Reduction, Diasteroselective

Highly diasteroselective and chemoselective reductions may be performed on the hydroxy functions of (r/6-arene)-tricarbonylchromium complexes. Treatment of the chromium-complexed benzylic alcohol 29 with triethylsilane and boron trifluoride etherate in dichloromethane at —78° to 0° gives only diastereomer 30 in 75% yield (Eq. 40).181 In a similar fashion, treatment of the complexed exo-allyl-endo-benzylic alcohol 31 with an excess of Et3SiH/TFA in dichloromethane at room temperature under nitrogen produces only the endo-aflyl product 32 in 92% yield after 1.5 hours (Eq. 41). It is noteworthy that no reduction of the isolated double bond occurs.182... 

The bromo-aryl groups are first linked by (5,5 )-stilbene diol to form the dibromide 33. Compound 33 is then dilithiated with t-BuLi at —78°C, followed by addition of CuCN. Intermediate 34 is presumably formed during the reaction. Reductive elimination promoted by molecular oxygen provides compound 35 at 77% yield with 93 7 diasteroselectivity. The final biaryl compound ellagi-... 

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

A similar diasteroselective reaction has been found in the reduction of 3-substituted 4,4-dichlorosuccinimides [208]. The stereochemistry of the products in an acidic medium is opposite to that in an alkaline medium. 

Because Zn+2 is a good chelating cation, highly diasteroselectivity reductions of a or p-hydroxy ketones and esters can be achieved with zinc borohydride. Reviews (a) Narasimhan, S. Balakumar, R. Aldrichimica Acta 1998, 31. 19-26. 

A large amount of activity on 1,4-benzodiazepine derivatives was reported in 2004. Tetrahydro-l,4-benzazepin-2-one derivatives are of interest as P-turn peptidomimetics and their solid-phase synthesis was reported by Kim et al. <04JC0207>. The diasteroselective synthesis of two enantiopure tetrahydro-l,4-benzodiazepin-5-ones was also achieved based on intramolecular azide cycloaddition and subsequent stereoselective reduction of the 1,4-benzodiazepinone products <04TA687>. A different approach to tetrahydro-1,4-benzodiazepin-5-ones 80 involves the 1,2-thiazine 1-oxides 77 as key intermediates. These intermediates were then converted to the nitroaryl amides 78 (R , R, R = H or Me) which could be cyclised to 80 after hydrogenation of the nitro group via the intermediates 79 <04T3349>. 

Aziridines are commonly prepared from imine precursors. Carbene addition to the C=N bond is illustrated by the formation of aziridine 127 from imine 126. ° Difluorocarbene, generated from HFPO (1), also adds to imines such as 128 to give the highly fluorinated aziridine 129. In the presence of Lewis acids, diazo compounds react with imines to produce aziridines. Ethyl diazoacetate and imine 130 gave aziridine 131 in 93% yield, with a cis/trans ratio of 95 5. Chiral diazo compound 132 reacted with the aldimine precursor 133 to afford aziridine 134 in 81 % yield.The reaction displayed both high cis selectivity (>95 5) and excellent diasteroselectivity (94% de). Reductive removal of the chiral auxiliary gave the optically active hydroxymethylaziridine 135. 

Intramolecular 1,3-DC of sugar-derived nitrones followed by reductive cleavage of the isoxazolidine N-0 bond have been used in the synthesis of aminocyclopentitols and anellated carbasugar derivatives <01TL4925, 0ITL5769, 01EJO759>. In all the reported examples the polycyclic isoxazolidines were obtained with high or complete diasteroselectivity. 

Reaction of furyllithium (60) with L-threonine derived lithium salt 61 afforded the expected ketone 62 in 30% yield. Reduction of 62, using lithium aluminium hydride, gave two alcohols (63 and 64) in a 3 1 ratio. In both carbinols (63 and 64) the oxazoline ring was opened by acid hydrolysis to give the N-benzoyl derivatives 65 and 66, respectively. Alcohol 66 can be used in the synthesis of lincosamine enantiomer, but unfortunately this approach has limited preparative value because of the low yield obtained in the condensation step and, on the other hand, opposite diasteroselectivity obtained in the reduction reaction. 

Scheme 13.15 Total synthesis of (—)-maoecrystal Z (106) employing a diasteroselective Sm -mediated reductive cascade cyclization reaction.

The first total synthesis of (-)-maoecrystal Z was reported by Reisman and coworkers in 2011 (Scheme 13.15) [17]. The crucial step featured a diasteroselective Sm -mediated reductive cascade cyclization reaction, which enabled the preparation of (-)-maoecrystal Z in only 12 steps. 

P-Borylation of a,P-Unsaturated imines. Fernandez and coworkers have also developed a route to y-ainino alcohols via a tandem sequence of enantioselective -borylation of a,p-unsaturated imines, followed by iterative imine reduction and boronic ester oxidation. In the presence of B2pin2, CuOTf and a binapthol-derived phosphoramidite ligand, asymmetric conjugate addition of (V-protected Q ,/3-unsaturated imines occurred in high yield and with excellent enantioselectivity. Diasteroselective reduction of the imine to the corresponding jyn-y-amino alcohol was achieved with BH3 THF (eq 56). The authors postulated that... 

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