Macrocyclic ketones synthesis

I E G L E R Macrocyclic synthesis Synthesis ol macrocyclic ketones from dinitnles using high dilution... 

Raney nickel desulfurization of the macrocyclic ketones or their reduction products confirmed the structures assigned to these compounds and simultaneously offers new methods for the synthesis of macrocyclic alicyclic compounds. =°... 

Electrophilic substitution reactions on alkynylsilanes are also known. In 1978 K. Ultimootd, M. Tanaka and coworkers by an intramolecular reaction carried out the synthesis of a macrocyclic ketone. 

Challenging applications in the field of macrocyclic furans have been investigated. The major synthetic advantage is the cyclization to the furan after the macro-cyclization. This will avoid a problematic ring closure to macrocycles (to 1,3-furano-phanes) with a furan substrate ( furan latest strategy ). Test substrates demonstrated the viability of this concept [50], as shown below for the synthesis of the [8]furano-phane 91 from the macrocyclic ketone 90 (Scheme 15.22) [39]. 

The classical scent of the sea is afforded by ambergris, which is also the best fixative for perfumes. Once secured from whales, ambergris can now be legally provided by chemical synthesis (Science whaling 2000). Other fixatives are obtained from land animals, such as castoreum, civet, and musk. The first one is a phenolic substance and the latter two macrocyclic ketones that have stimulated the earfy methodologies for the synthesis of macrocyclic conqjoimds... 

Macrocyclic ketones. This reagent has been used for cycloolefination of acetylenic dialdehydes (Wittig-Horner reaction) as a route to muscone, exaltone, and civetone. A synthesis of the last ketone (3) is formulated (equation 1). 

Free radical reactions have been used in organic synthesis not only for ring expansion, but also for formation of macrocyclic ketones [48] [51]. 

In another work, Meyers and coworkers found that in asymmetric synthesis of macrocyclic ketones and a-alkyl ketones by using chiral imines, two intermediate lithioenamines were obtained. One of them was formed in the reaction with LDA at — 30 C and is the kinetically controlled is-isomer 36. The second product formed on reflux with LDA is the Z-isomer 37, which is the thermodynamically more stable isomer. Both formed anion 38 on heating (equation 10). 

The preparation of doubly unsaturated macrocyclic ketones is provided (3). The synthesis of functionalized macrocycles by ring closing metathesis methods are described (4). 

Macrocyclic ketones. A recent method for synthesis of macrocyclic ketones involves intramolecular alkylation of protected cyanohydrins. Sodium hexamethyidisilazide... 

The first total synthesis of sarcophytol A (3), which was reported by Takayanagi et al. in 1990, ° was achieved in a highly stereo- and enantioselective manner starting from , -famesol (91) it included (1) a newly developed Z-selective (Z > 35 1) Horner-Emmons reaction with a phosphonate nitrile, (2) modified cyanohydrin macrocyclization, and (3) enantioselective (93% ee) reduction of macrocyclic ketone 100 as its key steps (Scheme 6-1). 

Extension of the low-valent titanium dicarbonyl coupling reaction to ketoesters leads to cyclic enol ethers, and hydrolysis of these affords the corresponding cycloalkanones. This methodology has been applied to the synthesis of various natural products, as exemplified by the preparation of the highly unsaturated C(14) macrocyclic ketone shown below. 

Synthesis of macrocyclic ketones form dinitriles using high dilution (see 1 st edition). 

C17H30O, Mr 250.42. Crystals with a sweet animalish, musk-like odor mp. 31-32°C, bp. 103 °C (6.7 Pa), soluble in alcohol and other organic solvents. Occurrence In civet (ca. 3%) together with other macrocyclic ketones. Recognized as the component responsible for the civet odor in 1915 by Sack, structure elucidation in 1926 by Ruzicka, for synthesis, see C. is used in fine perfumes for a flxating musk-like odor. 

Due to their unique olfactive characteristics, the macrocyclic ketones (R)-muscone and (R,Z)-5-muscenone are highly prestigious musk odorants. A short and practical synthesis of these exceptional musk odorants has been recently developed by Knoplf and Kuhne starting from a readily available... 

Figure 11.9 Gas chromatograph of the distribution of macrocyclic ketones 31. HRMS found the most abundant ion at t = 19.4 to be 322.3222, the calculated for n = 21 is 322.3235. (Reprinted with permission from K.J. Shea, S.Y. Lee and B.B. Busch, A new strategy for the synthesis of macrocycles. The polyhomologation of boracyclanes, The Journal of Organic Chemistry, 63, 17, 5746-5747, 1998. 1998 American Chemical Society.)...

The synthesis of macrocyclic ketones of olfactive interest has been reported using a one-pot Favorskii process with a one-C-atom ring contraction. ... 

Various organotin reagents react with acyl and aroyl halides under mild conditions without decarbonylation to give carbonyl compounds[390,39l]. Alkyl- or alkenyltin reagents react with acyl and aroyl chlorides to give ketones[548.733,734]. One example is the preparation of the a,/3-dnsaturated 7-keto esters 860 and 861, carried out under a CO atmosphere[735]. The reaction has been applied intramolecularly to the synthesis of the macrocyclic keto... 

Other interesting synthetic applications of the ketone-derived enamine alkylation are found in the monomethylation of steroid enamines (249), extension of the benzylation reaction (250) to a ferrocene derivative (251), the use of a-bromoesters (252) and ketones (252) or their vinylogues (25J), in the syntheses of alantolactone (254-256), isoalantolactone (257), and with a bridged bis-enamine (258). The use of bifunctional alkylating agents is also seen in the introduction of an acetylenic substituent in the synthesis of the characteristic fragrant constituent of jasmine (259), the synthesis of macrocyclic ketolactones (260), the use of butyrolactone (261), and the intermolecular or intramolecular double alkylations of enamines with dihalides (262). 

The use of macrocyclic compounds of the thiophene series for the preparation of macrocyclic alicyclie ketones has been mentioned earlier. " A new synthesis of exaltone has been carried out using (136) as the starting material. ... 

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