Allyl alcohols reductive cleavage

The synthesis of the trisubstituted cyclohexane sector 160 commences with the preparation of optically active (/ )-2-cyclohexen-l-ol (199) (see Scheme 49). To accomplish this objective, the decision was made to utilize the powerful catalytic asymmetric reduction process developed by Corey and his colleagues at Harvard.83 Treatment of 2-bromocyclohexenone (196) with BH3 SMe2 in the presence of 5 mol % of oxazaborolidine 197 provides enantiomeri-cally enriched allylic alcohol 198 (99% yield, 96% ee). Reductive cleavage of the C-Br bond in 198 with lithium metal in terf-butyl alcohol and THF then provides optically active (/ )-2-cyclo-hexen-l-ol (199). When the latter substance is treated with wCPBA, a hydroxyl-directed Henbest epoxidation84 takes place to give an epoxy alcohol which can subsequently be protected in the form of a benzyl ether (see 175) under standard conditions. 

REDUCTIVE CLEAVAGE OF ALLYLIC ALCOHOLS, ETHERS, OR ACETATES TO OLEFINS 3-METHYLCYCLOHEXENE... 

The combination of PMHS and Pd(PPh3)4 reduces allyl ethers to propene and alcohols.270 The best combination for the reductive cleavage of ethers appears to be Et3SiH/(C6F5)3B, which gives excellent yields of the alcohol (via the silyl ether) and alkane (Eq. 127).145... 

Unlike with sodium borohydride (see Section 11.01.5.2), pyrrolizin-3-one 2 reacts with lithium aluminohydride mainly as an amide. No conjugate addition occurs, and only the reductive lactam cleavage takes place to give stereoselectively the (Z)-allylie alcohol 77. Similarly, benzo-annulated pyrrolizin-3-one 17 gives the corresponding benzylic alcohol 78. The same reactivity was observed with organometallics such as methyllithium which gives exclusively the tertiary (Z)-allylic alcohol 79 (Scheme 7). 

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 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. 

Another route to a methyl-branched derivative makes use of reductive cleavage of spiro epoxides ( ). The realization of this process was tested in the monosaccharide series. Hittig olefination of was used to form the exocyclic methylene compound 48. This sugar contains an inherent allyl alcohol fragmenC the chiral C-4 alcohol function of which should be idealy suited to determine the chirality of the epoxide to be formed by the Sharpless method. With tert-butvl hydroperoxide, titanium tetraisopropoxide and (-)-tartrate (for a "like mode" process) no reaction occured. After a number of attempts, the Sharpless method was abandoned and extended back to the well-established m-chloroperoxybenzoic acid epoxida-tion. The (3 )-epoxide was obtained stereospecifically in excellent yield (83%rT and this could be readily reduced to give the D-ribo compound 50. The exclusive formation of 49 is unexpected and may be associated with a strong ster chemical induction by the chiral centers at C-1, C-4, and C-5. 

Reduction of unsaturated halides 0-78 Reduction of allylic alcohols 0-82 Reductive cleavage of enamines 0-86 Coupling of vinylic halides 0-87 Coupling of unsaturated halides with organometallic reagents 0-88 Coupling of allylic halides, tosylates, or acetates... 

Dihydroisoxazoles can be formed by stereoselective 1,3-dipolar cycloaddition of nitrile oxides, for example, to enantiopure allylic alcohols, and these products can be converted into -amino acids 510 by a characteristic nucleophilic addition to the C=N bond in 509 followed by reductive cleavage of the N—O bond and oxidative cleavage of the diol moiety. The facial selectivity in the nucleophilic addition is dictated by the C(5) substituent (Scheme 109), e.g., <2003JA6846, 2004SL1409, 2005JA5376>. 

Epoxy-l-haloalkenes undergo novel reductive cleavage reactions with samarium diiodide to give cyclopropanols or allylic alcohols depending upon the substrates and reaction conditions. Formation of the cyclopropanol is believed to proceed through a diradical intermediate <1998SL1073>. 

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