Ligands on boron

The reactions of 1-trimethylsilyl- or l-trimethylstannyl-2-butenyl-9-borabicyclo[3.3.1]-nonancs in the presence of pyridine are adequately explained by the usual transition structure 20 since the aldehyde should be capable of displacing pyridine as a ligand on boron. 

The final aldol reaction used in our synthesis of spongistatin 1 was one of the more remarkable reactions of this type our group has witnessed over the years. The aldol union of ketone 64 with ( )-4-chloro-2,4-pentadienal 65 required the creation of the (475) stereochemistry in the resultant alcohol 66. Formally, this would require 1,5-syn induction from the ketone 64, which is opposite to that observed previously for boron aldol reactions with simple [i-alkoxy methyl ketones. However, ketone 64 is densely packed with stereocentres, and predicting the influence of these remote centres on the reaction outcome was not possible with any degree of certainty. It was hoped that should 64 display undesirable 1,5-anti bias, this may be overturned by appropriate choice of Ipc ligands on boron. 

Enantioselective allylation is possible with optically pure ligands on boron... 

Scheme 9-6). The. seleclivity for adducts such as 12 can also be improved using reinforcing chiral ligands on boron. 

Using chiral ketone 11 instead of a chiral aldehyde, the same principle of enhancing substrate control can be applied. In this case, the induction from ketone 11 was moderate (82%ds), while using matched Ipc ligands on boron, the reaction proceeded with 98% ds to afford adduct 12 which was then transformed into aldehyde 97 [6 b]. 

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. 

Unless there is a chiral ligand on boron, assemblies a and b of Scheme 5.2 are enantiomeric and the product will be racemic. If the ligand is chiral, then the transition structures are diastereomeric and the products will be formed in unequal amounts under conditions of kinetic control (Chapter 1). Figure 5.1 illustrates several chiral boron reagents that have been tested in the allyl boration reaction, with typical enantioselectivities for each. 

Table 5.6. Asymmetric aldol additions of ketone enolates using chiral ligands on boron (Ipc = isopinocampheyl MeMn = methylmenthyl). See Schemes 5.16 and 5.17.

Asymmetric allylation and crotylation, synthetically equivalent to the aldol reaction, have been extensively studied and have become a very useful procedure for preparation of propionate units. Among various chiral ligands on boron-developed, isopinocampheyl- and tartrate-derived reagents, 51 and 52, which were developed by Brown et al. [18] and Roush et al. [19], respectively, are the most commonly used (Scheme 7). Reaction of aldehyde with (Sl-Sla or 52a gave anu -adduct 54, while that using (Z)-51b or 52b afforded syn-adduct 53 with high asymmetric selectivity. 

Complexes 7a-c was reported by Reetz et al. in 1999. Complex 9a was reported by Ashe et al. in the same year. The synthetic route to 7a-c is shown in Scheme 5.2. Base-catalyzed isomerization of PhB(HInd)2 to a more stable isomer with vinylic instead of allylic B-C bonds before metallation of the ligand improved the yield of 7a. Replacement of the Et20 ligand on boron with PMes afforded 7c as a mixture of rac and meso isomers, from which the rac isomer was selectively crystallized in 12% yield. 

In addition to all examples discussed so far, chiral information can be introduced into enolate via the metal. The use of readily available chiral ligands on boron, as in enolates (Z)-180 or ( )-180, was pioneered by Paterson et al. who was inspired by the earlier work of Meyers and Yamamoto. Initial experiments lead to aldol 181 in 80% yield (Scheme 10.39). 

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