Hydroxy enone moiety

A diastereoselective epoxidation of a tetrasubstituted double bond was accomplished with mCPBA in the total synthesis of (-)-21-isopentenylpaxilline by A.B. Smith et al." The tetracyclic lactone substrate containing the tetrasubstituted double bond was exposed to mCPBA in toluene at room temperature. The reaction mixture also contained sodium bicarbonate to neutralize the by-product m-chloro benzoic acid. The epoxidation exclusively took place from the less hindered a-face of the molecule. At a later stage, this epoxide was converted to the y-hydroxy enone moiety present in the natural product. 

Scheme 24) [38]. Chemoselective enolization of the less substituted enone moiety under hydrogenation conditions accompanied by subsequent aldol reaction provided the corresponding hydroxyl-enones, such as 87-89, which could be converted to various building blocks for polypropionate synthesis. p-Me2N styryl vinyl enone also was employed successfully as an enolate precursor, as demonstrated by the formation of hydroxy enone 90. 

The high enantioselectivity shown in the above reactions can be attributed to two important factors. First, coordination of the Lewis acid with the a-hydroxy ketone moiety of dienophile 17 or 19 leads to the formation of a rigid five-membered chelate 21. This chelate causes the differentiation of the two dia-stereotopic faces of the enone system. Second, arising from the established absolute configuration of 17 and 19, within 21, the Diels-Alder reaction proceeds with the enone fragment at its cisoid position (yyu-planar). 

Two consecutive enolate alkylations were utilized to generate the quaternary carbon atom (Scheme 38). Alcohol 238 was transformed into the protected hydroxy enone 244. Regioselective deprotonation at the a-position of the ketone 244 led to a cross-conjugated enolate that was alkylated with the allylic iodide 245. The vinyl silyl moiety in 245 represents a masked keto group [127]. The choice of the TBS protecting group for the hydroxyl group at of 244 was crucial in order to prevent the deprotonation at the y-posi-... 

In an alternative approach to molecules of this type, Dauben and Hart examined the base-catalyzed rearrangement of vinylogous 0-hydroxy ketones such as 305 and 308 (Scheme 48).321 Their conversion to 306 and 309 can be accounted for in terms of a vinylogous retro-aldol condensation followed by intramolecular 1,4 addition of an intermediate dienolate to the resulting enone moiety. Subsequent to this reaction, conjugation of the double bond away from the ring juncture followed by a transannular vinylogous aldol condensation produces the observed products. 

High levels of regio- and stereoselectivity were observed in metal-catalyzed 1,3-DC of acyclic nitrones with a -hydroxy enones. The reaction probably occurs through the formation of reactive 1,4-metal-chelated intermediates. The remarkable diastereo- and enantiocontrol could be obtained through two complementary approaches by using a camphor-derived a -hydroxy enone in combination with Cu(OTf)2 or an achiral enone such as 81 in combination with the bis(oxazoline)-Cu(II) catalyst 83. At the end, the hydroxylated auxiUaiy could be easily removed. For example, treatment with periodic acid released a carboxylic moiety as in 86 and 87 <05AG(E)6187>. 

This finding is also in agreement with another three-component Michael/aldol addition reaction reported by Shibasaki and coworkers [14]. Here, as a catalyst the chiral AlLibis[(S)-binaphthoxide] complex (ALB) (2-37) was used. Such hetero-bimetallic compounds show both Bronsted basicity and Lewis acidity, and can catalyze aldol [15] and Michael/aldol [14, 16] processes. Reaction of cyclopentenone 2-29b, aldehyde 2-35, and dibenzyl methylmalonate (2-36) at r.t. in the presence of 5 mol% of 2-37 led to 3-hydroxy ketones 2-38 as a mixture of diastereomers in 84% yield. Transformation of 2-38 by a mesylation/elimination sequence afforded 2-39 with 92 % ee recrystallization gave enantiopure 2-39, which was used in the synthesis of ll-deoxy-PGFla (2-40) (Scheme 2.8). The transition states 2-41 and 2-42 illustrate the stereochemical result (Scheme 2.9). The coordination of the enone to the aluminum not only results in its activation, but also fixes its position for the Michael addition, as demonstrated in TS-2-41. It is of importance that the following aldol reaction of 2-42 is faster than a protonation of the enolate moiety. 

This reaction allows the synthesis of (i) p,p -dienols by oxidation of p-hydroxy-y-alkenyl sel-enides or more conveniently from a-lithioalkyl selenoxides and enones (Scheme 136 and 166) (ii) p,5-dienols from l-lithio-3-alkenyl phenyl selenoxides and carbonyl compounds (Scheme 177) and (iii) 2-(r-hydroxyalkyl)-1,3-butadienes from 1-methylselenocyclobutyllithium and carbonyl compounds (Scheme 178). a,p-Unsaturated alcohols bearing a methylselenoxy or a phenylselenoxy group at the a-position do not lead on thermolysis to propargyl alcohols however, those be ng a (trifluoro-methylphenyl)selenoxy moiety at the a-position are valuable precursors of such con unds (Scheme 179). ... 

The auto-oxidation product of 4,6-di-t-butyl guaiacol has been shown to be 5,6-epoxy-4-hydroxy-2-methoxy-4,6-di-t-butylcyciohex-2-enone (2) by a further direct methods 2f-ray diffraction study. The hydroxy-group and the epoxide moiety are cis as indicated. The cyclohexenone ring is held in a boat conformation by two intermolecular hydrogen bonds formed between epoxide and hydroxy on adjacent molecular pairs present in the lattice. 

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