Chiral ketals reaction

Further examination of the chiral ketals reveals that the lone pairs available for reagent coordination are oriented either in a syw or an anti relationship to the neighboring methyl substituents. The influence of the chiral auxiliary over the reaction is now clear. If zinc coordination must occur proximal to the double bond. 

Although the rationalization of the reactivity and selectivity of this particular substrate is distinct from that for chiral ketals 92-95, it still agrees with the mechanistic conclusions gained throughout the study of Simmons-Smith cyclopropa-nations. StOl, the possibility of the existence of a bimetallic transition structure similar to v (see Fig. 3.5) has not been rigorously ruled out. No real changes in the stereochemical rationale of the reaction are required upon substitution of such a bimetallic transition structure. But as will be seen later, the effect of zinc iodide on catalytic cyclopropanations is a clue to the nature of highly selective reaction pathways. A similar but unexplained effect of zinc iodide on these cyclopro-panation may provide further information on the true reactive species. 

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. ... 

This reaction was extended to a synthesis of a chiral tertiary alcohol in 72% ee from the corresponding chiral ketal. 

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. ... 

Finally, the carbometallation reaction of spirocyclic cyclopropenes with a chiral ketal attached to the substrate was described. Thus, carbocupration of the chiral cyclopropene 96 proceeded with 96% diastereoselectivity with a higher-order organocuprate [134] (Scheme 7-114). 

Oxidation of chiral ketals.2 The chiral ketal 1 is oxidized by Rc.->07 and 2,6-lutidinc to 2-hydroxy ketal 2 with high (>99 1) enantiosclectivity. This reaction is believed to... 

Further support for the difference in mechanism for addition with Br2 and Bra" comes from the observation that the two reagents give different stereochemical results upon addition of bromine to 3-substituted cyclohexenes. Bellucci, G. Bianchini, R. Vecchiani, S. /. Org. Chem. 1986,51,4224. Furthermore, the two reagents yield diastereomeric products upon reaction with chiral ketals. Giordano, C. Coppi, L. /. Org. Chem. 1992, 57,2765. 

Structures of mulberrofurans F (131), G (27), and K (179) have been established by correlation with chalcomoracin (103) and with mul-berrofuran C (130) using a ketalization reaction 91, 112). Therefore, the configuration of the three chiral centers in the methylcyclohexene ring of the ketal compounds is the same as those of 103 and 130. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Chiral acetals/ketals derived from either (R,R)- or (5,5 )-pentanediol have been shown to offer considerable advantages in the synthesis of secondary alcohols with high enantiomeric purity. The reaction of these acetals with a wide variety of carbon nucleophiles in the presence of a Lewis acid results in a highly diastereoselective cleavage of the acetal C-0 bond to give a /1-hydroxy ether, and the desired alcohols can then be obtained by subsequent degradation through simple oxidation elimination. Scheme 2-39 is an example in which H is used as a nucleophile.97... 

When the reaction was applied to a chiral cyclic ketal instead, very low selectiv-ities were obtained. Introduction of chelating substituents into the ketal made improvement possible, though (Scheme 8.14) [23, 26]. 

The first asymmetric synthesis of (-)-monomorine I, an enantiomer of the natural alkaloid, by Husson and co-workers starts with the chiral 2-cyano-6-oxazolopiperidine synthon (385) prepared from (-)-phenylglycinol (384), glu-taraldehyde (383), and KCN (443). Alkylation of 385 with an iodo ketal led to the formation of a single product (386). The cyano acetal (386) was treated with silver tetrafluoroborate and then zinc borohydride to afford a 3 2 mixture of C-6 epimeric oxazolidine (387) having the (2S) configuration. Reaction of 387 with... 

Allylzincation of the monosubstituted cyclopropenone ketal 137 with the chiral reagent 138 proceeded regioselectively so as to generate the less substituted secondary cyclo-propylzinc species 139. After hydrolysis, the resulting cyclopropanone ketal was obtained with high enantiomeric excess ( = 99%). The reaction was very slow at 20 °C but was considerably accelerated under high pressure (1 GPa) (equation 67)102. 

The reaction with optically active hydrazones provided an access to optically active ketones. The butylzinc aza-enolate generated from the hydrazone 449 (derived from 4-heptanone and (,S )-1 -amino-2-(methoxymethyl)pyrrolidine (SAMP)) reacted with the cyclopropenone ketal 78 and led to 450 after hydrolysis. The reaction proceeded with 100% of 1,2-diastereoselectivity at the newly formed carbon—carbon bond (mutual diastereo-selection) and 78% of substrate-induced diastereoselectivity (with respect to the chiral induction from the SAMP hydrazone). The latter level of diastereoselection was improved to 87% by the use of the ZnCl enolate derived from 449, at the expense of a slight decrease in yield. Finally, the resulting cyclopropanone ketal 450 could be transformed to the polyfunctional open-chain dicarbonyl compound 451 by removal of the hydrazone moiety and oxymercuration of the three-membered ring (equation 192). 

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