Palladium-catalyzed 1,4-chloroacetoxylation

An increased chloride ion concentration in the palladium-catalyzed oxidation of 1,3-cyclohexadiene resulted in a highly stereo- and regioselective 1,4-chloroacetoxylation35. The product selectivity was also high. Thus, palladium-catalyzed chloroacetoxylation afforded an 89% isolated yield of chloroacetate 29 which was >98% cis (Scheme 5). Only 1-2% of diacetate was observed in the crude product. 

Amino alkenols have been prepared by palladium-catalyzed chloroacetoxylation and allylic amination of 1,3-dienes. 1,4-Acetoxychlorination is stereospecific and cyclic dienes give an overall cis- 1,4-addition12. Acetoxychlorination of 6-acetoxy-l,3-cycloheptadiene afforded only one isomer as shown in equation 8. Sequential substitution of the allylic chloro group can occur with either retention or inversion, thereby allowing complete control of the 1,4-relative stereochemistry (equation 9). 

Palladium, benzylchlorobis(triphenylphosphine)-, trans-, 67, 86 Palladium-catalyzed aryl-aryl coupling, 66, 70 PALLADIUM-CATALYZED ALLYLIC AMINATION, 67,105 PALLADIUM-CATALYZED CHLOROACETOXYLATION, 67, 105 PALLADIUM-CATALYZED COUPLING OF ACID CHLORIDES WITH ORGANOTIN REAGENTS, 67, 86 PALLADIUM-CATALYZED COUPLING OF ARYL HALIDES, 66, 67 PALLADIUM-CATALYZED syn-ADDITION OF CARBOXYLIC ACIDS,... 

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... 

The chloroacetoxylation reaction is synthetically useful since the chloride can be substituted with either retention [Pd(0)-catalyzed reaction] or inversion (Sjv2 reaction) by a number of nucleophiles. In this way both the cis and trans isomers are accessible and have been prepared from a number of allylic acetates (Schemes 5 and 6). In a subsequent reaction the allylic acetate can be substituted by employing a copper- or palladium-catalyzed reaction. The latter reactions are stereo specific. 

The chloroacetoxylation proceeds via the same type of intermediate as that involved in the palladium-catalyzed 1,4-diacetoxylation, i.e. via a 4-acetoxy-l,2,3-(jr-allyl)palladium intermediate (cf. Scheme 8-7). The high selectivity for iinsymmetrical product formation (usually >98%) is remarkable. Since chloride is the stronger nucleophile of the two amions present (CI and AcO ), the 4-chloro-l,2,3-( r-allyl)palladium intermediate 60 is initially formed. However, the chloride in the 4-position is rapidly exchanged for acetate to give a more stable, jr-allyl intermediate 61, which leads to product. The presence of intermediate 60 was confiimed by its trapping by a faster oxidant (isoamyl nitrate) than benzoqiiinone (BQ), which furnished l,4-dichloroalk-2-ene [78,84], In the case of cyclohexa-1,3-diene, this product was c -1,4-dichlorocyclohex-2-ene [84]. 

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. 

Another example is based on the palladium-catalyzed 1,4-chloroacetoxylation methodology, where a common intermediate, by proper choice of reaction conditions, can be transformed into cis- or Irans-annulated products. ... 

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