Dithiane, anions, conjugate addition

Michael addition. ° The synthesis of the naturally occurring benz[a]anthraquinones, X-14881 (64 R = Me) and ochrotnycinone (R H) utilizes 2-phenyldithiane anion (Scheme 38), while 11-deoxydauno-mycinone was prepared using 2-methyldithiane. The formation of bicyclo[3.3.0]oct-l(5)-ene-2,6-dione utilizes 2-(2,2-diethoxyethyl)-l,3-dithiane anion. Conjugate addition of the highly stabilized anion (65) occurs readily with enamide (66), whereas the related acyclic anion (67) appears to be less reactive than the cyclic analog (Scheme 39). Conjugate addition of lithiated a-alkylthio monosulfoxide provides a new route for the synthesis of dihydrojasmone. ... 

Acyl Anion Conjugate Additions. The lithio reagent readily undergoes 1,4-addition to unsaturated substrates (eq 6), in direct contrast to the corresponding 2-lithio-2-trimethylsilyl-l,3-dithiane, which is a poor Michael donor. The initial Michael adducts can also be alkylated to provide highly functionalized products. Very good levels of diastereoselectivity have been observed in the 1,4-addition and enolate alkylations of cyclic enoates (eq 7)2 and acyclic enones (eq 8). ... 

The conjugate addition of aryl dithiane anions to 2-butenolide has been examined as a route to ( )-podorhizol and ( )-isopodophyllotoxone (78JOC985). The dithiane of piperonal (802) was deprotonated and reacted with 2-butenolide to give the lactone anion which was trapped in turn with 3,4,5-trimethoxybenzaldehyde to afford a mixture of the threo and erythro aldol products (803). Desulfurization of the erythro dithiane with Raney nickel gave ( )-podorhizol (804 Scheme 188). 

The realization of the principle of umpolung , in which reactivity at a normally electrophilic site is inverted to that of a nucleophilic species,161 has resulted in the development of numerous masked acyl anion equivalents for carbon-carbon bond formation.162 The use of masked acyl anion equivalents for conjugate additions was made possible by several observations. First, Stork reported that protected cyanohydrins afforded preferential kinetic 1,4-addition with ot, 3-enonesl6b and second, Brown reported that preferential kinetic 1,4-addition of 1,3-dithianes was effected by the use of HMPA.163... 

Stereoselective intramolecular conjugate addition reactions (Scheme 4) of dithiane anions tethered to an a,/ -unsaturated nitrile have been developed to advantage for the synthesis of axially substituted indolizidines and quinolizidines.81 The control of axial nitrile orientation by a peg-in-a-pocket template effect has been discussed. 

Dithiane anions undergo intramolecular conjugate addition to die a,/ -unsaturated nitrile moiety in (150) to produce indolizidine and quinolizidine (151), in which the nitrile group exhibits a strong, thermodynamic preference for die axial orientation.108... 

We have met the acyl anion or d1 synthon in chapter 23 but for the disconnection 8 on 1,4-diketones we need a d1 reagent that will do conjugate additions on enones such as 36. Sadly that eliminates dithians from consideration as they are too basic (hard) and tend to add direct to carbonyl groups. 

Though the anion of dithiolane decomposes as described in the chapter and cannot be used as a d1 reagent, the example shown here works well without any decomposition. Explain and comment on the regioselectivity of the reaction. Anions of dithianes are notorious for preferring direct to conjugate addition. 

Diethoxyphosphinyi-2-buten-4-oli reacts with lithiated dithianes followed by an intermolecular Wittig-Homer reaction to produce fused y-lactones (equation 37). The reaction of 2-lithio-l,3-di-thianes with nitroarenes gives 2- or 4-[(l,3-dithian)-2 -yl]cyclohexa-3,5(or 2,5-)-diene-l-nitronate compounds (conjugate addition products), free nitroarene r cal anions (redox products), 1,3-dithianes and 2,2 -bis( 1,3-dithianes). ... 

The conjugate addition of the anion of 1,3-dithiane to a conjugated ketone, followed by unmasking of the aldehyde, produces a 1,4-keto-aldehyde, e.g. 15, the thiophene derived from which has a 2,4-disubstitution pattern, as is demonstrated in Scheme 13 [27],... 

The anions of dithianes, which are masked aldehydes, also add to enones and unsaturated esters, though the selectivity for 1,4-addition to enals is poorer. Selectivity for conjugate addition is improved by the addition of HMPA, which acts to complex lithium and separates the ion pairs (Figure 20.31). 

---