Boryl enolates

In summary, boryl enolate 38 can be obtained via in situ O-borylation of N-propionylsultam 37 and converted to aldol product 40 upon treatment with aliphatic, aromatic, or a,/l-unsaturatcd aldehdyes at - 78°C in the presence of TiCU- As aldol product 40 can normally be obtained in crystalline form, in most cases diastereomerically pure anti- Ao 40 can also be obtained after the recrystallization. 

Diastereoselective aldol reactions The boryl enolates of chiral crotonate imides (1) and (2) react with aldehydes to form adducts (3) and (4), respectively, with high diastereoselectivity and complete a-regioselectivity. The method of choice for reductive cleavage of the adducts is formulated for 3 hydrolysis can also be effected with LiOH and H202. 

A large number of studies have addressed the condensation of cyclic ketones with both aliphatic and aromatic aldehydes under conditions that reflect both thermodynamic (cf. Table 2) and kinetic control of stereochemistry. The data for cyclohexanone enolates are summarized in Table 8. Except for the boryl enolates cited (6), the outcome of the kinetic aldol process for these enolates... 

Several investigations have addressed the synthesis of boryl eno-lates by carbonyl enolization. Kbster has examined in detail the thermal reaction of triethylborane with substituted ethyl ketones catalyzed by diethylboryl pivalate (58) (eq. [40]) (61). The boryl pivalate 58 is undoubtedly the active reagent in this system, and it is regenerated by the illustrated protonolysis (eq. [41]) (62). The vigorous conditions employed in this procedure probably result in the generation of the equilibrated boryl enolates. The enolate ratios obtained by way of this procedure are summarized in Table 18. 

Aldol Condensations of Acyclic Ketone Boryl Enolates (6)... 

The interplay between solvent polarity and boron ligand structure in the enhancement of aldol stereoselection has been examined in several systems (6). The representative trends that have been noted for the boryl enolates derived from both cyclohexanone and tert-butyl thiopropionate (eqs. [49] and [50]) are summarized in Table 21. 

Reaction carried out in pentane. All other boryl enolates were mn in ether except where noted. 

In large measure, the problem associated with the execution of a stereoselective aldol condensation has been reduced to the generation of a specific enolate geometry. The recent results of Kuwajima (66a), which demonstrate that enolsilanes may be transformed into boryl enolates without apparent loss of stereochemistry (eq. [53]), should enhance the utility of vinyloxyboranes in stereoselective synthesis. The only current drawback to this procedure is associated with the presence of trimethylsilyl triflate (69), which must be removed from the reaction medium before the aldol condensation. It has recently been established that 69 is an effective catalyst for the aldol process (4). 

One of the first careful studies of the influence of chirality proximal to ketone enolates is illustrated in eq. [95] (113). Condensation of the enolate 126 (M = Li) with propanal (THF, -100 C) afforded a modest bias for the (5,i )-diastereomeric aldol adduct 127 (127 128 = 57 43). The influence of the metal center in this condensation has recently been examined. The boryl enolate 126 [M = B(n-C4H9)2l afforded a ratio 127 128 = 64 36 in pentane (-78°C) (6a, 113). Similar studies designed to probe the dependence of diastereoface selection on metal enolate structure have been carried out with metal enolates 129 (eq. [96], Table 32). 

It is significant to note that the sense of asymmetric induction noted for amide enolates 157 and 158 is the same as that found for the boryl enolates derived from the chiral oxazolidone imides 146 and 145, respectively (cf. Scheme 22). The arguments presented... 

Erythro diastereoselection has also been examined in these addition reactions. The addition of the (Z)-2-butenylboronate ester 179 [>95% (Z)-isomer] to representative aldehydes (Me, CjHj, i-CsH, Ph) was found to exhibit excellent erythro selection (eq. [117]) (132c), in direct analogy with the similar stereoselection observed with boryl enolates (6). 

Boryl enolates prepared from A-propionylsultam reacted with aliphatic, aromatic and a,/Tunsaturated aldehydes to provide diastereomerically pure. qw-aldols (Equation (174), whereas the presence of TiCl4 caused complete reversal of the diastereoface selectivity giving anti-aldols (Equation (175)).676-678 Camphor-derived chiral boryl enolates 423 were highly reactive and highly anti-selective enolate synthon system in aldol addition reactions promoted by TiCl4 or SnCl4 co-catalyst (Equation (176)).679... 

Treatment of chiral oxazolidinone with Bu2BOTf and Et3N quantitatively produced a novel doubly borylated enolate, which afforded the double aldol products with high diastereoselectivity in the reaction with aldehydes (Equation (182)).687 688... 

