Reductive dehalogenation and deoxygenation

Reductive removal of vinyl phosphate groups is one of the better methods for conversion of a carbonyl compound to an alkene. The required vinyl phosphates are obtained easily from the enolate. The enolate can be phosphorylated either 

CHAPTER 5 REDUCTION OF CARBONYL AND OTHER FUNCTIONAL GROUPS 

Since reductions by metal atoms often occur as one-electron processes, intermediate radicals are frequently involved in dissolving-metal reductions. When the reaction conditions are adjusted so that coupling of these intermediates competes favorably with other processes, the formation of carbon-carbon bonds will occur. A useful example which has been known for a long time is the reductive coupling of acetone to 2,3-dimethylbutane-2,3-diol (pinacol). Considerable effort has been 

Titanium metal generated by reduction with stronger reducing agents such as UAIH4, Li, or K results in the coupling and reduction proceeding to an alkene.  

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Scheme 5.11. Reductive Dehalogenation and Deoxygenation by Dissolving Metals... 

Nitropyridazines are reduced catalytically either over platinum, Raney nickel or palladium-charcoal catalyst. When an N-oxide function is present, palladium-charcoal in neutral solution is used in order to obtain the corresponding amino N-oxide. On the other hand, when hydrogenation is carried out in aqueous or alcoholic hydrochloric acid and palladium-charcoal or Raney nickel are used for the reduction of the nitro group, deoxygenation of the N- oxide takes place simultaneously. Halonitropyridazines and their N- oxides are reduced, dehalogenated and deoxygenated to aminopyridazines or to aminopyridazine N- oxides under analogous conditions. 

Amino-5-chloromethyl-3-cyanopyrazine 1-oxide was also deoxygenated by sodium hydrosulfite (dithionite) in boiling water to give a poor yield of 2-amino-5-chloromethyl-3-cyanopyrazine, but 2-amino-6-chloromethyl-3-cyanopyrazine 1-oxide under the same conditions underwent both deoxygenation and reductive dehalogenation to 2-amino-3-cyano-6-methylpyrazine (529,534). 

A different approach to methyl ohvosides (24), starting from L-arabinose, is much more laborious and involves chain extension through the Henry reaction (Scheme 2). The 2-deoxy function is introduced by elimination/hydro-genation and 6-deoxygenation is achieved either via tosylation/LAH reduction or iodination/Raney nickel reductive dehalogenation of the primary hydroxyl group [52]. 

Examples of application of the iert-dodecanethiol/silane couple include typical reductive dehalogenations, but also Barton-McCombie deoxygenations of alcohols, through conversion of the latter into xanthate esters (eq 6), hydrosilylations of alkenes (eq 7), and preparation of silanethiols. The thiol can also be used as a polarity reversal catalyst in conjunction with tris(trimethylsilyl)silane and hexabutyldistannane/malonic acid. ... 

The low reactivity of alkyl and/or phenyl substituted organosilanes in reduction processes can be ameliorated in the presence of a catalytic amount of alkanethiols. The reaction mechanism is reported in Scheme 5 and shows that alkyl radicals abstract hydrogen from thiols and the resulting thiyl radical abstracts hydrogen from the silane. This procedure, which was coined polarity-reversal catalysis, has been applied to dehalogenation, deoxygenation, and desulfurization reactions.For example, 1-bromoadamantane is quantitatively reduced with 2 equiv of triethylsilane in the presence of a catalytic amount of ferf-dodecanethiol. 

The synthetic potential of reductions by formate has been extended considerably by the use of ammonium formate with transition metal catalysts like palladium and rhodium. This forms a safe alternative to use of hydrogen. In this fashion it is possible to reduce hydrazones to hydrazines, azides and nitro groups to amines, to dehalogenate chloro-substituted aromatics, and to carry out various reductive removals of functional groups. For example, phenol triflates are selectively deoxygenated to the aromatic derivatives using triethylammonium formate as reductant and a palladium catalyst. - These recent af li-cations have been reviewed. 

Beginning with reductions, we must remember that this class of reactions results in a decrease in the molecules oxidation state. In other words, there is a net loss of functionality on the molecule being reduced. This loss of functionality may be manifested in the conversion of a double bond to a single bond (olefins to alkanes and carbonyls to alcohols), or in the complete removal of heteroatom-based functionalities (deoxygenation, dehalogenation, deamination). In all cases, the net result of a reduction reaction is the formation of a simpler and less reactive structure from one... 

The many useful reactions of organophosphites include dehalogenation (12.294), desulphurisation (12.295), deoxygenation (12.296, 12.297), reductive cyclisation (12.298-12.300), reduction of peroxides to ethers (12.301), synthesis of quinolines (12.302) and cleavage of cyclic thionocarbonates (Corey-Winter reaction) (12.303) [15]. 

Danishefsky formulated a strategy to staurosporine [41], in which epoxidation of glycal (-)-98 with maleimide 97 resulted in one of the indole N-glycosidic linkages to form 99. Treatment of olefin 99 using Barton deoxygenation, iodine and f-BuOK followed by radical dehalogenation provided the pyranosylated indolocarbazole 101 with 64% yield. Deprotection and methylation followed as shown in Scheme 14 (i.e., 101—102), after which reduction of imide 102 led to a 1 1 mixture of 1 and la. 

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