Grignard reagents acetylenic alcohols

Sodium acetylide and acetylenic Grignard reagents react with aldehydes and ketones to give alcohols of the type... 

Selenienylalkynylcarbinols were prepared by the addition of Grignard reagents or the sodium salts of acetylenes to 2-formylselenophene and its derivatives. The alcohols were oxidized and the resulting ketones treated with hydrazine and hydroxylamine to give the diheteroaryls 81 and 82.94... 

In the general context of donor/acceptor formulation, the carbonyl derivatives (especially ketones) are utilized as electron acceptors in a wide variety of reactions such as additions with Grignard reagents, alkyl metals, enolates (aldol condensation), hydroxide (Cannizzaro reaction), alkoxides (Meerwein-Pondorff-Verley reduction), thiolates, phenolates, etc. reduction to alcohols with lithium aluminum hydride, sodium borohydride, trialkyltin hydrides, etc. and cyloadditions with electron-rich olefins (Paterno-Buchi reaction), acetylenes, and dienes.46... 

Hence in all experiments with Grignard reagents moisture must he completely excluded. Alcohols, phenols, carboxylic acids, primary and secondary amines, oximes, acetylene, etc., react in the same way as water. 

Dibenzocycloheptenone (24-6) also serves as a starting material for the preparation of one of the few medicinal products that contains an acetylenic linkage. Reaction of (24-6) with the Grignard reagent from propargyl bromide leads to the alcohol (27-1). The free proton acetylene is sufficiently acidic for that center to take part in a Mannich reaction. Thus, reaction of (27-1) with formaldehyde and dimethylamine gives the adduct (27-2). Dehydration by means of thionyl chloride completes the synthesis of intriptyline (27-3) [28]. 

In chapter 15 we saw that dienes could be made by the Wittig reaction and also by the addition of vinyl lithiums or Grignard reagents to ketones followed by dehydration of the allylic alcohol product. Derivatives of acetylenes can do the same job. The first disconnection is the same but a reagent for the synthon 40 replaces the vinyl metal derivative. 

Our first goal was to develop a scaleable route to the single enantiomer propargylic alcohol. The racemic alcohol was readily produced on a multi-kilogram scale by alkylation of the phenol with inexpensive bromoacetaldehyde diethyl acetal, hydrolysis to the aldehyde, and addition of the acetylenic Grignard reagent. With this material at hand we developed an efficient bioresolution process that esterified the alcohol in the presence of Chirazyme L9 (Scheme 30.7).26 At this point... 

Tertiary unsaturated alcohols, obtained by the addition of acetylenic or vinylic Grignard reagents to polyhaloacetoncs, react mainly in an S i -type reaction to yield rearranged products... 

Reaction of H2C—CHSiMeCh (obtained from the catalyzed hydrosilylation of acetylene with MeSiChH) with an ephedrine-derived lithium dialkylamide produces Ae chiral vinylsilane (1). Addition of BuLi to this vinylsilane followed by treatment with MgBr gives the corresponding Grignard reagent (2). This latter species can be transformed as shown in Scheme 5 into chiral alcohols in reasonable enantiomeric excess (ee). ... 

Acetylenic carbinols are prepared by the interaction of sodium acety-lides or acetylenic Grignard reagents with aldehydes. The formation and reaction of the metallic acetylide may be combined into a single operation. For example, an alkylacetylene in ether solution is treated successively with ethylmagnesium bromide and formaldehyde to give the acetylenic alcohol such as 2-heptyn-l-ol (82%). ... 

Acetylenic tertiary alcohols are prepared from sodium acetylides or acetylenic Grignard reagents and ketones in the same manner as described for primary and secondary alcohols (method 88). Dimethylethynylcarbinol is prepared from acetone, aqueous potassium hydroxide, and acetylene in an autoclave at 100° and 300 p.s.i. Ketones ate sometimes treated with an acetylide prepared from acetylene and a solution of sodium or potassium alkoxide in /-amyl alcohol. " Another procedure utilizes... 

In a side-chain containing a double-bond 3 to the oxirane, double-bond migration has also been observed. The effects of the solvent and the reagent have been examined in the reaction of vinyl-magnesium bromide and phenyloxirane. Acetylenic oxirane gives a complicated mixture of products with a Grignard reagent, but the Cu halide-catalyzed reaction leads to an allene alcohol (Eq. 

The enhanced activity of allylic Grignard reagents enables them to react with acetylenic alcohols by an anti-addition [21]. In oxygenated solvents (Et20 or THF), reactions occur regioselectively by oxygen assistance to give the desired carbometallation reaction product [Eq. (9)]. 

We shall want to disconnect at (a) in (3a), so making (3) from alcohol (4) is sensible. Disconnection at (a) now gives ketone (5) and synthon (6) which ould be a Grignard reagent but FGA provides an alternative in acetylene (7). This is the point of convergence as both (5) and (7) must be made. 

Apart from the technical route described to p-apo-8 -carotenal, readily available vitamin A alcohol (Cjo) has served as an intermediate in the form of the phosphonium salt by reaction with the monodiethyl acetal of a Cio dial (ref. 54). The required Cjo monodiethylacetal was obtained (ref.5, p409) by the reaction of the mono aldehyde-protected derivative, the enol ether of methylmalonaldehyde, (C4) with the acetylenic Grignard reagent from trans 3-methyl-2-penten-4-yn-l-ol (C ) followed by acidic dehydration and partial reduction with Lindlar catalyst to give firstly 8-hydroxy-2,6-dimethylocta-2, 4,6-triene-l-al (Cio). Protection of the hydroxyl group by acetylation in pyridine solution with acetyl chloride and formation of the diethyl acetal with ethyl orthoformate followed by hydrolysis of the acetyl group and oxidation afforded the final CIO aldehyde component (D)shown in Scheme 15a. 

Allenic alcohols. Claesson et al. have prepared organic cuprate reagents by the reaction of Grignard reagents with Cul in the ratio of 4-5 1 eq. in ether at -30° under Nj. These cuprates displace methyl and tetrahydropyranyl ether groups of acetylenic alcohols with shift of the unsaturated linkage to give a- and 0-aUenic alcohols as shown in the examples. 

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