Boron triflate

Ketones, in which one alkyl group R is sterically demanding, only give the trans-enolate on deprotonation with LDA at —12°C (W.A. Kleschick, 1977, see p. 60f.). Ketones also enolize regioseiectively towards the less substituted carbon, and stereoselectively to the trans-enolate, if the enolates are formed by a bulky base and trapped with dialkyl boron triflates, R2BOSO2CF3, at low temperatures (D A. Evans, 1979). Both types of trans-enolates can be applied in stereoselective aldol reactions (see p. 60f.). 

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. 

Boron triflates 45a and 45b are very useful chiral auxiliaries. Boron azaenolate derived from achiral35 and chiral36 oxazolines gives good stereoselectivity in the synthesis of acyclic aldol products, particularly for the rarely reached threo-isomers. By changing the chiral auxiliary, the stereochemistry of the reaction can be altered.37... 

Because anti/syn ratios in the product can be correlated to the E(0)/Z(0) ratio of the involved boron enolate mixture,10b initial experiments were aimed at the preparation of highly E(0)-enriched boron enolate. The E(0)/Z(0) ratio increases with the bulk of the alkanethiol moiety, whereas the formation of Z(O) enolates prevails with (S )-aryl thioates. (E/Z = 7 93 for benzenethiol and 5 95 for 2-naphthalene thiol esters). E(O) reagent can be formed almost exclusively by reaction of (5)-3,3-diethyl-3-pentyl propanethioate 64 with the chiral boron triflate. High reactivity toward aldehydes can be retained in spite of the apparent steric demand (Scheme 3-22).43... 

Boron tris(trifluoromethanesulfonate). This triflate is obtained by reaction of BC1, with triflic acid in S02C1F at -78°. Distillation at reduced pressure provides a solid, m. p. 45°, b. p. 68-73°/0.5 mm. It is extremely hygroscopic, and is soluble m CRiC, CHjNOi, CH CN. Aluminum and gallium triflate are poorly soluble in the common solvents. All three triflates can function as Friedel-Crafts catalysts, but the boron triflate is the most effective as a soluble catalyst. ... 

The is-boron enolates of some ketones can be preferentially obtained with the use of dialkylboron chlorides.17 The data in Table 2.3 pertaining to 3-pentanone and 2-methyl-3-pentanone illustrate this method. Use of boron triflates with a more hindered amine favors the Z-enolate. The contrasting stereoselectivity of the boron triflates and chlorides has been discussed in terms of reactant conformation and the stereoelectronic requirement for perpendicular alignment of the hydrogen being removed with the carbonyl group.18 The... 

A stock solution (1 M) of dicyclohexylboron trifluromethanesulfonate was prepared according to the accompanying procedure (Abiko, A. Org. Synth. 2002, 79, 103). Two equivalents of the boron triflate are necessary for complete enolization of the ester. When one equivalent is used, the enolization proceeds only to 50% conversion. 

The submitter obtained a colorless solution of boron triflate, but the checkers observed development of a yellow-orange color upon addition of triflic add. Regardless of the color, the triflate solution could be used without a decrease in yields. 

Di-n-butyl boron triflate (di-n-butylboryl trifluorosulphonate) [60669-69-4] M 274.1, b 37°/0.12mm, 60°/2mm. Distil in vacuum under argon and store under argon. Should be used within 2 weeks of purchase or after redistn. Use a short path distn system. It has IR bands in CCI4 at v 1405, 1380, 1320, 1200 and 1550cm- and 3c NMRfCDCb) with 8 at 118.1, 25.1, 21.5 and 13.6ppm. [Org Synth 68 83 7990 JACS 103, 3099 7957]. 

Acidity measurements were again limited for the lack of suitable indicator base and even 1,3,5-trinitrobenzene, the weakest base used, was fully protonated (Ho —18.5) in the 22mol% solution of boron triflate. Extrapolation of this system to 40% B(CF3S03)3 in CF3SO3H would lead to an H0 value of —20 in the Hammett scale. Consequently, the acidity is comparable to that of the ternary system HSO3F-SbF5-S03. 

Reactions with Sulfur Trioxide and Boron Triflate. 87... 

E)- or (Z)-Enol borinates. These ends are useful for stereoselective preparation of anti- or jyn-aldols, respectively, and have usually been obtained stereoselec-tively by variation of the alkyl group attached to boron triflates. They can also be prepared in essentially quantitative yield by reaction with dialkylboron chlorides at... 

An asymmetric synthesis of the aminocyclopentitol has been achieved from an acylated oxazolidinone (Scheme 38).110 Thus, the acylated oxazolidinone 295 was subjected to boron triflate-catalyzed condensation with 3-butenal to yield the syn aldol product 297 in 63% yield. Similarly, the A-acyloxazoI idineth ione 296 delivered the aldol adduct 298 in 75% yield when enolized with TiCl4-(—)-sparteine and then... 

Diamine protonic acids have been used for catalytic asymmetric aldol reaction.Boron triflate derivatives, R2BOTf, have been used for the condensation of ketals and ketone to give (3-alkoxy ketones. 

