Diastereoselective //-hydroxyketones

L1A1H4 is the most effective reducing system for the reduction of ketene homodimers and ketene heterodimers to diastereoselective / -hydroxyketones (dr up to >99 1 and yield 62 >99%), though LiBH4 reduced methylphenylketene dimer in THF with optimal diastereoselectivity up to 6 1 and 69% conversion. ... 

Sodium or tetramethylammonium triacetoxyborohydride has become the reagent of choice for diastereoselective reduction of P-hydroxyketones to antidiols. Trialkylborohydrides, eg, alkaH metal tri-j -butylborohydrides, show outstanding stereoselectivity in ketone reductions (39). 

Fig. 10.21. Diastereoselective reduction of /3-hydroxyketones to syn-configured 1,3-diols (Narasaka-Prasad reduction).

Diastereoselective reduction of /3-hydroxyketones to anti-configured 1,3-diols. 

LiInH4 is increased by the introduction of phenyl group(s) LiPhInH3 and LiPh2InH2 readily reduce aldehydes, ketones, acid chlorides, and even esters to the corresponding alcohols. Hydroxy ketones and diketones are reduced with lithium indium hydride to give meso-diols selectively. a-Hydroxy ketones and a-diketones are reduced to meso-1,2-diols with high diastereoselectivities, whereas the selectivities of /3-hydroxyketones and /3-diketones are less satisfactory.365... 

Reduction of the carbonyl group using DIBAL at low temperatures afforded the desired alcohol with complete diastereoselectivity. Deprotection yielded the protected a-hydroxyketone in good yield and with > 98% ee (Scheme 24). 

Cerium chloride (CeCl3 7H20) in the presence of Nal catalyzes the diastereoselective dehydration of P hydroxyketones and esters such as 4.8 to the corresponding a, (3-unsaturated compound 4.9. 

In earlier studies, we reported remarkable rate and diastereoselectivity enhancements in allyl- and crotylborations involving a-hydroxyketones,6 a-oxocarboxylic acids7 and fi-hydroxyaldehydes and ketones, We now wish to report that fi-allyldiisopropoxyborane reacts with (3-ketoacids to produce tertiary homoallylic 13-hydroxycarboxylic acids. The reaction presumably proceeds through a bicyclic transition state (Scheme 1) to yield the desired product in good yield (Table 1). 

The highly enantioselective and diastereoselective asymmetric Mannich-type reaction of N-phosphinoylimines (487) with hydroxyketone (488) was catalysed by (S,S) linked BINOL, affording N-phosphinylated aminoalcohols (489). The observed complementary anti-selectivity, in combination with the facile removal of diphenylphosphinoyl group make this reaction synthetically attractive (Figure 92). ... 

Dioh. Acyclic 2-hydroxyketones and a-diketones undergo ultrasound-assisted reduction with LilnH (prepared from InBrj and LiH) in a highly diastereoselective manner. For example, benzoin is converted to the meso-diol exclusively. 

Recently, Flowers and co-workers proposed the use of the Sml2-H20-Et3N system for the reduction of p-hydroxyketones to the corresponding 1,3-diols. In all cases, the reaction occurs without any by-product formation and with excellent diastereoselectivity with the syn-diol as the major isomer (Scheme 8.13).15... 

Replacement of the aldehyde component of the aldol reactions with imines (either preformed or generated in situ) opened access to synthetically relevant P-amino- and syn-P-amino-a-hydroxyketones, which were obtained in moderate to good yields (up to 80%) and good to high diastereoselectivity and enantioselectivity (Scheme 8.11 Equation b ee-value up to 97%) [36]. As far as catalyst recycling is... 

Of course, a systematic comprehensive analysis of all literature published on the asymmetric cross aldol reaction goes beyond the purpose of this chapter, thus attention is focused on the best achievements reported for catalysts working under neat conditions in the presence of an aqueous phase (Scheme 1.2). Generally, zzzZz-diastereoselectivity is observed, while the opposite. sv/z-diaslcr-eoselectivity is often exhibited by oc-hydroxyketones. 

The selectivity (>99 1) is astounding butmade all the more impressive when we see that substrates with other chiral centres react very selectively too. So, both syn and anti P-hydroxyketones 168 and 170 give excellent anti diastereoselection. But this reaction can be as fickle as frustrated chemists rather expect - compound 172 does not react at all under these conditions while compound 173 reacts as expected. 

