With L-Selectride

Benzyl-nitrogen, sulfur, or -oxygen bonds are somewhat susceptible to hydrogenolysis, either during catalytic hydrogenation (30, 31), or upon treatment with L-selectride (32), or even lithium aluminium hydride (33). 

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... 

Bond constructions similar to those just discussed can be achieved using an alkylidene malonate which is tethered to an alkyl bromide [72]. Of particular interest in this context is the controlled potential reductive cyclization of 263. As illustrated, the method provides a reasonably facile and modestly efficient entry to cyclobutanes 264. Presumably, the process is initiated by reduction of the alkylidene malonate rather than the alkyl halide, since alkyl bromides are more difficult to reduce. The same substrate, when reduced with L-Selectride undergoes conjugate addition of hydride and a subsequent cyclization leading to the five-membered ring 265. The latter transformation constitutes an example of a MIRC reaction [71-73], a process which is clearly complementary to the... 

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. 

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. 

E) configuration. The dipolar cycloaddition of 141 with a silyl nitronate shows a slight increase of facial selectivity over 132 (Eq. 2.9). Because the cycloadducts are converted directly to the corresponding isoxazolines, only the facial selectivity can be determined. It is believed that the cycloaddition proceeds on the Re face of the dipolarophile due to shielding of the Si face by the auxihary. Both chiral auxiliaries can be liberated from the cycloadduct upon reduction with L-Selectride. 

The synthesis of a -amino allylic alcohols is particularly difficult, yet this functionality is important in natural products (such as sphingosine) or as a synthon for further elaboration to amino sugars. In synthetic studies of this moiety204, the corresponding enones, with adjacent stereocenters, have been efficiently reduced to the allylic alcohol in quantitative yields and in both a regiocontrolled (1,2) and a stereocontrolled fashion (equation 53). The syn anti ratio of the product depends upon the hydride reductant and solvent being utilized. A 4 1 ratio was obtained with L-selectride and a 1 6 ratio obtained by the use of DIBAL in toluene. 

The phenyl 1-thioparatoside 145 was activated with TV-iodosuccinimide and silver triflate and reacted with a convenient derivative of the disaccharide (1-d-GalpNAc-(l ->4)-p-D-GlcpNAc. After removal of the pivaloyl-protecting group with sodium methoxide, isomerization of paratose to tyvelose was performed in a one-pot reaction by oxidation with dimethyl sulfoxide and acetic anhydride, followed by reduction with L-Selectride. Selectivity of the reduction was better... 

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... 

Figure 10.9 shows an application of this principle in the diastereoselective addition of a hydride donor to a bicyclic ketone With L-Selectride [= Li BH(sec-Bu)3] the endo-alcohol is produced exclusively. 

Fig. 10.11. Addition of various hydride donors to 4-tert-butylcyclohexanone. With L-Selectride the equatorial approach (Formula A) is preferred, with sterically (less) demanding hydride donors the reaction proceeds axially via transition state B (cf. text and, particularly. Side Note 10.1). For comparison see the Felkin-Anh transition state C (in Figure 10.16 EWG = electron-withdrawing group).

Fig. 13.20. Generation of enolates from a,/3-unsaturated ketones via Birch reduction (top line) or by reduction with L-Selectride (bottom line).

An ingenous method for the preparation of the lateral macrobicycles has been developed by Newkome and co-workers 30). The method consists on bis-quatemization of the macrocycles 25 with bis(2-iodoethoxy)ethane (26) in boiling acetonitrile to afford the bis-quaternary salts 27 in ca. 40% yield. Those were not isolated, but directly demethylated with L-selectride to form the desired macrobicycles 28 in a 40 % overall yield (Scheme 4). 

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). 

Initially, the diquaternary ammonium macrocycle is synthesized by the quatemi-zation of a diamino compound by a diiodoether the diquatemary salt is, subsequently, demethylated with L-Selectride . Repeating this sequence of events results in the formation of a cryptand. In most cases the Air-quaternary ammonium salts were not... 

Secondary enamino sulphoxides were reduced through their imino forms, with L-selectride [lithium tri(s-butyl)borohydride] to give jS-aminosulphoxides of R, R configuration with high stereoselectivity120 (Scheme 89). 

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>. 

Acryloyl esters bearing c/ Vo-inositol derivatives as chiral auxiliaries reacted with a consistently high degree of stereoselectivity (92TL5763). For example, the ter/-butyldiphenylsilylether (98) reacted with benzoni-trile oxide (3) to give the cycloadduct (99) in 90% diastereomeric excess (Scheme 49). The stereochemical outcome of the reaction indicates si-face attack to the s-cis conformer of the acrylate (98). The chiral auxiliary was recovered after treatment of the isoxazoline (99) with L-Selectride. 

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... 

Of the large number of reducing agents, the most useful are DIBAH and lithium tri-i -butylborohydride. Regardless of the nature of R, DIBAH reduces 3 mainly to the alcohol 4 (the tzn/i-Cram product) in 60-80% de. Reduction with L-Selectride usually proceeds in the opposite sense and in aeeordanee with Cram s chelate rule, but high selectivity is observed only when R is a primary or tertiary alkyl group. 

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