Stereoselectivity Selectride reductions

Syn stereoselectivity in reduction of acylic chiral ketoxime ethers of type 91 (equation 63) can be obtained using bulky tetramethylammonium triacetoxyborohydride that produces FeUdn-type products with high selectivity . Reaction of a-tolylsulfinylketoximes 92 (equation 64) with L-Selectride also results in syn products 93. 

Monomorine (664), isolated from the cosmopolitan ant Monomorium pharaonis (L.) as a major component displaying attracting and trail-initiating activity, is another example in which stereoselective hydride addition to a prochiral ketone creates easy access to cmcial stereogenic centers. L-Selectride reduction of 647 affords, with high syn selectivity, alcohol 662 (98 2). This is similarly converted in six steps to the (25, 5i )-pyrroline 663 which, after... 

Stereoselective Carbonyl Reductions. L-selectride reduction of U-acyl-Y-lactones has been shown to furnish the syn-reduction products in good yield and high diastereoselection which may be hydrolysed to threo-diols. The stereochemistry appears to be largely independent of the size of the acyl group and is in accord with reduction following the Felkin-Ahn transition-state model (Scheme 2). ... 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

The first asymmetric synthesis of (-l-)-abresoline was achieved from the chiral piperidine derivative 153, which upon treatment of its hydroxy side-chain substituent with carbon tetrabromide, triphenylphosphine, and triethyl-amine cyclized to the frarcr-quinazolidine 154. Deketalization and silyl protection of the phenolic group, followed by stereoselective reduction with lithium tri-t -butylborohydride (L-Selectride ), gave an alcohol, which after acylation and deprotection furnished (-l-)-abresoline 155 (Scheme 25) <2005TL2669>. 

Complex hydrides have been used rather frequently for the conjugate reduction of activated dienes92-95. Just and coworkers92 found that the reduction of a,ft-unsaturated ketene 5,5-acetals with lithium triethylborohydride provided mixtures of 1,4- and 1,6-reduction products which were transformed into enals by treatment with mercuric salts (equation 27). Likewise, tetrahydro-3//-naphthalen-2-ones can be reduced with L-Selectride to the 1,6-reduction products93 -95 this reaction has been utilized in the stereoselective synthesis of several terpenes, e.g. of (/ )-(—)-ligularenolide (equation 28)95. Other methods for the conjugate reduction of acceptor-substituted dienes involve the use of methylcopper/diisobutylaluminum hydride96 and of the Hantzsch ester... 

Other reagents used for the preparation of lactones from acid anhydrides are lithium borohydride [1019], lithium triethylborohydride (Superhydride ) [1019] and lithium tris sec-butyl)borohydride (L-Selectride ) [1019]. Of the three complex borohydrides the last one is most stereoselective in the reduction of 3-methylphthalic anhydride, 3-methoxyphthalic anhydride, and 1-methoxynaphthalene-2,3-dicarboxylic anhydride. It reduces the less sterically hindered carbonyl group with 85-90% stereoselectivity and is 83-91% yield [1019]. 

In the reduction of the ketone F, product G is favored with increasing stereoselectivity in the order NaBH4 < LiAlH2(OCH2CH2OCH3)2 < Zn(BH4)2. With L-Selectride, stereoisomer H is favored. Account for the dependence of the stereoselectivity on the various reducing agents. 

The methyl group was introduced by a two-step procedure. Thus, the hydrazone Michael adducts 52 were converted into the enol pivaloates 53 in excellent yields and diastereomeric excesses de > 96%) by treatment with pivaloyl chloride and triethylamine. After treatment with lithium dimethylcuprate the chiral auxiliary was removed by addition of 6n HCl in order to obtain the 5-substituted 2-methylcyclopentene carboxylate 54 in good yields and with excellent stereoselectivity (de, ee > 96%). Finally, the asymmetric synthesis of dehydroiridodiol (55, R = Me, = H) and its analogues was accomplished by reduction of 54 with lithium aluminum hydride or L-selectride leading to the desired products in excellent yields, diastereo- and enantiomeric excesses (de, ee > 96%). 

