Reactions with aldehydes boron-mediated

Allyl tetrafluoroborates are also useful allylboration reagents. They can be made from allylic boronic acids and are stable solids.63 The reaction with aldehydes is mediated by BF3, which is believed to provide the difluoroborane by removing a fluoride. The addition reactions occur with high stereoselectivity, indicating a cyclic TS. 

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-... 

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. 

Ketone enolates have also been investigated in the asymmetric boron-mediated aldol reaction. The chiral boron reagents (+)- or (-)-diisopinocampheylboron tri-flate [(lpc)2BOTf], derived from a-pinene, allow the formation of the m-enolate and promote enantioselective aldol reactions with aldehydes to give either enantiomer of the syn aldol product. For example, the asymmetric aldol reaction between pentan-3-one and 2-methylpropenal takes place in the presence of (-)-(Ipc)2BOTf and diisopropylethylamine to give the syn aldol product 74 as the major enantiomer (1.84). 

The reactivity of acylzirconocene chlorides towards carbon electrophiles is very low, and no reaction takes place with aldehydes at ambient temperature. In the reaction described in Scheme 5.12, addition of a silver salt gave the expected product, albeit in low yield (22—34%). The yield was improved to 79% by the use of a stoichiometric amount of boron trifluoride etherate (BF3OEt2) (1 equivalent with respect to the acylzirconocene chloride) at 0 °C. Other Lewis acids, such as chlorotitanium derivatives, zinc chloride, aluminum trichloride, etc., are less efficient. Neither ketones nor acid chlorides react with acylzirconocene chlorides. In Table 5.1, BF3 OEt2-mediated reactions of acylzirconocene chlorides with aldehydes in CH2C12 are listed. 

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-... 

In the total synthesis of (+)-trienomycins A and F, Smith et al. used an Evans aldol reaction technology to construct a 1,3-diol functional group8 (Scheme 2.1i). Asymmetric aldol reaction of the boron enolate of 14 with methacrolein afforded exclusively the desired xyn-diastereomer (17) in high yield. Silylation, hydrolysis using the lithium hydroperoxide protocol, preparation of Weinreb amide mediated by carbonyldiimidazole (CDI), and DIBAL-H reduction cleanly gave the aldehyde 18. Allylboration via the Brown protocol9 (see Chapter 3) then yielded a 12.5 1 mixture of diastereomers, which was purified to provide the alcohol desired (19) in 88% yield. Desilylation and acetonide formation furnished the diene 20, which contained a C9-C14 subunit of the TBS ether of (+)-trienomycinol. 

A kinetic study of the Ph2BOH-catalysed reactions of several aldehydes with 2 revealed that the rate of the disappearance of 2 followed first-order kinetics and was independent from the reactivity of the aldehydes used. Taking into account this result, we have proposed the reaction mechanism in which a silyl enol ether is transformed to the corresponding diphenylboryl enolate before the aldol addition step takes place (Scheme 13.1). The high diastereoselectivity is consistent with the mechanism, in which the aldol step proceeds via a chair-like six-membered transition state. The opposite diastereoselectivity in the reaction with the geometrical isomers of the thioketene silyl acetal shown in Table 13.3 also supports the mechanism via the boron enolate, because this trend was also observed in the classical boron enolate-mediated reactions in dry organic solvents. Although we have not yet observed the boron enolates directly under the reaction conditions, this mechanism can explain all of the experimental data obtained and is considered as the most reasonable one. As far as we know, this is the first example of... 

The synthesis of the C19-C32 subunit 73 employed the boron-mediated anti aldol reaction of enolate 19 (see Scheme 9-8) with aldehyde 75 followed by an anti reduction to install the four contiguous stereocenters (Scheme 9-25). Both reactions proceeded with characteristic high selectivities (>97%ds) and further manipulations then afforded aldehyde 73. 

In the Evans synthesis of the polypropionate region (Scheme 9-45), the boron-mediated anti aldol reaction of -ketoimide ent-25 with a-chiral aldehyde 145 afforded 146 with 97% ds in what is expected to be a matched addition. Adduct 146 was then converted into aldehyde 147 in readiness for union with the C -Cs ketone. This coupling was achieved using the titanium-mediated syn aldol reaction of enolate 148 leading to the formation of 149 with 97% ds. 

In our synthesis, iterative aldol reactions of dipropionate reagent (R)-18 allowed for the control of the C3-C10 stereocenters (Scheme 9-72) [89]. Hence, a tin-mediated, syn aldol reaction followed by an anti reduction of the aldol product afforded 270. Diol protection, benzyl ether deprotection and subsequent oxidation gave aldehyde 271 which reacted with the ( )-boron enolate of ketone (/ )-18 to afford anti aldol adduct 272. While the ketone provides the major bias for this reaction, it is an example of a matched reaction based on Felkin induction from the... 

TBS-protection, a second, boron-mediated, syn aldol reaction led to the formation of 277 with 95% ds. In this case, ketone 278 controlled the stereochemical outcome of the reaction, and chiral ligands on boron were not required. A simple steric model accounts for this selectivity (see Scheme 9-11), and a titanium-mediated aldol reaction would be expected to give the same product. Following elaboration, including an Ireland-Claisen rearrangement, aldehyde 279 was prepared. 

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