Ketones absolute configuration determination

Addition of enantiomerically pure cnamines derived from (.Y -jmethoxymethyfipyrrolidine (SMP) and ketones (cyclohexanone, cycloheptanone, propiophenone) to AGY-dimethylmethylene-iminium tetrachloroaluminate11,42 give the corresponding Mannich bases in moderate to good yields (56 -79%) and low to moderate enantioselectivities (30-66% ce)12, l3. The (-)-isomer is the major enantiomer in each case. The absolute configuration of the major enantiomer has not been determined. The auxiliary can be recovered. 

Preparative-scale fermentation of papaveraldine, the known benzyliso-quinoline alkaloid, with Mucor ramannianus 1839 (sih) has resulted in a stereoselective reduction of the ketone group and the isolation of S-papaverinol and S-papaverinol M-oxide [56]. The structure elucidations of both metabolites were reported to be based primarily on ID and 2D NMR analyses and chemical transformations [56]. The absolute configuration of S-papaverinol has been determined using Horeau s method of asymmetric esterification [56]. The structures of the compounds are shown in Fig. 7. 

It has been shown that CD measurement is a proper tool to determine the absolute configuration of the C-3 stereo center in corynantheine and yohimbine alkaloids (300). The chiroptical properties of stereoisomeric yohimbanes and 17-ketoyohimbanes also have been studied. Cotton effects due to aromatic and ketone absorptions have been considered in terms of the appropriate sector and... 

Extracts of the male oil palm bunch moths, Tirathaba mundella Walker (Lepidoptera Pyralidae), were shown to contain four compounds namely, 5S, 65)-2,2,6-trimethyl-6-vinyl-tetrahydro-pyran-3-ol, 4-hydroxy-3-methoxy benzaldehyde (vanillin), 6,10,l4-trimethyl-2-pentadecanone, and the corresponding alcohol 6,10,l4-trimethyl-2-pentadecanol, which elicited responses from the females. However, when synthetic compounds were used in lures, the ketone and alcohol by themselves did not attract females, suggesting that they might not be an essential part of the blend. This can only be confirmed once their absolute configuration has been determined and the proper stereoisomers tested in the... 

Ketones. The lithio derivative of ( +)-(.S )-. Y,.S -dimethyl-S-phenylsulfoxiinine (16), or its enantiomer, may be used both to resolve racemic ketones164 and to determine absolute configurations of ketones. For example, rac-19 on addition of 16 formed the diastereomeric /j-hydroxy-sulfoximines 17 and 18 which were separated. The configuration of 17 was established by an X-ray analysis. The ketones can be regenerated from the /1-hydroxysulfoximines by thermolysis. Thus, heating of 17 and 18 to 80 °C (for 12 h) furnished 19 [a precursor of (+ )-modhephen] and ent-l9165. 

Reaction of the chiral lithium enolate of meso-2,6-dimethylcyclohexanone (6), generated by deprotonation with (R)-l-phenylethylamine and (/ )-camphor/(R)-l-phenylethylaniine derived chiral lithium amides (Table 1, entries 17 and 64) with 3-bromopropene, leads to homoallyl ketones of opposite absolute configuration in acceptable yield with poor to modest enantiomeric excess14, which can be determined directly by H-NMR spectroscopy in the presence of tris [3-(heptafluorohydroxymethylene)-D-camphorato]europium(III) [Eu(hfc)3]. 

Enzymatic reduction of 23a with recLBADH and CPCR resulted in unsatisfactory results (60% and 49% ee) as well. The results mentioned above indicate that a bulky substituent at the alkyne moiety results in a higher selectivity of the reduction. Furthermore, Bradshaw et al. reported that Lactobacillus kefir ADH, an enzyme highly homologous to LB ADH, affords (R)-4-trimethylsilyl-3-butyn-2-ol [(R)-25j with an ee of 94% in 25% yield [39bj. In our investigations ketone 23b was reduced by recLBADH with almost quantitative conversion. The enantiomeric excess and absolute configuration of the product were determined by desi-lylation with borax converting alcohol (R)-25 into enantiopure (R)-3-butyn-2-ol [(R)-24j (Scheme 2.2.7.14). 

