Enolboration-aldolization

Figure 5. Synthesis ofsyn- or anti- 2-alkyUI-hydroxy-3-ketones via stereoselective enolboration-aldolization reactions...

Paterson developed asymmetric enolboration-aldolization involving diisopinocampheylboron triflate (57, 32), He has shown the utility of enolboration for the synthesis of various macrolide molecules. His recently completed target molecules include Concanamycin F (33) and the potential anticancer agent, Discodermolide (34) (Figure 6). 

A reversal of diastereoselectivity from syn to anti is found on reducing the temperature from room temperature to -78 °C for enolboration-aldolization reaction of methylphenylacetate with RCHO promoted by Chx2BOTf/i-Pr2NEt in CH2CI2 the converse temperature dependence applies in nonpolar solvents. ... 

A review of the current status of the applications of chiral organoboranes derived from a-pinene for the synthesis of fluoroorganic molecules has been made. Our three-pronged approach for the synthesis of asymmetric fluoro-organics involve (i) asymmetric reduction of fluoiinated ketones, (ii) asymmetric allylboration of fluoiinated aldehydes, and (iii) asymmetric enolboration-aldolization of fiuoro-ketones and aldehydes. It appears that the presem e of fluorite atom(s) in the molecule influences the stereoctemi< outcome in asymmetric reduction and asymmetric enolboration-aldolization using cMorodiisopinocampheylborane. 

We were interested in flying DlP-Chloride for the enolboration-aldolization of ring-fluorinated acetophenones and benzaldehydes. During this research, we encountered a very interesting phenomenon. When we carried out the aldolization of diisopinocampheylboron enolate from 2 ,3, 4 ,S ,6 -pentafluoroacetophenone with pent uorobenzrddehyde at -78 °C, we obtained the product aldol, within 5 d, in 79%... 

Figure 19. Increase in enantioselectivity at higher temperature in enolboration-aldolization of pentafluoroacetophenone-pentafluorobenzaldehyde...

Figure 20. Tandem enolboration-aldolization-intramolecular reduction...

Figure 22. Effect of fluorine on tandem enolboration-aldolization-reduction...

The tandem enolboration-aldolization-intermolecular reduction normally provides the product syn-dioh in high diastereoselectivity (48), However, in die case of the reduction of the enolboration-aldolization product from trifluoroacetone-acetaldehyde combination with UBH4, we observed that a 1 1 mixture of syn/anti mixture is obtained. The intramolecular reduction process still gave 94% anti-product (Figure 23) (Wang, B unpublished results). 

Very recently, a tandem sequence consisting of enolboration/hydroform-ylation/aldol reaction has been described [88]. Here configuration of the enol boronate is transferred to the aldol product, allowing good to excellent di-astereoselectivities in the hydroformylation/aldol reaction. With this method, 5-7-membered rings are obtained in excellent yields (Scheme 35). 

General Procedure for Sequential Enolboration/Hydroformylation/Aldoladdition. Synthesis of Cyclic Aldol Products. NEt3 (1.05 eq to carbonyl compound) was precomplexed under an argon atmosphere with (cy-hex)2BCl (1.05 eq) in dry CH2C12 at 0 °C for 15 min. The unsaturated carbonyl compound was then added slowly via syringe and the enolbo-... 

Scheme 35 Enolboration/hydroformylation/aldol reaction - Diastereoselective access to cyclic aldols...

Enolboration of Ketones and Opening of meso-Epoxides. Methyl alkyl ketones have been successfully enolized by IpciBX (X = OTf or Cl) in the presence of a tertiary amine. The corresponding enolborinates have been used in asymmetric aldol condensations (eq 5). The reagent has also been applied to the enantioselective opening of mcj o-epoxides to form the corresponding nonracemic chlorohydrins (eq 6). ... 

Aldolization. Using Et iN as a base, the enolboration of carbonyl compounds is stereoselective therefore, aldolization can be controlled. The substitution pattern at the -carbon of an ester influences the configuration of the resulting ketene boryl ethers. Generally only a relatively small group can be accomodated by a (Z)-related dicyclohexylboroxy residue. 

Aldol reaction of esters. The combination of reagents promotes enolboration, and subsequent reaction under kinetically controlled conditions (-78°) leads predominantly to the anti isomers. At higher temperatures (-40° 0°) the syn isomers are produced with high facial selectivity. The ( /Z)-isomerization of the boryl ketene ethers is promoted by EtjNHOTf that is present in the reaction mixture. 

Constructing quaternary carbon centers with adjacent functional groups is a constant goal in the total synthesis arena, especially in the synthesis of complex natural products. Furthermore, development of reactions that generate quaternary centers both stereoselectively and regioselectively are even more in demand. Keranen and Eilbracht developed a sequential enolboration/hydroformylation/aldol addition one-pot casacade sequence resulting in the formation of a cyclic ketone 57 with a new quaternary center. 

The rhodium-catalyzed one-pot enolboration/hydroformylation/aldol addition sequence was applied for the regioselective and diastereoselective formation of carbocydic quaternary centers from acydic olefins (Equation 7.13) [135]. 

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