Cyclic dienol ethers

Details Cyclic dienol ethers Cyclic dienol ethers

2001-01-17

2002-02-19

Padmanabhan, Sreeni (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C549S369000, C549S430000, C568S591000, C568S667000, C568S670000

Reexamination Certificate

active

06348606

ABSTRACT:

FIELD OF THE INVENTION
The present invention is concerned with a novel process for the manufacture of symmetrical, terminally ring-substituted polyenes, especially carotenoids of the canthaxanthin, astaxanthin, etc., types and the corresponding 2,2′-dinor-carotenoids (generally referred to as 4,4′-diketo-carotenoids) from acetalized polyene dialdehydes by an acid-catalyzed condensation reaction with cyclic dienol ethers.
BACKGROUND OF THE INVENTION
Lewis acid-catalyzed additions of &agr;,&bgr;-unsaturated ethers (aldehyde enol ethers) to acetals are known and date back to the work of Muller-Cunradi and Pieroh (see U.S. Pat. No. 2,165,962). Hoaglin and Hirsch [J.A.C.S. 71, 3468 et seq. (1949)] investigated this reaction further and broadened the possible applications, which Isler et al. likewise did in the nineteen fifties with respect to the synthesis of &bgr;-carotene, crocetin dialdehyde, lycopene, as well as, &bgr;-apocarotenoids [Helv. Chim. Acta 39, 249 et seq. and 463 et seq. (1956), ibid. 42, 854 et seq. (1959) and U.S. Pat. Nos. 2,827,481 and 2,827,482]. Later, Mukaiyama [Angew. Chem. 89, 858 et seq. (1977) and Org. Reactions 28, 203 et seq. (1982)] extended the reaction by using the readily accessible trimethylsilyl enol ethers.
Also enol ethers of aliphatic and alicyclic ketones, including alkyl enol ethers and silyl enol ethers, react with acetals to give &bgr;-alkoxy-ketones or, with cleavage of alcohol, to give the corresponding elimination products [Chem. Lett. 1974, 16 et seq., J.A.C.S. 102, 3248 et seq. (1980), Chem. Lett. 1987, 1051 et seq. as well as ibid., 1975, 569 et seq.].
The first Lewis acid-catalyzed condensations of 1-alkoxy-1,3-dienes (dienol ethers) with &agr;,&bgr;-unsaturated acetals were reported by Nazarov and Krasnaya [J. Gen. Chem. USSR 28, 2477 et seq. (1958)] and by Makin [Pure & Appl. Chem. 47, 173 et seq. (1976), J. Gen. Chem. USSR 31, 3096 et seq. (1961) and 32, 3112 et seq. (1962)]. Here, the coupling of the acetal to the dienol ether takes place as far as can be seen exclusively at its &ggr;-position with the formation of a chain-lengthened &agr;,&bgr;-unsaturated acetal, which, however, in competition with the first acetal reacts with further dienol ether with the formation of a Pa/27.7.1999 further, chain-lengthened (&agr;,&bgr;-unsaturated acetal, etc. [telomer formation; see also Chemla et al., Bull. Soc. Chim. Fr. 130, 200 et seq. (1993)]. For this reason such a condensation has been found not to be workable for synthetic purposes, especially for the synthesis of apocarotenals [Isler et al., Adv. Org. Chem. 4, 115 et seq. (1963)].
1-Alkoxy-1,3-dienes and trimethylsilyloxydienes [of the CH
2
═CH—CH═CH—OSi(CH
3
)
3
-type] can be condensed with &agr;,&bgr;-unsaturated acetals in the presence of Lewis acid catalysts, as disclosed by Mukaiyama et al. in Chem. Lett. 1975, 319 et seq. In this coupling, the attack also seems to take place exclusively at the terminal (&ggr;) carbon atom of the diene system [“&ggr;-attack”; Mukaiyama et al., Bull. Chem. Soc. Japan 50, 1161 et seq. (1977) and Japanese Patent Publication (Kokai) 36,645/1977/Chem. Abs. 87, 201825 t, (1977)]. In contrast to the reaction with 1-alkoxy-1,3-dienes, in which an &agr;,&bgr;-unsaturated acetal results, the reaction of trimethylsilyloxydienes with acetals forms an aldehyde that does not react further with the diene (no telomer formation). Thereby, zinc bromide and many other Lewis acids are required as catalysts only in small amounts [Fleming (et al.), Tetr. Lett. 1979, 3209 et seq. and Chimia 34, 265 et seq. (1980) as well as Brownbridge, Synth. 1983, 85 et seq]. By using this method, Mukaiyama et al. were able to synthesize vitamin A [Kokai 36,645/1977, Chem. Lett. 1975, 1201 et seq. and Bull. Chem. Soc. Japan 51, 2077 et seq. (1978)] and workers from Rhône-Poulenc developed new routes to carotenoids and vitamin A [German Patent Publication, i.e., Deutsche Offenlegungsschrift (DOS), 2,701,489 and A.E.C. Sociétéde Chimie Organique et Biologique No. 7824350].
