Acetylenic Amino effect

Radical cyclizations are often used in ring formations and are an effective methodology in the synthesis of piperidines. The intramolecular cyclization of an oxime ether, such as 63 onto an aldehyde or ketone gives a new entry into cyclic amino alcohols <99JOC2003, 99H(51)2711>. Similarly, reaction of a terminal acetylene with BujSnH generates a vinyl radical, which will cyclize with an imine moiety to give 3-methylenepiperidine <99TL1515>. The indolizidine alkaloid ipalbidine was prepared by a sulfur-controlled 6-exo-selective radical cyclization of an a/p/ia-phenylthio amide <99H(50)31>. 

Rh complexes are examples of the most effective catalysts for the polymerization of monosubstituted acetylenes, whose mechanism is proposed as insertion type. Since Rh catalysts and their active species for polymerization have tolerance toward polar functional groups, they can widely be applied to the polymerization of both non-polar and polar monomers such as phenylacetylenes, propiolic acid esters, A-propargyl amides, and other acetylenic compounds involving amino, hydroxy, azo, radical groups (see Table 3). It should be noted that, in the case of phenylacetylene as monomer, Rh catalysts generally achieve quantitative yield of the polymer and almost perfect stereoregularity of the polymer main chain (m-transoidal). Some of Rh catalysts can achieve living polymerization of certain acetylenic monomers. The only one defect of Rh catalysts is that they are usually inapplicable to the polymerization of disubstituted acetylenes. Only one exception has been reported which is described below. 

Hug GL, Bonifacic M, Asmus K-D, Armstrong DA (2000a) Fast decarboxylation of aliphatic amino adds induced by 4-carboxybenzophenone triplets in aqueous solutions. A nanosecond laser flash photolysis study. J Phys Chem B 104 6674-6682 Hug GL, Carmichael I, Fessenden RW (2000b) Direct EPR observation of the aminomethyl radical during the radiolysis of glycine. J Chem Soc Perkin Trans 2 907-908 Hunter EPL, DesrosiersMF, Simic MG (1989) The effect of oxygen, antioxidants and superoxide radical on tyrosine phenoxyl radical dimerization. Free Rad Biol Med 6 581-585 Ito O (1992) Flash photolysis study for reversible addition reactions of thiyl radicals with olefins and acetylenes. Trends Phys Chem 3 245-266... 

Table V summarizes the reduction activity of acetylene with the Co(II)-complex catalysts of various sulfhydryl-containing peptides. Of interest is the high activity of the sulfhydryl- and imidazole-containing peptides such as N-mercaptoacetyl-L-histidine and N-mercaptoacetyl-DL-histidyl-DL-histidine. In addition, the effect of amino-acid residues on the reduction of acetylene with these Co(II) complexes decreases in the order histidine > glycine > cysteine > tryptophan.

Table V. Effect of Amino-Acid Residues on Acetylene Reduction...

The amidic bonds within amino acids can be also used to effect the organization of polymers into superstructures (Fig. 10). Thus, the formation of artificial helices on the basis of assembling polymers has been described by use of poly(acetylenes) bearing pendant L-valine side-chains. [71,72] Two effects are important for the association of these ladder-type polymers into double-stranded helices (a) the reduction of conformational freedom by the poly(acetylene) chain with respect to a conventional alkyl-chain and (b) the selective association of the L-valine residues by specific hydrogen bonding. An AFM image of the associates on a fiat surface demonstrates the presence of a string-pearl structure reminiscent of natural DNA. 

The selective hydrogenation of an aryl nitro group has been accomplished even in the presence of an easily hydrogenated acetylene group. Cobalt polysulfide and ruthenium sulfide have been reported to be effective for the selective hydrogenation of the nitro group in m-nitrophenyl acetylenes giving the amino-acetylenes in 75-85% yields (Eqn. 19.2). Ruthenium catalysts were also effective for this reaction but since the order of reactivity over these catalysts was found to be ... 

Most syntheses of aza-indoles start from pyridines and parallel the standard indole syntheses discussed above. However, the Fischer reaction using pyridyl-hydrazones is much less consistent and useful than for arylhydrazones the Madelung reaction is also not as useful, however the Bartoli route" (20.16.1.9) and the Gassman approach" (20.16.1.12) can be used to effect. The most successful methods involve palladium-catalysed coupling of acetylenes with amino-halo-pyridines either as one-" or two-step " processes. The starting amino-halo-pyridines are generally available via directed metaUations. 

Generally speaking, unsymmetrical 1,3-dicarbonyl components produce mixtures of 1,2-azole products/ Sometimes this difficulty can be circumvented by the use of acetylenic-aldehydes or -ketones, for here a hydrazone or oxime can be formed first by reaction at the carbonyl group and this can then be cyclised in a separate, second step/ Pyrazole itself can be formed by the reaction of hydrazine with propargyl aldehyde/ Using /3-chloro-, / -alkoxy- or /3-amino- -enones as 1,3-dicarbonyl synthons is another way to influence the regiochemistry of reaction, and in favourable situations this can be effective. ... 

The l,2-di-(D-flrabt o-tetritol-l-yl)pyridin-4-one C-nucleoside 842 was reported to be formed, among other products, when 1-amino-l-deoxy-D-fructose (239) reacted with malondialdehyde (92MI6) (Scheme 236), Formation of the pyridine nucleus of the nucleoside 844 was effected by cobalt-catalyzed co-cyclotrimerization of the L-threononitrile derivative 843 with acetylene (94TA299) (Scheme 237). 

The first example of chiral polymer from a disubstituted acetylene is a polyd-trimethylsilyl-l-propyne)-based polymer, poly(46), which was synthesized in moderate yields using TaCls-PhaBi (112). Poly(46) displays small optical rotations, and its molar ellipticities of the Cotton effects are up to a few hundreds. The main chain of poly(46) is, therefore, not a well-ordered helix. This is probably because of the less controlled geometrical structure (cis and trans) of the polymer backbone. However, the free-standing film of this polymer achieves an enantioselective permeation of various racemates including alcohols and amino acids. For example, the concentration-driven permeation of an aqueous solution of tryptophan by poly(46) gives 81% enantiomeric excess (ee) of the permeate at the initial stage. A characteristic of the membrane of poly(46) is its ability to enantioselectively recognize 2-butanol and 1,3-butanediol, because the direct resolution of these racemates by hplc is impossible. 

It is interesting to mention that possible conjugation between the acetylenic tt electrons with the p electrons of the nitrogen substituents results in delocalization. Such a change in the transmission of the effect of the amino groups is illustrated in the bromination of the vinyl acetylenic amine (37), which occurs predominantly at the triple... 

N-acetyl-DL- Areo-l,3-dihydroxy-2-amino-octadecyne and the N-octanyl-deri-vative were quite effective in the formation of sphingomyelin. The acetylenic derivatives of the J)-erythro configuration were not active. 

The reaction was most effective when X was an electron withdrawing substituent, but only because this suppressed the competing ionic chlorination of the double bond. In some cases, the ionic chlorination was the predominant reaction. Protonated amino radical addition to unsubstituted olefins, acetylenes and al-lenes, however, gave acceptable yields of products, particularily in the case of the sterically unhindered substrates. The products obtained from the acetylenes were the a-chloroketones or aldehydes. 

---