Benzothiazolyl sulfones

The stereoselectivity of the Julia olefinations has been well documented, and as a rule of thumb, a-lithioalkyl benzothiazolyl sulfones deliver cz s-olcfins and a-lithiobenzyl benzothiazolyl sulfones trans-olefins <05SL289>. However, unexpected high cw-selectivity... 

Mechanistic and stereochemical aspects of the reaction of benzothiazolyl sulfones with aldehydes were thoroughly analyzed in the JuUa works [8,9] and in the Blakemore review [98]. 

The Julia-Julia coupling reaction has been extended to sugar derived lactones to furnish methylene exoglycals in good yields as exemplified by the conversion of lactone 188 to exomethylene derivative 190 upon treatment with lithiomethyl benzothiazolyl sulfone from 189 <05SL520>. This approach serves as an alternative to the Tebbe reagent commonly used... 

Herboxidiene 154 shows potent herbicidal activity and up-regulates gene expression of low density lipoprotein receptors. Kocienski and coworkers synthesized herboxidiene 154 successfully from two key fragments using a modified Julia olefmation based on the benzothiazolyl sulfone activator. The yield was 81% with excellent selectivity 0E Z = 91 9) by one-port reaction between sulfone 152 and the aldehyde 151. 1-Phenyl-1/f-tetrazolyl sulfone 149 was used as activator in the synthesis of the C -Cio oxane fragment 151. Addition of KHMDS to the mixture of sulfone 149 and aldehyde 148 in 1,2-dimethoxyethane at -60 °C gave a 93% yield of the alkene 151 with good stereoselectivity (E Z = 93 1). 

W alkyl, aryl, ester, CN, S02Ph Scheme 7 Fluorinated benzothiazolyl sulfone synthesis... 

Tributyltin-1,3-dienes have been synthesized from tributyltin substituted benzothiazolyl sulfones and aldehydes via a Julia olefination reaction. The selectivity of the process proved higher in the presence of KHMDS as base (Scheme 96) [190]. 

Systematic Studies on Benzothiazolyl, 2-Pyridyl and Phenyltetrazolyl Sulfones... 

Juha and coworkers conducted extensive studies [7-9] of the reaction of benzothiazolyl and pyridyl sulfones, with emphasis given to the former, and selected carbonyl compounds, mainly aldehydes. Some pyrimidyl sulfones were also examined. A large number of experiments were siunmarized in ta-... 

Representative results for the reaction of benzothiazolyl and pyridyl sulfones with unbranched aliphatic and benzyhc aldehydes are shown in Table 12. Anions were generated in situ with LDA (BT sulfones) or separately using n-butyllithium (Pyr sulfones). The yields vary between low and 95%. High stereoselectivities with -isomers favored were recorded for aromatic aldehydes. 

Benzothiazolyl anions were generated in situ (method B) or pre-formed with LDA (method A) for Pyr sulfones method A with n-butyllithium was used. High yields were obtained for some allyhc and propargylic sulfones. In general, relatively high stereochemical preferences were noted. 

In 1998 Kocienski et al. [10] reported the results of systematic studies on the reaction of selected heterocychc sulfones with carbonyl compoimds. The best results were obtained using l-phenyl-lH-tetrazol-5-yl (PT) sulfones. hi the first series of experiments, the representative PT sulfone 241 (Scheme 74) was compared with its benzothiazolyl (BT) counterpart. The comparison was... 

Table 12 Reaction of benzothiazolyl and pyridyl sulfones with unbranched aliphatic and benzylic aldehydes according to Scheme 73 (BT sulfones—under Barbier conditions, Pyr—sulfones with premetalation)...

The reaction involves several steps. The absolute and relative rate of the separated steps depend upon the nature of the heterocyclic (aromatic) portion of the sulfone. Reactions of benzothiazolyl- and pyridylsulfones were compared by Julia. However, there are only a few direct mechanistic comparisons with other sulfones. 

The olefination based upon the reaction of benzothiazolyl- and phenyltetra-zolyl sulfones with carbonyl compounds is widely used in the target-oriented synthesis. In order to illustrate the reaction scope, yields and stereoselectivities, in this section we present selected examples of these reactions. The examples include reactions of saturated sulfones with saturated aldehydes, saturated sulfones with o, j6-unsaturated carbonyl compounds, -unsaturated sulfones with saturated aldehydes, and /l,y-imsaturated sulfones with a, -unsaturated aldehydes. The emphasis is given to recent work. A complete account of earlier applications of the modified Julia reaction has been given in the Blakemore review [98]. 

The sulfones prepared can be metallated with KHMDS at low temperature and, unlike the related benzothiazolyl and 1-phenyl-li/-tetrazolyl systems, show excellent stability with little tendency to self-condense. Selectivities observed in olefinations are good to excellent in favor of the Z-isomers (eq 3). 

The second recent variant, developed by Julia and co-workers, avoids reductive elimination altogether and provides a remarkable one-pot connective synthesis of alkenes. The procedure, illustrated in eq 14, involves condensation of an aldehyde or ketone with a lithiated benzothiazolyl alkyl sulfone to give an adduct which first cyclizes and then fragments with extrusion of sulfur dioxide, benzothiazolone (which then tautomerizes to 2-hydroxybenzothiazole), and the alkene. Generally a mixture of ( )- and (2)-alkenes is obtained, hut in stericaUy hindered substrates the ( ) isomer can be obtained selectively. The same reaction has been observed with the pyridinyl sulfone analogs, in which case the separable /8-hydroxy sulfone intermediates undergo stereospecific and elimination to the corresponding alkene. 

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