Esters reductive cleavage

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The o-nitrobenzyl ester, used in this example to protect penicillin precursors, can be cleaved by irradiation (H20/dioxane, pH 7). Reductive cleavage of benzyl or p-nitrobenzyl esters occurred in lower yields. 

A classical method for the vicinal hydroxylation of a double bond involves treatment with osmium tetroxide to give a cyclic ester, followed by reductive cleavage to the glycol ... 

The carbon-oxygen bond is strong, like the normal carbon-fluorine bond, it is difficult to reduce However, some structural features facilitate its reductive cleavage Aryl esters of perfluoroalkanesulfomc acids can be cleaved in good yield by... 

The reductive capability of CgK has been a subject of interest (LA). Uses for CgK include the reductive cleavage of carbon-sulfur bonds (S5), the reductive alkylation of nitriles and esters (S6), and the reductive alkylation of aldehydes and ketones (S7). The activity of CgK has... 

Among other methods for the preparation of alkylated ketones are (1) the Stork enamine reaction (12-18), (2) the acetoacetic ester synthesis (10-104), (3) alkylation of p-keto sulfones or sulfoxides (10-104), (4) acylation of CH3SOCH2 followed by reductive cleavage (10-119), (5) treatment of a-halo ketones with lithium dialkyl-copper reagents (10-94), and (6) treatment of a-halo ketones with trialkylboranes (10-109). 

See Wallace, O.B. Springer, D.M. Tetrahedron Lett., 1998, 39, 2693 for cleavage of thiol esters to thiols with NaSMe in methanol and Choi, J. Yoon, N.M. Synth. Commun., 1995, 25, 2655 for borohydride exchange resin-Pd(OAc)2 reductive cleavage of thiol esters to thiols. 

Reductive removal of oxygen from aromatic rings can also be achieved by reductive cleavage of aryl diethyl phosphate esters. 

Takahashi and coworkers have used INOC for synthesis of the chiral CD rings paclitaxel, which is an antitumor agent. Synthetic strategy starting from 2-deoxy-D-ribose is demonstrated in Scheme 8.22.110 The precursor of INOC was prepared by 1,2-addition of a,(3-unsaturated ester to ketone. INOC and subsequent reductive cleavage by H2/Raney Ni afford the desired CD ring structure. 

It was further shown that the nonracemic stannane 70 can be prepared from the Mosher ester derivative 69 through reductive cleavage and BOM protection (equation 28). Lithiation and methylation gave the nonracemic ether with retention of configuration59. 

Electroreduction of esters (R COOR ) is classified into three types of reaction. The first type of reaction is the reductive cleavage of a bond between oxygen and R. This type of reaction is similar to the cathodic reduction of alcohols (Sect. 7.2) and ethers (Sect. 7.3). That is, activated esters such as allylic and benzylic esters are electrochemically reduced to the corresponding hydrocarbons and acids (Schemes) [1,16,19-21]. 

The Pd(0)-catalyzed displacement of allylic acetates (297) with various nucleophiles via the allylic Pd(II) complex (298) is a well-established procedure (Scheme 114). Through attack of electrons (+2e ) in place of nucleophiles, (298) is expected to undergo a reductive cleavage providing allylic carbanions (299) and the acetate anion along with Pd(0) complexes. The latter can then be captured by various electrophiles (polarity inversion. Scheme 114) leading to (300) [434]. This procedure is useful for the deprotection of allyl esters under neutral conditions. Recently, a mechanistic study of the Pd-catalyzed reaction of allylic acetate (297), using carbonyl compounds as an electrophile, has been reported [435]. 

The same basic strategy was applied to the synthesis of the smaller fragment benzyl ester 28 as well (Scheme 4). In this case, aldehyde 22 prepared from (S)-2-hydroxypentanoic acid [9] was allylated with ent-10 and tin(IV) chloride, and the resulting alcohol 23 was converted to epimer 24 via Mitsunobu inversion prior to phenylselenenyl-induced tetrahydrofuran formation. Reductive cleavage of the phenylselanyl group, hydrogenolysis of the benzyl ether, oxidation, carboxylate benzylation, and desilylation then furnished ester 28. 

---