Allenyl ketones cycloisomerization

Disubstituted furans 62 are obtained from a gold-catalyzed cycloisomerization/dimerization pathway involving terminal allenyl ketones and a,(3-unsaturated ketones <00AG(E)2285>. 

The latter mode of reaction has even been reported to proceed in presence of sil-ver(I) ions [127], which is not easy to understand in the context of Marshall s silver-catalyzed cycloisomerization of allenyl ketones (see Chapter 15). 

Marshall et al. noted that under the catalysis of Ag+ or Rh+, 1,2-allenyl ketone or aldehyde 417 may undergo cycloisomerization to afford furans 418. The reaction proceeded via the interaction of Ag+ or Rh+ with the relatively electron-rich C=C bond in the allene moiety followed by nucleophilic attack of the carbonyl oxygen [187]. Through a labeling study, it was found that the reaction proceeds by the mechanism shown in Scheme 10.162 [188]. 

Hashmi et al. investigated a number of different transition metals for their ability to catalyze reactions of terminal allenyl ketones of type 96. Whereas with Cu(I) [57, 58] the cycloisomerization known from Rh(I) and Ag(I) was observed (in fact the first observation that copper is also active for cycloisomerizations of allenes), with different sources of Pd(II) the dimer 97 was observed (Scheme 15.25). Under optimized conditions, 97 was the major product. Numerous substituents are tolerated, among them even groups that are known to react also in palladium-catalyzed reactions. Examples of these groups are aryl halides (including iodides ), terminal alkynes, 1,6-diynes, 1,6-enynes and other allenes such as allenylcarbinols. This che-moselectivity might be explained by the mild reaction conditions. 

Although, as shown above, a number of metals [Hg(II), Rh(I), Ag(I), Pd(II), Au(III) and Cu(I)[ are active for the cycloisomerization of allenyl ketones, some substrates are still restricted to the use of Hg(II) as Leclerc and Tius demonstrated recently for 113, the cyclopentane-anellated furan 114 was only accessible with the mercury catalyst (Scheme 15.32) [73],... 

The cycloisomerization of allenyl ketones was initially described as being catalyzed by rhodium(I) or silver(I) by Marshall et al.21 The activity of copper, silver, and gold for this reaction was first compared in two papers published later (Scheme 12.7).22 In the case of copper and silver, only a cycloisomerization was observed (Table 12.4, entries 1 and 2) with gold, a dimer is obtained as well (entry 3). 

TABLE 12.4. Cycloisomerization or Cycloisomerization/Dimerization of Allenyl Ketones (R1 = Me)... 

The cycloisomerization of allenyl ketones can be exploited for the synthesis of 2,3,4- or 2,3,5-trisubstituted and tetrasubstituted furans, when the Pd(0)-catalyzed cyclization of a,7-disubstituted substrates is combined with the coupling of an aryl halide or substituted allyl halide, as has been reported by Ma et al. (Equation 14) <20000L941, 2000CC117, 2003CEJ2447>. 

Hashmi et al. have found that terminal allenyl ketones give dimerization products when Pd(ll)-catalysts are employed furnishing 2,4-disubstituted furans (Equation 15) <1995AGE1581, 1997JOC7295>. Tetrakis(2,2,2-trifluoroethoxycarbonyOpalladacyclopentadiene proved to be the most effective catalyst to obtain predominantly dimerization instead of cycloisomerization. 

In the presence of 1 mol% AuCls, allenyl ketones undergo a rapid cycloisomerization and can be reacted with a Michael acceptor. In a cross-dimerization of terminal allenyl ketones and a,/3-unsaturated ketones, 2,5-disubstituted furans can be obtained (Equation 16) <2000AGE2285>. 

It has been shown by Marshall and Sehon that in the presence of AgNOs absorbed on silica gel, /3-alkynyl allylic alcohols, which are more accessible than allenyl ketones, also undergo cycloisomerization to furans (Equation 19) <1995JOC5966>. Similarly, 3-trifluoromethylfurans can be prepared utilizing a Pd(ii) catalyst <2000JOC2003>. 

Allenyl ketones undergo cycloisomerization on exposure to (PhCN)2PdCl2. Dimeric products are produced if an a-substituent (at the aUenyl group) is absent from the substrates. ... 

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... 

Cycloisomerization of allenyl ketones 11 into furan products 12 was further elaborated by Hashmi (Scheme 8.5). It was found that this transformation could be effectively catalyzed by other transition metals, such as Cu(I), Ag, Rh(II), and Ru(II) [100, 101], Several aryl-containing furans were synthesized via the silver-catalyzed protocol in high yields (Scheme 8.6) [102]. 

The same researchers also reported a very facile cycloisomerization reaction of allenyl ketones 15 into furans 16 in the presence of gold(III) catalyst (Scheme 8.7) [46, 103-112]. Furthermore, the authors extended this reaction to the cydoisomeriza-tion-addition cascade process of allenyl ketones 15 with enones 17 to produce 2,5-disubstituted furans 18 (Scheme 8.8) [111]. Formation of the latter products was rationalized via two proposed pathways. According to path A, fiiran intermediate 16 undergoes an auration with Au(III)-catalyst to produce the furyl-gold species, which, upon subsequent 1,4-addition to the Michael acceptor 17, generates intermediate 19... 

Gevorgyan has shown that Cu(I)-catalysis can be successftilly employed for the transformation of allenyl ketones 22 into the corresponding furans 23 (Scheme 8.11) [116]. Most importantly, cycloisomerization of 4-thio-substituted... 

Kirsch et al. reported that vinyl propargyl ethers 36 could be converted into the densely substituted furans 38 via the Au(I)-catalyzed cycloisomerization reaction (Scheme 8.17) [125] A variety of substituted furans 38 (Table 8.1) could be obtained under very mild reaction conditions at only 2 mol% catalyst loading. It is believed that this cascade process begins vith the Au(I)-catalyzed Claisen-type rearrangement of 36 leading to the formation of skipped allenyl ketone 37, vhich, upon the Au(I)-catalyzed 5-exo-dig-cyclization, provides furan 38. 

In 2000, Hashmi reported the gold(III)-catalyzed cyclization of a-allenyl ketones to form substituted furans [15]. As an example, treatment of allenyl p-methoxybenzyl ketone 70 with a catalytic amount of AuCls formed a 2 1 mixture of the cycloisomerization product 71 and the cycloisomerization/hydroarylation product 72 in 91% combined yield (Eq. (12.40)). Marshall had previously demonstrated the Ag(I)-catalyzed conversion of allenyl ketones to furans [111]. The Ag(I)-catalyzed transformation was four orders of magnitude slower than was the gold(III)-catalyzed transformation, but the silver-catalyzed process forms the 2-substituted furan as the exclusive product without the competing secondary hydroarylation. The selective conversion of a-allenyl ketones to substituted furans is also catalyzed by gold(III)-porphyrin complexes [112]. 

Analogous 1,2-alkyl migration of an intermediary metal carbene complex is proposed in catalytic cycloisomerization reactions of o-alkynylbenzaldehyde acetal [36], alkynyl azides [37], 1,2,4-trienes [38], allenyl ketones [39], and o-alkynylanilides [40]. 

---