utilize the nucleophilic addition of a Grignard or organo-lithium reagent to form carbon-carbon bonds. For example, a key step in the synthesis of ethy-nylestradiol (Section 11.4), an oral contraceptive component, is the addition of lithium acetylide to a ketone, as shown in Figure 20.5. 

A new preparative method for allenes has appeared (Scheme 4). Several alk-2-ynyl carbonates (prepared by nucleophilic addition of magnesium and lithium acetylides to ketones or aldehydes followed by quenching with methyl chloroformate) were selectively hydrogenolysed with ammomium formate under palladium catalysis to give allenes in good yields. 

Because of their ready accessibility and their ease of reduction to give alkenes of predictable geometry, acetylenes have featured prominently in the synthesis of vitamin h (1) and carotenoids, principally by nucleophilic addition of metal acetylides RC=CM (M = Li, Na, K, MgX, X = halogen) to aldehydes and ketones to produce the corresponding a-hydroxyalkynes [2]. 

Diketone anions of 1-aryl-4,4,4-trifluorobutane-l,3-dione (85) undergo nucleophilic addition of sodium acetylide to give tertiary 1,4-alkynediols (86). Double cyclization gives a 2,2 -bifuran. While the mechanism of acetylide addition has not been proved, a likely first step is the formal reaction of two carbanions to give a C-C bond. °... 

Movassaghi and Hill developed a ruthenium-catalyzed cycloisomerization of 3-azadienynes to the corresponding pyridines [11]. The alkynyl imines were produced from a variety of iV-vinyl and iV-aryl amides by amide activation and nucleophilic addition of copper(I) (trimethylsilyl) acetylide sequence reaction. Then by Ru-catalyzed protodesilylation and cycloisomerization, the desired pyridine derivatives were formed selectively in good to excellent yields (Scheme 2.7). For the reaction mechanism, C-silyl metal vinylidene was found to be the key intermediate. 

As the final conclusion, the authors assumed that a mechanism involving nucleophilic addition of an allene double bond to a phosphinegold-complexed phos-phinegold acetylide to be more likely than an oxidative cyclization or simple nucleophilic addition to phosphinegold-complexed substrate. The corresponding catalytic cycle for the more probable pathway is shown in Scheme 4.9. 

Usachev BI (2011) First nucleophilic addition of acetylideto 1,3-diketonate anions reaction of l-aryl-4,4,4-trifluorobutane-l,3-diones with sodium acetylide. Tetrahedron Lett 52 6726-6728... 

The monolithium salt of 4-hydroxy-4-(phenylethynyl)-2.5-cyclohexadienone (12), prepared in situ by the addition of lithium acetylide to /7-benzoquinone, was treated with methylmagnesium chloride in l HF-TMEDA or in THF —DMPU. The syn-, 4-addition adduct 13, derived from intramolecular delivery of the carbon nucleophile by the hydroxy oxygen, as well as the <7s-1,4-diol 14, obtained via intermolecular 1,2-addition, were obtained in varying amounts depending on the conditions. The selectivity on 1,4- to 1,2-addition increased by the addition of cation chelating agents such as DMPU, TMEDA, and 15-crown-5. Although the 1,4 to 1,2... 

In 1991, Park reported123 the first synthesis of iron alkynylcarbene complexes (184), involving the nucleophilic attack of a lithium acetylide on pentacarbonyl iron, followed by electrophilic quench. With such compounds in hand, he proceeded to investigate their reactivity123,124 and found that upon addition of cyclopentadiene to the alkynylcarbene complexes 184, the products formed were 774-vinylketene complexes (185). During column chromatography, some of these products (185.a and 185.b) were transformed into the tricarbonyl(norbornadiene)iron derivatives 186. Others (185.C and 185.d, not shown) were hydrolyzed as part of the workup procedure, to afford pure samples of the norbornadiene complexes 186.C and... 

Ab initio calculations at the HF/6-31G level have been used to explore energy changes, structural variation, and electron density shifts during jr-face selective addition of substituted acetylide ions to cyclohexanone and cyclohexanethione. Charge polarization of the jr-bond on approach of the nucleophile is such that the carbonyl carbon becomes considerably electron deficient for most of the reaction path (and may... 

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