Asymmetric 1,3 diyne

More often such bromo- and iodoalkynes are employed with another synthetic goal in mind, namely, in the Cadiot-Chodkiewicz reaction for the formation of symmetric or asymmetric 1,3-diynes by reaction of the haloalkyne with a terminal alkyne (Figure 13.25). Additional reagents essential for the success of this reaction are one equivalent or more of an amine and a substoichiometric amount of Cul. As with the Cacchi and Stephens-Castro coupling reactions of Section 13.3.4, a Cu-acetylide is the reactive species in the Cadiot-Chodkiewicz coupling. It is formed in step 1 of the mechanism illustrated in Figure 13.25. 

The dppm-subsituted complexes of the asymmetric diynes RC=CC=CSiMe3 (R = Ph, tol) are readily obtained from thermal reactions of the hexacarbonyl complexes with dppm or by direct reactions of the diynes with Co2(M-dppm)(CO)6. In these cases there is some evidence for regioselectivity due to steric interaction... 

Table 2 Nickel-catalyzed cycloaddition of C02 and asymmetrical diynes...

Asymmetrical diynes, including diynes possessing one sterically demanding substituent, did undergo clean conversion to pyrones [22], As shown in Table 2, when the steric difference between the two terminal substituents on the diyne is small (e.g., Me vs. Et), a nearly equal mixture of two py-... 

Additionally, several nickel-catalyzed systems for pyridines synthesis have also been developed by Louie and coworkers. In 2005, they reported that with Ni(COD)2 as the catalyst and carbene as the ligand, the cyclization can be carried out at room temperature (Scheme 3.23a) [51]. Both intramolecular and intermolecular reactions were proceeded well and the cycloaddition of an asymmetrical diyne afforded a single pyridine regioisomer. This catalytic system was extended to cyanamides as well [52], In their systematic studies, they found the in situ formed dimeric [Ni(IPr)RCN]2 from the reaction of Ni(COD)2, IPr, and nitrile are catalytically competent in the formation of pyridines from the cycloaddition of diynes and nitriles. X-ray analysis revealed that these species display simultaneous f- and 17 -nitrile binding modes. Kinetic... 

Similarly, asymmetrically diynes afford pyrones in a regioselective nickel(o) catalyzed cycloaddition reaction in 63-83 % yield... 

The asymmetric diyne-substituted cluster [Os3(GO)9(/x-GO)(/X3- 7 -HG2G=GSiMe3)] 233 may be generated from [Os3(GO)9(/i-GO)(/i3-77 - -Me3SiG2G=GSiMe3)] 232 by desilylation in methanol as illustrated in Scheme 19. Only one isomer of 233 is obtained. 

So far the discussion has concentrated on the reactions of symmetric 1,3-diynes with trinuclear ruthenium and osmium clusters. Related reactions occur with asymmetric diynes. For example, the reaction of [Ru3(CO)8(/tt-dppm)2] with HC CC CSiMes in thf gives [Ru3(/t-H)(CO)s(/r-dppm)2(/t3-7 --L-C2C GSiMe3)] 263 via the oxidative addition of the terminal C CH component of the diynyl ligand across one of the dppm-bridged Ru-Ru bonds. 

Scheme 2.60) [4, 111]. Asymmetric diyne 2.171b formed the meta-isomer 2.172b only. 

The reaction of diacetylene and its asymmetric homologs (penta-l,3-diyne, hexa-1,3-diyne) with semicarbazide (72ZOR2605) affords the amides of 3-methyl-pyrazole- 1-carboxylic acid (27) (80°C, EtONa, EtOH, 40 h). Amide 26 undergoes irreversible rearrangement to amide 27 at 80°C (EtONa, EtOH). 

Asymmetric hydrosilylation can be extended to 1,3-diynes for the synthesis of optically active allenes, which are of great importance in organic synthesis, and few synthetic methods are known for their asymmetric synthesis with chiral catalysts. Catalytic asymmetric hydrosilylation of butadiynes provides a possible way to optically allenes, though the selectivity and scope of this reaction are relatively low. A chiral rhodium complex coordinated with (2S,4S)-PPM turned out to be the best catalyst for the asymmetric hydrosilylation of butadiyne to give an allene of 22% ee (Scheme 3-20) [59]. 

