Hajos—Parrish ketone

After the known intermediate 79 (contaminated with ca. 6 % < /.v isomer) [39] was prepared from Hajos-Parrish ketone [40] 78, the tert-butyl ether was cleaved (quant.) and the ketone protected as the acetal (96 %). The secondary alcohol was oxidized by pyridinium chlorochromate (PCC) to provide ketone 80 in good yield (71 %) and after fractional crystallization afforded material absent of any m-hydrindane (Scheme 10.6). [NOTE All compounds shown in Schemes 10.6 and 10.7 are shown in the ent-configuration, as published]. The oxidation of protected hydrindane 80 under Saegusa-Ito conditions [41, 42] gave enone 81 (82 %), confirmed by X-ray crystallography. 

Organisms Lactobacillus kefir DSM 20587, Saccharomyces cerevisiae, Candida magnoliae, Bacillus megaterium, Thermoanaerobium brockii, Clostridium beijerinckii, Thermoanaerobacter ethanolicus, Rhodococcus ruber DSM 44541. Solvents ace = acetone iPr = i-PrOH. Substrates WM Wieland-Miescher ketone 4-Me-HP 4-methyl Hajos-Parrish ketone COBE ethyl 4-chloro-3-oxobutanoate. 

The first enantioselective total synthesis of tetracyclic sesquiterpenoid (+)-cyclomyltaylan-5a-ol, isolated from a Taiwanese liverwort, was accomplished by H. Hagiwara and co-workers. They started out from Hajos-Parrish ketone analogue, (S)-(+)-4,7a-dimethyl-2,3,7,7a-tetrahydro-6/-/-indene-1,5-dione, that could be synthesized from 2-methylcyclopentane-1,3-dione and ethyl vinyl ketone in an acetic acid-catalyzed Michael addition followed by an intramolecular aldol reaction. The intramolecular aldol reaction was carried out in the presence of one equivalent (S)-(-)-phenylalanine and 0.5 equivalent D-camphorsulfonic acid. The resulting enone was recrystallized from hexane-diethyl ether to yield the product in 43% yield and 98% ee. Since the absolute stereochemistry of the natural product was unknown, the total synthesis also served to establish the absolute stereochemistry. 

The Wharton fragmentation was used as a key step in an approach toward the total synthesis of xenicanes by H. Pfander et al. ° Two optically active substituted frans-cyclononenes were synthesized starting from (-)-Hajos-Parrish ketone. First, the bicyclic 1,3-diol was protected regioselectively on the less sterically hindered hydroxyl group with p-toluenesulfonyl chloride in quantitative yield. Next, the monosulfonate ester was exposed to dimsylsodium in DMSO, which is a strong base, to initiate the desired heterolytic fragmentation. 

Scheme 17.3 r2.31-Wittig rearrangement on Hajos-Parrish ketone derivative. 

Medarde and co-workers have prepared a number of truncated cardenolide analogs these compounds incorporate the C-D rings of the steroid skeleton. This work began with modifications of the readily available Hajos-Parrish ketone 2 or the dehydrated analog thereof A summary of the preparation of an oxime analog 55 is shown below. In addition to the protected carbonyl compound shown, the corresponding keto analog was also prepared. The aldehyde intermediate obtained after hydroboration-oxidation was converted into other derivatives (not shown) as well. 

Medarde and co-workers prepared modified Hajos-Parrish ketones 56 and 57 as simple cardenolide analogs. ... 

Cerri and his co-workers looked at a different class of truncated analogs these compounds were prepared in multi-step syntheses from Hajos-Parrish ketone. The inspiration for the oxime substitution in this series came from a series of novel, highly active oxime substituted steroid analogs prepared in the same laboratory. While the truncated compound 58... 

Lastly, the figure below lists a number of other natural products for which Hajos-Parrish ketone and other derivatives from the Hajos-Wiechert reaction were employed as chiral building blocks to achieve partial or complete total synAeses. 

D. B. Ramachary, M. Kishor, Org. Biomol. Chem. 2008, 6, 4176-4187. Direct amino acid-catalyzed cascade biomimetic reductive alkylations application to the asymmetric synthesis of Hajos-Parrish ketone analogues. 

In our subsequent search for the conditions leading to the mild and selective formation of the B-ring, we were able to explore the pyrrolidine acetate-promoted reaction that is most likely to proceed through the formation of enamine (30) and results in monocyclized aldol condensation product 29a-e (Scheme 15). When subjected to pyrrolidine/acetic acid conditions, substrates 14 were selectively monocyclized to the corresponding enones 29a-e in good yield and with no erosion in enantiomeric excess. In addition to substrates 29a-c, this protocol provided access to functionalized Wieland-Mischer and Hajos-Parrish ketones 29d and 29e, which cannot be... 

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