Stereoselective synthesis chlorination

An unprecedented one-pot stereoselective synthesis of 2-azetidinone P-chlorinated allylic alcohols 23, which can also be considered as functionalized allylsilanes, has been developed, by tin(IV) chloride-mediated reaction of propargyltrimethylsilane and 4-oxoazetidine-2-carbaldehydes <02CEJ1719>. An explanation for the formation of P-chlorovinyl alcohols involves a stepwise process with the chlorination proceeding via a silicon stabilized carbocation. 

The oxidative chlorination-cyclization processes developed for the stereoselective synthesis of 373 and 374 (see Section 4.05.9.1.1) can be applied for the synthesis of other isothiazolidinones through a methodology providing C-N bond formation <20050L5067>. 

A very elegant stereoselective synthesis of juvenile hormone has been achieved by Johnson and co-workers,who employed the olefinic ketal Claisen reaction to great advantage. Thus, the hydroxy-ester (15), on treatment with the olefin-ketal (16) in acidic medium was converted into the ester (17). Sodium borohydride reduction to the corresponding allylic alcohol and a second Claisen-reduction sequence as described above yielded the trienol-ester (18). Chlorination under Sni conditions and selective reduction of the resultant primary allylic chloride produced the well-known triene-ester (19) which was converted to juvenile hormone (11). 

In 2002, Cavaleiro et al. [38] developed the stereoselective synthesis of glycoconjugated isoxazoUdine-fused chlorines (potential photosensitizers in photodynamic cancer therapy) by 1,3-dipolar cycloadditions of meso-tetrakis(pentafluorophenyl)porphyrin (83) with glycosyl nitrones 41-43 and 84. In all cases of sugar moieties, the configuration of the major products 85 indicated an endo addition, as shown in Fig. 18. 

Another unique methodology for the highly stereoselective synthesis of the chlorinated peptides has been developed by Zakarian and co-workers (Scheme 43.51). Their method has culminated in the asymmetric total synthesis of neodysidenin 291. The new methodology for the stereoselective installation of chlorinated functionality relies on the highly diastereocontrolled radical assembly between a halogenated carbon, such as BrCCl3,... 

All other methods for obtaining bacteriochlorins are by partial synthesis from porphyrins, chlorins or chlorin derivatives. The bacteriochlorin is thereby produced by reactions which occur at the peripheral /J-C — C double bonds of the higher unsaturated systems. The main problem of these syntheses is the lack of regio- and stereoselectivity because three or four C —C double bonds, which are present in the starting products may be attacked, so that rcgio-and stcreoisomcric products can be formed. 

A three-step reaction sequence starting from /3-amino alcohol 212 has been utilized in the synthesis of 2-cyanoazetidine (Scheme 42) <2002TA297, 2006SL78>. The A-benzyl-substituted /3-amino alcohol was first N-cyanomethylated to give the corresponding A-benzyl-A-cyanomethyl /3-amino alcohol 213. The latter compound was stereoselectively transformed into chlorinated amine 214 using thionyl chloride. An intramolecular alkylation of... 

Furthermore, much work has been devoted to the development of stereoselective methods for preparing terminally functionalized 3,5-dihydroxy carboxylates. Muller et al. developed a new chemoenzymatic synthesis of the chlorinated 5-hydroxy-3-keto ester as the precursor for the dihydroxy hexanoate [169, 170]. The diketo ester is reduced exclusively in the C5 position by NADP+-dependent ADH from L. kefir or L. brevis. NADPH is regenerated by an excess of isopropanol by the same enzyme [171, 172] (Fig. 43). High concentrations of isopropanol are... 

Cyclopentanone annelation (10, 139-140) - The iterative cyclopentenone anne-lation has been extended to a synthesis of hirsutic acid (7) starting with the ester I. This alkene surprisingly does not react with chloromethylketene, but does react stereoselectively with dichloroketene to give 2 as the major product One of the chlorine atoms was replaced by methyl by treatment with (CH,) CuLi (3 equiv. ) and then with CH,I and HMPT. Ring... 

Cross aldol reaction between two different aldehydes and/or ketones without prior activation or protection should provide a straightforward methodology for the synthesis of aldols, Mahrwald recently reported that treatment of aldehydes with TiCU and NEta (or TMEDA) gives rise to syn- do reaction in good yields (Eqs 38 and 39) [141], This method was extended to the aldehyde-ketone cross aldol reaction catalyzed by TiCU [142], an advantage of which is that reaction occurs at the more encumbered a-position of unsymmetrical ketones, as illustrated in Eqs (40) and (41) [143], The use of aliphatic aldehydes instead of PhCHO usually reduced stereoselectivity. When TiCU was replaced by a catalytic amount of BuTi(0-/-Pr)4Li, the aldol reaction was followed by the Tischenko reaction [144], Methyl vinyl ketone trimerized to give a chlorinated cyclic product with TiCU [145],... 

The synthesis of ( )-Epibatidine 76b and analogs thereof was realized by regioselective chloroacetoxylation of 2-aryl-l,3-cyclohexadiene [99]. Subsequent stereoselective substitution of the chlorine atom by tosylamide with either... 

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