Acetylenic ketones synthesis

Heasley VL, Buczala DM, Chappell AE, Hill DJ, Whisenand JM, Shellhamer DF (2002) Addition of bromine chloride and iodine monochloride to carbonyl-conjugated, acetylenic ketones synthesis and mechanisms. J Org Chem 67 2183-2187... 

Kobayashi, T. and Tanaka, M. (1981) Carbonylation of organic halides in the presence of terminal acetylenes novel acetylenic ketone synthesis. Journal of die Chemical Society, Chemical Communications. 333-334. 

Equation 11.19 Synthesis of conjugated acetylenic ketones with Cul-catalysis. 

The preparation of acetylenic ketones from soluble silver acetylenides and acid chlorides was reported in 1956 (Scheme 108).512 Analogously to that report, the reaction of silver acetylenides with acylpyridinium salts was reported to proceed effectively.513 This chemistry was applied to the synthesis of cotarnine derivatives, as exemplified in Scheme lQ9.514 514a... 

A similar substituted furan synthesis was realized via a Pd-catalyzed tandem carbonylation-arylation using an a,p-acetylenic ketone, carbon monoxide, and bromothiophene [104],... 

The transition metal-catalyzed domino reactions will undoubtedly have a splendid future which is underlined by the increasing number of publications in this area Steglich et al. presented an approach to arcyriacyanin A via a domino Heck reaction between a bromo(indolyl)maleiimide and 4-bromoindole.1811 The synthesis of 33 -bifurans by Ling et al. was achieved using a novel palladium-catalyzed domino dimerization and subsequent cyclization of acetylenic ketones.1821 Other applications of a combination of Heck reactions for domino processes are the syntheses of aza-heterocydes developed by our group.1831... 

The Darvon alcohol-LAH complex was used in the reduction of the acetylenic ketone (93) in one step of an asymmetric total synthesis of lla-hydroxypro-gesterone (97), a key intermediate in the production of hydrocortisone acetate... 

In the course of a synthesis of vitamin E intermediates, a study was carried out of the reduction of a-0-acetylenic ketones with the Mosher-Yamaguchi LAH-Darvon complex, as well as with a series of new chiral 1,3-amino alcohols (103). The results of the reductions with the Mosher-Yamaguchi complex and... 

Acetylenic ketones.3 PdCl2(dppf) is generally the most satisractory catalyst for synthesis of acetylenic ketones by carbonylation of aryl and vinyl halides in the presence of a terminal acetylene. 

Alkyl-y-butyrolactones.1 a-Acetylenic ketones (2) are reduced by this complex to the corresponding (R)-alcohols (3) with an optical purily of 75-90% (9, 308). These alcohols can be used for synthesis of 4-alkyl-y-bulyrolactones with an optical purity of about 95% (equation I). 

For the synthesis of optically pure building blocks we mainly focused on the synthesis of protected noncoded (R)- and (S)-amino acids, as they can be synthesized reliably in enantiomerically pure form with a large variety of side chains using asymmetric hydrogenation of a-amino-a, 3-didehydroamino acids using cationic diphosphine rhodium catalysts.216,217 As a typical example of a reactophore we present a-alkynyl ketones, which is a representative bis-acceptor molecule. In Scheme 5 are depicted some of the many synthetic applications of acetylenic ketones in heterocyclic synthesis, which have great potential for combinatorial and parallel organic synthesis. 

This multigeneration strategy for the synthesis of pyrimidines combines efficiently a novel cyclocondensation reaction using the highly reactive acetylenic ketones 153215,218 to build the pyrimidine skeleton, with a multicomponent reaction, and a multidirectional cleavage procedure. The Ugi four component reaction is especially useful in the context of building peptidomimetic-derived combinatorial libraries as it affords directly dipeptide analogues of type 159. 

Let us now consider the synthesis of isoxazole 4.28, a drug for the treatment of bronchial asthma. The most direct preparation of isoxazolyl ketone 4.24 is the cycloaddition of unstable bromonitrile oxide 4.22 (prepared in situ by dehydrobromination of 4.21) with acetylenic ketone 4.23. Observe the regioselectivity of this reaction. Both electron-donating and electron-withdrawing groups on the acetylenic components in such cycloadditions tend to occur at the C5 position in the final isoxazole and not at C4. Bromination of ketone 4.24 affords bromoketone 4.25 which is 4.23 n... 

Acetylenes, homologation to allenes, 63, 203 Acetylenes, in peptide synthesis, 63, 175 a,B-ACETYLENIC KETONES, ASYMETRIC REDUCTION OF, 63, 57 ACID CHLORIDES FROM a-KETO ACIDS, 61, 1 Acrolein [107-02-8], 62, 140... 

Acetylenic ketones are important synthetic intermediates in the synthesis of a variety of natural products. Optically active propargyl alcohols of either configuration are readily available in high optical purity by asymmetric reduction of propargyl ketones with B-3-pinanyl-9-borabicyclo(3.3.1)nonane761 (Eq. 31). 

A more general method for the synthesis of a,P-acetylenic ketones has been recently reported, and is indicated in Eq. 34 80). 

Bishop BC, Brands KMJ, Gibb AD, Kennedy DJ (2004) Regioselective synthesis of 1,3,5-substituted pyrazoles from acetylenic ketones and hydrazines. Synthesis 43-52... 

Cabarrocas G, Ventura M, Maestro M, Mahia J, Villalgordo JM (2001) Synthesis of novel optically pure quinolyl-P-amino alcohol derivatives from 2-amino thiophenol and chiral a-acetylenic ketones and their IBX-mediated oxidative cleavage to IV-Boc quinolyl carboxamides. Tetrahedron Asymmetry 12 1851-1863... 

Obrecht D (1989) Acid-catalyzed cyclization reactions of substituted acetylenic ketones a new approach for the synthesis of 3-halofurans, flavones, and styrylchromones. Helv Chim Acta 72 447 56... 

OL-Acetylenic ketones (8, 313). Details are available for use of an RMnI reagent for synthesis of 2,2-dimethyl-4-nonyne-3-one (equation I). ... 

Lithium organocuprates are reagents for cross-coupling, conjugate addition, epoxide opening, ketone synthesis and addition to acetylenes ... 

---