1.3- Dienes 1.4- chloroacetoxylation

The chloroacetoxylation is a quite general reaction and works well with a number of conjugated dienes. Some additional examples are given in Scheme 6 and in equations 15 and 16. The reaction is highly syn stereoselective for a number of cyclic dienes tried. Also, for acyclic dienes the reaction leads to a 1,4 syn addition and the reaction takes place with good stereospecificity (94 -96% syn). Thus (Zi,.E)-dienes give the R R isomer whereas (E,Z)-dienes produce the R S isomer (equations 15 and 16). The reaction has also been extended to include other carboxylic acids than acetic acid (chloroacyloxylation)33d. 

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). 

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... 

Nystrom, J. E. Rein, T. Backvall, J. E. 1,4-Functionalization of 1,3-dienes via Pd-cata-lyzed chloroacetoxylation and allylic animation l-acetoxy-4-diethylamino-2-butene and l-acetoxy-4-benzylamino-2-butene. Org. Synth. 1993, Coll. Vol. VIII, 9-13. 

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]. 

Chloroacetoxylation of 6-benzyloxycyclohepta-1,3-diene was highly diastereoselective and produced only the diastereoisomer 65 shown. Transformation of the chloroacetate 65 to 66 was realized by a Pd(0)-catalyzed substitution of the chloride by a sulfonamide, which occurs with retention of configuration. Reaction of the allylic chloride with the sulfonamide... 

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... 

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. 

Procedure A 1s very effective for a range of acyclic and cyclic conjugated dienes. The major side reaction in the chloroacetoxylation Is Diels-Alder addition of p-benzoquinone to the diene. The purpose of the pentane phase 1s to ensure a low concentration of diene In the acetic acid phase, which depresses the Diels-Alder reaction. The reaction can also be performed without the pentane phase with slow addition of the diene using a syringe pump. 

Scheme 8-20 Functionalization of conjugated dienes via Pd-catalyzed 1,4-chloroacetoxylation and allylic substitution.

---