A hydrosilylation/cyclization process forming a vinylsilane product need not begin with a diyne, and other unsaturation has been examined in a similar reaction. Alkynyl olefins and dienes have been employed,97 and since unlike diynes, enyne substrates generally produce a chiral center, these substrates have recently proved amenable to asymmetric synthesis (Scheme 27). The BINAP-based catalyst employed in the diyne work did not function in enyne systems, but the close relative 6,6 -dimethylbiphenyl-2,2 -diyl-bis(diphenylphosphine) (BIPHEMP) afforded modest yields of enantio-enriched methylene cyclopentane products.104 Other reported catalysts for silylative cyclization include cationic palladium complexes.105 10511 A report has also appeared employing cobalt-rhodium nanoparticles for a similar reaction to produce racemic product.46... 

Scheme 4.67 Asymmetric synthesis of allene 260 by rhodium-catalyzed hydrosilylation of diyne 258.

Various acetylenes having functional groups such as halide, alcohol, ether, amine, alkene and nitrile, are tolerated in the reaction. An asymmetric (2+2+2) cydoaddition of a,03-diynes with alkyne was achieved by a [IrCl(cod)]2 catalyst combined with a chiral phosphine ligand such as MeDUPHOS and EtDUPHOS, and gave axially chiral aromatic compounds [20]. 

Cyclization—distannylation, bis(l,3-dienes), 11, 408 cyclization—hydrogermylation, 1,6-Dienes, 11, 408 Cyclization-hydrosilylation asymmetric, example, 10, 833 cascade, trienes, 11, 395 dienes, 11, 379 diynes... 

Carreira employed this method in the context of the total syntheses of the complex natural products epothilones A (12) and B (13) [29] and leucascandrolide (14) (Schemes 5 and 6) [30], The synthesis of strongylodiol B (Scheme 7) expands the scope of the process to include the activation and asymmetric addition of 1,3-diynes such as 15 [31]. 

The increased reactivity of isocyanates, relative to carbon dioxide, was reflected in the wider range of cycloaddition partners. For example, terminal diynes as well as nontethered alkynes (e.g., 3-hexyne) were also successfully converted to 2-pyridones rather than undergoing rapid telomerization to aromatic by-products. Importantly, the cycloaddition of an asymmetrical... 

Cycloadditions feature in syntheses of thiopyrans and their dihydro derivatives. The Rh-catalysed [2+2+2] reaction between 1,6-diynes and isothiocyanates and CS2 leads to cyclopenta[c]thiopyran-2-imines and -2-thiones, respectively. An asymmetric version of the former reaction shows some potential (Scheme 40) <060L907>. 

As is clear from the introductory discussion, most, if not all, of the d-block transition metals are expected to participate in reactions that are related to those discussed here. In addition to the Co-based methodology mentioned earlier, some related reactions of Pd and are known. Also related are the cyclization reactions of metal-carbene complexes containing Cr, Mo, W and other transition metals with alkynes and alkenes and a recently reported Nb- or Ta-promoted diyne-alkyne cyclization reaction, which appears to be closely related to a number of previously developed alkyne cyclotrimerization reactions, such as those catalyzed by Co. Investigations of reactions involving other transition metals may prove to be important especially from the viewpoint of developing asymmetric and catalytic procedures. 

Sato, F., Urabe, H., Okamoto, S. Bicyclization of dienes, enynes, and diynes with Ti " reagent. New developments towards asymmetric synthesis. PureAppi. Chem. 1999, 71,1511-1519. 

In a recent communication, an asymmetric dibenzosilole moiety was reported [43]. Using an iridium-catalysed [2 + 2 + 2] cycloaddition of silicon-bridged diynes and alkynes, various asymmetric dibenzosilole units were obtained in yields of up to 93% (Scheme 5). These novel dibenzosilole compounds can potentially lead to AB monomers for polymerisation. Ladder-... 

The regioselectivity of the Ni-catalysed cycloaddition of CO2 to asymmetrical tethered diynes 40 is controlled by the relative sizes of the terminal substituents and to a lesser extent by the nature of the catalyst. The bulkier group tends to occupy the 3- rather than the... 

By the use of the chiral bromo precursor of the bicycioheptane (at step i) an asymmetric synthesis of estrone was envisaged by the authors, in a highiy novel approach an alkylation reaction of a diyne with a vinyicyciopentene derivative has given an intermediate which by cobalt-mediated... 

---