Chiral Boron Reagents

Asymmetric Reduction of Unsymmetrical Ketones Using Chiral Boron Reagents Review Synthesis 1992, 605. 

Keywords chiral boron reagents, Diels-Alder reaction, stereoselective... 

Kobayashi and colleagues227 prepared chiral boron reagent 355 from BBr3 and chiral prolinol derivative 354 (equation 100). This catalyst afforded the exo Diels-Alder adduct of cyclopentadiene and methacrolein with 97% cc (equation 101). In the same way, norbomene (2/J)-357 was obtained from 356 and cyclopentadiene. 

Reviews on stoichiometric asymmetric syntheses M. M. Midland, Reductions with Chiral Boron Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 2, Academic Press, New York, 1983 E. R. Grandbois, S. I. Howard, and J. D. Morrison, Reductions with Chiral Modifications of Lithium Aluminum Hydride, in J. D. Morrison, ed.. Asymmetric Synthesis, Vol. 2, Chap. 3, Academic Press, New York, 1983 Y. Inouye, J. Oda, and N. Baba, Reductions with Chiral Dihydropyridine Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 4, Academic Press, New York, 1983 T. Oishi and T. Nakata, Acc. Chem. Res., 17, 338 (1984) G. Solladie, Addition of Chiral Nucleophiles to Aldehydes and Ketones, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 6, Academic Press, New York, 1983 D. A. Evans, Stereoselective Alkylation Reactions of Chiral Metal Enolates, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 1, Academic Press, New York, 1984. C. H. Heathcock, The Aldol Addition Reaction, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 2, Academic Press, New York, 1984 K. A. Lutomski and A. I. Meyers, Asymmetric Synthesis via Chiral Oxazolines, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 

Asymmetric Synthesis, Ed. J. D. Morrison, Academic Press, New York (1983), Chpt 2 (chiral boron reagents), Chpt 3 (LiAIJi, derived reagents)... 

The Claisen rearrangement has attracted much attention as an attractive tool for the construction of new carbon-carbon bonds. Taguchi et al. reported the enantioselective and regioselective aromatic Claisen rearrangement of catechol mono allylic ether derivatives by means of Corey s chiral boron reagent (Eq. 70) [53a,54]. The mechanism of enantioselectivity is that a rigid five-membered cyclic intermediate is formed by reaction of catechol mono allylic ethers with the chiral boron reagent and this is fol-... 

In the presence of a Zr complex of (J )-6,6 -dibromo-BINOL, A -(2-hydroxyphenyl)-aldimines participate in asymmetric hetero-Diels-Alder reactions It is an improvement to the reactions involving stoichiometric chiral boron reagents. 

Several other chiral boron reagents are available for asymmetric aldol reactions however, each of these compounds must be synthesized in the laboratory. In certain situations, some will give higher stereocontrol than the Ipc ligands, and hence for a given reaction their application could be pursued. Chiral reagents 53 and 54 have been used in the synthesis of bryostatin 7 [36] and the Taxol side-chain [37], respectively, while bis-sulfonamide 55 has been used in the synthesis of a C24-C35 segment of FK-506 (Scheme 9-18) [38]. 

A highly enantioselective and regioselective aromatic Claisen rearrangement was carried out using the reaction of catechol monoallyl ethers 192 with the chiral boron reagent 193. This reaction occurs without the formation of either the para-rearrangement or the abnormal Claisen rearrangement products (equation 89) . 

It is all very well knowing what enolates give rise to what aldol products, but this is not much use unless we can choose to have cis or trans enolates. Clearly with cyclopentanone there is no option but to form a trans enolate. But with an acyclic ketone we will need a little more care. Boron enol ethers provide an answer. Two common boron reagents used are 9-BBN chloride 46 (derived from 9-BBN 45) and another is dicyclohexylboron chloride 47. Other reagents include the corresponding triflates. There are also the chiral boron reagents that we shall meet later chapters. 

Indeed, the forwards reaction uses a boron triflate and a bulky base of the type we have seen in order to make the cis boron enolate and achieve exactly this control. There are, of course, two. wn-aldol products possible here, 58 and 60, by virtue of the chiral centres present in the aldehyde fragment, and both do indeed form (in a 16 84 ratio). Trying to achieve selective formation of one of these syn diastereomers rather than the other syn diastereomer is beyond the scope of this chapter, even though that too is relative stereocontrol. It is complicated because it involves enantio-merically pure reagents in combination with the enantiomerically pure aldehyde and a match/mis-match issue. These issues are explored more fully in Chapter 30. Examples include combinations of chiral or achiral aldehydes with both achiral and chiral boron reagents. 

Corey used an ester and a thioester in combination with an optically pure boron reagent in order to control both relative and absolute aldol stereochemistry.10 The optically pure boron reagent was busy with the absolute control (the details belong in chapter 27 but 69 was 94% ee and 71 97% ee by virtue of the chiral boron reagent). 

Now, whether this local syn arrangement is anti or syn to the more remote chiral centre in the enol borinate (1,3-control) can be controlled by the use of one enantiomer or other of a chiral boron reagent. The cis enol borinate with achiral boron reagent does not have much will of its own and leads to a 1 1.2 ratio of syn, syn anti, syn. 

Midland MM (1983) Reductions with chiral boron reagents. In Morrison JD (ed) Asymmetric synthesis. Academic, New York, vol 2, chap 2, p 45 Itsuno S (1996) The Alembic, Morton Performance Chemicals 53 1 Fiaud JC, Kagan HB (1969) Bull Soc Chim Fr 2742 Borch RF, Levitan SR (1972) J Org Chem 37 2347 Grundon MF, McCleery DG, WUson JW (1976) Tetrahedron Lett 295 Grundon MF, McCleery DG, WUson JW (1981) J Chem Soc Perkin Trans 1 231 Johnson CR, Stark CJ (1979) Tetrahedron Lett 4713... 

In 1981 Meyers and Yamamoto reported the use of an external reagent in the construction of a 2,3-anti unit. The boron azaenolate (85), prepared from the chiral boron reagent (86 diisopinocampheylbotyl triflate lpc2BOTf) and the achiral oxazoline derivative (87), reacts with aldehydes in ether at -78 C (Scheme 36). The direct products (88) are converted, after hydrolysis and esterification, to the corresponding a-methyl-P-hydroxycarboxyl derivatives (89), which are rich in the anti isomer (antiisyn... 

Application of the external chiral boron reagent (90) in the totd synthesis of bryostatin, a natural product, is shown in Scheme 45. The convergent approach adopted involves coupling of the boron enolate derived from (111) with aldehyde (112). The reaction mediated by an achiral boron reagent (Et2BOTf) provides only a 2 1 preference for the formation of the desired isomer (115) in adduct (113). The use of chiral (2/ ,5 )-dimethylborolanyl triflate in this reaction increases the selectivity to a 6 1 preference as... 

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