Terminal diynes, synthesis

Z-tamoxifen 403 tandem cyclization 290, 295 tandem Heck reaction-anion capture 253-4 tandem Heck reaction-phenoxide capture 253 tandem Heck reactions 251, 252-4 tandem intramolecular Heck-intermolecular Stille cross-coupling 255 taxol 140, 143,243,245 ( )-tazettine 146,234 telomerization 352 telomerization products 343, 345 template effect 140 teraconic anhydride 468 terminal acetylenes, synthesis of 216-20 terminal alkynes 6, 213 terminal 2,2-diorgano-l-aIkcnylboronates 51 terminal diynes 207 ternary complex 444 ternary coupling 177... 

Krafft, M. E., Hirosawa, C., Dalai, N., Ramsey, C., Stiegman, A. Cobalt-catalyzed homocoupling of terminal alkynes synthesis of 1,3-diynes. Tetrahedron Lett. 2001,42, 7733-7736. 

The apphcation of the rhodinm(l)-catalyzed double [2+2+2] cycloaddition approach to the synthesis of symmetric biaryl diphosphoms compounds was first accomplished in the reactions of l,4-bis(diphenylphosphinoyl)bnta-l,3-diyne with terminal diynes to give achiral biaryl bisphosphine oxides [23a]. Cj-Symmetric axially chiral biaryl diphosphonates were obtained with perfect enantioselectivity by using a phosphonate-substituted 1,3-bntadiyne and internal 1,6-diynes (Scheme 21.19) [23b]. Axially chiral biaryl dicarboxylates were also obtained by this method [23b]. 

The Co2(CO)8-catalysed tandem 2- -2- -1/2- -2-f 2-cycloaddition reaction of terminal diynes (180) provides a simple one-pot synthesis of novel tetracyclic compounds (181) (Scheme 69). A computational study of the thermal nl + ct2 -I- a 2-cycloaddition of quadricyclane with acetylene, ethylene, DCE, and DMAD... 

Wender, PA., Christy, J.P. (2007). Nickel(0)-catalyzed [2+2+2-I-2] cycloadditions of terminal diynes for the synthesis of substituted cyclooctatetraenes. Journal of the American Chemical Society, 129, 13402-13403. 

The [2 -I- 2 -I- 2] cycloaddition reaction was used successMly in the synthesis of the sesquiterpene alkaloid illudinine (Scheme 2.6) [5], The terminal diyne 27 bearing a gm-dimethyl group in the backbone successfully undergoes a nickel-catalyzed cycloaddition reaction with protected homopropargyl amine 28 to afford cycloadduct 29. This intermediate (29) was converted successfully to the natural product illudinine 30 in five simple steps. 

Scheme 18 Homopolycyclotrimerizations of terminal and internal diynes and synthesis of hb-PAPs with functional end groups...

Tlie cross-coupling of a terminal alkyne 9 with a 1 -bromoalkync 8 in the presence of an aliphatic amine and a catalytic amount of a Cu(I) salt affords unsymmetrically substituted diynes [10, Eq.(5)]. This useful reaction, discovered by Cadiot and Chodkiewicz [8], can be employed advantageously for the synthesis of several polyunsaturated systems. Generally the bromoalkyne is introduced dropwise to a mixture of the alkyne, ethylamine, and MeOH or EtOH in the presence of a catalytic amount of CuCl, and a small amount of NH OH-HCl. The reducing agent, NHjOH-HCl, is used to reduce the copper(TI) ion. The alkynylcopper(I) is assumed to be the reactive intermediate. The formation of the symmetrical diyne can be suppressed by maintaining the concentration of the bromoalkyne. This side reaction is particularly significant in the case of less acidic alkynes such as alkylalkynes [9J. 

An illustration of the preparation of six-membered rings by enyne cycloisomerizations is found in Trost s total synthesis of (-t-)-cassiol (113) (Scheme 6-19) [44]. The key step of this synthesis involved conversion of enyne 111 to 1,4-diene 112. Although a mixture of diastereomers is produced, the offending stereocenter is not found in the natural product, allowing both diastereomers of 112 to be used. A reductive diyne cyclization (114 115) was recently described as the key step in a total synthesis of ( )-siccanin (116) [45]. Hydropalladation of the terminal alkyne, insertion of the internal alkyne, hydride transfer to palladium, and reductive elimination are proposed to account for the observed reaction. 

The synthesis of conjugated diynes via the Glaser coupling reaction " is the classical method for homocoupling of terminal alkynes. The coupling reaction is catalyzed by CuCl or Cu(OAc)2 in the presence of an oxidant and ammonium chloride or pyridine to yield symmetrically substituted diynes. " The oxidative dimerization appears to proceed via removal of the acetylenic proton, formation of an alkynyl radical, and its dimerization. 

During the biomimetic total synthesis of endiandric acids A-G by K.C. Nicolaou and co-workers, the key polyunsaturated precursor was assembled via the Giaser coupiing of two different terminal alkynes. " One of the alkynes was used in excess so the yield of the heterocoupled diyne could be maximized. In a solvent mixture of pyridine methanol (1 1), the two reactant alkynes were treated with Cu(OAc)2 at 25 °C to provide the desired diyne in 70% yield. 

The heterocoupling of a terminal alkyne with a 1-bromoalkyne in the presence of an aliphatic amine and a catalytic amount of a copper(I) salt affords unsymmetrically substituted diynes (2 equation 5). This useful reaction, discovered by Chodkiewicz and Cadiot, can be employed advantageously for the synthesis of several polyunsaturated systems. 

Klein and Kdnig," for example, have reported the synthesis of a sulfonamide substituted 1,2-aryldiyne 111, where the sulfonamide group, being a cr-acceptor, should facilitate the Bergman cycloaromatization. However, as reported by Zaleski for a series of l,S-bis substituted oct-4-ene-2,6-diyne derivatives 113, steric hindrance and hydrogen bond formation between the terminal substituents can influence the temperature of the cyclization, and therefore the reactivity of the sulfonamide compound 111 is comparable with the one of the unsubstituted analog 112, since the electron withdrawing effect of the substituent is compensated by its steric hindrance (Scheme 19.30). 

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. ... 

Metathesis with alkynes is also quite useful in synthesis,particularly for internal alkynes although terminal alkynes are not good partners in this reaction.358 internal metathesis reactions with alkynes are known,including the conversion of 439 to 440 (in 73% yield) in FUrstner s synthesis of prostaglandin E2-1,15-lactone.360 Note the use of a molybdenum metathesis catalyst for this reaction. Diynes also react with alkynes in an intermolecular reaction to form aromatic rings. An example is the conversion of 441 to a 6 1 mixture of 442/443, in 82% yield.36la a similar, palladium-catalyzed cycloaromatization is also known.362 The metathesis disconnections are... 

A general method for the preparation of 1,3-diynes is exemplified by the synthesis of compound 45 condensation of the acetylene 43 with cis-1,2-dichloroethene in the presence of Pd(PPh3)4.CuI gives 44, which is dehydrochlorinated by the action of tetra-butylammonium fluoride in THF . Conjugated ( )-enynes 48 are obtained from terminal acetylenes 46 (R = Bu, Ph or Me3Si) and the ( -bromo ester 47 under catalysis by (Ph3P)2PdCl2. Cul and triethylamine. The same catalyst system promotes the condensa-... 

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