When the absolute configuration of the ketone is known, the conformation can often be determined by applying the octant rule—as in (f) and (g) of Table 4. In other examples, low-temperature CD measurements have been used to extract conformational information when the absolute configuration is known. Although a wide variety of ketones have been investigated, several classical examples are worthy of note. 

The absolute configuration of Wieland-Miescher ketone analogues bearing an angular protected hydroxymethyl group was unambiguously determined after regio- and stereoselective reduction of the saturated ketone function to cis -alcohols and application of the exciton chirality method to bicyclic enone-benzoate chromophoric systems 155-158352. 

Among the cockroaches, two chemical releasers of sexual behavior have been recently characterized. Females of Blattella germanica produce two sex pheromones, both of which appear to be active by contact chemoreception. One of these compounds, 3,11-dimethyl -2-nonacosanone, produces wing raising in the male and is perceived through antennal chemoreceptors (30). The absolute configuration of this diastereomeric ketone has not been determined. 

The origins of two chirality rules, the Octant Rule for ketones and the Exciton Chirality Rule, have been explained, and it has been shown how the rules can be applied to the determination of molecular absolute configuration. In applications of the Octant Rule, when the absolute configuration of a ketone is known, the rule may be used to determine its conformation. Applications of the Exciton Chirality Rule to determine the absolute configuration of diols follows from the derivatization with strongly UV-visible absorbing chromophores. 

Enantiomerically pure Diels-Alder adducts of Ceo were prepared by Tsuji and co-workers by use of a chiral auxiliary in the diene component and separation of the diastereoisomeric intermediates.385 The starting material for the diene component was a cyclic cyclopentenone acetal (224, Scheme 1.21) derived from L-threitol, reacting via its cyclopentadiene-containing enol ether isomer.385,386 The diastereoisomeric products 225 and 226, formed without significant diastereoselectivity, were isolated as the acetals, separated and subsequently hydrolyzed to afford the enantiomeric ketones (+)-227 and (—)-227. NOE measurements allowed the determination of the absolute configuration of the diastereoisomeric intermediates 225 and 226 and, therefore, also of the enantiomeric ketones (+)-(R,R)-227 and (—)-(S,S)-227 (Scheme 1.21).385... 

Mori M, Saitoh F, Uesaka N, Shibasaki M (1993) Formal Total Synthesis of (—)-Dendrobine Using Zbconium Promoted Cyclization. Determination of the Absolute Configuration of the Intermediary Tricyclic Ketone. Chem Lett 213... 

The relative and absolute configuration of Stigmatellin A, one of the most potent inhibitors of the electron transport chain, was determined via alkylation of diethyl ketone SAMP hydrazone. ... 

Aldol-Type Addition. Aldol-type addition of the magnesium enolate of (R)-(+)-7-butyl 2-(p-tolylsulfinyl)acetate, prepared with 7-butylmagnesium bromide, with aldehydes and ketones afforded, after desulfurization with Aluminum Amalgam, p-hydroxy esters in very high diastereoselectivity (eq Two chiral centers are created in the first step with very high diastereoselectivity (mainly one diastereomer is formed). A model M based on the structure of the sulfinyl ester enolate (determined by C NMR) and on electrophilic assistance of magnesium to the carbonyl approach, was proposed to explain and predict the absolute configuration of the two created chiral centers. ... 

The unusual pentacyclic system of (+)-pentacycloanammoxic acid (1) was created in 21 steps with an overall yield of 2%. The stereochemistry of the target was established relatively late in this convergent synthesis by a novel diastereoselective de Mayo reaction using the chiral cyclopentanone 7. Determination of the absolute configuration of (+)-l was accomplished in the course of the total synthesis by X-ray diffraction of the a,P-unsaturated ketone 25. Although many photochemical transformations occur in this total synthesis, the authors are in doubt about the involvement of photochemical processes in the biosynthesis of 1, as the natural environment of C. B. anammoxidans is dark and anaerobic. 

The optically active Wieland-Miescher ketone 33 has been widely employed as an important key compound as discussed above. However, it was surprising that irrespective of such a significance of compound 33, its absolute configuration has never been directly determined by the X-ray crystallographic method. The abso-... 

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