Corey aldehyde

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). 

Reaction of (T)-(-)-2-acetoxysuccinyl chloride (78), prepared from (5)-mahc acid, using the magnesiobromide salt of monomethyl malonate afforded the dioxosuberate (79) which was cyclized with magnesium carbonate to a 4 1 mixture of cyclopentenone (80) and the 5-acetoxy isomer. Catalytic hydrogenation of (80) gave (81) having the thermodynamically favored aH-trans stereochemistry. Ketone reduction and hydrolysis produced the bicycHc lactone acid (82) which was converted to the Corey aldehyde equivalent (83). A number of other approaches have been described (108). 

Treatment of (89) with lead tetraacetate generates the unstable open-ring aldehyde (90) which is quickly converted to a dimethylacetal (91). Following basic hydrolysis of the methyl ester and acetates, the acetal is cleaved with aqueous acid to produce TxB2. A number of other approaches, including one starting from the Corey aldehyde, have been described (58). 

Oxidation of alkyl trimethyl- and triethylsilyl ethers, ROSi(CH3)3 or ROSi-(C2H5)3.1 Silyl ethers of this type can be oxidized directly to carbonyl compounds by the Swern reagent. This oxidation provides an efficient route to the Corey aldehyde (2). 

Lithium chloride (2.6 g) is dissolved in THF (170 mL). Dimethyl-(2-oxo-4-phenylbutyl)phosphonate (7.87 g) and triethylamine (4.3 mL) are added. The mixture is stirred and cooled to -10°C. A solution of the Corey aldehyde benzoate, (lS,5R,6R,7R)-6-formyl-7-(benzyloxy)-2-oxabicyclo[3.3.0]octan-3-one (8.42 g) in THF (75 mL) is added to the reaction mixture over three hours. The resulting mixture is stirred for 18 hours at -10°C. At the end of this time, methyl t-butyl ether (MTBE) (100 mL) is added and the mixture warmed to 0-20°C. Sodium bisulfite (38%, 100 mL) is added and the two-phase mixture was stirred for 10 min. The phases are separated and the organic phase is washed with saturated aqueous sodium bicarbonate solution (100 mL). The organic phase is separated and concentrated under reduced pressure to a volume of <100 mL. Ethyl acetate (200 mL) is added and the... 

The Pfizer process to latanoprost starts with the Corey aldehyde benzoate (13, CAB), available as a relatively stable crystalline solid via the historic Upjohn prostaglandin synthesis (Scheme 3).17 The reaction of the phosphonate with CAB (13) is done using... 

A new route to the Corey aldehyde avoiding use of thallium is reported by an ICI group. Cyclopentadiene is converted into acetoxyfulvene, which adds to chloro-acrylonitrile to give the adducts (583) in 73% overall yield. Acid hydrolysis gives first one and then, after equilibration, the other aldehyde, which can be converted, in 40 % overall yield from (583), into the keto-acetal (584) whose conversion into PG s... 

Prostaglandins, Methylenomycins, and Related Compounds.—The major development in prostaglandin synthesis during 1980 has come from Paquettes group, which has described an extraordinarily facile approach to all the primary prostaglandins based simply on anionic [3,3] sigmatropic shift from the carbinol (83), produced from commercially available 1,5-cyclo-octadiene (Scheme 11). Elaboration of the aldehyde (84), as shown in Scheme 11, then provides a very attractive route to the well-known Corey aldehyde (85). 

An alternative route to the Corey aldehyde (A), developed at Pfizer, commences with an unusual Prins reaction on norbornadiene. Oxidation and acid catalyzed opening of the cyclopropane ring in (C), followed by Baeyer-Villiger oxidation gave the key chloro-lactone (D) which is cleanly converted to the desired 6-lactone upon treatment with base. 

The conversion of primary alcohols and aldehydes into carboxylic acids is generally possible with all strong oxidants. Silver(II) oxide in THF/water is particularly useful as a neutral oxidant (E.J. Corey, 1968 A). The direct conversion of primary alcohols into carboxylic esters is achieved with MnOj in the presence of hydrogen cyanide and alcohols (E.J. Corey, 1968 A,D). The remarkably smooth oxidation of ethers to esters by ruthenium tetroxide has been employed quite often (D.G. Lee, 1973). Dibutyl ether affords butyl butanoate, and tetra-hydrofuran yields butyrolactone almost quantitatively. More complex educts also give acceptable yields (M.E. Wolff, 1963). 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

Isolated carbonyls always give epoxides from the Corey-Chaykovsky reaction. Take the aldehyde substrate as an example. Spiro epoxide 30 was produced from the reaction of trisnorsqualene aldehyde 28 (R20 represents the polyene side-chain with 20 carbons) with substituted sulfur ylide 29, prepared in situ from cyclopropyldiphenylsulfonium tetrafluoroborate and KOH. " For the epoxidation of ketones, the Corey-Chaykovsky reaction works well for diaryl- (31), arylalkyl- (32), ... 

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

Retrosynthetic cleavage of the A13,14 double bond in 6 significantly simplifies the side-chain appendage attached to C-l2 and affords aldehyde 7 and ketophosphonate 8 as potential precursors. In the synthetic direction, a Homer-Wadsworth-Emmons reaction10 would appear to provide a very simple means of joining intermediates 7 and 8 with concomitant formation of the requisite trans C13-C14 olefin. Retrosynthetic simplification of aldehyde 7 provides intermediate 9, a molecular assembly commonly known as the Corey lactone. 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

Corey used a chiral bromoborane 75 (1.1 equiv.) to promote the addition of tert-butyl bromoacetate (76) to aromatic, aliphatic, and a,P-unsaturated aldehydes to give the halo alcohols 77 with high enantio- and diastereoselectivities (Table 1.10) [35]. 

Corey and Chaykovsky were the first to investigate the reaction of dimethyl sulphoxide anion (dimsyl anion) with aldehydes and ketones400,401. They found that the reaction with non-enolizable carbonyl compounds results in the formation of /1-hydroxyalkyl sulphoxides in good yields (e.g. Ph2CO—86%, PhCHO—50%). However, with enolizable carbonyl compounds, particularly with cycloalkanones, poor yields of hydroxyalkyl products are observed (e.g. camphor—28%, cyclohexanone—17%, but... 

Similar enantioselective Diels-Alder reactions between cyclopentadiene and a,p-acetylenic aldehydes catalyzed by a chiral snper Lewis acid were reported by Corey and Lee [58],... 

The combination of a Corey-Kwiatkowski [147] and a HWE reaction efficiently furnishes a, 3-unsaturated ketones of type 2-288 in good yields [148]. This unique domino reaction, developed by Mulzer and coworkers, probably proceeds via the intermediates 2-285 and 2-286 using the phosphonate 2-283, the ester 2-284, and the aldehyde 2-286 as substrates (Scheme 2.66). 

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