Chiral ketals reduction

An interesting asymmetric Baeyer-Villiger reaction of prochiral ketones via chiral ketals (9) allowed the synthesis of chiral 3-butyrolactones in ees of up to 89%.167 An SnCU mCPBA ratio of >1 in dichloromethane at —100 °C gave the best results and this is attributed to a high 5k 1 character due to lowered nucleophilicity of peracid by coordination to S11CI4. This is mirrored by die beder selectivity of BH3 dian EtjSiH in acetal reductions. 

Reaction with chiral acetals. The chiral ketals derived from (2R,4R)-(-)-2,4-pentanediol (1) can be cleaved with high diastercoselectivity by aluminum hydride reagents, in particular DIBAH, CI2AIH, and Br,AlH. Oxidative removal of the chiral auxiliary affords optically active alcohols. This process provides a useful method for highly asymmetric reduction of dialkyl ketones. ... 

Asymmetric reduction of ketones. Chiral ketals 2, obtained by reaction of 1 with prochiral ketones, are reduced diastereoselectively to 3 by several aluminum hydride reagents, the most selective of which is dibromoalane (LiAIHj-AIBr, 1 3). Oxidation and cleavage of the chiral auxiliary furnishes optically active alcohols (4) in optical yields of 78-96% ee (equation 1). 

With cyclic acetals and ketals, selective reductions allow the blocked hydroxy groups of the diol to be deprotected one at a time, a matter of some importance in carbohydrate chemistry. Although there have been a few studies of stereoselective reductions at the masked carbonium center of chiral ketals, more has been done with the formally related reactions in which C—C bonds are formed stereoselectively. ... 

The cis-2,3-diaryl-2,3-dihydro-l,4-benzoxathiin is a very unique structural motif. Other than scattered reports in the literature on the formation of this scaffold, there was no effective asymmetric synthesis for it [6]. We explored two major synthetic approaches to realize the key chiral as-diaryl dihydrobenzoxathiin scaffold, as shown in Scheme 5.3. One was the quinone ketal route in which the quinone ketal 13 and the chiral mercaptol alcohol 14 were the key intermediates. The other approach was the stereo- and enantioselective reduction of the diaryl benzoxathiin 16. The key mercaptol alcohol 14 and the diaryl benzoxathiin 16 were both envisioned to be prepared from the key, common iodoketone intermediate 15. 

New routes to ( + )-427 that employ the late-stage reductive cyclization of aminoketones continue to flourish. In Ae synthesis by Higasfaiyama et al, ketal 445 and (i )-A -benzylphenylglycinol 446 were condensed to form the chiral oxazolidine 447 (Scheme 55) 410). The heterocycle was cleaved diastereoselectively with pent-... 

As for the diols, the symmetric compounds have found most uses for nonsymmetric diols, a versatile synthesis via silyl ketones using the SAMP/RAMP methodology has been developedl5. Both enantiomers of the simplest symmetric diol, 2,3-butanediol (11), are often used in asymmetric synthesis, mostly for the formation of acetals and ketals with carbonyl compounds and subsequent reactions with acidic catalysts (Section D. 1.1.2.2.), Grignard reagents (Section D. 1.3.1.4.) and other carbanions (Sections D. 1.5.1., D. 1.5.2.4.), and diastereoselective reductions (Section D.2.3.3.). Precursors of chiral alkenes for cycloprotonations (Section D.1.6.1.5.) and for chiral allenes (Section B.I.), and chiral haloboronic acids (Section D. 1.1.2.1.) are other applications. The free diol has been employed as a chiral ligand in molybdenum peroxo complexes used for enantioselective epoxidation of alkenes (Section D.4.5.2.2.). 

A review of the preparation, structures, and stereochemistry of cyclic acetals of the aldoses and aldosides has appeared. Pyridinium toluene-p-sulphonate has been reported to be a mild catalyst for the formation and cleavage of dioxolane-type acetals, although no carbohydrate examples were quoted. Acetals and ketals of carbohydrates have been used as co-agents to introduce chirality into the products of sodium borohydride reduction of acetophenone, propiophenone, etc ... 

Asymmetric reductions of a-fiinctionalized ketones, such as a-hydroxy ketones, a-halo ketones, a-sulfonoxy ketones, 1,2-diketones, a-keto acetals or thio ketals, acyl cyanides and a-amino or imino ketones with boron-based chiral reducing agents in a stoichiometric or catalytic manner have been reviewed. The oxazaborolidine-catalyzed borane reduction of protected a-hydroxy ketones, a-keto acetals and a-sulfonoxy ketones has been discussed in more detail. 

Cheap and readily available cyclopentadecanone is alpha-brominated to (30) and ketalised with (29), and the resulting a-bromoketal (31) subjected to base induced elimination of HBr, giving (32). The key asymmetric step is now at hand. The Simmons-Smith cyclopropanation proceeds with very high facial selectivity, giving almost entirely the diastereomer of (33) shown. The result is rationalised on the basis of zinc chelation by the oxygens of the ketal. The synthesis is completed by acid hydrolysis of the ketal (the chiral diol may be recovered for reuse), reductive opening of the cyclopropane ring under Birch conditions, and re-oxidation of the alcohol back to the ketone. 

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