Monoynes, reactions

Members of the cannabinoid class of natural products were accessed using a crossed [2 + 2 + 2] cycloaddition, as shown for the synthesis of cannabinol (86) (Scheme 7.18) [28], Sterically encumbered substituents, on both the diyne and the monoyne reaction partners, were used to direct the regioselective outcome of this crossed alkyne cyclotrimerization. The Cp RuCl(cod) complex (10 mol %) was employed as catalyst, allowing the reaction of diyne 84 with an excess of propar-gyltrimethylsilane under microwave conditions to deliver the pyrane 85 in 88% yield as a single regioisomer. The latter was used as a synthetic intermediate to access cannabinol (86) as well as cannabinodiol within five additional synthetic steps. 

The reaction described above can also be performed in a fully intermolecular fashion. When monoyne 49 is used in presence of isocyanate 47 and catalytic amount of [Ni(COD)j]/SlPr, pyridone 50 is formed in 90% yield (Scheme 5.15) [18], However, when an excess of isocyanate 47 is used in the same reaction... 

A few further general examples of zinc catalytic activity or reactivity include the following. Other zinc-containing systems include a zinc phenoxide/nickel(0) catalytic system that can be used to carry out the chemo- and regioselective cyclotrimerization of monoynes.934 Zinc homoenolates have been used as novel nucleophiles in acylation and addition reactions and shown to have general utility.935,936 Iron/zinc species have been used in the oxidation of hydrocarbons, and the selectivity and conditions examined.362 There are implications for the mechanism of metal-catalyzed iodosylbenzene reactions with olefins from the observation that zinc triflate and a dizinc complex catalyze these reactions.937... 

Rothwell and colleagues352 studied the titanium mediated [2 + 2 + 2] cycloaddition of alkenes with monoynes and diynes. Among the reactions studied, the reaction between styrene (29) and diyne 609 in the presence of titanium catalyst 610 proved cleanest (equation 175). The reaction yielded 614 via a [2 + 2 + 2] cycloaddition followed by a titanium mediated suprafacial [1,5] H-shift involving 611-613. The cis relationship between the trimethylsilyl group and the phenyl group indicated that the initially formed titananorbornene 611 had an endo stereochemistry. 

Kotha and Brahmachary353 prepared some constrained a-amino acids using a rhodium mediated [2 + 2 + 2] cycloaddition reaction. The indane type of a-amino acids were synthesized by reacting diynes with monoynes using Wilkinson s catalyst354. Thus, the reaction of diyne 615 with 616 afforded a-amino acid derivative 617 (equation 176). 

As mentioned above, the homopolycyclotrimerization was limited to a small number of diynes in terms of generation of soluble polymers. To overcome the problem of uncontrolled cross-linking reactions and to improve the solubility of the polymers, copolycyclotrimerizations of aromatic diynes with monoynes (V-XI) were carried out (cf., Scheme 24). This approach worked very well all the copolycyclotrimerization reactions proceeded smoothly with good controllability, producing completely soluble hyperbranched copoly-... 

The chemo- and regioselectivity problems can be solved by the [2+2+2] cycloaddition of diynes with monoynes, although the accessible products are limited to bicyclic compounds. The [2+2+2] cycloaddition of diynes with monoynes has been applied to the synthesis of biologically active molecules and functional materials. The first application in the natural product synthesis was the dl-estrone synthesis using CpCo(CO)j as a catalyst. The [2+2+2] cycloaddition followed by the benzocyclobutane to ort/jo-quinodimethane rearrangement and intramolecular Diels-Alder reaction afforded a dZ-estrone precursor (Scheme 21.8) [11]. 

The [2+2+2] cycloaddition of sUicon-hnked diynes with monoynes afforded 9-sUafluorene (sUole) [15]. This reaction was apphed to the synthesis of a densely substituted ladder-type sdafluorene (Scheme 21.12) [15]. 

There is only one example where methyleneaziridines undergo a C-C bond cleavage reaction The nickel-catalyzed reaction of methyleneaziridine 119 and nona-2,7-diyne gave [3-1-2] annulation product 120 via ring expansion of a nickelacycle by P-carbon elimination (Scheme 2.77) [129]. Monoyne failed to show reactivity, suggesting the free alkyne unit on the diyne plays a crucial role. 

Yu S, You X, Liu Y (2012) Unexpected multi-component reactions of conjugated 1,3-butadiynes or monoynes with acyl cyanide derivatives mediated by zirconium. Chcm Eur J... 

