3- Pentanone enolate

Identify the thermodynamie enolate for each system shown above (2-pentanone enolate A and B 2-methylcyclopentanone enolate A and B decalinone enolate A and B). Also, compare eleetrostatic potential maps for eaeh pair of enolates. What struetural and/or electronic features, if any, appear to dictate which enolate is favored ... 

The photostimulated reaction of 2-bromo-3-f-propoxypyridine (278) and ketone enolate ions in liquid ammonia afforded the substitution products 279, which gave quantitatively the furo[3,2-6]pyridines (280) (equation 173). With 2-pentanone enolate ion, 278... 

Dimethyl- 3-pentanone Enolate 5-Hydroxy-2,2,4-trimethyl-3-heptanone (81%)... 

Masamune et al. used the chirality of aldehydes in the synthesis of the antibiotic rifamycin S 199 (Scheme 8.30). Chiral aldehyde 189 reacted with enolate 190 via transition state 191 to give syn aldol 192. After protection of the resulting alcohol as TBS ether, 193 was derived to the Z-enolate, which reacted with a-methyl-(3-alkoxyalde-hyde 195 via the six-membered ring transition state with chelation 196, giving syn aldol adduct 197. The four chiral centers of rifamycin were constructed within a few steps and C15-C29 fragment 197 was synthesized by convergent strategy with 3-pentanone enolate 190. 

Fig. 7.3. Crystal structures of some lithium etiolates of ketones. (A) Unsolvated hexameric enolate of methyl t-butyl ketone (B) tetrahydrofuran solvate of tetramer of enolate of methyl r-butyl ketone (C) tetrahydrofuran solvate of tetramer of enolate of cyclopentanone (D) dimeric enolate of 3,3-dimethyl-4-(r-butyldimethylsiloxy)-2-pentanone. (Structural diagrams are reproduced from Refs. 66-69.) by permission of the American Chemical Society and Verlag Helvetica Chimica Acta AG.

Compare electrostatic potential maps of enolates derived from 2-butanone, 4,4-dimethyl-2-pentanone, 4,4,4-trifluoro-2-butanone and l-phenyl-2-propanone with those of acetone. Which substituents cause significant changes in the electronic structure of these enolates and what are the nature of these changes Justify your answers by making drawings of any important resonance contributors. 

Still s synthesis of monensin (1) is based on the assembly and union of three advanced, optically active intermediates 2, 7, and 8. It was anticipated that substrate-stereocontrolled processes could secure vicinal stereochemical relationships and that the coupling of the above intermediates would establish remote stereorelationships. Scheme 3 describes Still s synthesis of the left wing of monensin, intermediate 2. This construction commences with an aldol reaction between the (Z) magnesium bromide enolate derived from 2-methyl-2-trimethylsilyloxy-3-pentanone (21) and benzyloxymethyl-protected (/ )-/ -hydroxyisobutyraldehyde (10).2° The use of intermediate 21 in aldol reactions was first reported by Heathcock21 and, in this particular application, a 5 1 mixture of syn aldol diastereoisomers is formed in favor of the desired aldol adduct 22 (85% yield). The action of lithium diisopropylamide (LDA) and magnesium(n) bromide on 21 affords a (Z) magnesium enolate that... 

The following C2-symmetric bis-sulfonamide is a more efficient controller of stereoselectivity in aldol additions. The incorporation of this ligand into the bromodiazaborolane, subsequent generation of the boron enolate derived from 3-pentanone, and addition to achiral aldehydes preferentially leads to the formation of ijn-adducts (synjanti 94 6 to >98 2) with 95-98% ee. Chemical yields of 85-95% are achieved51. 

Achiral ketones, for example, 3-pentanone, can be converted predominantly into (Z)-boron enolates [(Z)/( )>97 3] by treatment with (- )-diisopinocampheylboron triflate. Subsequent addition to aldehydes, followed by an oxidative workup procedure, delivers /i-hydroxy ketones with a diastcrcomeric ratio of 95 5 to 98 2 (synjanli) and the xpn-products with 66 to 93% ee33. 

Note also that dialkyl ketones such as acetone and 3-pentanone are slightly more acidic than the simple alcohols in DMSO. Use of alkoxide bases in DMSO favors enolate formation. For the amide bases, -K b-h) << a(c-H)> and complete formation of the enolate occurs. 

Many enolates can exist as both E- and Z-isomers.11 The synthetic importance of LDA and HMDS deprotonation has led to studies of enolate stereochemistry under various conditions. In particular, the stereochemistry of some enolate reactions depends on whether the E- or Z-isomer is involved. Deprotonation of 2-pentanone was examined with LDA in THF, with and without HMPA. C(l) deprotonation is favored under both conditions, but the Z.E ratio for C(3) deprotonation is sensitive to the presence of HMPA.12 More Z-enolate is formed when HMPA is present. 

In contrast to LDA, LiHMDS favors the Z-enolate.14 Certain other bases show a preference for formation of the Z-enolate. For example, lithium 2,4,6-trichloroanilide, lithium diphenylamide, and lithium trimethylsilylanilide show nearly complete Z-selectivity with 2-methyl-3-pentanone.15... 

The first element of stereocontrol in aldol addition reactions of ketone enolates is the enolate structure. Most enolates can exist as two stereoisomers. In Section 1.1.2, we discussed the factors that influence enolate composition. The enolate formed from 2,2-dimethyl-3-pentanone under kinetically controlled conditions is the Z-isomer.5 When it reacts with benzaldehyde only the syn aldol is formed.4 The product stereochemistry is correctly predicted if the TS has a conformation with the phenyl substituent in an equatorial position. 

The E.Z ratio can be modified by the precise conditions for formation of the enolate. For example, the E.Z ratio for 3-pentanone and 2-methyl-3-pentanone can be increased by use of a 1 1 lithium tetramethylpiperidide(LiTMP)-LiBr mixture for... 

Z-Boron enolates can also be obtained from silyl enol ethers by reaction with the bromoborane derived from 9-BBN (9-borabicyclo[3.3.1]nonane). This method is necessary for ketones such as 2,2-dimethyl-3-pentanone, which give E-boron enolates by other methods. The Z-stereoisomer is formed from either the Z- or E-silyl enol ether.20... 

Little steric differentiation is observed with either the lithium or boron enolates of 2-methyl-2-pentanone.102... 

Several enolates of 4,4-dimethyl-3-(trimethylsiloxy)-2-pentanone have been investigated.106 The lithium enolate reacts through a chelated TS with high 2,2 -anti stereoselectivity, based on the steric differentiation by the f-butyl group. 

Tin(II) enolates having 3 -benzyloxy substituents are subject to chelation control. The enolate from 2-(benzyloxymethyl)-3-pentanone gave mainly 2,2 -syn-2,2>-syn product, a result that is consistent with a chelated TS.108... 

A lower molecular weight methyl ketone and an olefin are isolated as products of this reaction. That the enol is formed as a primary product which rearranges to the ketone follows from its detection in the IR spectrum of gaseous 2-pentanone upon photolysis. 3 In addition to the ketone and olefinic products, one usually obtains varying amounts of cyclobutanols. 

A jy -diastereoselective aldol reaction based on titanium enolates from (A)-l-benzyloxy-2-methyl-3-pentanone was developed by Solsona et al. (Equation (12)).64 The titanium enolate of this chiral ketone afforded the corresponding syn-syn aldol adducts in high yields and diastereomeric ratios with a broad range of aldehydes. 

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