Enynes allenes

The reactive structural element for the Myers cyclization is an enyne allene, the heptatrienyne 6, which reacts to form a diradical species 7 ... 

The chemistry of enediynes, enyne allenes and related compounds ... 

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. 

The cross-coupling reactions of allenes with components containing sp-carbon atoms are useful synthetic transformations since they provide yne-allenes and enyne-allenes, respectively. Due to the synthetic potential of these classes of carbon-rich unsaturated compounds, the scope and limitations were systematically investigated [1, 16-18]. The first synthetic application was reported in 1981, describing the preparation of alkynyl-substituted allenes by coupling of alkynylzinc chlorides with allenyl halides (Scheme 14.8) [11]. 

Wang s approach for the synthesis of enyne-allenes focused on ene-allenyl iodide 45 (Scheme 14.12) [24]. Palladium-catalyzed Sonogashira reaction of 45 with terminal alkynes 46 (R= Ph or CH2OH) proceeded smoothly under mild reaction conditions in the presence of the cocatalyst cuprous iodide and n-butylamine. The initially formed enyne-allene 47b with substituent R= CH2OH cyclized spontaneously to the corresponding a-methylstyrene derivative 48. 

Wang s synthesis of enyne-allenes by cross-coupling of ene-allenic iodides with alkynes has already been mentioned in Sect. 14.2.1.1 (Scheme 14.12). In a continuation of this work, the same group developed an alternative coupling reaction of allenylzinc chlorides 74 with enyne iodides 75 catalyzed by Pd(PPh3)4, which provided the expected enyne-allenes 76 in high yield and with excellent Z/E selectivity (Scheme 14.17) [38],... 

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. 

The ability of (Z)-l,2,4-heptatrien-6-ynes (enyne-allenes) and the benzannulated derivatives to undergo cyclization reactions under mild thermal conditions to produce biradicals has been the main focus of their chemical reactivities [1-5]. With the development of many synthetic methods for these highly conjugated allenes, a variety of biradicals are readily accessible for subsequent chemical transformations. Cyclization of the enyne-allene 1 could occur either via the C2-C7 pathway (Myers-Saito cyclization) leading to the a,3-didehydrotoluene/naphthalene biradical 2 [6-10] or via the C2-C6 pathway (Schmittel cyclization) producing the fulvene/benzofulvene biradical 3 [11] (Scheme 20.1). 

The enyne-allene 12 having a methyl substituent at the allenic terminus was likewise prepared from the corresponding enediynyl propargylic alcohol 11 (Scheme 20.4). The presence of a methyl group accelerates the rate of cyclization by approximately sixfold and 12 cyclizes with a half-life of -3.6 min at 78 °C. The formation of a more stable secondary benzylic radical is apparently responsible for the rate enhancement. 

An alternative one-step procedure involving treatment of the enediynyl propargylic alcohols 14a and 14b with triphenylphosphine, DEAD and finally o-nitro-benzenesulfonylhydrazine to give the corresponding enyne-allenes 15a and 15b, respectively, under mild thermal conditions has also been reported (Scheme 20.5)... 

Scheme 20.5 One-step synthesis of enyne-allenes from enediynyl propargylic alcohols.

Scheme 20.6 Enyne-allenes from condensation between allenic aldehydes and a y-(tert-butyldimethylsilyl)allenylborane.

The enyne-allene 20b having two sterically demanding iert-butyl groups exhibited a slower rate of cydization (t /2 60 min at 76 °C) when compared with 20a (Eq. 20.2). It is worth noting that the benzylic radical center in 22 is an a,a-di-t-butyl-benzylic radical, which has been shown to be persistent in dilution solution at room temperature for several days [32],... 

Condensation between the allenic aldehydes 25 and the allenylboranes 24, derived from the allenylsilanes 23, also exhibited high diastereoselectivity (Scheme 20.7) [33-35], However, unlike 17, a reversal of diastereoselectivity in favor of the RR/SS pair of the a-silyl alcohols 26 occurred. Consequently, treatment of 26 with potassium hydride to promote the syn elimination furnished the enyne-allenes 27 having predominantly the E configuration (fc Z>% 4) for the central carbon-carbon double... 

Table 20.1 Synthesis of the a-silyl alcohols 26 and the enyne-allenes 27 and 28.

The presence of a methyl substituent at the acetylenic terminus of the enyne-allenes 28e-n appears to reduce the rate of cydization, presumably for steric reasons. The higher thermal stability allows their isolation and purification at ambient temperature without special precautions. 

Scheme 20.8 Enyne-allenes from Pd-catalyzed couplings with (Z)-2-bromoall

Scheme 20.9 Enyne-allenes from a /i-trimethyltin-substituted alkenylborane.

The aryl bromide 40, prepared from cross-coupling between 1,2-dibromobenzene and (trimethylsilyl)acetylene, was converted to the corresponding arylzinc halide 41a and arylboronic acid 41b for subsequent coupling with the haloallenes 42 to produce the benzannulated enyne-allene 43 in -40% yield (Scheme 20.10) [38]. Desilylation with tetrabutylammonium fluoride (TBAF) then afforded 44 in 67% yield. 

Scheme 20.10 Synthesis of benzannulated enyne-allenes via Pd-catalyzed couplings.

The benzannulated enyne-allenes 48 were likewise synthesized in situ from coupling between 41b and the bromoallene 47 (Scheme 20.11) [39]. Under the reaction conditions, 48 presumably underwent a spontaneous cation-mediated Myers-Saito cyclization reaction with a concomitant 1,2-shift of the trimethylsilyl group to give the naphthalene derivatives 49. 

Scheme 20.12 Enyne-allenes via the Horner-Wittig reaction.

The use of l-iodo-9-fluorenone (59) for cross-coupling with phenylacetylene produced 60, which on treatment with 51 gave the benzannulated enyne-allenes 61 (Scheme 20.14) [43], Thermolysis of 61 in 1,4-CHD at 75 °C promoted the Myers-Saito cyclization reaction, leading to 63 in excellent yields. Again, the benzylic radical center in 62 is a stabilized triarylmethyl radical. 

Scheme 20.17 Enyne-allenes via titanium-substituted ylides.

Scheme 20.18 Enyne-allenes via prototropic rearrangement of enediynyl sulfones.

The benzannulated analogs were also found to behave in a similar fashion. Attachment of a pendent olefin to the benzannulated enyne-allene system as depicted in 89 allowed the aryl radical in 90 to be captured in a 5-exo radical cyclization reaction leading to 91 and then the dihydrobenz[e]indene 92 (Scheme 20.20) [55, 56]. 

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