Medium-ring acetylenes

Medium-ring acetylenic lactones,2 Cyclization to medium size acetylenic lactones is difficult because of geometric constraint imposed by the triple bond, and has been considered practicable only for at least fifteen-membered rings. Surprisingly, the acetylenic w-hydroxy acid 1 when complexed with Co2(CO), is cyclized in 28% yield to the seven-membered complexed acetylenic lactone 2 by Mukai-yama s reagent, 2-chloro-l-methylpyridinium chloride (8, 95-96). The yield is essentially the same as that observed in lactonizaton to a complexed 10-membered... 

Medium-ring acetylenes (8- to 11-membered) with one triple bond are isolable compounds. Eight- and ten-membered cyclic acetylenes containing more than one unsaturated bond have been prepared and isolated. Isolable substituted cycloheptyne derivatives will also be discussed in this section. 

The enthalpies of hydrogenation of some medium-ring acetylenes to the corresponding cycloalkanes are summarized in Table 3 It has been suggested that the result for cyclooctyne (69-1 kcal/mole) may be somewhat in error. Cyclooctyne,... 

The medium-ring acetylenes show typical C C stretching vibration - at ca. 2210 cm. The fairly strong band in cyclooctyne in the same region suggests that an angle strain at the triple bond would render the C=C rtretching vibration more unsymmetric. This fact indicates that, in spite of an appreciable strain, the essential character of acetylenic bond is preserved in cyclooctyne. 

Medium-ring Acetylenes.— The structures and heats of formation of several alkynes have been calculated using force-field calculations. The calculated heats of formation include cycloheptyne, 59.31 cyclo-octyne, 43.43 cyclononyne, 33.45 cyclodecyne, 21.39 kcal mol The lowest energy conformation of cycloheptyne was calculated to be chair-like with a second conformation, in which all the atoms except C-5 are in one plane, only slightly greater in energy. 

A simple, high yielding (65-90%) procedure has been described for the preparation of medium ring and macrocyclic acetylenic lactones which is mechanistically related to the well known Eschenmoser fragmentation reaction, and the following example is representative. Bromination of the tosylhydrazone of 1 was carried out with NBS at -10°C in a water/t-butanol/acetone mixture. The reaction mixture was then treated with aqueous NaHSC>3 solution and the resulting mixture heated at 50-60°C for one hour, which gave the acetylenic lactone 2. 

A large number of cyclic acetylenes have been synthesized to investigate the proximity interactions between two triple bonds or between a triple bond and other unsaturated systems. Such transannular proximity interactions have been observed in some cyclic acetylenes of medium ring size. However, no appreciable evidence of the interaction was detected in the electronic spectra of diacctylenes 1 2 - and 3... 

Of all methods certainly azide-acetylene addition is the most common for example, Sasaki and his collaborators have studied medium ring diazides and their 1,2,3-triazole products (Eqs. 1,2). In an earlier paper they described a number of analogous reactions that occur in generally excellent yield... 

As illustrated in the early achievements from Reppe on the cyclotetramerization of acetylene and from Wilke on the cyclodimerization and cyclotrimerization of butadienes, nickel-catalyzed cycloadditions possess considerable potential in the construction of medium ring systems. Pioneering studies by Wender have demonstrated many practical implications that have advanced the... 

In building up the pyrrole ring from ketoximes and acetylene in the superbase KOH/DMSO medium, it is not only OH, but also the CH acidity of ketoximes leading to the anions 157-159, that may play an important role (Scheme 79). 

The two-carbon ring expansion which involves the [2 + 2] cycloaddition of enamines of cyclic ketones with electron-deficient acetylenes followed by thermal rearrangement of the resulting fused cyclobutenes (see Section II.E) has been successfully used in the synthesis of medium-size heterocycles. Examples include the preparation of compounds 407246, 408247 and 409248. 

The reaction of 1,2-dibromocycloalkenes (13) with magnesium in the presence of l,3-diphenylbenzo[c]furan (16) affords a cycloalkyne adduct (17). Also, the mercuric oxide oxidation of bishydrazone, which has been used extensively in the preparation of open-chain and medium or large cyclic acetylenes " , is adapted for small ring bishydrazones (18) . Treatment of 18 with mercuric oxide in the presence of 16 or of phenyl azide results in the adducts, 17 and 19, respectively. It seems... 

The ring-closure mechanism of 2-chloroethanol has been studied on the basis of kinetic and equilibrium chlorine isotope effects. Epoxidation of the terminal double bond of farnesyl acetate has been achieved via the bromohydrin, obtained with NBS. A stereospecific method has been elaborated for the preparation of 1-alkynyloxiranes, starting from the monotosylate ester of acetylenic diols. 1-Alkynyloxiranes are also formed from a-hydroxy quaternary ammonium salts in alkaline medium (Eq. 57). ... 

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