Meerwein enantioselectivity

On the other hand a direct hydrogen transfer through a Meerwein-Ponndorf mechanism, involving coordination of both the donor alcohol and the ketone to the copper site may also be considered. In this case, by using alcohols other than 2-propanol, we could expect some difference in stereochemistry. This would also imply the possibility of carrying out the enantioselective reduction of a prochiral ketone with a chiral alcohol as donor. 

As shown in Figure 1.26, a chiral Sm(III) complex catalyzes asymmetric reduction of aromatic ketones in 2-propanol with high enantioselectivity. Unlike other late-transition-metal catalysis, the hydrogen at C2 of 2-propanol directly migrates onto the carbonyl carbon of substrate via a six-membered transition state 26A, as seen in the Meerwein-Ponndorf-Verley reduction. ... 

In the course of some stereoselective reactions the inducing chiral unit is destroyed. A classical example is the enantioselective Meerwein Ponndorf reduction of a ketone with a chiral Grig-nard compound33 ... 

The highly enantioselective production of ( + )-(S )-benzenemethan-a-configurational determination of 8 rests on an asymmetric Meerwein-Ponndorf reduction (with isobornyloxymagnesium bromide). On mechanistic grounds the reduction of benzaldehyde-rf was assumed to produce preferentially the 7 -isomer225. 

An enantioselective synthesis of CR)-amino acids has been developed which utilizes L-valine as the chiral auxiliary (81AG(E)798). The diketopiperazine cycZo-(L-Val-Gly) (780) was converted to its bis-lactim ether (781) by methylation with Meerwein s salt, and the ether metallated in the glycine portion by n-butyllithium. Alkylation of the delocalized... 

Evans reported an enantioselective Meerwein-Ponndorf-Verley reduction using a catalytic amount of chiral samarium complex 26 prepared from samarium (III) iodide and a chiral amino diol (Scheme 9.16) [34], Even when a partially resolved ligand (80% ee) was used, the enantiopurity of the resulting alcohol 27 reached 95% ee, which is the same value as that obtained when the enantiopure amino diol was used. 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

The enantioselective biomimetic total synthesis of the alkaloid (+)-aristotelone was accomplished by C.H. Heathcock and co-workers." The synthetic sequence commenced with a Hg(N03)2-mediated Ritter reaction between (1S)-(-)-P-pinene and 3-indolylacetonitrile. Upon protonation, the pinene underwent a Wagner-Meerwein rearrangement to generate a tertiary carbocation which reacted with the cyano group. The initially formed imine product was reduced to the corresponding amine by sodium borohydride in methanol. 

Brunner, H., Bluchel, C., Doyle, M. P. Asymmetric catalysis. Part 108. Copper catalysts with optically active ligands in the enantioselective Meerwein arylation of activated olefins. J. Organomet. Chem. 1997, 541, 89-95. 

Plieninger, H., Kraemer, H. P. Enantioselective Wagner-Meerwein rearrangement in chiral solvents under high pressure. Angew. Chem. 1976, 88, 230-231. 

Yu and coworkers reported that use of PrSBEt2 as an additive accelerates the chiral Zr-catalyzed asymmetric allylation reaction and suppresses the concomitant Meerwein-Ponndorf-Verley reduction. The presence of the additive is thought to dissociate the product from the reaction complex and to regenerate the chiral catalyst [28]. This method was further extended to asymmetric propargylation with allenyltributylstannane by the same group [19]. In contrast, Taghavini and Umani-Ronchi and their group have shown that an enantioselective allylation of... 

Scheme 8.43. Enantioselective Wagner-Meerwein rearrangement in chiral solvents.

Linton and Kozlowski have installed quaternary centers at oxindole C3 in enantioselective fashion via the Pd-catalyzed rearrangement of 2-allyloxy indoles (Scheme 2) [16]. For example, indole 7 underwent an enantioselective Meerwein-Eschenmoser-Claisen rearrangement in the presence of Pd(SbF6)2 and the chiral phosphinooxazoline ligand 8 to afford oxindole 9 in 89% yield and 89% ee. A two-point coordination of the chiral palladium catalyst to the C3 carbonyl and C2 oxygen (6-membered coordination system) has been proposed to rationalize the enantioselectivity of the transformation. Modest to good enantioselectivities were also observed for a series of bisphosphine chiral ligands. 

Scheme 9.4 Enantioselective vanadium salen 10 and salalen 11-catalysed Meerwein-Ponndorf-Verley (MPV) cyanation, reported by Katsuki. ...

An enantioselective version of the Meerwein-Pondorf-Verley (MPV) reaction was developed by Nguyen and coworkers (331-333). A combination of (i )-(- -)-2,2 -dihydroxy-l,l -biphenyl ((i )-(- -)-binol) and AlMes, in a 1 1 ratio, catalyzes the ATH of alkyl/aryl ketones, with 2-propanol as the hydride source. Reductions can be achieved in high yield (up to 99%) and enantioselectivity (up to 80% ee). 

A highly enantioselective Meerwein-Schmidt-Ponndorf-Verley (MSPV) reduction of N-phosphinoyl ketimines by (BINOL)Al(iii)/2-propanol has been reported. High yields and enantiomeric excesses were observed for a wide range of structurally diverse ketimines. A [2.0.4] bicyclic chelation model was proposed to account for the... 

Although the Meerwein-Ponndorf-Verley (MPV) reduction was discovered over 80 years ago, it has not been until relatively recently that catalytic variants utilising chiral aluminium have been realised. " In 2002, the Nguyen group reported a practical, enantioselective catalytic MPV reduction. Isopropanol was used as the hydride source, and trimethylaluminium with (R)-BINOL as the catalyst (Scheme 19.54). ... 

It is important to realise that chirality is a symmetry property of a whole molecule and cannot be localised in a particular centre or group (although it may be associated with the presence of a particular stereogenic unit). For this reason the intramolecular transfer of chirality is an impossibility. Transfer of chirality can only occur between two molecules and is quite uncommon. [An example is the enantioselective Meerwein-Ponndorf-Verley reduction of a ketone with a chiral alcohol.] What some authors refer to incorrectly as transfer of chirality is, in fact, retention of chirality in the course of modification of the stereogenic units present. 

Trost BM, Xie J (2008) Palladium-catalyzed diastereo- and enantioselective Wagner — Meerwein shift control of absolute stereochemistry in the C — C bond migration event. J Am Chem Soc 130(19) 6231-6242. doi 10.1021/ja7111299... 

An enantioselective semipinacol rearrangement has been reported. For example, the cyclobutanol derivative (184) reacts with an iodonium source (186) to provide the rearrangement product (185) in good yield (Scheme 39). In the presence of a chiral phosphoric acid, good chrial induction is obtained in product formation. The key steps in this conversion involve facial selectivity of iodonium attack and stereocontrol of the Wagner-Meerwein rearrangement step (187). Both steps are thought to be controlled by the chiral counterion. 

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