Geranylacetone synthesis

Geranylacetone is an intermediate in the synthesis of other fragrance substances. It is used in perfumery in rose compositions, for example, in soap perfumes. 

As mentioned before (2.1.1) Arfmann et al. [133] studied the co-hydroxylation of the sesquiterpenes nerolidol and famesol and the related compounds neryl- and geranylacetone. This was done because co-hydroxylated sesquiterpenes are important intermediates in the synthesis of industrially used fragrances and flavours. Aspergillus niger ATCC 9142 and Rhodococcus rubropertinctus DSM 43197 were unable to hydroxylate nerylacetone or its -isomer geranylacetone, at the co-position of the molecule. Incubation of nerylacetone with Mucor circinelloides CBS 27749 for 25 hr resulted in seven transformation products, including one co-hydroxylation compound, in 3% yield [140]. 

Many other C-C bond forming reactions involving organometallic catalysis have been successfully performed in an aqueous biphasic system. Examples are shown in Fig. 7.13 and include Heck [47, 48] and Suzuki couplings [48] and the Rhone-Poulenc process for the synthesis of geranylacetone, a key intermediate in the manufacture of vitamin E, in which the key step is Rh/tppts catalyzed ad-... 

Yue et al. reported on the total synthesis of / -(—)-cembrene A by using the mod-ihed Wittig reaction and titanium-induced intramolecular carbonyl coupling as key steps the overall yield is 29% starting from -geranylacetone (164) and R-(+)-limonene (168) (Scheme 6-15). ... 

Thus, an efficient and convergent total synthesis of ( )-isocembrene has been accomplished in seven steps from the known geranylacetone through an intramolecular Stille cross-coupling reaction. The strategy is of great potential for the divergent synthesis of complex cembrane-type diterpenoids such as cembrene-C and sarcophytols. 

Geranylacetone is an intermediate in the synthesis of other fragrance substances. It is mainly produced from linalool. Another route starts from myrcene, to which methyl acetoacetate is added under rhodium catalysis geranylacetone is subsequently obtained after saponification and decarboxylation [70a]. It is used in perfumery in rose compositions, for example, in soap perfumes. 

In particular the use of Cu/Si02 in 2-propanol, under N2 or under H2, allows the chemoselective reduction of the carbonyl group also in polyfimctional molecules such as geranylacetone 1. In hydrocarbon solvent the reaction can be addressed towards the one pot synthesis of valuable ethers. 

This insertion reaction has been applied to the syntheses of various natural terpenoids and related products. An example is the synthesis of geranylacetone. Note that trans-isomers are formed almost exclusively. 

Bromocyelization. Wolinsky and Faulkner have published a synthesis of 10-bromo-a-chamigrene (5), the key step of which involves a bromonium ion initiated cyclization of geranylacetone (1) to the vinyl ether (2). This product was... 

An efficient synthesis of squalane (7) from the readily available geranylacetone (6) has been described (Scheme 1)."... 

For the linear synthesis of spheroidene (97) [20] that is described in Section B.4, the Cig-ketone 51 is used as starting material. This is prepared (Scheme 17) from commercially available (5jF)-6,10-dimethylundeca-5,9-dien-2-one (geranylacetone) (52). This ketone 52 is coupled in an Horner-Emmons reaction with the commercially available triethyl phosphonocrotonate (53), in the presence of BuLi as base. Yields for this reaction are almost doubled (from 45 to 85%) when HMPA is added. The ester 54 is converted in one step into the Ci8-ketone 51 by addition of an excess of MeLi (55) in the presence of five equivalents of trimethylsilyl chloride at -100°C, giving, after acidic work-up, the all-E" Cig-ketone 51 in 69% yield [20]. 

The reaction of the ester 51 with MeLi (55) in the presence of trimethylsilyl chloride cannot be performed on a large scale in a reproducibly high yield. For the synthesis of the Ci8-ketone 51 on a large scale, an alternative, a three-step route is used (Scheme 18). First the geranylacetone (52J is coupled in an Horner-Emmons reaction with diethyl cyano-methylphosphonate (4) with NaH as a base. Reduction of the nitrile by DEB AH then gives the aldehyde 56 in 73% yield. Aldol condensation of 56 with acetone (57) in the presence of a... 

C-C coupling is a central step in the Rhone-Poulenc process for production of geranylacetone, which is nsed in the manufacture of vitamin E (199). Myrcene is reacted with methyl acetoacetate in a highly regioselective manner (>99%), catalyzed by Rh-TPPTS in an aqueous-organic biphasic system. The product is hydrolyzed and decarboxylated to jneld geranylacetone (Scheme 32). The reaction proceeds faster in a H2O-CH3OH (3 1) mixture as the aqueous phase in which the catalyst can be recycled without considerable losses. The intermediate /3-ketoesters can also be used for the production of pseudoionone, which is a key intermediate in the synthesis of vitamin A. 

The utility of haloboration-conjugate addition sequence has been demonstrated in the selective synthesis of several natural products such as sulcatol, trans-geranylacetone, and trans-nerolidol (Scheme 13.4) [20]. 

Behr and Johnen reported [38] that myrcene is an important starting point for the synthesis of menthol, nerol/geraniol, and Unalool. Further derivates are citral, citroneUal, and citronellol, which are used because of their lemon-like smeU. Based on the diene structural component, it can be used for Diels-Alder reactions with unsaturated structures, which leads to synthesis of amberUke flavors and anticancer therapeutics. By a C-C linkage, geranylacetone and p spiingene can be obtained, derivates which can be used to synthesize side chains of vitamin E. 

Methylation of LXXD with lithium dimethylcuprate allows the synthesis of trans,trans-fa.Taeso (LXXIII) from geranylacetone (Corey et al., 1967). 

The synthesis of the side chain started from acetone and followed the pattern of the isophytol synthesis in Pig. 9. Cis-irana isomerism at the newly formed double bonds must be taken into account. Geranylacetone was sep-... 

As described above, phytol (301) and isophytol (302) can be manufactured from gera-nylacetone in a sequence exactly analogous to those for the production of geraniol and linalool from methylheptenone. Geranylacetone, in turn, can be obtained from either myr-cene or linalool. Both phytol and isophytol are important as intermediates in the synthesis of vitamins E and K and isophytol is used as a diluent in higher price fragrances (82). 

A new efficient synthesis of polyunsaturated ketones via an oxy-Cope rearrangement is exemplified in equation (33) by the preparation of geranylacetone (20).The conversion of aliphatic and aromatic aldehydes and cyclic ketones... 

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