Enolate Halogenation. Enolate halogenation is achieved by reaction of the boryl enolate with N-Bromosuccinimide, affording configurationally stable a-bromo imides in >94 6 diastere-... 

Aldol Reactions. The dibutyl boryl enolates of chiral acylox-azolidinones react to afford the syn-aldol adducts with virtually complete stereocontrol (eq 32). 14,43.61-64 Notably, the sense of induction in these reactions is opposite to that predicted from the analogous alkylation reactions. This reaction is general for a wide range of aldehydes and imide enolates. - Enolate control overrides induction inherent to the aldehyde reaction partner. 

The second strategy involves a bromination-azide displacement-hydrogenolysis protocol. Treatment of boryl enolates of N-acylsultams (8) with NBS provides the key... 

In addition to enol silyl ethers, an optically active boryl enolate underwent the highly anri-stereoselective aldol reaction with a wide variety of aldehydes in the presence of TiCU (Eq. 34) [120]. The vinyl sulfides shown in Eq. (35) reacted with a,fi-unsaturated ketones via the 1,4-addition pathway in the presence of a titanium salt, but the reaction was followed by the cleavage of a carbon-carbon bond in the cycloalkane to give open chain products in a stereoselective manner [121]. The 1,2-type addition was observed, if the olefinie acetal was used instead of the corresponding carbonyl compound, as shown in Eq. (36) [121], The successive scission of the carbon-carbon bond took place analogously to give the same type of products as shown in Eq. (35). 

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. 

Similarly, using bornane [10,2] -sultam as a chiral auxiliary, provides, via the bromination of the intermediate boryl enolates, an alternative route to diastereoisomerically pure a-halo esters (ref. 10) (Fig. 5) ... 

Alkenyloxyboranes formulated as R R C==CR OBXY are perhaps more conventionally called boryl enolates and both terms are used in this article. Alkenyloxyboranes may be categorized as alkenyloxy-dialkylboranes, alkenyloxyalkylalkoxyboranes and alkenyloxydialkoxyboranes. To avoid confusion the terms borinyl , boronyl and borate are not used. Although the majority of the stereoselective aldol reactions reported involve alkenyloxydialkylboranes, alkenyloxydialkoxyboranes have also been utilized. The stereochemical course of the latter aldol reaction has been evaluated both experimentally and computationally and is discussed separately in Section 1.7.2.4. 

Mukaiyama et al. prepared boryl enolates from thiol esters in this way and unambiguously demonstrated that enolate (9) is capable of effecting directed aldol reactions.Similarly, alkenyloxyboranes prepared in the two other ways mentioned above afford the expected aldol products, as shown in Scheme 5, confirming that alkenyloxyboranes are responsible for the directed aldol reactions. 

A boryl enolate of an ester can be generated in situ by treatment of ethoxyacetylene with diphenyl-hydroxy borane in the presence of mercury(II) acetate, as shown in Scheme 6. ... 

Direct enolization of carbonyl compounds using dialkylboryl trifluoromethanesulfonate (dialkylboryl triflate R2BOTf) in the presence of a tertiary amine base is versatile and advantageous in many ways compared with the foregoing indirect methods (see Sections 1.7.2.3 and 1.7.2.4).2° The resulting boryl enolates, e.g. (10), react cleanly with various aldehydes to provide high yields of crossed aldol products (Scheme 7). 

A study on stereodefined boryl enolates that employed both pure (Z)- and ( )-dialkylboryl enolates has been carried out by Masamune et al Hooz reaction involving a-diazocarbonyi compounds (Scheme 3) and a trialkylborane provides exclusively (0)-alkenyloxyboranes, which can be isomerized cleanly to the corresponding Z(0)-isomers.- The Z((9)-dibutylboryl enolates (17) react with various aldehydes exhibiting uniformly high syn selectivities (syn.anti > 95 5), while the corresponding (0)-isomers (18) are converted into the anti aldol products with somewhat lower selectivities (Scheme 15). 

Van Horn and Masamune have shown that it is possible to prepare either boryl enolate stereoisomer from the same ketone by changing the steric demand of the dialkylboryl triflate (Scheme Evans et al. also carried out independent studies on the stereochemical course of these aldol reactions and demonstrated that dialkylboryl enolates were kinetically stable even at elevated temperatures. The results obtained from the Evans group also established that exceptionally high levels of aldol dia-stereoselection are governed by the stereochemistry of the dialkylboryl enolates (Table 1). 

It has been shown by Evans et al. that the aldol reaction of diboryl enediolates (23), with one exception, exhibit varying degrees of anti stereoselection (Scheme 18). This implies that (23) reacts more effectively as an (0)-boryl enolate than as a Z(0)-enolate. ... 

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