Chloroacetoxylation synthesis

While the process works for a great number of conjugated dienes, a few, such as 1,3-cyclopentadiene and those acyclic dienes that have an oxygen substituenl in an allylic position, did not give a chloroacetoxylation product.23 Control of the 1,4-relative stereochemistry and preparation of compounds analogous to the title compounds also work for acyclic dienes,23 5 This process was used to obtain remote stereocontrol in acyclic systems and applied to the synthesis of a pheromone.5... 

The chloroacetoxylation approach was also used for the stereoselective synthesis of tropine and pseudotropine employing a sulfonamide as nucleophile [80]. By the same approach, scopine and pseudoscopine were synthesized (Scheme 8-23) [81]. 

An S 2 copper-catalyzed nucleophilic substitution of the chloride in a cyclic chloroacetate by butylmagnesium bromide was employed in a synthesis toward perhydrohistrionicotoxin [Eq.(47)] [79]. Histrionicotoxins are found in South American dart-poison frogs of the Dendrobatid family. Palladium-catalyzed chloroacetoxylation of 2-substituted diene 68 gave a highly regio- and stereoselective 1,4-addition product where the chloride ends up in the 1-position. Copper-catalyzed reaction of the chloroacetate 69 with butylmagnesium... 

A stereocontrolled synthesis of polyfused ring systems utilizing the chloroacetoxylation approach is shown in Scheme 8-26 [95]. Sequential ally lie substitution of the chloroacetates afforded key intermediate 75. Subsequent palladium-catalyzed tandem metalloene/Heck insertion reactions gave polyfused ring systems 76 and 77. 

Additional examples where chloroacetates from acyclic dienes have been used include the synthesis of pentadienylamines [96], dienesulfones [97], c-methylenecyclopentenones [98], marine natural products [99], and the carpenter bee pheromone [82]. Some additional Synthetic applications of the chloroacetoxylation of cyclic dienes are given in Refs. [100-104]. Chloroacetoxylation was also used to prepare a number of starting materials for the intramolecular reactions discussed in this chapter. 

The chloroacetoxylation approach was also used for the stereoselective synthesis of tropine and pseudotropine employing a sulfonamide as the nucleophile [91]. Using the same approach, scopine and pseudoscopine were synthesized (Scheme 11.26) [92]. The chloroacetoxylation of 6-benzyloxy-l,3-cycloheptadiene was highly diastereoselective, and produced only the diastereoisomer 73 shown. Transformation of the chloroacetate 73 to 74 was realized by a Pd(0)-catalyzed substitution of the chloride by a sulfonamide, which occurred with retention of configuration. Reaction of the aUyUc chloride with the sulfonamide salt in DMSO-water at 80 °C afforded the inversion product 75. Subsequent stereoselective epoxidation, cyclization, and deprotection afforded the target molecules scopine and pseudoscopine. 

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... 

The high regio- and stereocontrol of the chloroacetoxylation reaction makes it useful in organic synthesis. This was shown in a formal total synthesis of ( )-Pancracine, in which a chloroacetoxylation of 1,3-cyclohexadiene and subsequent Pd(0)-catalyzed amination of the chloroacetate 88 with p-methoxybenzylamine (PMB-NH2) to afford aminoacetate 89 were utilized (Scheme 11.31) [107]. The latter compound was converted to 90, which was subsequently transformed to ( )-Pancracine by a stereoselective radical cyclization. 

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