Aldol reactions boron mediation

Other reactions adapted from asymmetric aldol reactions suffer in comparison from the fact that (probably due to the strength of the boron-nitrogen bond) boron-mediated processes generally yield the intermediate 2-halo-3-aminoester products rather than aziridine products directly [51]. 

In boron enolate-mediated aldol reactions, stoichiometric amounts of boron reagents are necessary. However, it has been reported that only a catalytic amount of a boron source is sufficient for boron enolate-mediated aldol reactions in water (Scheme 65).302 It should be noted that even water-sensitive boron enolates can be successfully employed in water. 

Double asymmetric induction (See section 1.5.3) can also be employed in aldol reactions. When chiral aldehyde 15 is treated with achiral boron-mediated enolate 14, a mixture of diastereomers is obtained in a ratio of 1.75 1. However, when the same aldehyde 15 is allowed to react with enolates derived from Evans auxiliary 8, a syn-aldol product 16 is obtained with very high stereo-... 

The aldol reactions introduced thus far have been performed under basic conditions where enolate species are involved as the reactive intermediate. In contrast to the commonly accepted carbon-anion chemistry, Mukaiyama developed another practical method in which enol species can be used as the key intermediates. He is the first chemist to successfully demonstrate that acid-catalyzed aldol reactions using Lewis acid (such as TiCU) and silyl enol ether as a stable enol equivalent can work as well.17 Furthermore, he developed the boron tri-fluoromethane sulfonate (triflate)-mediated aldol reactions via the formation of formyl enol ethers. 

Tandem processes mediated by triethylborane involving conjugate addition to enones followed by aldol reaction are reported (Scheme 52, Eq. 52a). More recently, a tandem process involving addition of an isopropyl radical to an o ,/3-unsaturated oxime ether afforded an azaenolate intermediate that reacts with benzaldehyde in the presence of trimethylaluminum. The aldol product cyclizes to afford an isopropyl substituted y-bulyroloaclonc in 61% overall yield (Scheme 52) [116]. In these reactions, triethylborane is acting as a chain transfer reagent that delivers a boron enolate or azaenolate necessary for the aldolization process. 

This radical cyclization strategy was utilized for the synthesis of the smaller fragment silyl ether 54 as well (Scheme 8). Evans aldol reaction of the boron eno-late derived from ent-32 with aldehyde 33, samarium(III)-mediated imide methyl ester conversion, and protecting group exchange led to tosylate 51. Elaboration of 51 to ketone 53 was achieved under the conditions used for construction of the second tetrahydrofuran moiety of 49 from 46. A highly diastereoselective reduc-... 

ANTI-SELECTIVE BORON-MEDIATED ASYMMETRIC ALDOL REACTION OF CARBOXYLIC ESTERS SYNTHESIS OF (2S, 3R)-2,4-DIMETHYL-1,3-PENTANEDIOL... 

The present procedure is based on the original report by the author and co-workers, and utilizes the characteristic features of the boron-mediated aldol reaction of carboxylic... 

Table Boron-Mediated Asymmetric Aldol Reactions...

Dialkylboron trifluoromethanesulfonates (triflates) are particularly useful reagents for the preparation of boron enolates from carbonyl compounds, including ketones, thioesters and acyloxazolidinones.4 Recently, the combination of dicylohexylboron trifluoromethanesulfonate and triethylamine was found to effect the enolization of carboxylic esters.5 The boron-mediated asymmetric aldol reaction of carboxylic esters is particularly useful for the construction of anti (3-hydroxy-a-methyl carbonyl units.6 The present procedure is a slight modification of that reported by Brown, et al.2... 

ANTI-SELECTIVE BORON-MEDIATED ASYMMETRIC ALDOL REACTION OF 116... 

Chlorodifluoromethylketones underwent aldol reactions (Eq. 124) via zinc enolates, to afford good yields of a,a-difluoro-/ -hydroxy ketones, in a study by the Kyoto group [327]. Copper(I) or silver salt catalysis was essential and boron-trifluoride additive appeared to exert a key role in the conversion to the enolate. Earlier [328], chlorodifluoromethyl ketones had been converted to the di-fluoroenoxy silanes by the action of zinc in the presence of chlorotrimethyl silane. A difluoroenoxy silane was used by McCarthy and co-workers [329] to synthesise a kynureninase inhibitor (Eq. 125) Lewis acid-mediated reaction with a chloroglycinate installed the key carbon-carbon bond. 

Anti-selective Boron-mediated Asymmetric Aldol Reaction of Carboxylic Esters. 

Previous work by our group had demonstrated that high levels of 1,4-syn diastereosclection were possible in boron-mediated aldol reactions of... 

Our persistence with the boron-mediated aldol reaction of 4 and 5 was rewarded when the reaction was conducted without recourse to the usual oxidative workup. Other work conducted by our group had shown that oxidative cleavage of certain aldol borinates under standard conditions (H2O2, pH 7 buffer, H20/Me0H) led to poor yields of the aldol products. In the case of 44, the oxidative step was omitted and the reaction mixture was placed directly on silica gel and then eluted to afford aldol adduct 44 in excellent yield (89%) and with improved diastereoselectivity (90 10 ds) relative to the corresponding lithium conditions.17... 

A new thiol auxiliary (45, R = COEt) participates in boron-mediated anti-aldol reactions with aldehydes with high yield and de.124 Reaction of the product with (g> nucleophiles displaces it (in the form of the thiol, 45 R = H), converting the aldol product under mild conditions into esters, thiolates, phosphonates, alcohols, or acids. 

Modern Aldol Reactions contains several pertinent reviews (i) catalytic enantiose-lective aldols with chiral Lewis bases 97 (ii) the aldol-Tishchenko reaction 98 (iii) titanium—enolate aldols 99 (iv) crossed aldols mediated by boron and silicon enolates 100 (v) amine-catalysed aldols 101 and (vi) aldols catalysed by antibodies.102... 

Boron-mediated ketone-ketone aldol reactions have been described, using boron enolates formed with dicyclohexylboron chloride and triethylamine.124 Following addition of the acceptor ketone to form a boron aldolate, oxidation with peroxide yields the aldol product. 

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