Stereoselective reduction ether

Other Borohydrides. Potassium borohydride was formerly used in color reversal development of photographic film and was preferred over sodium borohydride because of its much lower hygroscopicity. Because other borohydrides are made from sodium borohydride, they are correspondingly more expensive. Generally their reducing properties are not sufficiently different to warrant the added cost. Zinc borohydride [17611-70-0] Zn(BH 2> however, has found many appHcations in stereoselective reductions. It is less basic than NaBH, but is not commercially available owing to poor thermal stabihty. It is usually prepared on site in an ether solvent. Zinc borohydride was initially appHed to stereoselective ketone reductions, especially in prostaglandin syntheses (36), and later to aldehydes, acid haHdes, and esters (37). 

A McMurry coupling of (176, X = O Y = /5H) provides ( )-9,ll-dehydroesterone methyl ether [1670-49-1] (177) in 56% yield. 9,11-Dehydroestrone methyl ether (177) can be converted to estrone methyl ether by stereoselective reduction of the C —double bond with triethyi silane in triduoroacetic acid. In turn, estrone methyl ether can be converted to estradiol methyl ether by sodium borohydride reduction of the C17 ketone (199,200). 

Preparation of the bridging fragment 150 (Scheme 23) followed a similar pathway. In this case, stereoselective reduction of the cyclic enol ether 149 formed by the RCM of 148 was achieved using Et3SiH and TFA, leading after des-ilylation to the WVU ring system 150 [34b]. 

STEREOSELECTIVE REDUCTION OF 2,3-BUTADIONE MONOXIME TRITYL ETHER... 

In the later work, low optical activity (<30% ee) was observed for the products [e.g. 5] and the high asymmetric induction of the earlier work was attributed to carry over of the catalyst or chiral degradation derivatives (oxiranes) of the catalysts. Although the reported stereoselective reduction of acetophenone has been discredited, it has been suggested that the use of a chiral solvent, such as menthyl methyl ether, enhances the asymmetric reduction [7], The veracity of this claim has not been proven. 

Reductive defluorination reactions have also been described in ether, difluoroallylic alkoxides undergo stereoselective reduction (Eq. 138) to the E-mono-fluoro derivatives upon treatment with lithium tetrahydridoaluminate [354]. Sodium borohydride [355] and Red-Al [346] have also been used to achieve this transformation. 

Stereoselective reduction of a 2-chloro-1,3-diketone. The reduction of I (nonenolizable) proceeds predominately anti with respect to the C—Cl bond. The chlorine atom in the product can be removed by zinc dust reduction of the methoxymethyl ether. 

Stereoselective reduction of the carbonyl group in 21 by Zn(BH4)2 in ether to give the a-alcohol was followed by exchange of the protecting groups to give the properly protected alcohol 22. 

This resulted in a dramatic decrease of the reaction time to a mere 5 min with comparable yields. The sequence was accomplished upon full (H2/Pd- C) or partial and stereoselective reduction (Lindlar catalyst) of the double bond and cleavage of the PMB-ethers. 

The stereoselective reduction of the ketone function of 9 leads to a direct entry to selectively protected aldopentoses ( inversion strategy ) (Borysenko et al. 1989), which greatly expand the potential of this new protocol (Scheme 5). Following Evans protocol the tetramethylammo-nium triacetoxyborohydride-mediated reduction provides the yyn-diol 15 constituting a protected D-ribose (95%, >96% de). The anti-selective reduction to 17 was obtained after silyl protection of the free hydroxyl group of 9 to the OTBS-ether 16 using L-selectride. The aldopentose 18 was then accessible via chemoselective acetal cleavage followed by in situ cyclization (47% over two steps, >96% de). 

Parts B and C exemplify efficient procedures for the stereoselective reduction of acetylenic ethers to the corresponding Z- and E-enol ethers, synthetically useful intermediates.5 These procedures, which are optimized versions of previously described methods,3 6 also require only common reagents and standard laboratory... 

The in situ generated catalyst from ATBH and trimethyl borate has also been used in the stereoselective reduction of a-oxoketoxime ethers to prepare the corresponding chiral 1,2-amino alcohols. Thus the asymmetric borane reduction of buta-2,3-dione monoxime ether followed by acidic work-up and subsequent reaction with benzyloxycarbonyl chloride affords a 90% yield of 7V-(Z)-3-aminobutan-2-ol with excellent enantioselectivities (eq 5). A trityl group in the oxime ether is required for high enantioselectivity. This method has been successively applied to both cyclic and acyclic a-oxoketoxime ethers. 

Stereoselective reduction. Lithium aluminum hydride in ether reduces (1, bicyclo-[4.3.1]decalriene-2,4,8-onc-7) to the less hindered alcohol (2, e rfo-7-hydroxybicyclo-[4.3. l]decatricnc-2,4,8). ... 

Zinc borohydride was effective for the reduction of a,P-epoxy ketones (49) to the corresponding anti-a,3-epoxy alcohols (50) in ether at 0 °C irrespective of the substituents on the epoxide (equation 14). The selectivity was rationalized by intramolecular hydride delivery from a five-membered zinc chelate avoiding the epoxide ring. In a limited study of the stereoselective reduction of y,8-epoxy ketones (51), LAH and di-2-(o-toluidinomethyl)pyrrolidine in ether at -78 C gave the desired c/j-epoxy alcohols (52) required for ionophore synthesis with good selectivity (>10 1) (equation 15). ... 

Stereoselective reduction of a-alkyl-3-keto acid derivatives represents an attractive alternative to stereoselective aldol condensation. Complementary methods for pr uction of either diastereoisomer of a-alkyl-3-hydroxy amides from the corresponding a-alkyl-3-keto amides (53) have been developed. Zinc borohydride in ether at -78 C gave the syn isomer (54) with excellent selectivity ( 7 3) in high yield via a chelated transition state. A Felkin transition state with the amide in the perpendicular position accounted for reduction with potassium triethylborohydride in ether at 0 C to give the stereochemi-cally pure anti diastereoisomer (55). The combination of these methods with asymmetric acylation provided an effective solution to the asymmetric aldol problem (Scheme 6). In contrast, the reduction of a-methyl-3-keto esters with zinc borohydride was highly syn selective when the ketone was aromatic or a,3-unsaturated, but less reliable in aliphatic cases. Hydrosilylation also provided complete dia-stereocontrol (Scheme 7). The fluoride-mediated reaction was anti selective ( 8 2) while reduction in trifluoroacetic acid favored production of the syn isomer (>98 2). No loss of optical purity was observed under these mild conditions. 

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