Enol sulfonates synthesis

Unfortunately, it quickly became apparent that a shortfall in this proposal was an inability to prepare the desired vinyl halide 25 in a straightforward and selective manner [19]. In contrast, we reasoned that the selective formation of an enol sulfonate, such as the enol triflate 26a, could be controlled by judicious tuning of enolization conditions starting from the corresponding ketone, and that such an enol sulfonate would possibly be a substrate for a palladium-mediated coupling (Scheme 9.17). In this way a common intermediate from the previously defined synthesis, that is, the racemic ketone rac-13 or its cyano equivalent rac-5 could be used to generate the required enamide. 

The concept of silyl enol ether synthesis via / -elimination from a Brook rearrangement-derived carbanion also appeared in Wicha s studies on additions of 1-phenyl-l//-tetrazol-5-yl (PT) sulfonyl anions to acyl silanes. When PT sulfone 34 was deprotonated in the presence of acyl(triphenyl)silane, ketone 36 was isolated in good yield after hydrolysis of the silyl enol ether intermediate 35. The mechanism involved addition of the... 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

Cory and Renneboog53 have devised an efficient bicycloannulation for the synthesis of tricyclo[3.2.1.02,7]octane-6-one (66) as shown in equation 63. The method involves three steps (1) the enolate undergoes an initial conjugate addition to phenyl vinyl sulfone, (2) the resulting sulfone-stabilized carbanion undergoes an intramolecular Michael addition to the enone, and (3) the resulting enolate displaces phenylsulfinyl moiety from the tricyclooctanone. The amount of HMPA (3 mol equivalents) is critical for effective cyclization of the enolate. 

Nitroalkenes react with lithium dianions of carboxylic acids or with hthium enolates at -100 °C, and subsequent treatment of the Michael adducts with aqueous acid gives y-keto acids or esters in a one-pot operation, respectively (Eq. 4.52).66 The sequence of Michael addition to nitroalkenes and Nef reaction (Section 6.1) provides a useful tool for organic synthesis. For example, the addition of carbanions derived from sulfones to nitroalkenes followed by the Nef reaction and elimination of the sulfonyl group gives a,P-unsaturated ketones (Eq. 4.53).67... 

The elimination reactions of /l-acetoxy sulfones 114 to give the donor-acceptor-substituted allenes 115 by a Julia-Lythgoe process are less conventional (Scheme 7.18) [157]. A new one-step synthesis of allene-l,3-dicarboxylates 118 from acetone derivatives 116 was developed by the use of 2-chloro-l,3-dimethylimidazolinium chloride 117 [158, 159]. This elimination of water follows also the general Scheme 7.17 if a derivative of the enol, resulting from 116, is assumed as an intermediate for an elimination step. More complex processes of starting materials 119 furnished allenyl ketones 120 in high yields [160-162]. 

It is also appropriate to recognize the role of enolates stabilized by an exocyclic carbonyl function in C-glycoside synthesis. The use of LN to achieve reductive cleavage of anomeric sulfones to provide access to an ester-stabilized enolate and, ultimately, 2-deoxy- -C-glycosides has already been illustrated in Scheme 11 (Sect. 2.1.1). 

The utility of the creation of a y-lactone enolate through 1,4-addition of a carbanion and its interception by an electrophile has also been demonstrated in other classes of natural products, e.g., in the enantioselective synthesis of 10-oxa-l 1-methyl PGE2 analogues22. This synthesis starts with 1,4-addition of the sulfone-stabilized anion from 27 to ( + )-(S )-4-methyl-2-buteno-lide which has been prepared in three steps from (—)-(S)-l,2-epoxypropane. The intermediate enolate 28 is reacted with the acetylenic iodide to give the trisubstituted diastereomeric mixture of lactones 29, which is eventually converted into the pure compound 30, both reactions occurring with high diastereoselectivity. 

In fact, the sensitive disubstituted alkene of 14 turned out to not be stable to the subsequent A1C1, coupling conditions, so the alkene and the secondary alcohol were protected together as the bromoether 15. Condensation of the derived enol ether 16 with the sulfone 2 in the presence of DTBMP (2,6-di-/-butyl-4-methylpyridine) then gave 17. Yamaguchi lactonization followed by regeneration of the alkene by zinc reduction completed the synthesis of 1. 

These French chemists described a synthesis of ethyl 9-methylene-13E and 13Z-retinoates via the Julia strategy [74]. The required new C15 sulfone was prepared by O-silylation of P-ionone, followed by catalytic condensation (ZnBr2) of the enol with PI1SCH2CI. 

The Beckmann rearrangement is used in a similar way to produce the lactam 32, an intermediate in the synthesis of swainsonine 33. Stereoselective addition of dichloroketene to the enol ether 30 gave one isomer ( 95 5) of cyclobutanone 31. Beckmann rearrangement with a sulfonated hydroxylamine and dechlorination gave the lactam 32 in 34% yield over five steps7 from a precursor of 30. Note that the m-alkene 30 gives the trans cyclobutanone selectively. 

Complete details for synthesis of ( + )- or ( —)-l from (IS)- or (1R)-10-camphor-sulfonic acid in 77% yield are now available. In general, this oxaziridine is less active than other N-sulfonyloxaziridines, but it is the preferred reagent for hydrox-ylation of lithium enolates of esters, amides, and ketones in 30-95% ee.1... 

Nitrogen heterocycles such as azirines and aziridines are also used effectively as building blocks for the synthesis of a,a-disubstituted amino acids. The aziridine derivative 33 is prepared in optically pure form by addition of the lithium enolate 32 to the chiral sulfinimide 31 (Scheme 7) [42]. After oxidation of the sulfoxide to the sulfone and subsequent hydration, the a-methylated phenylalanine derivative 34 is obtained in good overall yield. 

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