SCIENCE & TECHNOLOGY
RHODIUM CATALYSIS IS ON A ROLL It's enabling regioselective and enantiospecific allylic substitutions, and more
a marked selectivity for forming the more highly substituted product. That is, sub stitution occurs predominantly at the site of the leaving group and with that group's original stereochemistry "The reaction has memory," Evans says. It maintains the regio- and stereochemical information of the leaving group.
"THE UNIQUE SELECTIVITY of the rhodium catalyst is presumably due to the electronic influence of the phosphites," Evans says. His studies suggest that the ATALYSIS BY TRANS ITION-METAL two isomeric forms erodes the original phosphite ligands cause the rhodium metal complexes ruled at the 37th Na regio- and stereochemical information held to bind to the ally! group in an tional Organic Chemistry Sym by the substrate. For this rea unsymmetrical mode, creat posium, held last June in Bozeson, allylic substitutions have ing a distorted rhodium-allyl man, Mont. Six of 14 speakers been most useful with sym complex that is stable under described new and better synthetic meth metrical substrates. the reaction conditions. This ods based on transition-metal catalysts. In 1998, Evans and gradu complex may be described Among them was P. Andrew Evans, a ate studentJade D. Nelson dis as a distorted ττ-allyl or enyl professor of chemistry at Indiana Univer covered that modifying the (σ + ττ) organorhodium inter sity, Bloomington. His group has been well-known Wilkinson cata mediate. The ability to use reexarnining rhodium-catalyzed allylic sub lyst makes allylic substitutions this intermediate in synthesis stitutions. In particular, his goal has been more discriminating than had has fascinated t h e Evans to control the regioselectivity of allylic sub been possible previously They group since they discovered stitutions for unsymmetrical substrates. found that in situ exchange of its unusual reactivity the phenyl ligands in the Wil Transition-metal-catalyzed allylic sub Although the exact nature kinson catalyst—the rhodium Ε VA N S stitutions offer ways to construct new car of t h e bonding between complex { ( Q H ^ P ^ R h C l bon-carbon and carbon-heteroatom bonds. rhodium and phosphite ligands is not with triorganophosphites {for example, The substitution increases molecular com entirely clear yet, it appears to prevent trimethylphosphite or P C O C H ^ } pro plexity because, typically, the incoming rapid isomerization of the rhodium-allyl group, or nucleophile, is more complex than duced a new catalyst. When this modified complex. "The complex does not isomercatalyst is used in alkylations of unsym the leaving group. The reactions would be ize relative to the rate of substitution, so metrical allylic carbonates, the reaction has even more useful if the substitution could that the memory of the orig be perfect: That is, the nucle inal bond between the car ophile would go to the same GENERAL bon and the leaving group is exact location and bind in the Rhodium-catalyzed allylic substitutions work with many retained," Evans says. "If the same exact stereochemical nucleophiles rate of isomerization is fast orientation as the leaving relative to substitution, the group. memory is either completely "This type of control has or partially lost." not been generally forth Enyl complexes of rho coming," Evans says. And dium, as well as other met allylic substitutions typically als, have been structurally have been limited to sym characterized. However, the metrical substrates. W h e n Evans lab is the first to use the substrates are unsym ^^\/OC02CH3 them as the basis of synthetic metrical, the reaction gener methods. ates two different sites for substitution and the poten These reactions comple Distorted rhodium One-pot allylic tial for the formation of rement existing enantioseleccomplex substitution and gioisomers. "Generally, what tive reactions, Evans says. Pauson-Khand annulation you want is attack on the "You may be doing a total C02CH3 more substituted site to cre asymmetric synthesis, and ate or retain a chiral center," you have built this substiEvans says. But that doesn't tutable allyl in your system. C02CH3 Η R1 happen with the usual cata Now, you can simply do the lysts for allylic substitutions. substitution with t h e triR1 = H, CH 3 , C,H 5 organophosphite-modified With those, the metal typ R2 = C 6 H 5 ,C 6 H 5 CH 2 ,alkyl,allyl rhodium catalyst and con ically forms symmetrical, soR3 = C(C0 2 CH 3 ) 2 , 0 , NTs Ts = tosyl tinue to build your molecule. called 3-allyl complexes. X, Y = aryl, alkyl, vinyl, halogen % u don't have to use a chiral However, interconversion of Ε = C0 2 CH 3 , CN, S0 2 C 6 H 5 catalyst every time." these complexes between A. MAUREEN ROUHI, C&EN WASHINGTON
C
°K3>
HTTP://PUBS.ACS.ORG/CEN
C&EN
/ AUGUST
6. 2 0 0 1
39
v
9ÎMI1 Fine Chemical China
iiif^TrttTSTa
ÊCPIT Sub-Council of Chemical Industry CCOIC Chemical Industry Chamber of Commerce Sponsor: China Petroleum and Chemical Industries Association
Profile: •
Dyestuff, Coatings, Pesticide, Pharmaceutical and intermediates;
•
Organic silicon and floride;
•
Feed additives, food additives;
•
Surface treatment water treatment detergent rubber auxiliary;
• •
Adhesives, sealants; Information chemical, magnetic recording materials, photosensitive material;
:;
1
^
· ; Biochemical, leameNrhdking Q t ^ ^ ^ ^ ^paper-making c h e m f é ^ É l ^ ^ ^ l S
www.Fineche.rv.-.40
C & E N / A U G U S T 6, 2001
Evans and graduate students Lawrence J. Kennedy, David K. Leahy, Nelson, and John E. Robinson, as well as postdoc Kristoffer K. Moffet, have very quickly exploited the unique reactivity of the triorganophosphite-modified rhodium catalyst. In rapid succession, they have worked up allylic alkylation, amination, and etherification reactions. By combining the rhodium-catalyzed substitutions with ringforming reactions—such as ring-closing metathesis with the Grubbs catalyst— they have started the ball rolling toward selective formation of highly substituted carbocycles, as well as heterocycles. "The fact that we can parlay these reactions with annulation reactions is extremely powerful for synthesis," Evans says. Recently, for example, they have constructed bicyclic cyclopentenones by combining allylic substitution with the socalled Pauson-Khand annulation reaction. Previously, two different catalysts were required to do this. A palladium catalyst mediates addition of an alkyne to an allylic substrate. Then a rhodium catalyst mediates condensation of the enyne with carbon monoxide and ring formation. INITIAL ATTEMPTS by Evans and Robinson to use the triorganophosphite-modified rhodium catalyst for a tandem process didn't work. On reexamining the rhodium catalysts that had been effective for the Pauson-Khand annulation, they found that a combination of carbon monoxide andDPPPKQH^PCCH^PCQH^lHgands exerts an electronic effect that's sufficient to produce the distorted rhodium complex required for regioselective allylic substitutions. The method developed by Evans and Robinson generates four carbon-carbon bonds and two asymmetric centers in one reaction using one catalyst \J.Am. Chem. Soc., 123,4609 (2001)1. "The amount of diversity we could introduce this way is immense," Evans says. "This reaction will be useful for people who want to do libraries." The two reactions are possible with or?ly one catalyst because they have different temperature requirements. Allylic alkylation can proceed at low temperature, so it goesfirst.Jacking up the temperature then allows ring formation to occur. Ultimately Evans and his group wish to incorporate these transformations into the synthesis of complex natural products. He says the new armory of synthetic transformations based on modified rhodium catalysts will allow convergent assembly of densely functionalized fragments under mild conditions. • HTTP://PUBS.ACS.ORG/CEN
