Efficient Regioselective Aldol Condensation of Methyl Ketones Promoted by Organoaluminium Compounds, and Its Application to Muscone Synthesis

Tsuji, Jiro; Yamada, Toshiro; Kaito, Mitsumasa; Mandai, Tadakatsu

doi:10.1246/bcsj.53.1417

Cited by 28 publications

(9 citation statements)

References 8 publications

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“…Such advantages were demonstrated for the aldol condensation, which is a valuable procedure for carbon−carbon bond formation, but presents problems associated with reversibility and lack of selectivity. − …”

Section: Resultsmentioning

confidence: 99%

“…Such advantages were demonstrated for the aldol condensation, which is a valuable procedure for carboncarbon bond formation, but presents problems associated with reversibility and lack of selectivity. [44][45][46] We required 3-methylcyclopent-2-enone (1; for some structures, see Figure 1) in high purity, on the hundreds of gram scale for other work. Ketone 1 can be prepared by intramolecular aldol condensation of 2,5-hexanedione (2), and published preparations have used aqueous base at reflux, sometimes in the presence of an organic solvent.…”

Section: Resultsmentioning

confidence: 99%

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Applications of High-Temperature Aqueous Media for Synthetic Organic Reactions

et al. 1997

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Preparative organic synthesis was investigated in aqueous media at temperatures up to 300 degrees C. Experiments were conducted with a recently disclosed pressurized microwave batch reactor (MBR) or in conventionally heated autoclaves. Thirty-six examples are presented. Among these, methods were developed for a Fischer synthesis, an intramolecular aldol condensation that was scaled up, decarboxylation of indole-2-carboxylic acid, Rupe rearrangement of 1-ethynyl-1-cyclohexanol, isomerization of carvone to carvacrol, and conversion of phenylacetylene to acetophenone. The applicability of high-temperature water was also demonstrated for biomimetic processes important in food, flavor, and aroma chemistry and for tandem reactions such as formation of 2-methyl-2,3-dihydrobenzofuran from allyl phenyl ether. When addition of acid or base was necessary, less agent was usually required for high-temperature processes than for those at and below boiling, and the reactions often proceeded more selectively. In some instances the requirement was orders of magnitude lower, with obvious consequences for safe, economic processing and for lowering costs of effluent disposal. The diversity of reactions indicates that high-temperature aqueous media could play an increasingly important role in the development of new preparative processes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Applications of High-Temperature Aqueous Media for Synthetic Organic Reactions

et al. 1997

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“…The E-isomer had to be obtained by separation of the E/Z-mixture resulting from an aldol reaction. 196 The lack of reactivity of ''remote'' double bonds has been exploited to prepare g,d-unsaturated amino acids from a,b,g,dunsaturated amino acids by hydrogenation in the presence of Rh-DuPhos (cf. Scheme 30).…”

Section: Substrate Screeningmentioning

confidence: 99%

Asymmetric homogeneous hydrogenations at scale

Ager¹,

2012

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Asymmetric hydrogenations are increasingly being used to introduce stereogenic centres into products used in the life sciences industries. There are a number of potential pitfalls when moving from a laboratory reaction to a manufacturing process, not least of which is safety. Time-to-market pressure leads to short development times, which in the past could be a large barrier for the implementation of catalytic steps; now there are new ways to minimise this problem. The potential problems associated with impurities and other methods that can shut down the hydrogenation reactions are highlighted in this critical review (353 references).

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“…For example, 2,15-hexadecanedione can undergo regioselective aldol condensation at the methyl side in the presence of a dialkylaluminum aryloxide and a tertiary amine to form two isomers of 3-methyl cyclopentadecenones, and the subsequent hydrogenation leads to racemic muscone. 5 In 1998, Nicolaou and coworkers realised solid phase synthesis of a (dl)-muscone library by an intramolecular ketophosphonatealdehyde reaction, where simultaneous cyclisation and release of the target product from the Merrifield solid support resin was achieved in the final step. 6 In a similar manner, Takahashi reported solid phase synthesis of aldehydes and their potential synthesis of a macrocylic ketone library.…”

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A Practical Synthesis of (rac)-Muscone and (R)-(–-)-muscone

Cheng

Ding

Shao-min

2011

Journal of Chemical Research

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A practical synthesis of (rac)-muscone in three steps is described, using commercially available 1,10-dibromodecane as the starting material. In the first step, an aldol reaction of 1,10-dibromodecane with ethyl acetoacetate affords the important intermediate 2,15-hexadecanedione in 70% yield. A cyclisation reaction in the second step aided by propyl zinc iodide gives dehydro-muscone in 84% yield. Hydrogenation of dehydro-muscone with Pd-C completes the synthesis of (rac)-muscone. Furthermore, (R)-(-)-muscone is enantioselectively prepared via the formation of a ketal intermediate from dehydro-muscone and 1,4-di-O-benzyl-D-threitol.

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Efficient Regioselective Aldol Condensation of Methyl Ketones Promoted by Organoaluminium Compounds, and Its Application to Muscone Synthesis

Cited by 28 publications

References 8 publications

Applications of High-Temperature Aqueous Media for Synthetic Organic Reactions

Applications of High-Temperature Aqueous Media for Synthetic Organic Reactions

Asymmetric homogeneous hydrogenations at scale

A Practical Synthesis of (rac)-Muscone and (R)-(–-)-muscone

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