Examples of improved chemoselectivity by immobilized diyne on a solid-support [19-21] or of improved reactivity of less reactive alkynes by use of microwave [21-24] were recently described. A wide variety of diynes and monoynes containing functional groups were applied to this reaction in the past decade. Arylboronates [25, 26] and diiodo benzenes [27, 28] [Eq. (12)] were thus obtained and involved in further transformatiOTis. Several types of compounds able to present biological activities could also be synthesized such as benzo-fused lactams and lactones [23, 29] [Eq. (13)], phtalans [19], indanones [20], indanes [21], phenanthridines [22], benzoproline and tetrahydroisoquinoline derivatives [30, 31], C-arylglycosides and C-arylribosides [32-35]. Recently, this ruthenium-catalyzed [2+2+2] cycloaddition between a diyne and a monoalkyne was also used as reaction step in total syntheses [20, 23, 24, 36]. 

The reaction of a,co-diyne with monoene instead of monoyne also gave an aromatic compound (Scheme 5.4) [9], The reaction included cleavage of a C—O bond. Diyne 7 reacted with 50 equiv of 2,3-dihydrofuran to give aromatic alcohol 8 in 97% yield. Acyclic vinyl ether such as n-butyl vinyl ether could be used in place of 2,3-dihydrofuran. The reaction of 7 with 25 equiv of n-butyl vinyl ether gave 9 and 10. The combined yield was nearly quantitative. n-Butyl vinyl ether acted as an acetylene equivalent when the reaction gave 9. Based on this result, an enol ether could be used as an acetylene equivalent in Rh-catalyzed [2 -j- 2 -j- 2] cycloaddition [11]. 

A fast entry toward (5)-(-)-3-n-butylphtalide (74), a constituent of celery that is used in Chinese folk medicine, was found in the rhodium-catalyzed crossed [2 + 2 + 2] cycloaddition of chiral diyne ester 73, which can be assembled enan-tioselectively within a few steps, and acetylene as the monoyne component (Scheme 7.15) [25]. Notably, the reaction provided the crossed cyclotrimerization product 74 (72% yield) at room temperature under an acetylene atmosphere (1 atm) without the need for pressurization. 

Patterns of [2 - - 2 - - 2] cycloaddition for the synthesis of cyclophane are depicted in Scheme 8.1. Intermolecular reaction of diyne and monoyne can provide ortho, meta, and para isomers as dipodal cyclophanes (pattern A). Linear triyne can be transformed into ortho-ortho and ortho-meta isomers by an intramolecular reaction (pattern B). In the reaction of branched triyne, symmetrical 1,3,5- and unsymmetrical 1,2,4-isomers can be obtained as tripodal cyclophanes (pattern C). The choice of catalyst and tether is very important for induction of the aforementioned regioselectivities. 

Shibata and Tsuchikama subsequently developed the enantio- and diastereoselec-tive [2 + 2 + 2] cycloaddition reactions of tetraynes with monoynes. These reactions proceeded in the presence of the same chiral iridium catalyst to give helically chiral quinquearyl compounds, possessing four consecutive axial chiralities, with perfect... 

For the synthesis of C2-symmetric axially chiral biaryls, Tanaka et al. using the cationic rhodium(I)/Segphos complex as a catalyst, reported various enantioselective double [2-I-2-I-2] cycloaddition reactions. The double [2-1-2-1-2] cycloaddition of readily prepared ether-linked tetraynes 49 with two molecules of monoynes 50 proceeded to give Ca-symmetric axially chiral biaryls 51 in good to high ee values, although the product yields were low to moderate (Scheme 9.18) [19]. 

The reaction tolerates a wide range of functional substituents and allows use of alkenes, alcohols, amines, esters, halogens, and nitriles. Reactions of 1,6-octadiynes with such monoynes results in ortho- and mefia-substituted derivatives. Regioselectivity of the reaction is controlled by the choice of the ligand. Thus, the interaction of diyne 2.10 and monoyne 2.11 in the presence of dppe [l,2-bis(diphenylphosphino)ethane] yields mainly the meta-isomer 2.12 (selectivity 88%), whereas in the presence of dppf [1,1 -bis(diphenylphosphino)ferrocene] the yield of ortho-isomerlA3 reaches 82% [39] (Scheme 2.5). 

Intermolecular cyclization of diyne with monoynes or intermolecular cyclization of triynes is a general method for the synthesis of substituted benzenes [51]. But a serious drawback of this reaction is the presence of a secondary process of diyne dimerization or monoyne trimerization. The selectivity and yield of the cyclic products strongly depend on the structure of the reactants, solvent, catalyst, etc. A highly efficient and selective [2-I-2-I-2] cyclization of diynes and monoynes was described. A rhodium catalyst allowed the reaction to proceed at room... 

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