The aforementioned Lewis acid-catalyzed condensation of a dienol ether with an &agr;,&bgr;-unsaturated acetal based on the work of Nazarov and Krasnaya, Makin, and Chemla et al. would be a very valuable access to apocarotenals and bis-apocarotenals if the yield of the desired primary product of the . . . CH═CH—CH(Oalkyl
1
)—CH
2
—CH═CH—CH(Oalkyl
1
)(Oalkyl
2
)-type could be increased and the telomer formation could be suppressed. Thus, the desired polyene aldehyde of the . . . CH═CH—CH═CH—CH═CH—CHO-type could be obtained from this primary product by hydrolysis of the acetal group C(Oalkyl
1
)(Oalkyl
2
) and elimination of alkyl
1
OH [European Patent Publication (EP) 0 816 334 A1].
Some examples are known wherein ketone dienol ethers of the . . . CH═CH—CH═C(O alkyl/trimethylsilyl)-CH
2
-alkyl-type are reacted with aldehydes, acetals, orthoesters and other electrophiles to give &agr;,&bgr;-unsaturated ketones of the . . . E—CH
2
—H═CH—CO—CH
2
-alkyl-type (E represents an electrophilic substrate) [Tetr. Lett. 22, 705 et seq. and 2833 et seq. (1981), ibid., 27, 2703 et seq. (1986), ibid. 29, 685 et seq. (1988) as well as Chem. Ber. 123, 1571 et seq. (1990)]. The usefulness of this reaction appears to be somewhat limited, not on reactivity grounds, but because of the difficult accessibility of the aforementioned ketone dienol ethers, because, inter alia, regioselectivity problems have to be taken into consideration in their production [formation of the undesired regioisomers of the . . . CH
2
—CH═CH—C(O-alkyl/trimethylsilyl)═CH-alkyl-type].
Based on the aforementioned dienol ether condensation, A. Rüttimann has recently developed a novel, economical synthesis of apocarotenals and bis-apocarotenals (EP 0 816 334 A1) that is advantageous because the C—C linkage is effected under catalytic conditions, namely using a Lewis acid catalyst. Moreover, no phosphorus- or sulphur-containing reagents are required in this approach.
SUMMARY OF THE INVENTION
A novel synthesis of canthaxanthin, astaxanthin, the corresponding 2,2′-dinor-carotenoids and structurally similar, symmetrical carotenoids having two terminal rings (4,4′-diketo-carotenoids) has now been found. This novel synthesis is likewise based on a catalyzed dienol ether condensation and also avoids the use of phosphorus- and sulphur-containing reagents, but makes use in a very refined and surprising manner of a cyclic compound as a reaction participant that has not only the main features of the terminal ring, but also the dienol ether grouping required for the condensation.
An object of the present invention is to manufacture the aforementioned symmetrical carotenoids starting from polyene diacetals while avoiding, as much as possible, the aforementioned disadvantages of the state of the art and replacing the Wittig, Horner or Julia reaction hitherto used for this purpose. This object is achieved in accordance with the invention by reacting a polyene diacetal with a cyclic dienol ether in the presence of a suitable catalyst, namely a Lewis acid or Brönsted acid, and, after hydrolyzing the resulting condensation product, undertaking a base- or acid-induced elimination of alcohol at the two ends of the mainly conjugated hydrocarbon chain bonded to the two rings in order to obtain the desired symmetrical, terminally ring-substituted fully conjugated polyene. Not only is the reaction of the cyclic dienol ether with the polyene diacetal novel, but, surprisingly, it is effected with an exclusive attack of the acetal at the &ggr;-position of the dienol ether. By the base- or acid-induced elimination of the alkanol subsequent to the hydrolysis, two conjugated C—C double bonds are formed without the need for a phosphorus- or sulphur-containing reagent, which is in contrast to the methodology hitherto usually employed in this field.
Accordin

Affiliated with

Also associated with

Rating

Cyclic dienol ethers does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Cyclic dienol ethers, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cyclic dienol ethers will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2956695