Phenylacetylene sequences

In the early 1990s, Moore et al. reported the syntheses of a tremendous variety of meffl-connected PAMs [5 b, 36]. They recognized that the structural rigidity of systems like 8 could be useful in supramolecular chemistry. The convergent, stepwise approach of linear oligomeric phenylacetylene sequences developed in the Moore laboratory permitted absolute control over chain length, order of... 

Cyclization of substituted phenylacetylene sequences afforded functionalized macrocycles that were amenable to subsequent manipulation. For example, transesterification of 42 with octanol in the presence of 18-crown-6 ether and potassium carbonate gave the corresponding ester in 85% yield (Scheme 13). The ester functionalities could be reduced by DIBALH to give the hydroxymethyl-substituted macrocycle (43) in 61 % yield. The low yield of this particular transformation is attributed to mechanical losses during purification, due to the highly polar nature of the product. Macrocycle 43 could then be treated with alkyl bromides to give a group of benzyl ether derivatized PAMs. 

An impressive achievement of this strategy has been the construction of three-dimensional structures. Utilizing branched phenylacetylene sequences, double cyclization yielded macrobicyclic arrays 54 and 55 [43]. The zenith of Moore s approach is macrotricycle 56, a freely hinged system with a sizable 36xl2xl2A molecular cavity [44]. 

Zhang JS, Moore JS, Xu ZF, Aguirre RA (1992) J Am Chem Soc 114 2273-2274 Nanoarchitectures 1. Controlled synthesis of phenylacetylene sequences... 

Scheme 6.3 Moore and coworkers repetitive synthesis of linear phenylacetylene sequences capable of undergoing high-yield macrocyclizations.

Many examples of insertions of internal alkynes are known. Internal alkynes react with aryl halides in the presence of formate to afford the trisubstituted alkenes[271,272]. In the reaction of the terminal alkyne 388 with two molecules of iodobenzene. the first step is the formation of the phenylacetylene 389. Then the internal alkyne bond, thus produced, inserts into the phenyl-Pd bond to give 390. Finally, hydrogenolysis with formic acid yields the trisubstituted alkene 391(273,274], This sequence of reactions is a good preparative method for trisubstituted alkenes from terminal alkynes. 

Next, select phenylacetylene from among the molecules on screen. This provides a small selection of 4-substituted phenylacetylenes. The only difference in the appearance of the display is that in this case, the name of the molecule in the collection (H, Me, OMe, Cl and N02) appears in place of the Frame i (i is the number of the frame in the overall sequence) to the right of the bar at the bottom of the screen. 

By using monomers with different substituents, multiple functionalities could be introduced into the phenylacetylene oligomer at any desired position along the sequence backbone, resulting in macrocycles with a wide variety of symmetries (e.g. 47-53). In principle, this versatile synthetic method should allow construction of PAMs in which anyparticular group couldbe placed at any particular site. Judicious choice of the type and placement of functionalities has... 

Few examples of the preparation of six-membered heteroaromatic compounds using Fischer-type carbene complexes have been reported [224,251,381]. One intriguing pyridine synthesis, reported by de Meijere, is sketched in Figure 2.35. In this sequence a (2-aminovinyl)carbene complex first rearranges to yield a complexed 1 -azadiene, which undergoes intermolecular Diels-Alder reaction with phenylacetylene. Elimination of ethanol from the initially formed adduct leads to the final pyridine. 

A reversible Ugation technique was desired that would aUow the use of the mPE system in dynamic combinatorial libraries (DCL) in an effort to identify masterpiece sequences [81]. The imine bond metathesis is known to have an equilibrium constant close to unity, undergoes reactions at reasonable rates at room temperature, and has a geometry that is compatible with the phenylacetylene unit [82] therefore it was chosen as a component for mPEs. 

Trimethylsilylphenyl telluride, by treatment with benzophenone in MeCN at room temperature, gives compound A which is treated in sequence with phenylacetylene at 100°C to give compound C in 85% yield (route a). The reaction can also be performed in one step by heating a mixture of the telluride (1.2 equiv), benzopheuone (1.0 equiv) and phenylacetylene (1.2 equiv) without solvent at 100°C for 12 h to give C in 93% yield (route b). 

SOLID-PHASE SYNTHESIS OF SEQUENCE-SPECIFIC PHENYLACETYLENE OLIGOMERS... 

Efficiency of the deprotection and coupling reactions are critical to the success of any iterative solid-phase synthesis. Shown in Scheme 1 is a triad of reactions for phenylacetylene oligomer synthesis trimethylsilyl deprotection,28 29 triazene unmasking of an iodobenzene,30 and the Sonogashira coupling of a terminal acetylene with an aryl iodide.31-33 Representative procedures for each step in this sequence are included at the end of this chapter. 

A 3-chloroketone may replace the enone in this sequence. For example, 3-chloro-l,3-diphenylpropan-l-one reacts with phenylacetylene to give 2,4,6-triphenylpyrylium. Tin(IV) chloride acts as both the condensing agent and the hydride transfer agent (65CB334). 

While the synthesis of the requisite methano[10]annulenes is not always easy, the [ 2 + 2 + 2] cycloreversion has provided the essential structural variations of cyclopropa fusion into an aromatic moiety that complement other methodologies (Section II.E). Moreover, the sequence lends itself to further exploitation. Thus Vogel s group50 has obtained the dicyanoacetylene adduct 40 which provides phenylacetylene on fvp (equation 9). It is likely that methylenecyclopropabenzene (9) is initially formed as a molecule too... 

The [2+2] cycloaddition of germadisilacyclopropene 74 with phenylacetylene affords the 3-germa-l,2-disilole 20 in 42% yield. As intermediates in this reaction sequence, the housene 75 and the isomeric silole 76 were discussed (Scheme 4) <2000JA12604, 2001JOM41>. 

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