Stereoselective reductions based on complexed borohydrides have also proved of value in many instances in particular they have been of use in the synthesis of epimeric cyclic alcohols. For example, the reduction of 4-t-butylcyclo-hexanone to the cis-alcohol [99.5%, arising from equatorial hydride ion attack (i)] is effected by L-Selectride (lithium tri-s-butylborohydride, cf. Section 4.2.49, p. 448), or LS-Selectride53 (lithium trisiamylborohydride, cf. Section 4.2.49, p. 448) but to the trans-alcohol [98%, arising from axial hydride ion attack (ii)] with lithium butylborohydride.54 The experimental details of these reductions are given in Expt 5.34. 

Coupling 3-iodo derivative with reactive 1-thiosugars proceeds with good yield, without inversion of configuration, and with expected stereoselectivity at C-3. This approach as depicted in scheme 4 constitutes a general methodology and opens a new route to new family of (l-3>S-thiodisaccharides, which are otherwise difficult to synthesize under normal conditions of multistep techniques of protection/coupling/deprotection sequences. Stereoselective reduction of the C-2 keto function with L-Selectride in anhydrous THF solution produces g/uco... 

In order to achieve chemodifferentiation of the two ketone groups, carbonyl reduction may be carried out prior to NBS-mediated hydrolysis. Reduction with L-Selectride was found to be highly efficient and stereoselective, producing only one diastereoisomer of the product alcohol (Scheme 12). 

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). 

Epoxidation of oxonine 93 with dimethyldioxirane, followed by reduction with diisobutylaluminium hydride (DIBAL-H), resulted in a separable mixture of alcohols 95 and 96, and the side product 94 (Scheme 16). Each of the isomers was submitted to Swern oxidation and sequential stereoselective reduction with L-selectride to achieve desired stereochemistry of the products 97 and 98. Formation of the side product 94 was explained by Lewis acidity of DIBAL-H and confirmed by treatment of oxirane derived from 93 with another Lewis acid, AlMe3, to produce oxocine aldehyde 99 in 35% isolated yield <1997CL665>. Similar oxidative synthetic sequence was utilized for the synthesis of functionalized oxonines as precursors of (-l-)-obtusenyne <1999JOG2616>. 

Reactions of the 5-acylisoxazolines (121) with L-Selectride were highly stereoselective and gave mainly the 5yn-5-(a-hydroxyethyl)isoxazo-lines (122) (Scheme 57) [91JCS(P1)2613], Yeast reduction of racemic 5-acetylisoxazolines gave the diastereomeric alcohols (123) and (124), each... 

Direct Asymmetric a-Amination Reaction of 2-Keto Esters. The cir-DiPh-Box copper complex catalyzes highly enantioselective direct a-amination reaction of 2-keto esters with dialkyl azodicarboxylates and thus provides convenient access to optically active jyn-3-amino-a-hydroxy esters (eq 2). This enantioselective, direct a-amination is applicable to a range of 2-keto esters when dibenzyl azodicarboxylate is used as the nitrogen source. The immediate product of the amination reaction is prone to racemization. Stereoselective reduction of the keto functionality by L-selectride enables further synthetic operations to be carried out without loss of enantiopurity. 

One means of stereoselective cleavage of biaryl lactones [53] is activation of the carbonyl group with a Lewis acid and subsequent attack with a chiral nucleophile. Conversely, activation can be effected with a chiral Lewis acid followed by attack of an achiral nucleophile. Complexation of a biaryl lactone to the chiral fragment [CpRe (NO)(PPh3)j then reduction with K(s-Bu)3BH (K-selectride) and ring opening of the intermediate rhenium lactolate gives the metalated aldehyde (dr = 75 25) which is converted to the alcohol without essential loss of optical purity (Sch. 6) [54]. 

The unsaturated linkage in enantiomerically pure a-methyl-. -y-unsaturated ketones (45) exerted a powerful stereochemical influence on their reduction with L-selectride, particularly when R is a tri-methylsilyl group. The anti homoallylic alcohols (46) were produced with uniformly excellent stereoselectivity (>93 7) via a Felkin transition state in which the double bond occupied the perpendicular position (equation 12). This Felkin selectivity was sufficient to overcome any chelation-mediated contribution in the reduction of a-vinyl-p-hydroxy ketones (47) to the, 2-syn diols (48) with LiEtsBH in THF at -78 °C (equation 13).58... 

Coupling of these two readily available precursors leads to bis-enone 413 elaborated to 414 by chemo- and stereoselective hydrogenation of the more strained, bicyclic alkene with PhSiH3 in the presence of catal)dic Mo(CO)6, and K-selectride diastereoselective reduction (O Scheme 81). 

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