4-octyn-3-one

B. The flask 1s cooled to 0°C (ice bath) and 35.3 g (0.285 mol) of 1-octyn-3-one (Note 5) is added. After an initially exothermic reaction, the reaction is allowed to warm to room temperature. The reduction can be monitored by gas chromatography (Note 6), but generally 8 hr is required for completion. The color of the reaction mixture is initially light yellow and darkens to red at the end of the reduction. 

Sih (38) has described the reduction of E-l-iodo-l-octen-3-one with Penicillium decumbens to give the desired S-alcohol. Based on optical rotation, the e.e. was about 80%, An asymmetric chemical reduction of this same ketone, using lithium aluminum hydride that had been partially decomposed by one mole each of S-2,2 -dihydroxy-l,T-binaphthol and ethanol (42), gave the desired alcohol in 97% e.e. This reagent also reduced l-octyn-3-one in 84% e.e. to the corresponding alcohol (43). A 92% e.e. could be obtained with B-3-pinanyl-9-borabicyclo[3.3.1]nonane as the reducing agent (44). 

The Bi2-catalyzed electrolysis of acetoxy bromo acetal 19a in DMF at -1.0 V alforded the diastereomeric acetal 20 as a product of a cyclization-elimination sequence. Starting from a chiral cyclopentene bromoacetal (19b) and l-octyn-3-one, a prostaglandin p2a precursor (21) containing all the structural features from C(, to C20 with SR, 11/ , and 12/ chirality, is obtained by the one-step formation of two carbon-carbon bonds in the B -catalyzed radical cyclization addition sequence (Scheme 7) [10]. 

Is a waxy solid which does not lend itself to recrystallization. Attempts to form crystalline salts of the phthalate derivative with achiral alkyl amines only lead to waxy solids or thick oils. The phthalic amine salt made with racemic l-octyn-3-ol requires 3-4 recrystal 1 Izations from methylene chloride to resolve enantiomers. The first recrystallization may take several days, with successive recrystal 1Izations becoming easier. If the 86% ee l-octyn-3-ol is used to make the phthalic amine salt only one facile recrystalHzation is needed to provide optically-pure alcohol. The pure amine salt melts at 132-134°C. The enantiomeric purity of the salt may be determined by NMR by observing the ethynyl hydrogen doublets at 6 2.48 (minor) and 2.52 (major) (CDClj solvent). 

The exceedingly bulky aluminum reagent aluminum tris(2,6-di-rert-butyl-4-methyl-phenoxide) (ATD) [140] was found to be superior to ATPH or MAD as a carbonyl protector in the alkylation of ynones [141]. Initial complexation of 3-octyn-2-one (13S) in toluene with ATD and subsequent addition of a hexane solution of BuLi at -78 °C generated 1,4 adduct 136 in 93 % yield together with a small amount of the 1,2 adduct (Sch. 103). 

The MaNP acid method has been successfully applied to various racemic alcohols listed in Table 9.3 for preparation of enantiopure secondary alcohols and the simultaneous determination of their absolute configurations. If the separation factor a is as large as in the case of l-octyn-3-ol 56 (entry 2 in Table 9.3, a. = 1.88), a large-scale HPLC separation of diastereomeric MaNP esters is feasible. For example, in the case of esters 64a and 64b derived from alcohol 56, ca. 0.85-1.0 g of the mixture was separable in one run by the HPLC (hexane/EtOAc = 20 1) using a silica gel glass column (22 x 300 mm) (Figs. 9.19 and 9.20). 

Recent evidence, using trapping with norbornene and 1-octyne, shows that in hydrochloric acid at 80 °C 2-methylisothiazolin-3-one exists in equilibrium with the ring-opened sulfenyl chloride (85)... 

Hexinylmagnesium chloride solution (0.25 mole), prepared as above, is cooled to — 30° and stirred vigorously while acetic anhydride (0.5 mole) in ether is added at a rate such that the temperature does not exceed —25° (2.5 h). The mixture is stirred for a further 2 h at —30°, then for 2 h at —5° (ice-salt bath), the product is decomposed by ice-water, and the ethereal layer is fractionated. This affords some 1-hexyne (8 g) and the product, 3-octyn-2-one (18 g, 98% calculated on hexyne consumed), b.p. 76-77°/15 mm. 

White and coworkers showed that 1 -octyne is metabolized via a different pathway than the one described above. The intermediary metabolites of 1-octyne bind very quickly to proteins and DNA. However, addition of thiol-containing compounds such as N-acetyl-cysteine diminishes this binding in a concentration-dependent manner. Under these conditions the final metabolite is an N-acetyl-cysteine conjugate of 3-oxo-1-octyne, implicating the latter as an intermediary metabolite (Scheme 6). The high reactivity of the 3-0X0 derivative is probably due to its Michael acceptor structure. 

Acetylene alcohols have been used as chiral synthon for the total syntheses of natural products. Therefore, general preparation protocols of enantiopure acetylene alcohols have been studied. The large separation factor a of MaNP esters enables a large-scale preparation of enantiopure acetylene alcohols. For example, diastereomeric MaNP esters of l-octyn-3-ol 100 (entry 15, a =1.88) were efficiently separated by HPLC on silica gel as shown in Figure 55.27, where 850 mg of the mixture was separable in one run by HPLC (hexane-/EtOAc = 20 l) using a silica gel glass column (22 c[) X 300 mm). ... 

Hypervalent //-spirophosphorane 4a has been found to add to alkynes (Schemes 9 and 10) [18]. However, //-spirophosphoranes 4b and 4c having catecholate and ethylene glycolate residues in place of pinacolate do not furnish similar adducts even imder forcing conditions. For instance, a reaction of 1-octyne with 4a effected using 3 mol% Pd(OAc)2 at 80°C for 2 h forms hypervalent adduct 5 in 95% yield. Other alkynes, inclusive of internal ones, also afford >73% yields... 

This catalyst (1) is a selective catalyst for hydrogenation of 4-octyne to cw-4-octene (90% yield). If the product is left in contact with 1, it isomerizes to the trans-isomer. Since monoalkenes are hydrogenated slowly with this catalyst, cyclo-octene can be obtained from either 1,3- or 1,5-cyclooctadiene. Of more interest, benzene can be hydrogenated to cyclohexane (83% yield). One drawback is that the catalyst loses about 90% of its activity after one cycle. 

In Table 19 are collected typical monomers that polymerize with group 5 and 6 transition metal catalysts to produce high-molecular-weight (Mw > 1 x 10s) polyacetylenes. Among them, tert-butylacetylene and 3-(trimethylsilyl)-l-octyne are monosubstituted acetylenes, while the others are disubstituted ones. It is noteworthy that all of these monomers are considerably sterically crowded. By judicious choice of polymerization conditions, the polymer yield becomes fair to quantitative in every case. The Rtw s of the polymers reach ca. 3 x 10s 2 x 106. 

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