Corey-Fuchs procedure

Fig. 14.32. Aldehyde alkyne chain elongation via [l,2]-rearrangement of a vinyl carbenoid (Corey—Fuchs procedure). The aldehyde and phosphonium ylide A generated in situ undergo a Wittig olefina-tion and form the 1,1-dibro-moalkene (B). In the second stage, the dibromoalkene is reacted with two equivalents of n-BuLi and the vinyl carbenoid D is formed stereoselectively. The carbenoid undergoes H migration to form the alkyne C. The alkyne C reacts immediately with the second equivalent of n-BuLi to give the lithium acetylide and is reconstituted by reprotonation during aqueous workup.

In the laboratory of J.H. van Boom, the synthesis of highly functionalized c/s- and frans-fused polycyclic ethers of various ring sizes via radical cyclization of carbohydrate-derived p-(alkynyloxy)acrylates was developed/ The radical cyclization precursors were prepared iteratively and the terminal alkyne moieties were installed using the Corey-Fuchs procedure. 

With a bountiful supply of 69 at our disposal, the synthesis was continued by PCC oxidation to the aldehyde level and application of the Corey-Fuchs procedure [35] for chain homologation via dibromo olefin 70 to the acetylenic ester 71. Since amide bond construction next had to be implemented, this ester was saponified under mild conditions and the resulting carboxylic acid was activated by formation of a mixed anhydride with mesitylenesulfonyl chloride in advance of in situ condensation with 59. In order to preclude hydrolysis of the silyl ether functionality in 72, deacetalization had to be performed under anhydrous conditions in dry acetone containing a catalytic quantity of p-toluene-... 

The presence of halogen atoms in a molecule is compatible with formation of an ylid and subsequent Wittig reaction. Carbon tetrabromide and triphenylphosphine have been used to give vinyl dibromide products, which are rapidly converted to the corresponding alkyne. Indeed, this is an important synthetic route to alkynes called the Corey-Fuchs procedure. The reaction of 511 with this reagent gave vinyl dibromide 512 in 77% yield as part of Marshall s synthesis of callystatin When 512 was treated with butyllithium... 

Dess-Martin oxidation of alcohol III-26 gave aldehyde III-27, which was used in the next step without further purification. Aldehyde III-27 reacted with the Bestmann-Ohira reagent [96-101] to give alkyne III-28, from which alkynylindole III-29 was obtained by Boc cleavage after a brief exposure to trifluoroacetic acid. This four step procedure can be routinely carried out without purification of any intermediate in 14—23 % overall yield. Alternatively, alkyne III-29 could be prepared from aldehyde III-27 by the Corey-Fuchs procedure, although the overall yield was lower using this procedure [102],... 

The one-step Seyferth procedure offers an alternative to the Corey -Fuchs sequence. After a Horner-Wadsworth-Emmons olefmation of an aldehyde 37 to an unsaturated diazo compound 38. elimination of nitrogen and [1,2]-rearrangement of the resulting vinylcarbene 39 leads here as well to a Cy-extended terminal alkyne 40.19... 

A general one-pot procedure for the synthesis of alkynes from aldehydes (Corey-Fuchs reaction) that involves the synthesis of the triphenylphosphonium dibromomethane reagent has been explored by Michel and coworkers. In general, the base of choice is f-BuOK, but in case of the N-Boc piperidine, use of BuLi in order to avoid unwanted side reactions between the carbamate and the acetylide function provides a cleaner reaction at low temperature (eq 64). 

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