Enynes organic synthesis

Few other examples of such reaction sequences have been described to date. Oh has reported the palladium-catalyzed reductive cyclizations of 1,6-enynes in the presence of formic acid or triethylsilane via an alkylpalladium intermediate and its application to organic synthesis. Palladium complexes also catalyze the conversion of a range of enynes to cyclic 6,7-unsaturated carboxylic acids in the presence of CO.260... 

When the TMS group is absent and if the reaction is carried out in methanol, a platinum(ll)-catalyzed alkoxycy-clization takes place (Scheme 87).308 This cyclization catalyzed by Pt(ll) was found to be mechanistically similar to the carbohydroxypalladation reported by Genet.309 310 This process has intrinsic importance in organic synthesis since it allows the simultaneous and generally stereoselective formation of a C-O and a C-C bond to occur from an enyne system. This reaction has been applied for the synthesis of a key intermediate of podophyllotoxin.311... 

Twenty chapters cover such new and exciting developments as metal-catalyzed synthesis of allenes, strained cyclic allenes, the numerous applications of different metallated allenes in organic synthesis, as well as the many addition and rearrangement reactions of allenes and allene units in natural products like the remarkable enyne-allenes. 

In view of this background, it is the aim of this chapter to organize the fundamentals of radical additions to 1,2-dienes and to present its state of the art in organic synthesis. All aspects of enyne allene cyclizations [19, 20] have been omitted since this topic is addressed in Chapter 20. In order to simplify the mechanistic discussion, the positions and Jt-bonds of allenes have been consistently numbered using the nomenclature outlined in Figure 11.1. 

Metathesis of enynes is another intriguing application in the laboratory. It would seem from the outcome, that it is a completely intramolecular reaction, but if the mechanism involves a metal alkylidene this is not true and the alkylidene group moves on from one substrate molecule to the next, see Figure 16.25. The methylene group moves to the next ring-closed diene. This is a useful tool in organic synthesis [47],... 

The direct coupling of allenic boranes with aldehydes and ketones affords reasonably good yields of homopropargylic alcohols477-480 (equation 120), which are extremely valuable intermediates in organic synthesis. Enynes and enediynes have been made in this... 

Enyne intramolecular metathesis reactions, of the type shown in equation 61, can be very useful in organic synthesis. A number of such reactions, catalysed by tungsten or chromium carbene complexes, have been reported634,635,737 - 740. The ruthenium carbene catalysts 18-20 (Table 2) are likely to be increasingly used for this purpose because of their stability, ease of handling and good yields, as in the synthesis of various 5-, 6- and 7-membered heterocycles, e.g. equation 67741. 

The intramolecular Alder-ene reaction (enyne cydoisomerization reaction) with alkynes as the enophiles has found wide application compared with diene systems. The reason may be the ready chemo-differentiation between alkene and alkyne functionality and the more reactive alkyne moiety. Furthermore, the diene nature of the products will promote further applications such as Diels-Alder reactions in organic synthesis. Over the past two decades the transition metal-catalyzed Alder-ene cycloisomerization of l,n-enynes (typically n= 6, 7) has emerged as a very powerful method for constructing complicated carbo- or heterocydic frameworks. The transition metals for this transformation indude Pd, Pt, Co, Ru, Ni-Cr, and Rh. Lewis acid-promoted cydoisomerization of activated enynes has also been reported [11],... 

Important progress has been made in the study of the process since the discovery and development of well-defined ruthenium carbene complexes. The interest in the reaction as a synthetic tool for organic synthesis has been growing, among others, because of its atom economy. For recent reviews on enyne metathesis see Refs. [91-93]. For a review on the application of enyne metathesis in organosilicon chemistry see Ref. [6]. 

Saito S, Yamamoto Y (2002) Palladium-Catalyzed Benzannulation Reactions of Conjugated Enynes and Diynes. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 1635... 

The results presented above indicate that the Zr-promoted bicyclization reactions of enynes and diynes constitute novel and attractive synthetic methods. The corresponding reaction of dienes remains to be developed. Somewhat unexpectedly, the reactions of monoalkynes and monoalkenes can, in many cases, be highly pair selective and regioselective. Many aspects of these reactions also need to be further developed. Besides being attractive from the viewpoint of organic synthesis, the chemistry of ZrCp2 provides a number of novel structural and mechanistic features that broaden the horizon of organometallic chemistry. 

The tetra-c/5-cyclononatetraene 241 is unstable and easily rearranges at 23 °C (Zi/t 50 min) to the isomeric c/5-8,9-dihydroindene 242 (equation 77) . It is interesting, however, that the iron(III) tricarbonyl complex of tetraene 241 is stable for many days at room temperature and isomerizes to the Fe-complex of 242 only upon heating in octane at 101 °C . The principle of stabilization of the reactive multiple bonds with metal carbonyl complexes is well-known in modern organic synthesis (e.g. see the acylation of enynes ). 

The Ramberg-Backlund reaction is now widely utilized in organic synthesis. It has been applied in synthesizing cyclobutenes, cyclopentenes, cyclohexenes, phenanthrenes, large ring systems, dienes, enynes, polyenes, alkynes, and many natural products. 

Radical attack at an uncoordinated C=C bond of vinylcarbene or enyne ligands was applied to organic synthesis. Thus, a Ti-induced radical attack at vinylcarbene-Cr complex afforded new carbene-Cr complex (Scheme 8.79) [152], while Mn-induced radical attack at enyne-Co complex led to furan synthesis (Scheme 8.80) [153]. 

Transition-metal-catalyzed intramolecular cycloisomerization is one of the most useful carbocyclization reactions, and specifically, the Rh-catalyzed cycloisomerization of 1,6-enynes provides a powerful tool in organic synthesis. Cyclization of l,6-en5me 452 catalyzed by Wilkinson s catalyst gave 1-exo-methylene-2-cyclohexene 453 via a 6-exo-trig mode in 83% yield (Scheme 2-50). Terminal substitution on the alkene moiety dramatically suppressed the cyclization, and substitution of the terminal alkyne moiety was detrimental to the reaction as well. 

Shibata and co-workers independently developed similar [2-I-2-I-2] cycloaddition of enynes 13 (Scheme 6) and alkynes 14, affording cyclohexadienes 15 (15). The significance of this work is the construction of quaternary carbon stereocenters, which remain a very challenging task in organic synthesis (16). The authors... 

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