Acids alkynes

The key feature of the first total synthesis of (+)-homopumiliotoxin 223G 418 was a Lewis acid-induced, chelation-controlled propargylation of the trifluoroacetate salt of (. )-2-acetyl pi peri dine 415, derived from iV-Cbz-L-pipecolinic acid. Alkyne 416 thus formed was transformed after several steps into 417, which was cyclized by activation of the primary hydroxyl with the carbon tetrabromide-triphenylphosphine system to give the natural product (Scheme 98) <1998TL2149>. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

The position of the triple bond can alter the reactivity of the alkynes. Acidic alkynes react with certain heavy metal ions, e.g. Ag+ and Cu+, to form precipitation. Addition of an alkyne to a solution of AgNOs in alcohol forms a precipitate, which is an indication of hydrogen attached to the triple bonded carbon. Thus, this reaction can be used to differentiate terminal alkynes from internal alkynes. 

Catalyst Acid Alkyne T (°C) Yield (%) Z selectivity Reference... 

The —C = C — carbon atoms in alkynes are very close to each other and this in turn weakens the C — H bond. This enables the H atom to leave easily from the R — C = C — H molecule. As a result, allqmes with the R — C C — H formula show weak acidic properties. Because of this acidity, alkynes can react with some metal salts to form all l metal acetylene salts. If an alkyne has the structure R — C = C — R, however, there is no reaction. 

Water-soluble palladium(O) complexes have also been used as homogeneous catalysts in aqueous-solution alkylation reactions. The particular complex that has been used is Pd(TPPMS>3. Aryl or heteroaromatic halides can be coupled with aryl or vinyl boronic acids, alkynes, alkenes, or dialkyl phosphites with this palladium(0) complex. This complex in aqueous solution can also be used for the coupling of alkynes with unprotected iodonucleotides, iodonucleosides, and iodoamino acids (133). 

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. 

The formation of the symmetrical diyne (4), generated as in equation (8), can be suppressed by maintaining the concentration of the bromoalkyne (3). This side reaction is particularly serious in the case of less acidic alkynes such as alkylalkynes. The reducing agent, NH2OH HCI, is used to reduce the cop-per(II) ion. 

Conjugate acids. Alkynes undergo carboxylation with NaFeH(CO). It appears to be quite sensitive to reaction conditions, since cyclobutenediones are formed at a different temperature. 

Keywords pyridine-2-carboxylate, amino acid, alkyne... 

The third example is more compUcated still. There is a normal OH group (pJCa of about 16) and a slightly acidic alkyne (pKa of about 32). The basic group is not a simple amine but a delocalized amidine. Protonation occurs... 

In Chapter 8 (p. 175) we talked about how hybridization affects acidity. Alkynes, with their C—H bonds formed from sp orbitals, are the most acidic of hydrocarbons, with pK s of about 25. 

Won et al. [19], have reported synthesis of polyesters with valine, leucine, isoleucine, methionine, and phenylalanine (Table 12.1). This three-step process involves synthesis of a diester and a dinitro compound that are copolymerized [19], An amino acid is first coupled with a diol (with 3, 4, or 6 methylene groups) in the presence of tosyl to yield a diester with acid salts of diamine at the terminal ends. The second monomer, di-p-nitrophenyl ester of carboxylic acids, is synthesized by a condensation reaction of adipoyl or se-bacoyl chloride with p-nitro phenol. The final polymerization step involves an arduous condensation reaction in the presence of a strong proton abstractor between acid salt of bis(amino acid-alkyne diester) and di-p-nitrophenyl ester of dicarboxylic acids. Following along the same lines, Chu and Guo [22] have copolymerized a mixture of nitro phenyl ester of succinate, adipate, or sebacate and nitrophenyl fumarate with toluenesulfonic acid salt of phenylalanine butane-1,4-diester. The addition of fumarate derivative to the monomer mixture provides an unsaturated double bond in the polymer backbone that can be functionalized for specific biomedical... 

The best results for this procedure are obtained with bromoaUcynes, whereas iodoalkynes suffer from their more strongly oxidizing nature toward the Cu(I) ion, which leads to an increased formation of the by-product 72, and chloroalkynes generally show a lower reactivity. The reactivity of the terminal alkyne is similar to that described for the Sonogashira reaction. In general, arylacetylenes provide better results than alkylacetylenes. Less acidic alkynes have also been shown to produce larger quantities of the undesired 72 [182]. 

Another carbon compound has an acidic proton, and the acid-base reaction is quite common. Alkynes (Chapter 5, Section 5.2) are categorized as internal alkynes (R-C=C-R) or terminal alkynes (R-C=C-H). The hydrogen atom of a terminal alkyne is a weak acid (pK of about 25), and strong bases such as sodium amide (NaNH2) remove that proton to give an alkyne anion (R-C=C ). In this reaction, the alkyne anion is the conjugate base of the alkyne, which is a weak acid. Alkyne anions are useful nucleophiles in many reactions (see Section 6.7). 

How are alkynes prepared Alkynes react as Br0nsted-Lowry bases in acid-base reactions with acids such as HBr or with aqueous acid. Alkynes react as Lewis bases with dihalogens such as Brg and in hydroboration reactions (see Chapter 10). Alkynes often come from reactions involving other alkynes, using the fact that a terminal alkyne is a weak acid, as introduced in Chapter 6 (Section 6.2.6). Treatment of a terminal alkyne with a base such as sodium... 

Alkynyltriisopropylsilanes. The acidic alkynic H can be protected with TIPS triflate. Silylation of 1-lithiopropyne with 1 equiv of TIPS triflate in ether at —40 to 0 °C gives an 87% yield of 1-TIPS-propyne (eq 4). l,3-Bis(triisopropylsilyl)propyne, derived from treatment of 1-TIPS-propyne with butyllithium in THF at —20 °C for 15 min followed by TIPS triflate at —78 to —40°C (eq 5), is lithiated with n-BuLi in THF at —20°C for 15 min and then allowed to react with aldehydes (eq 6). The cjs enynes are isolated in high yields. TlPS-propargylmag-nesium bromide together with copper(I) iodide has been used in the displacement of the mesylate derivative of farnesol. ... 

Figure 14.13 Synthesis of polyacryUc acid-alkynes polymers.

A similar strategy has been used by Kotha to synthesize naphthoquinones and anthraquinones containing amino acid functionahties [45]. In this case, the racemic amino acid alkyne hybrid 116 was treated with ethylene in an enyne metathesis fashion to yield the diene 117, which was then subjected to a Diels-Alder reaction with 2,3-dimethylbenzoquinone 118 (as shown in Scheme 17.23), to afford... 

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