Enolates silylation

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

Fluoroalkyl ketones may be used as the electrophilic partners in condensation reactions with other carbonyl compounds The highly electrophilic hexafluo-roacetone has been used in selective hexafluoroisopropyhdenation reactions with enol silyl ethers and dienolsilyl ethers [f] (equation 1)... 

Benzyloxy-2-fluoro-2-methylpropionaIdehyde was prepared in optically active form from (5)-monoethyl 2-fluoro-2-methylmalonate, which had itself been prepared by enzymatic hydrolysis A number of enol silyl ethers or enolates were added to the aldehyde in processes that occur with fair to good diastereoselectivity [6] (equation 6) (Table 2)... 

The fluoride anion has a pronounced catalytic effect on the aldol reaction between enol silyl ethers and carbonyl compounds [13] This reacbon proceeds at low temperature under the influence of catalytic amounts (5-10 mol %) of tetra-butylammonium fluoride, giving the aldol silyl ethers in high yields (equation 11). 

This condensation finds considerable generality, enol silyl ethers of a variety of ketones and both aromatic and aliphatic aldehydes are usable For enol silyl ethers of substituted cyclohexanones the reaction is regio- and stereospecific [id]. 

As an alternative to lithium enolates. silyl enolates or ketene acetals may be used in a complementary route to pentanedioates. The reaction requires Lewis acid catalysis, for example aluminum trifluoromethanesulfonate (modest diastereoselectivity with unsaturated esters)72 74 antimony(V) chloride/tin(II) trifluoromethanesulfonate (predominant formation of anti-adducts with the more reactive a,/5-unsaturated thioesters)75 montmorillonite clay (modest to good yields but poor diastereoselectivity with unsaturated esters)76 or high pressure77. 

A high degree of syn selectivity can be obtained from the addition of enamines to nitroalkenes. In this case, the syn selectivity is largely independent of the geometry of the acceptor, as well as the donor, double bond. Next in terms of selectivity, are the addition of enolates. However, whether one obtains syn or anti selectivity is dependent on both the geometry of the acceptor and the enolate double bond, whereas anti selectivity of a modest and unreliable level is obtained by reaction of enol silyl ethers with nitroalkenes under Lewis acid catalysis. 

Addition of Nitronates, Enolates, Silyl Ketene Acetals and Cyanide Ion... 

This method fails, however, with bicyclic ketones such as 1-tetralones even in the presence of TsOH, affording only enol trimethylsilyl ethers such as 107 a [114, 115]. A subsequent investigation revealed that cyclohexanone reacts with equivalent amounts of N-trimethylsilyldimefhylamine 463 in the presence of TMSOTf 20 at -30 °C to give the enol silyl ether 107 a, whereas reaction of cyclohexanone, benzaldehyde, and chlorodimethyl ether with 463 and TMSOTf 20 or TCS 14 at 1-20 °C afforded the iminium salts 547, 548, and 549 in high yield [116-118]. Analogously, N-trimethylsilylpyrrolidine 550 and N-trimethylsilylmorphoHne 294 convert aldehydes such as benzaldehyde, at ambient temperature in the presence... 

With trimethylsilyl iodide 17 the 0,N-acetal 457 gives the iminium iodide as reactive intermediate this converts the enol silyl ether 107 a in situ into the Man-nich-base 669, in 81% yield, and hexamethyldisiloxane 7 [195]. On treatment of the 0,N-acetal 473 (or the N-silylated Schiff base 489) with TMSOTf 20 (or Zny, the intermediate iminium triflate adds to the ketene acetal 663 to give mefhoxytri-methylsilane 13 a and silylated / -amino esters such as 670, which are readily transsilylated by methanol to give the free / -aminoester [70, 196] (Scheme 5.61). 

Benzaldehyde can be condensed with the N-silylated urethane 671 and aUyltri-methylsilane 82 in the presence of trityl perchlorate to give, via an intermediate 0,N-acetal, the substituted urethane 672 in high yield [197]. 0,N-Acetals such as 673 condense with the enol silyl ether of acetophenone 653 in the presence of TMSOTf 20 to give the co-hydroxyurethane 674 in 94% yield [198] (Scheme 5.62). 

