Reagent control

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

Reagent-controlled asymmetric cyclopropanation is relatively more difficult using sulfur ylides, although it has been done. It is more often accomplished using chiral aminosulfoxonium ylides. Finally, more complex sulfur ylides (e.g. 64) may result in more elaborate cyclopropane synthesis, as exemplified by the transformation 65 66 ... 

Reagent-controlled aziridination using camphor-derived chiral sulfide 47 has been reported with ee values of 84-98% for the trans isomer although the tram cis ratio was... 

Extension of this strategy enables syntheses of both protected c-threonine and t-allo-threonine, in which reagent-controlled stereoselecdve epoxidadon of a common intermediate is the key step fScheme 4.8. " ... 

Scheme 2. Substrate-controlled epoxidation of 12 and reagent-controlled epoxidation of 15.

The examples addressed thus far adequately convey the utility of the SAE reaction as a tool for the reagent-control strategy. Nonetheless, the power of the SAE reaction and the capabilities of the new reagent-control strategy are demonstrated even more forcefully in the total synthesis of all eight L-hexoses (compounds 1-8) by the groups of Masamune and Sharpless.11 The remainder of this chapter is devoted to this elegant joint venture. 

As discussed in Chapter 19, the concept of reagent control has revolutionized chemistry in the latter part of the 20th century. By... 

Scheme 2.5) was recently reported by Komatsu, Minakata, and coworkers [12]. The reaction with the (i ,i )-complex 12 provided the first reagent-controlled asymmetric aziridination of conjugated dienes, although enantioselectivities were only low to moderate (20-40% ee). 

Boland applied this methodology to Garner s aldehyde, and found the addition to be substrate-controlled rather than reagent-controlled (Scheme 9.13b) [68]. Viny-lepoxide 15 could thus also be obtained with high diastereoselectivity with achiral 9-MeO-9-BBN. 

Reagent-controlled enantioselective addition to achiral carbonyl compounds ... 

In addition to the problems of substrate- or reagent-controlled stereoselectivity, the problem of simple synjanti diastereoselectivity arises. Most studies have been performed on the crotyl derivatives. Table 2 summarizes some of these under the latter aspect. Essentially all types of reagents related to the appropriate 2-propenylmetal reagents collected in Table 1 are known. 

With Reagent-Controlled Stereoselectivity With Auxiliary Control... 

For additional examples in which reagent control is exercised in the reactions of chiral allylboron reagents and chiral aldehydes ... 

The reactions with (25,35,45,55)-5-(tm-butyldimethylsilyloxy)-3-(4-methoxyphenylmethoxy)-2,4-dimethylheptanal (15) are particularly informative reagent (5)-3 is incapable of overriding the intrinsic diastereofacial preference of 15, and the normal Felkin product 17 is obtained with >95% selectivity. In contrast, reagent-controlled mismatched double diastereoselectivity is evident in the reaction with (5)-4 that provides 16 as the major component of a 73 22 5 mixture. The minor product 18 apparently derives from a reaction with the contaminating (/ )-4, since (5)-4 that was used is not enantiomerically pure. 

The enantiomeric excess which is achieved for a given ally carbamate is independent of the carbonyl compound used it reflects the skill of the operator in the crystallization procedure. The high degree of reagent-controlled chirality transfer is also obvious from the reaction with either enantiomer of 2-benzyloxypropanal103a 107a. 

I.4.5.5. Asymmetric Bond Formation with Reagent Control... 

Oh T., Reilly M. Reagent-Controlled Asymmetric Diels-Alder Reactions. A Review. Org. Prep. Proced. Int. 1994 26 129-158... 

Reagent-Controlled Asymmetric Diels-Alder Reactions," Oh. T. Reilly, M. Org. Prep. Proceed. Int., 1994, 26, 129... 

Exothermic reactions require control strategies which may involve temperature control, dilution of reagents, controlled addition of one reagent, containment/venting and provision for emergencies. Refer to p. 248. 

P-Allyl-to-(isopinocampheyl)borane exhibits high stereoselectivity in reactions with chiral a-substituted aldehydes.40 The stereoselectivity is reagent controlled, in that there is no change in stereoselectivity between the two enantiomeric boranes in reaction with a chiral aldehyde. Rather, the configuration of the product is determined by the borane. Both enantiomers of (Ipc)2BH are available, so either enantiomer can be prepared from a given aldehyde. 

These reagents exhibit reagent control of stereoselectivity and have proven to be very useful in stereoselective synthesis of polyketide natural products, which frequently contain arrays of alternating methyl and oxygen substituents.44... 

Reagent-controlled stereoselectivity can provide stereochemical relationships over several centers when a combination of acyclic and chelation control and cyclic TS resulting from transmetallation is utilized. In reactions mediated by BF3 or MgBr2 the new centers are syn. Indium reagents can be used to create an anti relationship between two new chiral centers. The indium reagents are formed by transmetallation and react... 

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