Keck et al. have used the lactone annulation procedure developed in their laboratory to install the lactone moiety by reaction of the lithium enolate of methylacetate with a (3-acetoxy aldehyde [108]. The other key steps include a diastereoselective Lewis acid mediated (Z)-crotylstannane aldehyde addition, a highly selective Lewis acid promoted Mukaiyama aldol reaction and an arari-selective Sml2 reduction of a p-hydroxyketone. The preparation of the C8-C15 fragment of (-)-pironetin started with the chelation-controlled addition of (Z)-crotyl tri-n-butylstannane to the (3-benzyloxy-aldehyde 153 in the presence of TiCU [109] to give the... 

Our existing route to the C10-C16 aldehyde fragment was clearly not appropriate for this new plan. Reduction of )3-hydroxyketone ent-26 with triacetoxyborohydride proffered a 1,3-diol intermediate (ent-27) with no obvious means available for distinguishing the two secondary carbinol moieties. On the other hand, the Evans-Hoveyda variant of the classical Tishchenko reduction would provide a method to effect diastereoselective reduction of ent-26 while at the same time allowing differentiation of the C13 and C15 hydroxyl groups. According to the Evans-Tishchenko reduction protocol, a /3-hydroxyketone 80 is treated with an aldehyde and a catalytic quantity of Sml2 (Scheme 14). Transfer of hydride from the... 

The most important contributions to the synthesis of the optical isomers of zeaxanthin have been achieved by the research group of F. Hoffmann-La Roche. From 6-oxoisophorone (56) as starting material, the chiral centre was introduced by an enantioselective fermentative reduction of the double bond with baker s yeast. Subsequent diastereoselective and regioselective reduction of the resulting diketone 57 gave a mixture of epimeric hydroxyketones, (3R)-58 and (3S)-58, which could readily be separated by Craig distribution (Scheme 14). 

Radical reactions in synthetic organometallic chemistry are rare but gain increasing importance. A recent example demonstrated that molybdenum difluoroboroxycarbenes may serve as radical precursors and allow to generate acyl radicals under mild reaction conditions. [91] Coupling of molybdenum difluoro-boroxycarbene 84 to vinylketone 85 and aldehyde 86 leads diastereoselectively to vr -P-hydroxyketone 87 (Scheme 38). Using the chiral aldehyde 88 a diastereofacial selectivity of more than 99% d.e. was observed for the formation of 89 (Scheme 39). 

The method could be applied to reduce 1,3-diaryl-1,3-diketones to 1,3-diaryl-1,3-propanediols in 93-100% yields and high ee s (>97% ee). The products were obtained as a mixture of diastereomers (81 19 - 90 10) and could be purified by recrystallization.Symmetrical 2-substituted-l,3-diaryl-1,3-diketones underwent reductive desymmetrization to give rise to /8-hydroxyketones (45-97% yields) in high ee s (>91% ee) and diastereoselectivities (dr>99 l) (eq 32). Unsymmetrical 2-alky 1-3-ary 1-1,3-diketones were reduced chemoselectively at the aryl-substituted carbonyl group to yield 2-alkyl-3-aryl-3-hydroxyketones (41-48% yields) in high ee s (>95%) and diastereoselectivities (( >97 3). The yields could be further improved by the addition of a stoichiometric amount of sodium methoxide in a one-pot reaction. 1,4-Diaryl-1,4-butanediones were reduced to enantiopure l,4-diaryl-l,4-butanediols (60-100% yields), which... 

Gatling, S.C. Jackson. J.E. Reactivity control via dihydrogen bonding Diastereoselection in borohydride reductions of a-hydroxyketones. J. Am. Chem. Soc. 1999, 121, 8655. 

As key intermediate for the introduction of chirality in positions 3 and 6 of 133, hydroxy-2,6,6-trimethylhex-2-en-l-one 19 was chosen this is readily available from the hydroxyketone (18) [24]. Reaction of 18 with mesyl chloride gave the corresponding mesylate which, on treatment with tetrabutylammonium acetate, was converted into the acetoxyketone 20 with complete inversion of configuration. The introduction of the second chiral centre was achieved by diastereoselective epoxidation of the protected hydroxyketone 27 with dimethyl sulphonium methylide, yielding the crystalline epoxide 22. This was readily transformed into the protected hydroxy-a-cyclocitral (23). Subsequent chain lengthening by a Horner-Emmons reaction gave a nitrile which, on treatment with MeLi, was converted into the crystalline C 13-hydroxy ketone 24 in excellent optical yield. The compounds mentioned were identified by m.p, [a] , IR, H-NMR, X-ray, CD and MS [24],... 

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