Acylation Lithium acetylides

Isomerization of a-hydroxy alkynes and alkynones 2-15 Acylation of olefins 2-27 From lithium acetylides 2-32 From vinylic organometallic compounds... 

The mechanism of acylation of lithium phenylacetylide with a Weinreb amide has been investigated (Scheme 10).71 Dimeric lithium acetylide has reacted via a mono-solvated monomer-based transition structure. The robust tetrahedral intermediate (12) forms sequentially a C(l) 2 2 mixed tetramer with the excess lithium acetylide and a 1 3 (alkoxide-rich) mixed tetramer. The stabilities of the mixed tetramers are consistent with a pronounced autoinhibition. 

In a related fashion, certain types of vinylogous amides can be prepared by a modification of this same method, as reported by Suzuki (equations 45 and 46). The triphenylsilyl moiety is essential for this transformation. The corresponding t-butyldimethylsilylacetylene gave the simple acylation product without subsequent Michael addition of the amine. In Ae ring expansion process the use of unmodified lithium acetylide (LiC uCH) lead to the formation of by-products. A similar ring expansion process was reported for a-lactams with formation of five-membered ring vinylogous amides. ... 

Acyl Anions Derived from Lithium Acetylide... 

For acylation by sensitive carboxylic acids it has been recommended492 to treat lithium acetylides with mixed anhydrides of the carboxylic acid and a monoalkyl carbonate (prepared in situ from the carboxylic acid and ethyl chloroformate) ... 

Dialkyl (l-hydroxy-2-alkynyl)phosphonates [e.g. (64)], prepared by addition of lithium acetylides to acyl phosphonates, can be converted regioselectively into allenic phosphates via the phosphonate-phosphate rearrangement (e.g. Scheme 104). If sodium alkoxides in alcohols are used to effect the rearrangement, mixtures of allenic and acetylenic products are formed however, use of sodium bis(trimethylsilyl)amide in DMSO furnishes allenic phosphates almost exclusively. 

The growing number of chiral amines found in molecules of pharmacological interest is mirrored by an increasing need for efficient methods to achieve their synthesis [87, 162]. Significant developments involving the use of a variety of chiral catalysts for enantioselective additions of carbon nucleophiles to C=N bonds have been reported in recent years [20, 21, 23, 35). An important case study was reported by a group at Merck, who developed an enantioselective addition of lithium acetylides to the cyclic N-acyl imine 244 in the presence of a stoichiometric amount of quinine (246) as a chiral additive (Scheme 11.34) [163]. Careful optimization of the reaction conditions and the imine N-substituent allowed for the development of an addition process that gives adduct 247 in 97 % ee. This key intermediate was subsequently deprotected to provide a kilo-scale asymmetric synthesis of the HIV reverse transcriptase inhibitor 249. 

Fluonnated ylides have also been prepared in such a way that fluorine is incorporated at the carbon p to the carbamomc carbon Various fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyllithium or lithium dusopropy-lamide did not lead to y hde formation, rather, deprotonation was accompanied by loss of fluonde ion However deprotonation with hydrated potassium carbonate in dioxane was successful and resulted in fluoroolefin yields of45-80% [59] (equation 54) p-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydride The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyllithium to form a new ylide, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [61] such as an acetylide to form a fluonnated enyne [62] (equation 56)... 

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... 

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