2-Benzylidene ketones, synthesis

The synthesis of 3-benzoyl-A-homo-3-aza-5) -androstan-16-one (37), an analogue of the alkaloid samanine (36) from Salamandra maculosa, has been reported. Sodium borohydride reduction of the known compound (38) followed by tosylation alTorded the tosylate (39) the nitrile group was reduced by diborane and cyclized by benzoic anhydride-pyridine to the derivative (40a) similar cyclization with acetic anhydride-pyridine yielded the related acetamide (40b). This cyclization requires one equivalent of anhydride and the uncyclized amide is not an intermediate in the reaction. Jones oxidation of (40a) was followed by conversion into a benzylidene ketone derivative (41) with benzaldehyde-KOH in methanol. Reduction of (41) with sodium borohydride and acetylation furnished (42). Treatment of compound (42) with ozone followed by mild zinc reduction produced an acetoxy-ketone, which was further reduced by Zn-HBr-CH2Cl2 to the ketone (37). 

This section is completed with a brief review of the synthesis and properties of this epimer (20) of the precursor of thiazole in bacteria. This pentulose is conveniently accessible by an unconventional route (Scheme 19). Methyl 2,3 4,6-di-O-isopropylidene-a-D-mannopyranoside, readily available from methyl ot-D-mannopyranoside, is converted to the ketonic glycoside by butyllithium in 91% yield, following a method first published by Klemer and Rodemeyer43 and scaled up by Horton and Weckerle.44 This was converted by means of lithium hydroxide in a water-ether mixture into 3,5-0-benzylidene-l-deoxy-D-eryf/iro-2-pen-tulose in 55% yield. Hydrolysis to the free pentulose (20) proceeded in 73% yield in aqueous acetic acid. This product was obtained as a syrup with a characteristic absorption band at 1705 cm 1 as a film. Thus, there is a fair proportion of the open-chain ketone under these conditions, as with the D-threo epimer.45... 

Another reaction which can be brought about by PCI5 is the conversion of aldehydes and ketones into the corresponding geminal dichlorides and this is illustrated in Protocol 7 by the conversion of terephthalaldehyde 36 into the tetrachloride 37. Unusually for a reaction using PCI5, no HC1 is evolved here and the product is sufficiently unreactive to be isolated using an aqueous work-up. It should be noted that chlorination of aromatic aldehydes in this way is the method of choice for synthesis of benzylidene chlorides since the products obtained from the alternative chlorination of toluenes are always contaminated by the benzyl chlorides and benzotrichlorides. 

Several structural modifications of the C-9 ketone of erythromycin have been explored oximes and hydrazones are less prone to intramolecular cydization, but they often have less antibiotic activity than erythromycin (140). Synthesis of more complex oxime derivatives resulted in the development of roxithromycin, the 9-[0-(2-methoxyethoxy)methyl]oxime (33) (141). Reduction of the oximes and hydrazones produced 9(S)-erythromycylamine (34) as the principal product, with minor amounts of the 9(R)-isomer (140) however, clinical studies showed that 9(5)-erythromycyclamine and its N-benzylidene derivative were poody absorbed in humans (142). Evaluation of more complex oxazine derivatives of erythromycylamine led to dirithromycin, the 2-(2-methoxyethoxy)ethylidene oxazine derivative (35) (143). A third route to modification of the ketone utilized a Beckmann rearrangement of the 9-oxime to expand the 14-membered ring to a 15-membered intermediate, which was subsequently reduced and AT-methylated to yield azithromycin (36) (144,145). The term azalide was proposed to denote these 15-membered azalactones (10,145). 

Beilstein Handbook Reference) Aceto-cinnamone AI3-00944 Benzalaceton Benzalacetone Benzilidene acetone Benzilideneacetone Benzylidene-acetone BRN 0742046 3-Buten-2-one, 4-phenyl- CCRIS 5319 EINECS 204-555-1 FEMA No. 2881 Ketone, methyl styryl Methyl 2-phenylvinyl ketone Methyl styryl ketone Methyl (3-styryl ketone NSC 5605 4-Phenylbutenone 4-Phenyl-3-buten-2-one 2-Phenylvinyl methyl ketone Styryl methyl ketone. Used in organic synthesis and perfumery used as a fixative and in flavors. Solid mp = 41.5°. Lancaster Synthesis Co. Penta Mfg. Raschig GmbH. 

The final step of a synthesis of the alkaloid Monocrotaline [Scheme 3.94] required liberation of a hindered 1.2-diol encased in the methylene acetal 94,1. The task was accomplished by a hydride abstraction reaction using triphenylcar-benium tetrafluoroborate to give an intermediate of unknown structure whose hydrolysis afforded Monocrotaline in 86% yield. Triphenylcarbenium tetrafluoroborate can also be used to deprotect dioxolane derivatives of ketones and benzylidene derivatives. ... 

Despite the number of reports of the asymmetric synthesis of tertiary a-aryl cyclohexanones, there have only been three reports which describe the asymmetric synthesis of tertiary a-aryl cyclopentanones. The first of these was reported by Shi via asymmetric epoxidation of benzylidene cyclobutanes and epoxide rearrangement in a subsequent step [76]. Backvall used a dynamic kinetic resolution of aUyhc alcohols-aUylic substitution-oxidative cleavage sequence to access 2-phenylcyclopentanone [77]. The first direct catalytic asymmetric synthesis of tertiary a-aryl ketones was recently described by Kingsbury using a series of Sc-catalysed diazoalkane-carbonyl homologations with bis/tris oxazohne ligands [78]. 

Zeolites can promote the cyclisation of ketone phenylhydrazones [43]. The phenylhydrazones of acetone and cyclohexanone cyclise in good yields to methylindole and tetrahydrocarbazole, respectively, in the presence of CaX zeolite. Zeolite beta is a highly selective catalyst for the synthesis of 2-benzyl-3-methylindole from phenylhydrazine and l-phenyl-2-butanone (e.g. equation 4.5) [44]. Clays have been reported to promote the ring closure of phenylhydrazones in a similar way [45]. Montmorillonite clay catalyses the ring closure of iV-benzylidene anilines with vinyl ethers to yield tetrahydroquinolines and azetidine derivatives [46]. 

Synthesis and Reactions.—Stork s group has announced a general method for the alkylation of glycine esters in excellent yield by way of their A -benzylidene derivatives (Scheme 51). The carbanions are notable for their ability to undergo Michael additions e.g., with cyclohexenone in the absence of HMPT, a 90% yield of ketone... 

---