Heck reaction decalins

The palladium-catalyzed arylation and alkenylation of olefins, which were first discovered in the 1970 s by Heck (7,2) and Mizoroki (3) and have been often called the "Heck reaction", are versatile synthetic means for making a carbon-carbon bond. These reactions have been extensively used for organic synthesis during the past two decades (4-7). However, no reports on the "asymmetric Heck reaction" have been appeared until very recently. Shibasaki reported an asymmetric intramolecular cyclization of alkenyl iodides to give c/j-decalin derivatives of 80-91% ee (8-10). Overman reported an intramolecular cyclization of alkenyl triflate, giving a chiral quaternary carbon center of 45% ee (77). We report herein the first example of intermolecular asymmetric Heck-type arylation of cyclic olefins catalyzed by (7 )-BINAP-coordinated palladium complexes (Scheme 1) (12,13). 

The famous ligand BINAP controls an intramolecular Heck reaction to give decalin derivative... 

More common is use of intramolecular Heck reactions to fashion ckv-decalins. Several examples are found in our current program aimed at the total synthesis of complex cardenolides [14,15]. In a model study for a proposed synthesis of (-t-)-ouabagenin (48), trienyl triflate 45 was converted to pentacycle 47 in good yield (Scheme 6-8) [16]. The stereochemical outcome of this cyclization was rationalized by the preference for an eclipsed orientation of the two reacting bonds, which is readily achieved in a cyclization geometry (46), and led to the cis stereoisomer. This example also highlights the stability of... 

The famous ligand BINAP controls an intramolecular Heck reaction to give decalin derivatives with good enantiomeric excess. BINAP is the optically pure phosphine built into the palladium catalyst. The presence of silver ions accelerates the reaction as well as preventing double bond isomerization in the original substrate. This time the chiral ligand selects which double bond is to take part in the reaction. The vinyl palladium species is tethered to the alkene and can reach only the same face. The faces of the alkenes are diastereotopic but the two alkenes are enantiotopic and you must know your right from your left to choose one rather than the other. 

Figure 13.2 Enantioselective syntheses of cis-decalins using the desymmetrizing Mizoroki-Heck reaction of alkenyl iodides.

Ohrai, K., Kondo, K., Sodeoka, M. and Shibasaki, M. (1994) Effects of solvents and additives in the as3mmetric Heck reaction of alkenyl trillates catalytic asymmetric synthesis of decalin derivatives and determination of the absolute stereochemistry of (+)-vernolepin. J. Am. Chem. Soc., 116,11737 8. 

More recently, the Heck reaction has been used in cascade cyclisations, and under enantioselective conditions. For example, the intramolecular synthesis of decalin derivative 9 has been achieved in good enantiomeric excess, using an optically pure phosphine (Binap) as part of the palladium catalyst. ... 

Both intermolecular and intramolecular asymmetric Heck reactions are known. For the latter, an example is the desymmetrization of decaline systems (Scheme 5-38). ° In this case, JOSIPHOS (Figure 5-9) is a suitable ligand and gave the best enantioselectivities. 

Scheme 5-38. Asymmetric Heck reaction with decalines. ...

Sato Y, Nukui S, Sodeoka M, Shibasaki M. Asymmetric Heck reaction of alkenyl iodides in the presence of silver salts. Catalytic asymmetric synthesis of decalin and functionalized indolizidine derivatives. Tetrahedron 1994 50 (2) 371-382. 

Optically active cis-decalins can be obtained from substrates such as 4 by a Heck-type reaction with PdCl2/(R)-l (1 1) as the catalyst.8 Addition of various silver salts improves the yield and enantioselectivity. For cyclization of 4 to 5, the highest enantioselectivity was observed by use of Ag3P04 and CaC03 (2 equiv. of each) with 1 -methyl-2-pyrrolidinone (NMP) as solvent (60°). 

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