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. 

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 order to unambiguously ascertain the Cio stereochemistry, the Hoffmann group elected to separately synthesize both C(o epimers of aldehyde 269 (Scheme 9-73) via aldol additions of both enantiomers of ketone 18 to aldehyde 273 [88]. Notably, the boron-mediated syn aldol reactions of this ketone are non-selective in the absence of chiral ligands (see Scheme 9-8 for selective syn aldol reactions of 18). In this case, the C7 hydroxyl was ultimately oxidized to a ketone, and the Cg stereocenter epimerized during cyclization so the lack of selectivity was not detrimental to the synthesis. 

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. 

Table Kinetic Boron-mediated Aldol Reactions of Various Ketones with Representative Aldehydes ...

Several substituted allyl and crotyl derivatives have been designed to increase the usefulness of the boron-mediated allyl addition of aldehydes. For example, silanes such as those shown in Table 5.1, entries 7-9, can be stereospecifically converted to... 

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]. 

The synthesis of the E-ring 476 started with aldehyde 473, prepared via boron-mediated aldol reaction. FeUdn-selective Lewis acid-catalyzed aldol reaction of 473 with thioketene acetal afforded a-alcohol 474 (dr = 94 6). Fukuyama reduction of thioester to aldehyde followed by hemiacetalization and TBS protection furnished the E-ring 475, which was converted into phenylsulfone 476 in standard fashion. 

Excellent results have been obtained by using boron enolates (alkenyloxyboranes or enol borinates), in what is commonly known as a boron-mediated aldol reaction. The boron enolates are prepared easily from the corresponding ketone and a dialkylboron trifluoromethanesulfonate (dialkylboron triflate, R2BOTf) or chloride (R2BCI) and a tertiary amine base. Boron enolates react readily with aldehydes to give, after oxidative work-up of the resulting borinate species, high yields of the desired aldol product (1.58). 

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). 

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