Cyclopentenones, from 1,4-diketones

Cyclopentenones. from 1.4-diketones. 886-887 Cyclopropane, angle strain in, 115 bent bonds in. 115 from alkenes. 227-229 molecular model of, 111. 115 strain energy of, 114 torsional strain in, 115 Cystathionine, cysteine from. 1177 Cysteine, biosynthesis of, 1177 disulfide bridges from, 1029 structure and properties of, 1018 Cytosine, electrostatic potential map of, 1104... 

An interesting application of propargyl halides (22) is the formation of cyclopentenones from 1,4-diketones in a five-ring version of the Robinson annelation (Chapter 21). Disconnection of (26) at the a, 8 bond reveals a... 

Although it has been known since 1938 that alkoxy-substituted alkyl cyclopropanecar-boxylates can be opened to 1,4-dicarbonyl compounds it was not until 1970 that the synthetic merit of this route to a valuable class of intermediates was recognized. In this year Wenkert and coworkers described the preparation of cyclopentenones from this type of cyclopropane via 1,4-diketones as outlined in equation 83 " . Shortly later McMurry and Glass have published a ds-jasmone synthesis following the same principle ... 

Bicyclic and cyclic ketones are also useful intermediates and a series of preparations are given in BICYCLIC KETONES FOR TROPINONE SYNTHESIS 2a,4a-DIMETHYL-8-OXABI-CYCLO[3.2.1]OCT -6-EN-3-ONE CYCLOPENTENONES FROM a,a -DIBROMOKETONES AND ENAMINES 2,5-DI-METHYL-3-PHENYL-2-CYCLOPENTEN-1-ONE y-KETO-ESTER TO PREPARE CYCLIC DIKETONES 2-METHYL-1,3-CYCLOPENTANEDIONE, with the companion preparation y-KETOESTERS FROM ALDEHYDES VIA DIETHYL ARYLSUCCINATES 4-OXOHEXANOIC ACID ETHYL ESTER, which gives the procedure used to prepare the needed... 

Vinyllithiums of type 663 (R2 = R3 = H) reacted with primary alkyl bromides, carbonyl compounds, carbon dioxide, DMF, silyl chlorides, stannyl chlorides, disulfides and phenylselenyl bromide142,970-979. Scheme 173 shows the synthesis of dihydrojasmone 669 from the corresponding 1,4-diketone. a-(Phenylsulfanyl)vinyllithium 665, prepared from phenyl vinyl thioether, reacted with hexanal and the corresponding adduct 666 was transformed into its acetoacetate. This ester 667 underwent a Carrol reaction to produce the ketone 668, which was transformed into the cyclopentenone 669 by deprotection either... 

Intramolecular versions of reactions other than aldols can also be considered as useful options to prepare five- or six-membered rings from their corresponding bifunctional precursors. Several examples to illustrate the diverse approaches to construct five-membered rings are given in Scheme 2.110. A high-yield method to prepare cyclopentenone 284 is given in the sequence (i) alkylation of formyl-anion equivalent 285 to give 286 (ii) Michael addition of the latter to methyl vinyl ketone (iii) removal of the carbonyl protection and (iv) intramolecular cyclization of the 1,4-diketone, 287. 

The absolute stereochemistry of natural roseophilin was determined by means of asymmetric total synthesis by M.A. Tius and co-workers. The trisubstituted pyrrole moiety of the natural product was installed using the Paai-Knorr pyrrole synthesis starting from a macrocyclic 1,4-diketone. This diketone was prepared by reacting an exocyclic a, 3-unsaturated ketone with excess 6-heptenal in the presence of 3-benzyl-5-(hydroxyethyl)-4-methylthiazolium chloride as the catalyst. The major product was the trans diastereomer and the macrocyclization was achieved via aikene metathesis. It is worth noting that when the aldehyde was tethered to the cyclopentenone, all attempts to close the macrocycle in an intramolecular Stetter reaction failed. 

Cyclivttion. 1,4-Diketones generated from rearrangement of l,2 5,6-diepoxy-alkanes are prone to undergo cyclization under the mildly basic conditions, accordingly, cyclopentenones are obtained directly. ... 

The cyclopentenone 19 can be prepared by an intramolecular aldol reaction from the diketone 18. This reaction is best achieved with a base such as KOH in MeOH and heat. The diketone 18 can be prepared by Wacker oxidation of the alkene 17. Standard conditions for the Wacker oxidation are 10 mol% PdCla, CuCl, O2, DMF, H2O (see Scheme 5.115). The alkene 17 is prepared by allylation of the enamine of cyclohexanone. See J. Tsuji, I. Shimizu and K. Yamamoto, Tetrahedron Lett. (1976), 2975. 

