Homoallylic chlorohydrins

C-branched sugars or C-oligosaccharides are obtainable through indium-promoted Barbier-type allylations in aqueous media.151 Indium-mediated allylation of a-chlorocarbonyl compounds with various allyl bromides in aqueous media gave the corresponding homoallylic chlorohydrins, which could be transformed into the corresponding epoxides in the presence of a base (Eq. 8.62).152... 

Sequential nucleophilic and electrophilic alkylations of 1,3-dicarbonyl compounds with a trimethylenemethane zwitterion equivalent lead to [3 + 2]-annulation. The nucleophilic carbonyl alkylation step has been carried out via an indium-mediated allylation in water (Equation (30)).200 Indium-mediated allylation of a-chlorocarbonyl compounds with allyl bromides in aqueous media gives the corresponding homoallylic chlorohydrins, which can be transformed to allyloxiranes (Equation (31)).201 Allylation of the G3 position of the cephem nucleus has been accomplished by indium-mediated allylation reaction in aqueous media (Equation (32)).202... 

Hodgson et al. showed that a series of bis- and tris-homoallylic terminal epoxides underwent intramolecular cydopropanation to give a range of bicydic alcohols. A short asymmetric synthesis of sabina ketone based on this chemistry was demonstrated (Scheme 5.20). A practical advantage with this process is that the volatile epoxides can be replaced with readily available chlorohydrins, an extra... 

Chiral alkenyl and cycloalkenyl oxiranes are valuable intermediates in organic synthesis [38]. Their asymmetric synthesis has been accomplished by several methods, including the epoxidation of allyl alcohols in combination with an oxidation and olefination [39a], the epoxidation of dienes [39b,c], the chloroallylation of aldehydes in combination with a 1,2-elimination [39f-h], and the reaction of S-ylides with aldehydes [39i]. Although these methods are efficient for the synthesis of alkenyl oxiranes, they are not well suited for cycloalkenyl oxiranes of the 56 type (Scheme 1.3.21). Therefore we had developed an interest in the asymmetric synthesis of the cycloalkenyl oxiranes 56 from the sulfonimidoyl-substituted homoallyl alcohols 7. It was speculated that the allylic sulfoximine group of 7 could be stereoselectively replaced by a Cl atom with formation of corresponding chlorohydrins 55 which upon base treatment should give the cycloalkenyl oxiranes 56. The feasibility of a Cl substitution of the sulfoximine group had been shown previously in the case of S-alkyl sulfoximines [40]. 

Resin 60 was successively treated at -78 °C with n-BuLi, ClTi(NEt2)3, and benz-aldehyde in THF to afford the polymer-bound homoallyl alcohol 61. The cleavage of the linker group of 61 was achieved through treatment with ClC02CH(Cl)Me in CH2CI2 at room temperature. Thereby a mixture of chlorohydrins syn-57 and anti-57 in a ratio of 2 1 was obtained. These chlorohydrins were treated with DBU, which gave oxiranes trans-SS and cis-58 in a ratio of 2 1 in an overall yield of 34% based on sulfoximine 12. 

The stereochemical information is introduced by (J )-methyl p-toluenesulfoxide 110. This compound is deprotonated with lithium diisopropylamide and reacted with a-chloro methylacetate 109 to give a-chloroketone 111. This ketone when reacted with diisobutylaluminum hydride at —78°C gives (J )-chlorohydrine 112, whereas reaction of ketone 111 with diisobutylaluminum hydride and zinc chloride gives the corresponding (S)-chlorohydrine 113. Treatment of both chlorohydrines with potassium carbonate resulted in the formation of epoxides 114 and 116. These can now be reacted with either (Z)- or (T)-vinyl cuprates to give the desired homoallylic alcohols 115 and 117 in diastereomeric excesses around 90%. 

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