The N,N-bis(formylamido)acetal of cinnamaldehyde 687 condenses with the enol silyl ether of ethyl acetoacetate 724 a, in the presence of TiCl4, to give 79%... 

Normal yS-dicarbonyl compounds such as ethyl acetoacetate 723 a or acetylace-tone 723 b are converted, as the free yS-dicarbonyl compounds or as their sodium salts, by TCS 14, 14/pyridine, or HMDS 2/TCS 14 into their enol silyl ethers 724a [216, 217, 219] and 724b [218]. Yet treatment of / -triketones such as 2-acetyl-dimedone 725 with HMDS 2 results, via the corresponding 2-enol trimethylsilyl... 

Likewise, addition of enol silyl ethers such as 980 to the intermediate 977 a furnish the 5-trimethylsilylmethylisoxazolidine 981 in 61% yield and 15% isoxazoline 982 [73, 74] whereas addition of 2-trimethylsilyloxyfuran 827 to 977 a affords, via the intermediates 983, on work-up with CF3CO2H, 96% yield of a mixture of lactones 984 and 985 [75] (Scheme 7.23). More recently it has also been reported that Danishefsky (trimethylsilyloxy)dienes add to intermediates such as 977 to give the corresponding products [76]. 

Sila-Pummerer reaction of the /1-ketosulfoxide 1257 with the enol silyl ether of acetophenone 653 in the presence of BSA 22 a and stannous triflate affords the C-substituted sulfide 1258 in 82% yield and HMDSO 7 [52]. The allylic sulfoxide 1259 reacts with 653 in the presence of TMSOTf 20/DIPEA to give the unsaturated sulfide 1260 in 62% yield or, with the enol silyl ether of cyclohexanone 107a , the unsaturated sulfide 1261 in 63% yield and HMDSO 7 [53] (Scheme 8.21). 

The iodosobenzene HBF4 complex 2022 adds to the enol silyl ether 653 of acetophenone to give the labile iodonium salt 2023, which reacts with cyclohexene or tetramethylethylene to give the adducts 2024 and 2025 [188] (Scheme 12.55). 

Fe(OTf)2-catalyzed aziridination of enol silyl ethers with PhlNTs followed by ring opening led to a-N-tosylamido ketones in good yields (Scheme 27) [81]. With silyl ketene ketal (R = OMe) as substrate, the N-tosyl-protected amino acid ester was obtained in 50% yield. In contrast, the copper (I) salt CuClOq was found not effective for this substrate [82]. 

II and 12 indicate, the selenenylation of ketones can also be effected by reactions of enol acetates or enol silyl ethers. 

Combined use of Co(acac)2 and DiBAlH also gives selective reduction for a,(3-unsaturated ketones, esters, and amides.112 Another reagent combination that selectively reduces the carbon-carbon double bond is Wilkinson s catalyst and triethylsilane. The initial product is the enol silyl ether.113... 

As mentioned earlier, metal complexation not only allows isolation of the QM derivatives but can also dramatically modify their reactivity patterns.29o-QMs are important intermediates in numerous synthetic and biological processes, in which the exocyclic carbon exhibits an electrophilic character.30-33 In contrast, a metal-stabilized o-QM can react as a base or nucleophile (Scheme 3.16).29 For instance, protonation of the Ir-T 4-QM complex 24 by one equivalent of HBF4 gave the initial oxo-dienyl complex 25, while in the presence of an excess of acid the dicationic complex 26 was obtained. Reaction of 24 with I2 led to the formation of new oxo-dienyl complex 27, instead of the expected oxidation of the complex and elimination of the free o-QM. Such reactivity of the exocyclic methylene group can be compared with the reactivity of electron-rich enol acetates or enol silyl ethers, which undergo electrophilic iodination.34... 

Another useful method for the asymmetric oxidation of enol derivatives is osmium-mediated dihydroxylation using cinchona alkaloid as the chiral auxiliary. The oxidation of enol ethers and enol silyl ethers proceeds with enantioselectivity as high as that of the corresponding dihydroxylation of olefins (vide infra) (Scheme 30).139 It is noteworthy that the oxidation of E- and Z-enol ethers gives the same product, and the E/Z ratio of the substrates does not strongly affect the... 

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