Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2000-09-26
2003-04-22
Raymond, Richard L. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C558S251000, C558S257000, C560S193000, C560S205000, C564S142000, C564S143000, C564S152000, C564S160000, C564S161000, C564S162000
Reexamination Certificate
active
06552226
ABSTRACT:
TECHNICAL FIELD
The present invention relates generally to synthetic organic chemistry. More particularly, the invention relates to the Claisen rearrangement reaction and to a novel method of performing such reactions in tandem so as to give rise to chiral products. The invention finds utility in the fields of organic synthesis and stereospecific catalysis.
BACKGROUND
Since its discovery in 1912, the Claisen rearrangement has become one of the most powerful tools for carbon-carbon bond formation in chemical synthesis. See, e.g., Claisen (1912)
Chem. Ber
. 45:3157; Enders et al. (1996)
Tetrahedron: Asymmetry
7:1847; Blechert et al. (1989)
Synthesis
71; Kallmerten et al. (1989)
Stud. Nat. Prod. Chem
. 3:323; Moody et al. (1987)
Adv. Heterocycl. Chem
. 42:203; and Ziegler et al. (1988)
Chem. Rev
. 88:1423. The Claisen reaction is a [3,3]-sigmatropic rearrangement, which involves the conversion of an allylic compound, generally an allylic vinyl ether, to an &agr;,&bgr;-disubstituted, &bgr;,&ggr;-unsaturated carbonyl compound. The reaction may be illustrated as follows:
Allylic aryl ethers also undergo a Claisen rearrangement to give ortho-allylphenols:
Activation of Claisen reactions has traditionally been accomplished under thermal control, typically at temperatures of 200° C. or more. Activation has also been achieved through the incorporation of cationic or anionic charge in the bond reorganization event (see Takai et al. (1981)
Tetrahedron Lett
. 22:3985; Takai et al. (1984)
Bull. Chem. Soc
. 57:446; Stevenson et al. (1982)
Tetrahedron Lett
. 23:3143; and Takai et al. (1984)
Tetrahedron
40:4013; Arnold et al. (1949)
J. Am. Chem. Soc
. 71:1150; Ireland et al. (1973)
J. Am. Chem. Soc
. 94:5897; Denmark et al. (1982)
J. Am. Chem. Soc
. 104:4972; Wilson et al. (1984)
J. Org. Chem
. 49:722; Buchi et al. (1985)
J. Org. Chem
. 50:4664; and Alker et al. (1 990)
J. Chem. Soc. Perkins Trans
. 1, 1623). Despite its prolific use in chemical synthesis, very few examples of catalytic Claisen variants have been reported. See Vedejs et al. (1994)
J. Am. Chem. Soc
. 116:579, pertaining to protic acid (e.g., toluenesulfonic acid) catalysis of a Michael addition reaction, in turn initiating an aza-Claisen rearrangement. See also Saito et al. (1996)
Synlett
, 720, which describes the use of an aluminum catalyst, aluminum tris(4-bromo-2,6-diphenylphenoxide), in the Claisen rearrangement of allyl vinyl ethers.
In 1978, Bellus and Malherbe reported a ketene-Claisen reaction, in which treatment of an allyl ether with dichloroketene was found to result in the formation of a 1,3-dipolar allyl vinyl ether, which subsequently underwent [3,3]-bond reorganization, as follows:
(Malherbe et al. (1978)
Helv. Chim. Acta
61:3096; Malherbe et al. (1983)
J. Org. Chem
. 48:860). Subsequently, others have demonstrated utility of tertiary allylic amines in analogous [3,3]-sigmatropic rearrangement reactions. Edstrom et al. (1991)
J. Am. Chem. Soc
. 113:6690; Kunng et al. (1983)
J. Org. Chem
. 48:4262; Maruya et al. (1992)
J. Chem. Soc., Perkin Trans
, 1617; Vedejs et al., supra; Diederich et al. (1995)
Angew Chem., Int. Ed. Engl
. 34:1026; Deur et al. (1996)
J. Org. Chem
. 61:2871).
