Alkynones

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Pent-3-in-2-one, the simplest alkynone

Alkynones are chemical compounds that contain a C≡C triple bond and a non-terminal carbonyl group as functional groups . Those connections in which both functionalities are directly adjacent are of particular importance. As a conjugated system, they are related to the alkenones and, like them, represent a synthetic building block composed of three carbon atoms. Due to their reactivity as the Michael system, alkynones can be regarded as synthetic equivalents of 1,3-diketones . The simplest alkynone according to this system is pent-3-yn-2-one and thus analogous to acetylacetone (pentane-2,4-dione). Formally, but-3- yn -2-one is the simplest alkynone, but it differs in reactivity.

Manufacturing

Retro-synthetic pattern to represent the alkynones

Various approaches to alkynones have been presented in recent years. They can be classified according to the type of retrosynthetic cut . In general, a cut is made at point a (approaches 1 - 6 ). The procedures ( 1 ) and ( 2 ) represent the classic access options to alkynones. Starting from lithium acetylidene or the equivalent Grignard reagents , it is possible first to generate the corresponding propargyl alcohol , which is then oxidized to the desired product ( 1 ). The redox step required is a disadvantage of this variant .

The further synthesis routes therefore start from carboxylic acid derivatives . Approaches ( 2 ) describe the stoichiometric addition of lithium , magnesium or copper (I) acetylides to carboxylic acid derivatives such as acid chlorides , anhydrides , esters and acyl cyanides. The reaction of an N- methoxy- N- methyl Weinreb amide with a lithium acetylide can, as described in ( 3 ), be used to prepare alkynones , as can morpholine amides. Route ( 4 ) describes an unusual route to the synthesis of alkynones . An organyl boron alkynone previously presented in stoichiometric amounts is reacted with a lactone to form the corresponding aliphatic alkynone, which still bears a hydroxyl group . Approach ( 5 ) represents the cross-coupling reaction of tin or antimony acetylides with acid chlorides. The disadvantage is that the metal organyls have to be prepared separately in an upstream synthesis step. Alkynylsilanes can also be reacted with acid chlorides in the presence of Lewis acids such as AlCl 3 or iodine . There are now also catalytic processes with InBr 3 for this purpose .

The Sonogashira-Hagihara reaction of a benzoic acid chloride with a terminal alkyne ( 6 ) in THF and in the presence of only one equivalent of an amine base was developed in the Müller group. However, the origins go back over 30 years. In 1977, Kenkichi Sonogashira discovered that the already known palladium (0) - and copper (I) -catalyzed Sonogashira-Hagihara reaction can also be extended to benzoic acid chlorides and terminal alkynes as substrates. One method of forming bonds a and b at the same time is the carbonylative coupling of aryl halides with terminal alkynes ( 7 ). This variant is extremely efficient, especially in cases in which the corresponding acid chlorides are difficult to obtain synthetically. The carbonylative coupling has long been an underutilized method in the synthesis of alkynones. In particular, the high CO pressures required to carry out the reaction were a problem. In 2003, a more cost-effective process for carbonylating alkynylation under normal CO pressure was presented, in which ammonia is used as the base.

The synthesis via the bond formation at point c as in example ( 8 ) is one of the less common methods for the preparation of alkynones. A Sonogashira-Hagihara reaction is used here. However, iodonium salts must be used instead of aryl iodides.

Individual evidence

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  2. ↑ SJ Pastine, D. Sames: Concise Synthesis of the Chemopreventitive Agent (±) -Deguelin via a Key 6-endo Hydroarylation , Org. Lett. , 2003 , 5 , pp. 4053-4055 ( doi: 10.1021 / ol035419j ).
  3. ↑ ALKS Shun, ET Chernick, S. Eisler, RR Tykwinski: Synthesis of Unsymmetrically Substituted 1,3-Butadiynes and 1,3,5-Hexatriynes via Alkylidene Carbenoid Rearrangements , J. Org. Chem. , 2003 , 68 , p. 1339 -1347 ( doi: 10.1021 / jo026481h ).
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  22. ↑ T. Kobayashi, M. Tanaka, J. Chem. Soc., Chem. Commun. , 1981 , pp. 333-334.
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