Epoxy ketones, preparation

Table 4.2 a,p-Epoxy ketones prepared by epoxidation of ( )-2-alkyliden-l-oxo-l,2,3,4-tetrahydronaphthalenes using diethylzinc and (lR,2R)-V-methylpseudoephedrine[8l... 

Table 4.3 a, P-Epoxy ketones prepared by epoxidation of a-enones using diethylzinc and (1R, 2R)-/V-methylpseudoephedrine (according to the relevant publication)181. 

In a separate report, the Darzens reaction was recently used by Barluenga, Concellon, and coworkers for the preparation of enantiopure a"-amino a,P-epoxy ketones. Accordingly, the Z enolate of a"-amino a-bromo ketone 41 was generated with KHMDS at -100°C. Benzaldehyde was added, and trans epoxyketone 42 was isolated in 87% yield and >95% de. ... 

Epoxides can also be rearranged to aldehydes or ketones on treatment with certain metallic catalysts.A good way to prepare p-diketones consists of heating a,P-epoxy ketones at 80-140°C in toluene with small amounts of (Ph3P)4Pd and 1,2-bis(diphenylphosphino)ethane. ... 

Interestingly, we were intrigued by the ESI mass spectrum of the compound, as the observed base peak consisted of [M-S02+Na]+. This led us to explore a thermal retro-Diels-Alder reaction that could afford the desired enone 69. It is noteworthy that the chemistry of cyclic enol-sulfites would appear to be an under-explored area with a few references reporting their isolation being found [57]. At last, we were also able to prepare epoxy ketone 70 from 69 in three steps, albeit epoxidation did not take place unless the TES group was removed. Spartan models reaffirmed our initial conformational assessment of enone 69 and epoxy ketone 70, which contain sp3-hybridized C8a and s/r-hybridized C8b (p s e u d o-. v/r - h y b r i d i zed C8b for 70) at the AB-ring junction (Fig. 8.12) and displayed the desired twisted-boat conformation in A-ring. 

This reduction of epoxy ketones has been used to prepare a number of santan-olides from the diepoxide (1) of a-santonin.2 Thus reduction of 1 is accompanied by dehydration of the intermediate tertiary alcohol to give dehydroisoerivanin (2) in 80% yield. 

Reduction of a, ji-epoxy ketones with NaHTe (typical procedure) ji-Epoxy ketonesP To a solution of NaHTe (prepared from Te (1.30 g, 10 mmol) and NaBH (0.90 g, 0.24 mmol)) in EtOH is added isophorone oxide (0.616 g, 4 mmol) in EtOH (4 mL). An instantaneous... 

Asymmetric epoxidation of a,jS-unsaturated ketones represents an efficient method for the preparation of optically active a,jS-epoxy ketonesJ Recently, a new and very efficient catalytic system for enantioselective epoxidation of ( )-a,jS-enones to the corresponding trans-epoxy ketones has been developed based on a BlNOL-zinc complexJ Very high yields and excellent diastereo- and enantioselectivities are achieved at room temperature using cumene hydroperoxide (CMHP) as the terminal oxidant and performing the reaction in diethyl ether. A combination of enantio-merically pure BINOL and diethylzinc readily affords the active catalyst in situ (Figure 6.13). ... 

Cyclic a,p-unsaturated ketones370 can be cleaved by treatment with base of their epoxy tosylhydrazone derivatives to give acetylenic ketones.371 The reaction can be applied to the formation of acetylenic aldehydes (R = H) by using the corresponding, 2,4-dinitrotosylhy-drazone derivatives.372 Hydrazones (e.g., 47) prepared from epoxy ketones and ring-sub-... 

A catalytic method for the preparation of enantiomerically pure oc,/i-epoxy ketones as building blocks for organic synthesis is highly desirable. Unfortunately, the Julia-Colonna... 

Molander also showed that enantiomerically enriched a,(1-epoxy ketones, such as 42, prepared by Sharpless asymmetric epoxidation underwent efficient conversion to enantiomerically enriched (1-hydroxy ketones 43 upon treatment with Sml2 (Scheme 4.27).31... 