Masamune has documented the addition of optically active ester enolates that afford lanfi-aldol adducts in superb yields and impressive stereoselectivity (Eq. (8.3)) [4]. The generation of a boryl enolate from 8 follows from groundbreaking studies of ester enolization by Masamune employing dialkyl boryl tri-flates and amines [5]. Careful selection of di-n-alkyl boron triflate (di-n-butyl versus dicyclopentyl or dicyclohexyl) and base (triethyl amine versus Hiinigs base) leads to the formation of enolates that participate in the <2u//-selective propionate aldol additions. Under optimal conditions, 8 is treated with 1-2 equiv of di-c-hex-yl boron triflate and triethyl amine at -78 °C followed by addition of aldehyde the products 9 and 10 are isolated in up to 99 1 antv.syn diastereomeric ratio. The asymmetric aldol process can be successfully carried out with a broad range of substrates including aliphatic, aromatic, unsaturated, and functionalized aldehydes. 

With protected ketone 85 in hand, the next aldol coupling required its syn-selective reaction with aldehyde 74 to install the C15-C16 stereocenters in 86 (Scheme 9-28). A boron triflate reagent would be expected to generate the desired (Z)-enolate. However, studies earned out on the separate components indicated that this was a mismatched reaction, and it did not prove possible to overturn the aldehyde facial bias by use of a chiral reagent. 

B-C bonds are shorter than other metals with oxygen and carbon, the six membered Zimmerman-Traxler transition state in the aldol condensation tends to be more compact which accentuates steric interactions, thus leading to higher diastereoselectivity. When this feature is coupled with a boron enolate bearing a chiral auxiliary, high enantioselectivity is achieved. Boron enolates are generated from a ketone and boron triflate in the presence of an organic base such as triethylamine. Reviews (a) Abiko, A. Acc. Chem. Res. 2004, 57, 387-395. (b) Cowden, C. J. Org. React. 1997, 51, 1-200. 

Later in the book, when we deal with asymmetric enolate reactions, boron enolates will be very important. A simple example20 of an aldol reaction with a boron enolate, prepared from the ester 149 and a boron triflate using an amine as base, shows why. The boron enolate 150 could be prepared with a weak base and reacts with the aldehyde without catalysis to give essentially one diastereoisomer of the aldol 151 in good yield. If the titanium enolate (prepared with TiCI4 and an amine) was used, both the yield and the stereoselectivity were worse. In other circumstances enolates of titanium and other metals are very successful. 

Indeed, the forwards reaction uses a boron triflate and a bulky base of the type we have seen in order to make the cis boron enolate and achieve exactly this control. There are, of course, two. wn-aldol products possible here, 58 and 60, by virtue of the chiral centres present in the aldehyde fragment, and both do indeed form (in a 16 84 ratio). Trying to achieve selective formation of one of these syn diastereomers rather than the other syn diastereomer is beyond the scope of this chapter, even though that too is relative stereocontrol. It is complicated because it involves enantio-merically pure reagents in combination with the enantiomerically pure aldehyde and a match/mis-match issue. These issues are explored more fully in Chapter 30. Examples include combinations of chiral or achiral aldehydes with both achiral and chiral boron reagents. 

These results are interpreted as shown in Figure 6.79. The formation of 6.92 takes place via a cyclic transition state Cj Si. Chelate 6.91 is disrupted in order to allow the coordination of the aldehyde to the boron atom. As usual, steric interactions are minimized in the favored transition state. In the presence of excess boron triflate or of another Lewis acid which can activate the aldehyde carbonyl group, the boron chelate is no longer disrupted. Two acyclic transition-state models, A Re and A Si, can be envisioned according to the nature of the Lewis acid [106], Open transition states are also proposed for the reactions of 6.91 with CF3CHO, which does not require electrophilic assistance [1261]. 

Metal triflates can be easily prepared from metal halides and triflic acid at -78 C. They show several unique properties compared with the corresponding metal halides. In an early study, Olah reported the use of boron-, aluminum-, and gallium triflates [M(OTf)J as effective Friedel-Crafts catalysts. In the benzoylation and acetylation of toluene and benzene with acyl chlorides, the relative reactivity is boron triflate > gallium triflate > aluminum triflate, in agreement with the relative acidity strength. 

Following an early lead from the Meyers group [94,95], Paterson used the readily available diisopinocampheyl (Ipc) boron triflate to make Z(0)-boron enolates of 3-pentanone [93] and other ketones [96], which add to aldehydes to produce syn adducts in 83 - 96% es (Scheme 5.16 and Table 5.6). Based on molecular mechanics calculations [55,56], the transition structure analysis shown in Scheme 5.16 was suggested to rationalize the enantioselectivity. The axial boron ligand rotates so that the C-H bond is over the top of the Zimmerman-Traxler six-membered ring, and the equatorial ligand orients with its C-H bond toward the... 

A rationale similar to this may be used to explain the selective formation of fO)-enolates of tert-heptylthio- and rer/-butylthiopropionates (Scheme 5.15 and ref. [101]) the Et3CS- replaces the Me3CO- in the Scheme 5.18 rationale) and the selective formation of ketone Z(0)-enolates with dialkyl boron triflates and (0)-enolates with dialkylboron halides (Scheme 5.16 and 5.17 the triflates are more likely to ionize than the halides, thus favoring ionization over direct deprotonation of the zwitterion). 

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