Cross-coupling allenes + alkenes

The transition metal cross-couplings of allenes described here offer practical solutions for the modification of 1,2-dienes and access to the preparation of highly functionalized 1,3-dienes, alkynes and alkenes, which are often not easily accessible in a regio- and stereoselective manner by classical methods. Some of the prepared alkynes or functionalized allenes serve as important intermediates in syntheses of natural products, biologically active compounds, e.g. enynes and enyne-allenes, and new materials. It can be predicted that further synthetic efforts will surely be focused on new applications of allenes in transition metal-catalyzed cross-coupling reactions. 

Carbonyl couplings. Many variations of cross couplings are possible these include aldehydes with a-dicarbonyl compounds. Ketyl radicals derived from carbonyl compounds also add to alkenes such as acrylonitrile " or N-allyl moieties. Intramolecular cyclizations on terminal alkenes or allene species have also been exploited for synthetic purposes. 

In most of the palladium-catalysed domino processes known so far, the Mizoroki-Heck reaction - the palladium(0)-catalysed reaction of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - has been apphed as the starting transformation accordingly to our classification (Table 8.1). It has been combined with another Mizoroki-Heck reaction [6] or a cross-coupling reaction [7], such as Suzuki, Stille or Sonogashira reactions. In other examples, a Tsuji-Trost reaction [8], a carbonylation, a pericyclic or an aldol reaction has been employed as the second step. On the other hand, cross-couphng reactions have also been used as the first step followed by, for example, a Mizoroki-Heck reaction or Tsuji-Trost reactions, palladation of alkynes or allenes [9], carbonylations [10], aminations [11] or palladium(II)-catalysedWacker-type reactions [12] were employed as the first step. A novel illustrative example of the latter procedure is the efficient enantioselective synthesis of vitamin E [13]. 

Scheme 10.154 Proposed reaction steps in the titanium-mediated reductive allene-alkene cross-coupling [125].

Cross coupling of a,p-unsaturated alkenes with allenes could also be promoted. The reaction was catalyzed by the complex [CpRu(CH3CN)3]PFg with CeCl3 as a cocatalyst. A ruthenacyclopentane is proposed as an intermediate and this o-allyl complex allowing nucleophilic additions, an alkylative lactonization was carried out by using allenes with tethered carboxylic acid [113] [Eq. (51)]. 

The first syntheses of dendralenes by C2-C3 bond formation (Scheme 1.25) were reported by Tsuge and coworkers in 1985 and 1986, and proceed via substitution at either a bromide 160 or an epoxide 163, followed by elimination (Scheme 1.26) [116, 117]. Similar addition/elimination sequences to carbonyl groups or epoxides [120], and substitution reactions [121], followed. Such methods have been superseded by cross-coupling techniques that take place between a 2-functionalized 1,3-butadiene and an alkene (each can be either electrophilic or nucleophilic) or a 4-functionalized 1,2-butadiene and alkene, and occur with allylic transposition (Scheme 1.25). No doubt due to the ready availability of alkenyl halides and allenes, and the variety of increasingly mild and selective reaction variants, cross-coupling has provided access to a large number of diversely substituted dendralenes over the past 20 years, some of which have even been part of natural product syntheses [14,122,123]. 

Two final examples of cross-coupling to furnish [3]dendralenes via C2-C3 bond formation are part of very short and efficient total syntheses, and highlight the versatility and attractiveness ofthe approach. As an extension of their work on 1,1-divinylallene (153) (Scheme 1.22), Sherburnel /. [123] synthesized allenic [3]den-dralene 188 via Kumada cross-coupUng of a metallated alkene 187 and a chiral, propargyl mesylate. A subsequent Diels-Alder reaction produced cyclic [3]den-dralene 190 en route to a pseudopterosin aglycone 191 (Scheme 1.29). Allenic [3]dendralenes are prone to decomposition [136], so the subsequent DA reaction was carried out in situ. 

The cross-coupling of allenic alcohols with n-components (i.e., imines, alkenes, alkynes) has also been investigated by Micalizio to prepare substituted 1,3-dienes bearing ally lie amine functionality when reacted with imines (Scheme 23) [42]. The strategy is based on the reactivity of azatitanocyclopropanes 36 formed by... 

Since 2002, Ma et al. have demonstrated the cross-coupling/cyclization of 2,3-allenoic acids 346 in the presence of other functionalized allenes, such as 1,2-allenyl ketones 368 [121] or 2,3-allenols 370 [122], affording differently substituted 2(5/f)-furanones 369 and 371. They also studied the cascade cycUzation/cross-coupling reaction of 2,3-allenoic acids in the presence of simple monosubstituted allenes, which yielded the stereodefined 4-(bromo-2( )-alken-2-yl)-2(5 0furanones Z-372 [123] (Scheme 6.94). 

Crossed Alkene-Alkene Coupling 2323 Allene Synthesis by sp -sp Coupling... 

---