These reactions become more realistic if derivatives of a,/3-epoxy ketones are used. These can be easily prepared by oxidation of the corresponding a,/3-unsa-turated ketones with peracids or hydrogen peroxide (Scheme VIII/13). The driving force in studying this kind of reactions is the importance of the economic synthesis of the natural 15-membered ketones, muscone and cyclopentadeca-none, from cyclododecanone, an easy available and inexpensive starting material (Scheme VIII/14) [35] [36]. 

Epoxy ketone 10 was prepared from the enone 9 by the action of alkaline hydrogen peroxide and used for the synthesis of arglanine71. 

Epoxy ketones are prepared by the action of hydrogen peroxide on unsaturated ketones in alkaline medium. In this manner, dlbenzoyl-ethylene oxide (86%) is prepared from both cis- and traws-dlbenzoyl-ethylene. ... 

Epoxides will fragment if carbanions are formed adjacent to the epoxide ring. Decomposition of the hydrazone of an epoxy ketone in the presence of base may lead to an allylic alcohol (Scheme 2.24). Since the epoxy ketone may be prepared from an unsaturated ketone, this can form part of a sequence for the 1- 3 transposition of an oxygen function. 

This transformation has found extensive use in converting cyclopentenone and cyclohexenone ring systems to the rearranged allylic alcohols during the course of the total syntheses of natural products. In the preparation of ( )-quadrone (Scheme 12), the tricyclic enone was epoxidized and the resulting a,P-epoxy ketone treated with hydrazine to afford the allylic alcohol. The cyclopropane-directed epoxidation shown in Scheme 13 gives an allylic alcohol that is taken on to (-)- and (+)-carenones. In the total syn-... 

A good way to prepare p-diketones consists of heating a,p-epoxy ketones at 80-140°C in toluene with small amounts of (Ph3P)4Pd and l,2-bis(diphenyl-phosphino)ethane. ° Epoxides are converted to 1,2-diketones with Bi, DMSO, O2, and a catalytic amounts of Cu(OTf)2 at 100°C. a,p-Epoxy ketones are also converted to 1,2-diketones with a ruthenium catalyst or an iron catalyst. Epoxides with an a-hydroxyalkyl substituent give a pinacol rearrangement product in the presence of a ZnBr2 " or Tb(OTf)3 catalyst to give a y-hydroxy ketone. 

The first examples to demonstrate the synthetic power of this method were the preparations of exal-tone (118) and muscone (119), starting from the a,p-unsaturated ketones (135) and proceeding via the epoxy ketones (136), the tosylhydrazones of which are cleaved to the cycloalkynones (137 Scheme 44). A little later, Tanabe described the same reaction type starting from epoxydecalones, using this fragmentation for the synthesis of secosteroid alkynic ketones. ... 

During modei studies for the synthesis of botrydiane sesquiterpene antibiotics, B.M. Trost and co-workers prepared a compiex 1,6-enyne precursor for transition metal catalyzed enyne metathesis reactions. The 1,6-enyne was prepared from a heavily substituted alkynal, which was synthesized via the Eschenmoser-Tanabe fragmentation of an epoxy ketone. The resulting alkynal was unstable, so it was immediately subjected to a Wittig oiefination to afford the desired 1,6-enyne. 

P-Hydroxy tosylhydrazones, which are the products of a conventional aldol reaction between a dilithi-ated tosylhydrazone reagent and an aldehyde, can also be prepared by alternative routes. For example, Stork and Ponaras have described a procedure whereby an epoxy ketone is converted into an epoxy hydrazone. Subsequent addition of an alkyl- or aryl-magnesium bromide followed by hydrolysis yields either an a-alkyiated- or a-arylated-p-hydroxy ketone or an a,p-unsaturated ketone. Since the attack of the Grignard reagent on the epoxide occurs with inversion at the a-carbon, this reaction can be used to... 

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