applications. There are also examples of the coupling partners both being attached to allyl resins, with the Pd(0) catalyst effecting cleavage of the substrates and subsequent Sonogashira coupling in solution. Natural products Many metabolites found in nature contain alkyne or enyne moieties, and therefore, the Sonogashira reaction has found frequent utility in their syntheses. Several of the most recent and promising applications of this coupling methodology toward the total synthesis of natural products exclusively employed the typical copper-cocatalyzed reaction. An example of the coupling of an aryl iodide to an aryl acetylene can be seen in the reaction of an iodinated alcohol and tris(isopropyl)silylacetylene, which gave an alkyne, an intermediate in the total synthesis of the benzindenoazepine alkaloid bulgaramine. There are other recent examples of the use of aryl iodides for the preparation of intermediates under typical Sonogashira conditions, which, after cyclization, yield natural products such as benzylisoquinoline or indole alkaloids An example is the synthesis of the benzylisoquinoline alkaloids (+)-(S)-laudanosine and (–)-(S)-xylopinine. The synthesis of these natural products involved the use of Sonogashira cross-coupling to build the carbon backbone of each molecule. Enynes and enediynes The 1,3-enyne moiety is an important structural unit for biologically active and natural compounds. It can be derived from vinylic systems and terminal acetylenes by using a configuration-retention stereospecific procedure such as the Sonogashira reaction. Vinyl iodides are the most reactive vinyl halides to Pd0 oxidative addition, and their use is therefore most frequent for Sonogashira cross-coupling reactions due to the usually milder conditions employed. Some examples include: The coupling of 2-iodoprop-2-en-1-ol with a wide range of acetylenes. The preparation of alk-2-ynylbuta-1,3-dienes from the cross-coupling of a diiodide and phenylacetylene, as shown below. Pharmaceuticals The versatility of the Sonogashira reaction makes it a widely used reaction in the synthesis of a variety of compounds. One such pharmaceutical application is in the synthesis of SIB-1508Y, which is more commonly known as Altinicline. Altinicline is a nicotinic acetylcholine receptor agonist that has shown potential in the treatment of Parkinson’s disease, Alzheimer’s disease, Tourette’s syndrome, schizophrenia, and attention deficit hyperactivity disorder (ADHD). As of 2008, Altinicline has undergone Phase II clinical trials. The Sonogashira cross coupling reaction can be used in the synthesis of imidazopyridine derivatives. Related reactions Cross-coupling reactions Castro-Stephens coupling Heck reaction Stille reaction Suzuki reaction Negishi coupling Kumada coupling Transmetalation References Condensation reactions Carbon-carbon bond forming reactions Palladium Organometallic chemistry Name reactions