Hydroxylation stereospecific, diols

The synthesis of the key intermediate aldehyde 68 is outlined in Schemes 19-21. The two hydroxyls of butyne-l,4-diol (74, Scheme 19), a cheap intermediate in the industrial synthesis of THF, can be protected as 4-methoxybenzyl (PMB) ethers in 94% yield. The triple bond is then m-hydrostannylated with tri-n-butyl-tin hydride and a catalytic amount of Pd(PPh3)2Cl238 to give the vinylstannane 76 in 98 % yield. Note that the stereospecific nature of the m-hydrostannylation absolutely guarantees the correct relative stereochemistry of C-3 and C-4 in the natural product. The other partner for the Stille coupling, vinyl iodide 78, is prepared by... 

The stereospecific reduction of a 2-butyne-l, 4-diol derivative and silver( I)-mediated cyclization of the resulting allene were successively applied to a short total synthesis of (+)-furanomycin 165 (Scheme 4.42) [68], Stereoselective addition of lithium acetylide 161 to Garner s aldehyde in the presence of zinc bromide afforded 162 in 77% yield. The hydroxyl group-directed reduction of 162 with LiAlH4 in Et20 produced the allene 163 stereospecifically. Cyclization followed by subsequent functional group manipulations afforded (+)-furanomycin 165. 

From extensive analysis of recombinant proteins, and the crystal structure of A. thaliana protein, detailed reaction mechanisms have been proposed. The ANS reaction likely proceeds via stereospecific hydroxylation of the leucoanthocyanidin (flavan-3,4-cA-diol) at the C-3 to give a flavan-3,3,4-triol, which spontaneously 2,3-dehydrates and isomerizes to 2-flaven-3,4-diol, which then spontaneously isomerizes to a thermodynamically more stable anthocyanidin pseudobase, 3-flaven-2,3-diol (Figure 3.2). The formation of 3-flaven-2,3-diol via the 2-flaven-3,4-diol was previously hypothesized by Heller and Forkmann. The reaction sequence, and the subsequent formation of the anthocyanidin 3-D-glycoside, does not require activity of a separate dehydratase, which was once postulated. Recombinant ANS and uridine diphosphate (UDP)-glucose flavonoid 3-D-glucosyltransferase (F3GT, sometimes... 

In the achiral species 19, 20 and 21 the (R)- and (S)-1,2-propanediol binding modes are equivalent and no preferred retention or loss of the heavy oxygen isotope should be expected, even upon stereospedfic migration. This has been confirmed experimentally, i.e., about 50% of the 18O was retained in all three cases. In the chiral specimens 22, 23, 24 and 25, however, stereospecific migration of the unlabelled hydroxyl group should lead to chirally labelled geminal diols. Such a process should be preferred by the substrates 23 and 25 (Fig. 18). 

Both complexes are used in the hydroxylation of double bonds via diacetates or dibenzoates of vicinal diols. The reaction is stereospecific. In anhydrous medium (the Privost reaction [783]), the reaction takes place in the anti mode. In the presence of water (the Woodward modification [783]), the reaction results in a syn addition. The mechanisms of both reactions are shown in the section Hydroxylation of Alkenes and Cycloal-kenes in Chapter 3 see equation 78). 

Asymmetric dihydroxylation of trifluoromethylalkenes is also useful for construction of enantio-enriched trifluoromethylated diols usable for trifluoromethylated amino acids with chiral hydroxyl group. Thus, Sharpless AD reaction of 16 provides diol 17 with excellent enantioselectivity. Regioselective and stereospecific replacement of the sulfonate moiety in 18 with azide ion enables the introduction of nitrogen functionality. A series of well-known chemical transformation of 19 leads to 4,4,4-trifluorothreonine 20 (see Scheme 9.6) [16]. Dehydroxylative-hydrogenation of 21 by radical reaction via thiocarbonate and subsequent chemical transformation synthesize enantio-enriched (S)-2-amino-4,4,4-trifluoro-butanoic acid 22 [16]. Both enantiomers of 20 and 22 were prepared in a similar manner from (2R,3S)-diol of 17. 

It has been noted in Section 4.4.1.1 that naphthalene dioxygenase from a strain of Pseudomonas sp. also carries out enantiomeric monooxygenation of indan and dehydrogenation of indene (Gibson et al. 1995), and the stereospecific hydroxylation of (R)-l-indanol and (S)-l-indanol to rfs-indan-l,3-diol and trans (lS,3S)-indan-l,3-diol (Lee et al. 1997) the indantriols are also formed by further reactions. Essentially comparable reactions have been observed with Rhodococcus sp. strain NCIMB 12038 (Allen et al. 1997). 

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