Reduction anti selective

Syn selective reductions Anti selective reductions The Evans-Tishchenko reduction Kinetic diastereoselection of 1,3-diols Aldol revisited... 

Isayama described the coupling reaction of N-methylimine 157 and ethyl crotonate catalyzed by Co(acac)2 and mediated by PhSiH3 to produce Mannich product 158 in 82% with syn-selectivity (Scheme 41) [71]. The (i-laclam 159 was readily synthesized by heating 158. In 2002, Matsuda et al. reported cationic Rh complex [Rh(COD) P(OPh)3 2]OTf (1 mol%) as an active catalyst for the reductive Mannich reaction [72]. N-Tosylaldiminc 160 was coupled with methyl acrylate and Et2MeSiH (200 mol%) at 45 °C to give the b-amino ester 161 in 96% with moderate anti-selectivity 68%. 

Samarium(II) iodide also allows the reductive coupling of sulfur-substituted aromatic lactams such as 7-166 with carbonyl compounds to afford a-hydroxyalkylated lactams 7-167 with a high anti-selectivity [74]. The substituted lactams can easily be prepared from imides 7-165. The reaction is initiated by a reductive desulfuration with samarium(ll) iodide to give a radical, which can be intercepted by the added aldehyde to give the desired products 7-167. Ketones can be used as the carbonyl moiety instead of aldehydes, with good - albeit slightly lower - yields. 

Complete control of the diastereoselectivity of the synthesis of 1,3-diols has been achieved by reagent selection in a one-pot tandem aldol-reduction sequence (see Scheme l). i Anti-selective method (a) employs titanium(IV) chloride at 5°C, followed by Ti(OPr )4, whereas method (b), using the tetrachloride with a base at -78 °C followed by lithium aluminium hydride, reverses the selectivity. A non-polar solvent is required (e.g. toluene or dichloromethane, not diethyl ether or THF), and at the lower temperature the titanium alkoxide cannot bring about the reduction of the aldol. Tertiary alkoxides also fail, indicating a similarity with the mechanism of Meerwein-Ponndorf reduction. 

A desymmetrizing reduction of a dicarbonyl has also been achieved as a route to flMfi-aldol adducts. Yamada and coworkers have shown that a chiral cobalt complex catalyzes the desymmetrization of diaryl-1,3-diketones in excellent yield and enantioselectivity, greatly favoring the anti isomer [Eq. (10.65)]. Anti selectivity is rationalized using a Felkin-Anh model ... 

High yields and enantiopurity have been realized by a highly diastereoselective MPV reduction of protected a-amino aromatic ketones using catalytic amounts of aluminium isopropoxide. The high anti selectivity resulted from the chelation of the (g) nitrogen anion to the aluminium. In contrast, high syn selectivity was obtained with a-alkoxy ketones and other compounds via Felkin-Ahn control.354... 

Both biotransformations were performed on a gram scale. The /3-keto group of the enantiomeric keto esters thus obtained was reduced by syn- and anti-selective borohydride reductions (see Section 13.3.2). 

A rhodium bis(oxazoline) catalyst gives high ee and anti-selectivity in reductive... 

Reduction of 1,4-diketones with thexylborane (1 equiv.) is also stereoselective, with anti-selectivity of 17-47 1. Reduction of 1,5- and 1,6-diketones shows no stereoselectivity, but reduction of 1,3-diketones can show modest anti-stereoselectivity. 

Scheme 32 Anti-selective reduction of epoxides by Cp2TiCl/H20...

Scheme 5.17).40 A three-step reduction-deprotection protocol liberated the aratz -vicinal diamine 21. A six-membered cyclic transition-state structure was proposed to account for the anti selectivity after a two-electron reduction of the nitrone. The chiral A-tert-butylsulfinyl group directs the attack of the carban-ion to the Sz-face of the C=N double bond of the imine. 

The 1,3-anti-selective reduction was utilized in the total synthesis of the structurally unique compound (+)-clavosolide A (23)6 (Scheme 4.2g). The 1,5-anti -aldol reaction of a dibutylboron enolate of 24 with the aldehyde 25 proceeded smoothly to afford the (3-hydroxy ketone 26 in 93% yield and >96 4 diastereoselectivity. Compound 26 was subsequently treated with... 

To explain the high levels of anti-selectivity, Evans and Hoveyda proposed that the reduction occurs through a hydride-bridged six-membered transition... 

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). 

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