The aforementioned reactions are limited because of the ketene reactant used, as ketenes are highly unstable compounds. Furthermore, prior syntheses are generally not enantioselective; those who have attempted enantioselective Claisen rearrangements have met with substantial difficulties. For example, Corey et al. (1996),
J. Am. Chem. Soc
. 118:1229, developed an enantioselective Claisen reaction of an allylic ester, but the synthesis required a reaction time of fourteen days. Yamamoto et al. (1995),
J. Am. Chem. Soc
. 117:1165, also developed an enantioselective Claisen reaction for rearrangement of an allylic vinyl ether, but the synthesis required stoichiometric quantities of an aluminum promoter.
Applicant's commonly assigned U.S. patent application Ser. No. 09/670,863 for “Lewis Acid-Catalyzed Claisen Rearrangement in the Preparation of Chiral Products,” filed on even date herewith, now U.S. Pat. No. 6,359,174, addresses the aforementioned need in the art for an improved Claisen reaction that proceeds quickly, can be conducted as a “one-pot” synthesis, is activated using catalytic quantities of a catalytic composition, and can be used to produce chiral products in enantiomerically pure form. The- present invention provides a similar “one-pot” synthetic process wherein catalyzed Claisen rearrangement reactions proceed in tandem to produce enantiomerically pure chiral products.
Claisen rearrangements have previously been conducted in tandem with various other reactions. For example, Thyagarajan et al. (1967)
Chemistry and Industry
, pp. 401-402, report the use of Claisen rearrangements in conjunction with Cope rearrangements. Claisen-cyclization rearrangements are discussed by Kim et al. (1993)
Heterocycles
36(3):497-505 and Weiss et al.(1967)
Bull. Soc. Chim. Fr
. 34:2033-2038. Tandem Claisen-ene rearrangements have been developed by Mikami et al.; see Mikami et al. (1990)
J. Am. Chem. Soc
. 112:4035-4037, and Mikami et al. (1994)
J. Am. Chem. Soc
. 116:10948-10954. Mandai et al. (1991)
Tet. Lett
. 32(28):3399-3400 present a Claisen-aldol rearrangement for use in synthesizing a bicyclo [3.3.0] octane framework.
Successive double Claisen rearrangements (i.e., “tandem” C.laisen reactions) have been developed by Hiratani et al. in the synthesis of chelating agents for metal ions. That is, Hiratani et al. (1995),
Tet. Lett
. 36:5567-5570, and Hiratani et al. (1997),
Tet. Lett
. 38:8993-8996, describe a tandem Claisen rearrangement in the synthesis of crownophanes (macrocycles containing rigid aromatic moieties linked with flexible oligoethylene glycol moieties) using heat activation, i.e., a reaction temperature of 195° C. or 200° C. Uzawa et al. (1998)
Chem. Lett
. 4:307-308 describe a similar reaction wherein a thermally activated, Lewis acid-catalyzed, tandem Claisen reaction is used to prepare phenol-containing macrocyclic compounds. Synthesis of chiral crownophanes using a thermally activated tandem Claisen rearrangement reaction has been described as well; see Tokuhisa et al. (1999)
Tet. Lett
. 40:8007-8010. These tandem Claisen rearrangement reactions rely on thermal control and, consequently, are not suitable for synthesis of thermally unstable functional groups.
There is accordingly a need in the art for a tandem Claisen rearrangement reaction that proceeds quickly, can be carried out at or near room temperature, can be conducted as a “one-pot” synthesis, is activated using only catalytic quantities of a catalytic composition, and can be used to produce chiral products in enantiomerically pure form.
SUMMARY OF THE INVENTION
It is therefore a primary object of the invention to provide a novel tandem Claisen rearrangement reaction that addresses the above-mentioned need in the art.
It is another object of the invention to provide a method for preparing enantiomerically pure, chiral products via catalyzed Claisen rearrangement reactions that proceed in tandem.
It is still another object of the invention to provide a method for conducting two or more Claisen rearrangement reactions in tandem by reacting an appropriately substituted allylic compound with two or more equivalents of an acid chloride in the presence of a Lewis acid catalyst composition.
It is yet another object of the invention to provide a method for conducting Claisen rearrangement reactions in tandem by reacting an appropriately substituted allylic compound with a first acid chloride in the presence of a Lewis acid catalyst composition, and then reacting the product of the aforementioned reaction with a second acid chloride that may or may not be the same as the first.
It is a further object of the invention to provide such a method wherein the allylic compound is an allylic amine, an allylic ether, or an allylic thioether.
It is still a further object of the invention to provid
Raymond Richard L.
Reed & Associates
The Regents of the University of California
Tucker Zachary C.
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