Anti reduction

The following boronate derivative, formed by the reaction of 1,3-diol (3) with Et3B in the presence of air, reacts with Bu3SnH to form anti reduction product (4) with high stereocontrol (eq. 10.2) [1-4]. 

The 1,3-anti -reduction of (3-hydroxy ketones was utilized in the total synthesis of (+)-roxaticin (14), a pentaene macrolide isolated from streptomycete X-149944 (Scheme 4.2e). The (3-hydroxy ketone 15 underwent 1,3-anti -reduction to afford the diol 16 in 99% yield and greater than 95 5 diastereoselectivity. The resulting diol was then protected as a cyclopentylidene ketal (17) by using cyclopentylidene dimethyl ketal and pyridinium p-toluene sulfonate (PPTS). 

Gardinier and Leahy employed a samarium-catalyzed anti -reduction protocol to access one of the key intermediates en route to the synthesis of cryptophycin 1... 

Concerning stereoselectivity, it is not surprising that anti reductions predominate since trans are usually more stable than cis isomers (Table 8). This is likely to hold if any of the radical/anion species in equation (73) dXQ free of the cathode . Obviously, the cathode may be involved with the substrate and affect the selectivity, e.g. in equation (77) . ... 

The practice of selective reduction is stilt an art - . Note the different products for EtC CEt and PhC=CPh in Table 9 produced under different conditions. Now, Scheme 5 was devised to provide a broad rationale for diverse results in both named (Birch, Benkeser, Normant) and unnamed reductions. One learns that the presence of acids, i.e. NHJ in Na-NHj or /-BuOH in Na-HMPT, and low reaction temperatures favour anti reduction - Proton donors usually preclude alkyne-allene... 

The stereoselectivity in equations (90) and (91) indicates, albeit in oversimplified form, the possible difference in syn and anti reductions. Process (90) is stereospecific in THF—only the F-alkene is produced in toluene, both alkenes and the alkane are produced (see Table 11) . Process (91) is highly selective, yielding 98% of the -alkene in THF but yielding some of the Z-alkene, i.e. EjZ = 3/1, in ether . Our interpretation of these results is that in the more polar solvent, THF, in which LAH is probably somewhat dissociated , normal ionic addition occurs a coordinating metal ion (if any) and a final proton come in anti from the medium—hence the ionic representation. In the less polar solvents, ether and toluene, H and then metal (M) are delivered syn from associated LAH to one side of the alkyne—hence the aggregate representation. 

Figure 6-24. Transitions structure geometry for syn and anti reduction of 2 with AIH3 (3-2 tCi ).

The synthesis of the C19-C32 subunit 73 employed the boron-mediated anti aldol reaction of enolate 19 (see Scheme 9-8) with aldehyde 75 followed by an anti reduction to install the four contiguous stereocenters (Scheme 9-25). Both reactions proceeded with characteristic high selectivities (>97%ds) and further manipulations then afforded aldehyde 73. 

The synthesis of the C1-C9 fragment 120 began with an auxiliary controlled aldol reaction of the chloroacetimide 121, where chlorine is present as a removable group to ensure high diastereoselectivity in what would otherwise have been a non-selective addition (Scheme 9-39). The Lewis acid-catalyzed, Mukaiyama aldol reaction of dienyl silyl ether 122 with / -chiral aldehyde 123 proceeded with 94%ds, giving the 3-anti product 124, as predicted by the opposed dipoles model [3]. Anti reduction of the aldol product and further manipulation then provided the C1-C9 fragment 120 of the bryostatins. 

In our synthesis, iterative aldol reactions of dipropionate reagent (R)-18 allowed for the control of the C3-C10 stereocenters (Scheme 9-72) [89]. Hence, a tin-mediated, syn aldol reaction followed by an anti reduction of the aldol product afforded 270. Diol protection, benzyl ether deprotection and subsequent oxidation gave aldehyde 271 which reacted with the ( )-boron enolate of ketone (/ )-18 to afford anti aldol adduct 272. While the ketone provides the major bias for this reaction, it is an example of a matched reaction based on Felkin induction from the... 

SCHEME 2.145 Saksena-Evans reduction and Menche one-pot anti-reduction. 

The final C—C bond forming step turned out to be a mismatched boron enolate aldol reaction. Nevertheless, the use of (-l-)-DIPCl as a stereochemical inducer guaranteed the disposition for reagent control versus substrate control. Required product 324a was isolated in approximately 60% yield after chromatography on reverse-phase silica gel. The Evans group anti-reduction of the newly obtained aldol product gave substance 325, which was totally deprotected... 

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