Diynes strategies

The subsequent chain extension can be accomplished by the pedestrian step-by-step homologation sequence via the acyclic diyne 12 or by a more efficient block-to-block strategy. The step-by-step approach includes protiodesilylation of diyne 12 followed by coupling with the propargyl chloride 9 following the same protocol as for the preparation of 12 from 11 and subsequent repetitions of protiodesilylation and alkylation with chloride 9 to reach stages 16 and 18, respectively (Scheme 3). 

A number of stable heterobimetallic copper alkyne complexes have been reported, based on the strategy of using another metal bis(alkynyl) complex as a chelating ligand for copper. The 1,4-diyne [(r -CsFGSiMe Ti-(C=GSiMe3)2]180 (or related complex) was found to stabilize the copper units GuX, with X = alkyl,180,181 vinyl,180... 

Tsuda and coworkers350 used nickel(O) complexes to effect the [2 + 2 + 2] cycloadditions between two alkyne units and one alkene unit and employed this strategy to synthesize copolymers. Thus, the reaction of diyne 602 with A-octylmaleimide (603) catalyzed by Ni(CO)2(PPh3)2 afforded copolymer 604 with a maximum yield of 60% and a GPC molecular weight of as high as 35,000, which corresponds to n = 64 (equation 172). The exo,exo-bicyclo[2.2.2]oct-7-ene moiety of 604 arises through the reaction of the initially formed [2 + 2 + 2] adduct with another equivalent of A-octylmaleimide. 

The successful synthesis of the acetylene-linked bis(ger-menes) posed a question whether analog compounds with conjugated Si=C double bonds could be isolated by the reaction of a silylene with 1,3-diynes. Although attempted reactions can postulate the existence of intermediary compounds consisting of bis(silenes) linked by an acetylene unit, no stable compounds having Si=C-C=C-C=Si conjugated systems have been obtained by such a synthetic strategy. ... 

Figure 7. Synthetic strategy to obtain a [3]catenate by cyclodimerization of a difunctional precursor. The circles represent the templating transition metal, and the triangles the terminal diynes.

However, a suitable transformation must be devised in order to convert, under physiological conditions, the enediyne prodrug into the active drug. An alternative strategy is to use, as enediyne prodrug, a 1,5-diyne equipped with functional groups that allow the introduction of the missing double bond under appropriate conditions. 

Cyclic enediynes have been obtained also by elimination of a suitable propargylic alcohol on a preformed cyclic diyne.5 An example is shown in Scheme 19.7, where the cyclization was accomplished through a Nozaki-Hiyama intramolecular allyl bromide addition to an aldehyde.5 This method proved successful for the synthesis of a particular enediyne that, because of conformational biases, could not be obtained by the strategies described above. 

Only rarely is proton loss observed from the intermediate cation derived from acylation of a terminal alkyne. In contrast, acylation of alkynylsilanes provides an excellent strategy for the synthesis of alkynyl ketones. " Here, it is apparent that elimination of the silyl substituent competes very effectively with capture of a nucleophile. Acylation of bis(trimethylsilyl)ethyne" provides a convenient route to terminal alkynic ketones, particularly since desilylation can be carried out using bases as weak as dilute aqueous borax, conditions mild enough to prevent the ready hydration of the triple bond (Scheme 25)." Silylated diynes are also excellent substrates for Friedel-Crafts acylation. ... 

An elegant modification of this sort of intrmolecular cycloaddition strategy was reported by Funk and Vollhardt in 1980.81 Cooligomerization of bis(trimethylsilyl)acetylene with a substituted diyne under mild reaction conditions catalyzed by cyclopentadienylcobalt dicarbonyl gave a transfused tetracyclic adduct [Eq. (24)]. 

Probably the synthetically most useful versions of cyclotrimerization have been developed in the /ntromolecular sense through the pioneering work of Vollhardt. Since this topic has been thoroughly reviewed (95], we point out here only that the most powerful cyclocouplings have been two-component (e.g., diyne + mono-yne) or single component (e.g., ene-diyne) ones. The former strategy is elegantly illustrated in the CpCo(CO)2-catalyzed synthesis of estrone (61) depicted in Scheme 4-29 [105]. 

Cyclic-oligomers of a,c()-diynes prepared by this same strategy were used extensively by F. Sond-heimer et al. as synthetic precursors to the annulenes for a summary of the early work, see F. Sond-heimer. Pure Appl. Chem. 1963, 7, 363-388. 

The Pd-catalyzed couplings are not only useful for the preparation of fully alkoxy-substituted PPEs 1. Combination of dialkoxy-substituted diiodides with different aromatic diynes leads to other classes of PPEs (Scheme 4). WesH has utilized this strategy to make a PPE, 2d, in which unsubstituted benzene rings alternate with alkoxy-substituted ones (Table... 

Enantioselective intermolecular [2-F2-F2] cycloadditions of 1,6-diynes with a,fS-unsaturated carbonyl compounds are valuable methods for the synthesis of chiral cyclohexadienes in a single step [36]. The intramolecular Diels-Alder reaction (IMDA) is known to be a powerful strategy for the construction of complex multicyclic skeletons [37]. Tanaka reported an efficient enantioselective domino intermolecular [2-F2-F2]/IMDA cycioaddition reaction occurring between 1,6-diyne 106 and amide-linked 1,5-diene 107 bearing two sterically and/or electronically... 

In order to prepare polydiacetylenes with aromatic rings directly attached to the polymer backbone an interesting strategy has been employed. The aromatic ring is attached to one position of the diyne and a functionality for proper self-assembly (Fig. 1) is attached to the other position of the di5me. A carbamate functionality has commonly been used to provide the proper supramolecular stnictiu-e (Fig. 5). Advantages of this scheme are that the reduced nonbonded interactions... 

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