Reductive cleavage lithium - liquid ammonia

From intermediate 12, the path to key intermediate 7 is straightforward. Reductive removal of the benzyloxymethyl protecting group in 12 with lithium metal in liquid ammonia provides diol 27 in an overall yield of 70% from 14. Simultaneous protection of the vicinal hydroxyl groups in 27 in the form of a cyclopentanone ketal is accompanied by cleavage of the tert-butyldimethylsilyl ether. Treatment of the resultant primary alcohol with /V-bromosuccini-mide (NBS) arid triphenylphopshine accomplishes the formation of bromide 7, the central fragment of monensin, in 71 % yield from 27. 

The alkoxycarbonyl group activates the N — N bond, so that a racemization-free reductive cleavage by treatment with a large excess of lithium in liquid ammonia is possible (sec procedure below). This method is not suitable for hydrazines containing a benzylic C-N bond, because it is cleaved under the reducing conditions. 

Truce also examined a few examples of the cleavage of sulphones with sodium in liquid ammonia97 and found essentially similar results except that diaryl sulphones were reduced to sulphinate salts instead of to arylthiolates as with the lithium reductions. Dialkyl sulphones were unreactive towards sodium in liquid ammonia. 

For preparative purposes, titanium metal can be used in place of sodium or lithium in liquid ammonia for both the vinyl phosphate231 and aryl phosphate232 cleavages. The titanium metal is generated in situ from TiCl3 by reduction with potassium metal in tetrahydrofuran. 

Vinyl ethers were reductively cleaved by lithium, sodium or potassium in liquid ammonia especially in the absence of alcohols (except terf-butyl alcohol) A mixture of l-methoxy-1,3- and l-methoxy-l,4-cyclohexadiene gave in this way first methoxycyclohexene and, on further reduction, cyclohexene Reductive cleavage of a-alkoxytetrahydrofurans and pyrans will be discussed in the chapter on acetals (p. 104). 

The desulfurization of 1,4-oxathiane with sodium in refluxing hydrocarbon solvent, which allows the formation of diethyl ether in very good yield (>95%), can be reported here <1998TL2671>. Furthermore, 6-hydroxy-1,4-benzodithiin undergoes a reductive cleavage with lithium in liquid ammonia, provided the 3,4-dimercaptophenol <2004BML3753>. 

Reductive deacetoxylation.1 This naphthalenide in HMPT is recommended for reductive cleavage of a-aceloxy esters.2 Lithium in liquid ammonia can be used, but... 

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

Benzo[6]furan is cleaved on reduction with excess sodium in liquid ammonia, followed by quenching with ammonium chloride or methanol, to produce 2-ethylphenol (69%). 2-Methyl- and 2-phenyl-benzo[6]furan similarly yield 2-propylphenol (54%) and 2-(2-phenylethyl)phenol (45%) (59JA2795). Similarly, 5-methoxybenzo[6]furan, on reduction with 2 mol of lithium and a limited amount of t- butanol, gives the cleavage product, but by operating with 2 mol each of lithium and f-butanol, 5 -methoxy-2-methylbenzo[6 jfuran supplies the 2,3-dihydro compound. With excess of the alcohol, however, 5-methoxy-2,3,4,7-tetrahydrobenzo[6]furan is secured so that the reduction is stepwise (67JOC2794). 

Synthesis of Enantiomerically Pure C2-symmetric Vicinal Diamines via Chirality Transfer from DPEN. Several C2-sym-metric vicinal diamines and their derivatives are prepared in optically pure form by chirality transfer from DPEN. For example, condensation of (5, 5)-DPEN with butane-2,3-dione in benzene at the reflux temperature is followed by stereoselective reduction with NaBHsCN and PPTS at -20 °C to afford the (25,35,5R,6R)-piperazine 4 and its diastereomer in a 15 1 ratio (eq 12). The crude product is purified by silica gel column chromatography. Formation of the biscarbamate followed by reductive cleavage of benzylic C-N bonds with lithium in liquid ammonia, and then removal of isobutyloxycarbonyl with HBr in acetic acid results in (/ ,/ )-2,3-diaminobutane dihydrobromide 5 in 99% ee. 

The reduction of 1-methyl- and l,l-dimethylspiro[2.4]hepta-4,6-diene with sodium or lithium in liquid ammonia led to a mixture of products which were formed by the cleavage of either cyclopropane bond at the spiro center. ... 

Table 13. Spiroalkanones by Reductive Cleavage of Tricycloalkanones with Lithium in Liquid Ammonia...

Reductive cleavage of analogous cyclopropyl ketones with lithium in liquid ammonia normally gives exclusively the spirocyclic product (see Section 2.4.1.5.6.). 

Rearrangements of several ketones and alcohols containing the tricyclo[5.3.0.0 ]decane, and related structures, promoted by various reagents, have been examined. Reductive cleavage with lithium metal in liquid ammonia yielded spiroalkanones (see Section 2.4.1.5.2.6.). By way of contrast, fused ring systems were formed in reactions catalyzed by, for the ketones, e.g. 28 8. /7-toluenesulfonic acid or, for the corresponding alkanols, e.g. 30, perchloric... 

Little is known about the behavior of hydantoins in dissolving metal reductions. The reaction of hydantoin (132) with 5 equivalents of lithium in tert-butyl alcohol and liquid ammonia gives the 4-imidazolin-2-one 133. The use of methanol instead of r rt-butyl alcohol gives a mixture of reduced products, probably originated by ring cleavage as well as by reduction.325 ... 

In some instances an allylic oxygen bond can undergo reductive cleavage. For example, in a synthesis of Allopumiliotoxin 339A, Overman and co-workers showed that the reductive cleavage product 1403 was the major product on attempted deprotection of the two benzyl ethers in 140.1 with lithium in liquid ammonia at -78 C for more than 5 minutes [Scheme 4.140]. However, by terminating the reaction after 2 minutes, the desired triol 1403 was obtained in 86% yield. 

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