Corey synthesis

Fig. 5. Corey synthesis ofPGE2 and PGF2Q, where DiBAL-H = diisobutylaluminumhydride MCPBA = m — chloroperbenzoic acid py = pyridine ...

Because the Corey synthesis has been extensively used in prostaglandin research, improvements on the various steps in the procedure have been made. These variations include improved procedures for the preparation of norbomenone (24), alternative methods for the resolution of acid (26), stereoselective preparations of (26), improved procedures for the deiodination of iodolactone (27), alternative methods for the synthesis of Corey aldehyde (29) or its equivalent, and improved procedures for the stereoselective reduction of enone (30) (108—168). For example, a catalytic enantioselective Diels-Alder reaction has been used in a highly efficient synthesis of key intermediate (24) in 92% ee (169). 

The Corey synthesis began with an asymmetric Diels-Alder reaction between butadiene and 2,2,2-trifluoroethyl acrylate in the presence of the 5-proline-derived catalyst ent-59 to form the adduct ent-69 in excellent yield (97%) and with >97% ee (Scheme 7.10). Ammonolysis of 60 produced amide 61 quantitatively, which underwent iodolacta-mization using the Knapp protocol to generate lactam 62. A-Acylation of 62 with... 

Scheme 3 illustrates retrosynthetic analysis of the E and F series of PGs. The widely used Corey synthesis (2) takes notice of the presence of the two olefinic bonds in the side chains of PGF2a. The actual synthesis consists of a two-fold Wittig-type chain extension of a chiral dialdehyde equivalent with four defined stereogenic centers derived from cyclopentadiene via a series of bicyclic intermediates. A similar sequential synthesis has been developed at Upjohn Co. (la). These chemical syntheses are much more economical than enzymatic methods and are used for commercial synthesis of certain PGs. An alternative pathway pioneered by Sih is the conjugate addition approach (3). Nucleophilic addition of an E-olefinic co side-chain unit to a cyclopentenone in which the a side chain is already installed leads directly to PGE-type compounds. Untch and Stork used an co chain unit with a Z-olefinic bond (4). The most direct and flexible synthesis is the convergent three-component coupling synthesis via consecutive linking of the two side chains to unsubstituted 4-hydroxy-2-cyclopentenone derivatives (5, 6). 

The utility of the BINAL-H asymmetric reduction in other PG syntheses is shown in Scheme 16 (35, 39). This asymmetric reduction is a general method for generating the 15S configuration and is highly practical, because the binaphthol ancillary is easily recovered in reusable form from the reaction mixture. In fact, this reduction is undertaken on a multikilogram scale in the Corey synthesis (Ono Pharmaceutical Co.). The observed high diastereoselectivity leading to the desired 155... 

G. M. Gray and J. Y. Corey, Synthesis of polysilanes by new synthetic procedures Catalytic dehydro-polymerization of hydrosilanes , in Reference 4, pp. 401-418. 

The Corey synthesis [43] is worth revisiting for the originality of the approach in the construction both of ring C and of the D-E ring moiety, although it is flawed by the... 

C. Reaction with Sulfonium Ylides. Corey Synthesis... 

A Glaxo research group has used an oxirane ring opening with a dimethylaluminum alkynide, i.e. (25) -> (26), in one of their syntheses of prostaglandin F20 (Scheme 46). (The alkylation step in the Corey synthesis of hybridalactone was illustrated in Scheme 6.)... 

A slight modification of Corey synthesis (see Scheme 3.16) affords an estrane that bears a hydroxyl at C14. The 14-dehydroestrone intermediate from that synthesis is first reduced to give the corresponding 17[3-hydroxy analogue. This, in turn, is converted to its tert-butyldimethylsilyl ether (TBDMS) (32-1) by reaction with the silyl chloride (Scheme 3.32). Oxidation by means of w-chloroperbenzoic acid (mCPBA) affords the 14—15 epoxide 32-2 as a 3 1 mixture of a- and p-epimers. Treatment of the former with lithium aluminum hydride leads to the alcohol... 

Macrocyclic ring compounds (sec. 6.6.B) possess functionality and stereochemistry that can be as difficult to control as in acyclic systems. The use of cyclic precursors is of value here also. In the Corey synthesis of (-j-A-methylmaytansine, a sugar derivative, tri-O-acetyl-D-glucal (155), was used as a precursor to 156. This precursor contained the correct stereochemistry and functionality for elaboration of the eastern... 

Homopropargyl cyclohexanone reacts with the S-ylide from trimethyl sulfoxonium iodide in a Corey synthesis (cf p 21). The resulting spiroepoxide A can be subjected to a 5-exo-cyclization catalyzed by titanocene (Cp2TiCl2) in the presence of a stoichiometric amount of Mn yielding a product B in 90% yield. 

Hernandez has also reported a synthesis of 3 from 1 that differs from the Corey synthesis in that the orthoester Claisen rearrangement (3, 300-302 6, 607-608) is used to introduce the acetic acid side chain (equation I). 

Bromination of Olefins. In the Corey synthesis of epibati-dine the cyclohexene (19) reacts with NBS to give bromination with neighboring group participation, producing 20 (eq 47). This reaction has been studied in detail by Vasella. ... 

Corey synthesis commenced from D-glucal triacetate 17, which was converted into the epoxide 19 via 18 (summarized in Scheme 2). Conformation of the pyranose ring was analyzed to be axial C -OMe, equatorial C, so that opening... 

Around 1970, chemists at Schering (Ulrich Eder, Gerhard Sauer, Rudolf Wiechert) and concurrently at Hoffmann-La Roche (Zoltan Hajos, David Parrish) had found an improved Michael addition of 2-ethylcyclopentane-l,3-di-one [61] to methyl vinyl ketone. If water is used in place of methanol, and catalytic amounts of potassium hydroxide are present, then the yield is increased from 54 to 81%. [62, 63] The higher homologues can be synthesised in an analogous manner as well. [64] Robinson annulation, in presence of 30 mole% proline, leads in good yield to a bicydic hydroxy-ketone. After dehydration, crystallisation and reduction with sodium borohydride, the enantiomerically pure bicydic ketone is obtained, which is required for Coreys synthesis. 

Corey synthesis (J, 160), but in contrast to the earlier results, the rate of lactonisation by the method used in the present work seems to be independent of the configuration at C-15. This lack of selectivity is also observed for... 

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