Acyl-lithiums and their Equivalents. Details have appeared of the preparation of di-isopropylcarbamoyl-lithium (LiCONPr a) by reaction of di-isopropylformamide with t-butyl-lithium. Lithiated dithioacetals, particularly those derived from dithians, continue to be popular. Alkylations of such species have been important reactions in syntheses of 25-hydroxycholesterol, pyrenophorin and vermiculin," and several chain-elongated sugars. 2-(3,3-Dialkoxypropyl)-l,3-dithians may be converted via their lithiated derivatives into protected 2-hydroxycycIobutanone derivatives (Scheme 1), themselves potential synthons for 1,4-diketones and cyclopentenones. ... 

The first practical synthesis of the cyclopentenone was published in 1942 by Heinz Hunsdiecker. [88] In case of (Z)-jasmone, leaf alcohol, which was obtained from Japanese peppermint oil, served again as starting material. The central synthetic building block is a 1,4-diketone, which in aqueous alkali undergoes an intramolecular aldol condensation to close the five-membered ring the desired product is then obtained by hydrolysis and decarboxylation. 

Unlike the situation with the asterriquinones, a modular synthesis of illudins had already been developed through the efforts of Padwaand Kinder. The dipolar cycloaddition of a carbonyl yhde derived from a diazo-p-diketone with a cyclopentenone forms two C-C bonds and establishes the ring skeleton (Figure 9.7) in the key intermediate. The final carbon was added by a methyl Grignard addition to the more reactive ketone. Oxidation states and functional groups were adjusted to provide dehydroiUudin M, and it was converted to illudin M. 

PROBLEM 19.71 Write an arrow formalism mechanism for the conversion of diketone 1 into the important perfumery ingredient m-jasmone (2). There is another possible cyclopentenone that could be formed from 1. What is its structure Write an arrow formahsm mechanism for its formation. 

New acyl anion equivalents have proved to be popular targets for research and this year is no exception. For example anion (37) reacts with aldehydes (R CHO) to give acrylates (38), and amidrazones (39) provide access to the acyl anion equivalents (40). The latter undergo electrophilic attack to yield ketones [RCH2C(0)E] after unmasking. Similarly, 1,4-diketones are obtained from the addition products of acyl anion equivalent (41) and a,/3-unsaturated ketones. Cyclic a,/3-unsaturated ketones (42) are in turn formed by addition of the /S-acyl anion equivalent (43) to electrophiles. The 5-oxocyclopentenyl equivalent (44, X = Li) is generated in three steps from the cyclopentenone... 

Although problems of regiochemistry are inherent, the aldol condensation of diketones has found vide application. Typical examples are syntheses of cyclopentenones and cyclohexenones from 1,4- and 1,5-diketones, respectively. The concept is illustrated by a synthesis of jasmone 12 (Eq. (12)) [28] and of the homosteroid derivative 13, the latter arising under thermodynamic control in a Robinson annelation reaction (Eq. (13)) [29]. 

The reaction is a unique method for the one-step synthesis of ketones from alkenes, and allows alkenes to be regarded as masked ketones which are stable to acids, bases, and nucleophiles. Particularly useful is the oxidation of terminal alkenes, which provides methyl ketones (eq 3). As a typical application, the allylation of a ketone, followed by the oxidation, affords a 1,4-diketone. A cyclopentenone can then be prepared by an aldol condensation (eq 4). The annulation method has widespread uses in the synthesis of natural products such as pentalenene, muscone, and coriolin. 1,5-Diketones are prepared by 3-butenylation of a ketone followed by the oxidation. This process has been used to prepare cyclohexenones (eq 5). ... 

Consider the Johnson synthesis of progesterone. The q clization precursor (102) was derived from cyclopentenone 101, which was prepared by an intramolecular aldol-dehydration of 1,4-diketone 100. Johnson did not construct the 1,4-difunctional relationship present in 100. It was purchased in the form of 2-methylfuran (96). This simple heterocyclic compound is at the same oxidation state as the 1,4-dicarbonyl compound, released by hydrolysis of the furan, first in a protected form (98 and 99) and finally ready for use in the aldol dehydration (99 — 100). 

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