Boryl enolates aldol reactions

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. 

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). 

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... 

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. 

Titanium enolates of propionyloxazolidinones also undergo aldol reactions with the same sense of induction as the boryl counterparts, but require two or more equivalents of amine base to afford adducts in marginally higher yields but diminished selectivity (eq 33). ... 

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). 

Trimethylsilyl enol ethers react rapidly with boryl triflate reagents (Scheme 26). Subsequent aldol reaction occurs with apparent stereospecificity provided that the by-product trimethylsilyl triflate is... 

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 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. ... 

Puentes et al. have also used boron-mediated aldol reactions to prepare enantiomerically homogeneous P-lactam moieties. In the presence of a Lewis acid (ZnBra), enantiomerically homogeneous boryl enolate (76) provides adduct (77) with high diastereoselectivity (see acyclic transition state E Scheme 33). 

The first asymmetric total synthesis of xestodecalactone B and C was recently accomplished in 10 steps with an overall yield of 22%. The key step involves the use of Evans aldol reaction to establish the C-9 configuration. Initial attempts to use an N-acetyloxazolidinone boryl enolate afforded the corresponding aldol product as a nearly 1 1 ratio of diastereomers. A switch to the boryl enolate of thiomethylacetyloxazo-lidinone 68, which is an acetate aldol equivalent, generated the product 69 with high diastereoselectivity (92% de). Subsequent desulfiuization with n-BuaSnH and AIBN was required to remove the thiol functionality. 

---