Ketones, reaction with boron enolates

The excellent 1,5- yn stereoinduction (e.g.. Scheme 19) found for aldehyde reactions with boron enolates of methyl ketones bearing a bulky ether group (e.g., TBSO) at the /0-position has been rationalized by DFT analysis. ... 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

A one-pot reaction between a tryptophan ester, benzotriazole, and 2,5-dimethoxytetrahydrofuran in acetic acid gives the diastereomeric benzotriazolyl tetracycles, 349, in good yield. Substitution of the benzotriazole by reaction with silyl enol ethers and boron trifluoride etherate gives the corresponding ketones 350 and 351, and reaction with allylsilanes gives the corresponding alkenes 352 and 353. If the boron trifluoride etherate is added to the mixture before the silane, elimination of benzotriazole from 349 is also observed (Scheme 83) <1999T3489>. 

The use of Moriarty s hypervalent iodine system vide supra) has been extended to reaction with silyl enol ethers. In this case a more activated electrophile is required and the reactions are carried out with iodosylbenzene in the pres ice of boron trifluoiide etherate. However, yields are only moderate and the process seems less useful than the corresponding ketone/enol application. 

Perkins and coworkers reported on stereoselective aldol reactions with boron and titanium ketone enolates (equations 30 and 31) for the construction of a spiroacetal-dihydropyrone (108) related to natural products auripyrone A and Both are cytotoxic... 

Aldol Reactions. - Seebach et al. have published a detailed study of the diasteroselective aldol reaction of boron enolates, generated from an ethyl ketone by treatment with boron trichloride or an alkoxydichloroborane in the presence of Hunig s base. The reaction was found to occur with ul topicity in selectivities from 90-99%... 

Excellent results have been obtained by using boron enolates (alkenyloxyboranes or enol borinates), in what is commonly known as a boron-mediated aldol reaction. The boron enolates are prepared easily from the corresponding ketone and a dialkylboron trifluoromethanesulfonate (dialkylboron triflate, R2BOTf) or chloride (R2BCI) and a tertiary amine base. Boron enolates react readily with aldehydes to give, after oxidative work-up of the resulting borinate species, high yields of the desired aldol product (1.58). 

The driving force of the above-mentioned aldol reaction with boron eno-late is considered to be the interconversion of enol ketones (boron enolates) to their more stable ketones (j5-boryloxy ketones) [17]. When the boron... 

Condensation Reactions. Boron trichloride converts ketones into (Z)-boron enolates at —95 °C in the presence of Diisopropyl-ethylamine. These enolates react with aldehydes with high syn diastereoselectivity (eq 2). A similar condensation of imines with carbonyl compounds also provides crossed aldols in reasonable yields. The reaction was extended to the asymmetric aldoi condensation of acetophenone imine and benzaldehyde by using isobornylamine as a chiral auxiliary (48% ee). ... 

A mixture of an acid anhydride and a ketone is saturated with boron trifluoride this is followed by treatment with aqueous sodium acetate. The quantity of boron trifluoride absorbed usually amounts to 100 mol per cent, (based on total mola of ketone and anhydride). Catalytic amounts of the reagent do not give satisfactory results. This is in line with the observation that the p diketone is produced in the reaction mixture as the boron difluoride complex, some of which have been isolated. A reasonable mechanism of the reaction postulates the conversion of the anhydride into a carbonium ion, such as (I) the ketone into an enol type of complex, such as (II) followed by condensation of (I) and (II) to yield the boron difluoride complex of the p diketone (III) ... 

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

It was anticipated that two of the three stereochemical relationships required for intermediate 12 could be created through reaction of the boron enolate derived from imide 21 with a-(benzyloxy)ace-taldehyde 24. After conversion of the syn aldol adduct into enone 23, a substrate-stereocontrolled 1,2-reduction of the C-5 ketone car-... 

Note also the stereochemistry. In some cases, two new stereogenic centers are formed. The hydroxyl group and any C(2) substituent on the enolate can be in a syn or anti relationship. For many aldol addition reactions, the stereochemical outcome of the reaction can be predicted and analyzed on the basis of the detailed mechanism of the reaction. Entry 1 is a mixed ketone-aldehyde aldol addition carried out by kinetic formation of the less-substituted ketone enolate. Entries 2 to 4 are similar reactions but with more highly substituted reactants. Entries 5 and 6 involve boron enolates, which are discussed in Section 2.1.2.2. Entry 7 shows the formation of a boron enolate of an amide reactions of this type are considered in Section 2.1.3. Entries 8 to 10 show titanium, tin, and zirconium enolates and are discussed in Section 2.1.2.3. 

Boron enolates can be prepared by reaction of the ketone with a dialkylboron trifluoromethanesulfonate (triflate) and a tertiary amine.16 Use of boron triflates and a bulky amine favors the Z-enolate. The resulting aldol products are predominantly the syn stereoisomers. 

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... 

Diboration of a,/ -unsaturated ketones is promoted by platinum(O) complexes. Reaction of 4-phenyl-3-buten-2-one with bis(pinacolato)diboron in the presence of a platinum catalyst affords a boryl-substituted (Z)-boron enolate, that is, a 1,4-diboration product, in high yield with high stereoselectivity (Scheme 8). The isolated boron enolate is easily hydrolyzed by exposure to water, giving / -boryl ketones in high yields.66 Similar diboration of a,/ -unsaturated ketones has also been achieved with Pt(bian)(dmfu) (bian = bis(phenylimino)acenaphthene, dmfu = dimethyl fumarate).67 Although the... 

Brown proposed a mechanism where the enolate radical resulting from the radical addition reacts with the trialkylborane to give a boron enolate and a new alkyl radical that can propagate the chain (Scheme 24) [61]. The formation of the intermediate boron enolate was confirmed by H NMR spectroscopy [66,67]. The role of water present in the system is to hydrolyze the boron enolate and to prevent its degradation by undesired free-radical processes. This hydrolysis step is essential when alkynones [68] and acrylonitrile [58] are used as radical traps since the resulting allenes or keteneimines respectively, react readily with radical species. Maillard and Walton have shown by nB NMR, ll NMR und IR spectroscopy, that tri-ethylborane does complex methyl vinyl ketone, acrolein and 3-methylbut-3-en-2-one. They proposed that the reaction of triethylborane with these traps involves complexation of the trap by the Lewis acidic borane prior to conjugate addition [69]. 

Diketones are produced from nitroalkenes and the lithium enolates of ketones. Equation 132 shows the reaction of the enolate of 2-hexanone with 2-nitropropene in the presence of acetic anhydride. The resulting betaine 409, a greenish-blue liquid, is hydrolysed to the diketone by successive treatment with boron trifluoride and water441. 

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