Aldehydes reactions with boron enolates

Boron enolates react with aldehydes and ketones under neutral conditions to give intermediates which hydrolyze to aldol products. The reaction proceeds via a cyclic transition state (Equation B5.2) and is analogous to the allylborane reactions discussed above. 

Treatment of a-iodo ketone and aldehyde with an equimolar amount of Et3B yielded the Reformatsky type adduct in the absence of PhaSnH (Scheme 21), unlike ot-bromo ketone as shown in Scheme 15 [22], Ethyl radical abstracts iodine to pro-duee carbonylmethyl radical, which would be trapped by EtsB to give the corresponding boron enolate and regenerate an ethyl radical. The boron enolate reacts with aldehyde to afford the adduct. The three-component coupling reaction of tert-butyl iodide, methyl vinyl ketone and benzaldehyde proceeded to give the corresponding adduct 38, with contamination by the ethyl radical addition product 39. The order of stability of carbon-centered radical is carbonylmethyl radical > Bu > Pr > Ef > Me . 

An important modification of the aldol reaction involves the use of boron enolates. The boron enolates react with aldehydes to give aldols. A cyclic transition state is believed to be involved, and, in general, the stereoselectivity is higher than for lithium or magnesium enolates. The O—B bond distances are shorter than those in metal enolates, and this leads to a more compact structure for the transition state. This should magnify the steric interactions which control stereoselectivity. 

Although in the recent years the stereochemical control of aldol condensations has reached a level of efficiency which allows enantioselective syntheses of very complex compounds containing many asymmetric centres, the situation is still far from what one would consider "ideal". In the first place, the requirement of a substituent at the a-position of the enolate in order to achieve good stereoselection is a limitation which, however, can be overcome by using temporary bulky groups (such as alkylthio ethers, for instance). On the other hand, the ( )-enolates, which are necessary for the preparation of 2,3-anti aldols, are not so easily prepared as the (Z)-enolates and furthermore, they do not show selectivities as good as in the case of the (Z)-enolates. Finally, although elements other than boron -such as zirconium [30] and titanium [31]- have been also used succesfully much work remains to be done in the area of catalysis. In this context, the work of Mukaiyama and Kobayashi [32a,b,c] on asymmetric aldol reactions of silyl enol ethers with aldehydes promoted by tributyltin fluoride and a chiral diamine coordinated to tin(II) triflate... 

Boron enolates of thioglycolates. Esters do not form boron enolates because of the low acidity of the a-protons. However, methyl phenylthioacetate (2) forms a boron enolate on treatment with Hunig s base and dibutylboryl triflate, and this enolate undergoes aldol reactions with aldehydes with high syn-diastereoselectiv-ity.1... 

Boron enolates bearing menthol-derived chiral ligands have been found to exhibit excellent diastereo- and enantio-control on reaction with aldehydes " and imines. Highly diastereo- and enantio-selective aldol additions of geometrically defined trichlorosilyl ketone enolates (31) and (32) have been achieved by promoting the reactions with chiral Lewis bases, of which (S,S)-(33) proved to be the most effective. Moderate enantiomeric excesses have been achieved by using chiral amino alcohols as catalysts for the Baylis-Hilhnan condensation of aldehydes with methyl vinyl ketone the unexpected pressure effect on the reaction has been rationalized. ... 

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. 

Aldol and related reactions may also be chelation-controlled. Boron enolates of N-acyloxazolidinones 19 are chelated in the ground state. Their reactions with aldehydes will necessitate the coordination of the aldehyde with the boron atom at transition state, so that the initial bidentate chelate will be broken (Figure 1.26). However, the titanium atom of related titanium enolates can accommodate hexa-coordination so that the initial titanium chelate 20 does not need to be disrupted. In each case, the aldol reaction leads to different syn stereoisomers (Figure L26) via transition models 21 and 22. 

Table 4. It is interesting to note that the tin enolate corresponding to (57), upon reaction with aldehydes, also provides syn aldol products (60), diastereomeric to (59), with high diastereoselection. This opposite sense of asymmetric induction is believed to be due to coordination of the sultam oxygen to the metal (Sn) in the transition state, which is absent in the boron counterpart. Notably, the products can be easily purified by flash chromatography and/or crystallized to nearly perfect (>99% de) diastereomeric purity.

In some cases titanium enolates give as good, if not better, stereoselectivity as the corresponding boron enolate aldol reactions (Volume 2, Chapter 1.7). For example, the tri(isopropoxy)titanium enolate of the chiral ethyl ketone (27) has been found to undergo aldol reactions with aldehydes with very high dia-... 

Using the boron complex of the stien system, enantioselective aldol reactions were also possible. Ester 79 could be converted to the corresponding boron enolate using a derivative of 65, which could then undergo an aldol reaction with aldehydes 73 to afford 80.22... 

The simplest asymmetric induction involves a reaction of an achiral enolate with a chiral aldehyde. In this case, if the boron enolate geometry and facial selectivity to the aldehyde are well controlled, the stereoselective aldol reaction will proceed. For example, treatment of (Z)-boron enolate 11 with chiral aldehyde 12 effected stereoselective aldol reaction to give sy -aldol adduct 13 as a single product [3]. 

In addition to boron-mediated aldol reactions, the Lewis acid-catalyzed reactions of silyl enol ethers with aldehydes are also usefiil as shown in Scheme 6 [17]. 

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