Gold catalysis addition

Che et al. recently applied gold catalysis to the synthesis of lactams by the intramolecular addition of P-ketoamide to unactivated alkenes, as shown in Equation8.27 [83]. 

The reaction worked with both internal and terminal alkynes (except silylated alkynes) and in many solvents, even in the neat alcohol added [105]. The mechanism proposed involved two catalytic cycles first, gold catalysis would lead to dihydro-furan by a fast intramolecular reaction then, the subsequent slower intermolecular reaction would be produced by the addition of alcohol to the enol ether to deliver a ketal (Scheme 8.18). 

The activation of allenes is a rather new, but particularly promising area of gold catalysis.381,400 The first example for such a transformation is the cycloisomerization of allenic ketones 480 to furans 482 which probably occurs via intermediate 481 (Scheme 147). Hashmi et /.401,401a showed that this reaction proceeds much faster when gold(m) chloride in acetonitrile is employed as the precatalyst instead of the traditionally used silver salts (cf. Section 9.12.3.2). The products are usually contaminated by substituted furans originating from a Michael addition of aurated 482 to the substrates 480, thereby indicating that the gold catalyst is also capable to activate C-H bonds of furans. 

Apart from these two examples, in the rest of the olefin activations, gold coordinates to the olefin, turning it susceptible to nucleophilic attack. The early examples of alkene functionalization by gold catalysis (equation 144) focused on the intermolecular addition of 1,3-diketones to styrenes. " An intramolecular version with ketoamides to yield pyrrolidinones was later developed and followed by the intermolecular addition of phenols (equation 145) and carboxylic acids to double bonds,a work that included an example of intramolecular addition of an aliphatic alcohol to an olefin. 

The cycloisomerization of a-allenyl ketones to the corresponding substituted furans was the first example of a gold-catalyzed addition of an oxygen nucleophile to an allene (Scheme 4-86). Traditionally, silver or palladium catalysts were employed for cyclizations of this type advantages of gold catalysis incluiie shorter reaction times, milder conditions, an or lower catalyst loadings. Variable amounts of... 

C2-alkynylation of (benzo)furans 7 and 12 was achieved selectively under gold catalysis with hypervalent ethynylbenziodoxolone reagents (TIPS-EBX (10)) (Scheme 3) (2013AGE6743, 2013BJOC1763). Under mild conditions, a broad set of substituted furans 7 and benzofiirans 12 were successfully alkynylated (11 and 13) albeit for the latter a higher reaction temperature and an additional (super)stoichiometric zinc salt was needed. Waser has shown the instantaneous formation of bis(triisopropyl-silyl)diyne via reaction of TIPS-EBX 10 with AuCl (2012CEJ5655). Therefore the mechanism likely involves oxidative addition of Au with TIPS-EBX 10 followed by electrophUic C—H auration, with elimination of 14 and reductive elimination (Scheme 4). 

Waser reported the highly selective C2-alkynylation of thiophenes (15 18) via gold catalysis and TIPS-EBX 10 under conditions similar to those described for furan (Scheme 6) (2010AGE7304). With trifluoroace-tic acid as additive, high yields of the C2-alkynylated thiophenes 18 were obtained under ambient temperature. 

The development of new procedures for the creation of C-C bonds is of major importance in organic synthesis. In this respect, gold catalysis has emerged as a very efficient synthetic tool, allowing the generally easy and efficient formation of such bonds by addition of various carbone nucleophiles onto alkynes, allenes, and alkenes. These transformations, which can be performed in an intra- or intermolecular manner, are extremely varied. It should however be noted that tlie cycloisomerization of ene-ynes, diene-ynes, or ene-allenes remains the most frequently encountered. A very short selection of such transformations is presented in Scheme 16.16 [15g,k, 20]. 

Overall, the use of well-defined, silver-free catalysts in gold catalysis helps to design more cost-effective protocols and contribute to the overall sustainability of the procedure. To highlight the latter point, in this chapter we will mostly discuss gold-catalysed protocols that do not require silver additives in order to generate active catalysts. 

Scheme 7.34 Domino cyclisation-addition reaction catalysed by chiral phosphoric acid catalysis and gold catalysis.

Even from today s perspective, it is interesting to see how many different reaction types of homogeneous gold catalysis, which still are a topic in latest investigations, are already described in these two pubhcations. In addition, the reactions readily proceeded at room temperature, and neither water nor oxygen had to be excluded — two more principles reported for most of the reactions that followed. The first... 

The problem was the halide anion resulting from the aryl halide partner - it blocked the gold(I) center by coordination no further gold-catalysis was possible. One way to avoid this is the use of reagents for the oxidative addition not based on halogens as leaving group. 

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