Dihydroxylations aldehyde olefinations

SCHEME 13.51 Schreiber s synthesis of (—)-hikizimycin featuring a two-directional chain-elongation strategy involving an aldehyde olefination and face-selective dihydroxylations. 

Oxidative cleavage of the olefin is accomplished by the method of ijemieux-Johnson.12 The process begins with dihydroxylation of the double bond using osmium tetroxide (see Chapter 3)T leading to a cis diol and osmium(VI) oxide. The added periodate has two functions first, it reoxidizes the osmium(VI) species to os-mium(VIII), but it also cleaves the glycol oxidatively to an aldehyde. This is the reason for utilizing several equivalents of periodate. The periodate is in turn reduced from the +VH to the +V oxidation state. 

An orf/io-directed lithiation allows the conversion of 25 to aryl iodide 40. Reductive ether formation of aldehyde 40 with crotyl alcohol yields compound 41. Intramolecular Heck reaction of 41 affords a mixture of the olefins 42 and 43. The undesired alkene 42 can be isomer-ized quantitatively to the desired enol ether 43 with Wilkinson s catalyst. Sharpless dihydroxylation ee 94 %) of the enol ether 43 provides lactol 44, which is oxidized directly to lactone 45. Finally, the pyridone-O-methyl ester is cleaved under acid conditions (45 — 7). 

As a Chiral Starting Material in L Amino Sugar and l-Nucleoside Synthesis. The recent improved synthetic access to the (45)-aldehyde has facilitated non-natural sugar and nucleoside synthesis. Asymmetric synthesis of several L-amino sugars has been reported. Julia olefination of the (45)-aldehyde with the sulfone afforded the key olefin intermediate as a 4 1E/Z mixture, which was elaborated via Sharpless asymmetric dihydroxylation (SAD) and protecting group interchange to afford the protected 2-deoxy-2-amino-L-mannopyranose (eq 4). ... 

Optically active 1,2-diol units are often observed in nature as carbohydrates, macrolides or polyethers, etc. Several excellent asymmetric dihydroxylation reactions of olefins using osmium tetroxide with chiral ligands have been developed to give the optically active 1,2-diol units with high enantioselectivities. However, there still remain some problems, for example, preparation of the optically active anti-1,2-diols and so on. The asymmetric aldol reaction of an enol silyl ether derived from a-benzyloxy thioester with aldehydes was developed in order to introduce two hydroxyl groups simultaneously with stereoselective carbon-carbon bond formation by using the chiral tin(II) Lewis acid. For example, various optically active anti-a,p-dihydroxy thioester derivatives are obtained in good yields with excellent diastereo-... 

Spectacular enantioselection has been observed in hydrogenation (cf. Section 2.2) [3] and hydrometallation of unsaturated compounds (cf. Section 2.6) [4], olefin epoxidation (cf Section 2.4.3) [5] and dihydroxylation (cf Section 3.3.2) [6], hydrovinylation (cf Section 3.3.3) [7], hydroformylation (cf Section 2.1.1) [4a, 8], carbene reactions [9] (cf Section 3.1.10), olefin isomerization (cf Section 3.2.14) [10], olefin oligomerization (cf Section 2.3.1.1) [11], organometallic addition to aldehydes [12], allylic alkylation [13], Grignard coupling reactions [14], aldol-type reactions [15], Diels-Alder reactions [12a, 16], and ene reactions [17], among others. This chapter presents several selected examples of practical significance. 

The strategy eluded to in Scheme 7.3.6 is elaborated upon in Scheme 8.10.3 and involves the allyl sugar derivative shown. Conversion of the allyl group to the phosphonium salt is accomplished in eight steps. Wittig olefination with the illustrated protected aldehyde provides the cis olefin which is dihydroxylated under asymmetric conditions and selectively protected as the PMB ether. 

The final strategy, eluded to in Scheme 7.3.8, further exemplifies the range of C-disaccharides available from a single polyol when utilizing different methods of cyclizations. As shown in Scheme 8.10.7, the easily prepared aldehyde is coupled to the phosphonium salt described in Scheme 8.10.3. The resulting cis olefin was asymmetrically dihydroxylated and the resulting diol... 

Moving forward from 59, six steps were required to convert this compound to 60. Vicinal dihydroxylation of the olefin was followed by oxidative cleavage of the intermediate diol using lead tetraacetate. Reductive amina-tion of the resulting aldehyde with methylamine, followed by acylation of the intermediate secondary amine gave the desired carbamate. Swern oxidation of the secondary alcohol, followed by enol ether formation gave 60. Elimination of -toluenesulfinic acid from 60 provided 61. Oxidation of this dienol ether to dienone 62 was followed by release of the secondary amine, followed by a conjugate addition reaction to establish the critical C-N bond. The remainder of the synthesis followed known chemistry. The mixture of enones 63 was converted to codeinone (35), codeine (3) and then morphine (1). 

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