Barton deoxygenation

Treatment of 122 with (R,R)-tartrate crotyl-boronate (E.R.R)-W 1 provides the alcohol corresponding to 123 with 96% stereoselectivity. Benzylation of this alcohol yields 123 with 64% overall yield. The crude aldehyde intermediate obtained by ozonolysis of 123 is again treated with (Z,R,R)-111 (the second Roush reaction), and a 94 5 1 mixture of three diastereoisomers is produced, from which 124 can be isolated with 73% yield. A routine procedure completes the synthesis of compound 120, as shown in Scheme 3-44. Heating a toluene solution of 120 in a sealed tube at 145°C under argon for 7 hours provides the cyclization product 127. Subsequent debromination, deacylation, and Barton deoxygenation accomplishes the stereoselective synthesis of 121 (Scheme 3-44). 

Radicals formed by fragmentation of xanthate and related thiono esters can also be trapped by reactive alkenes.217 The mechanism of radical generation from thiono esters was discussed in connection with the Barton deoxygenation method in Section 5.4. 

A useful modification of the Barton deoxygenation of secondary alcohols involves the use of O-phenylthionocarbonates developed by Robins et al. [15]. Application of this method for the generation and cyclization of a hex-5-ynyI radical is shown is Scheme 5. The precursors are readily prepared from D-ribose by a Grignard addition, followed by selective alcohol derivatizations. The major exo-isomer has been converted into carba-a-D-ribofuranose [16]. 

The driving force for the fragmentation is formation of the C=0 double bond. If R reacts with Bu3SnH, a tributyltin radical is produced which continues the chain. Carried out in this manner this reaction is called the Barton deoxygenation of alcohols, since alcohols are precursors for the thiono esters. 

A derivative of L-oliose (54L) suitable for glycosylation was obtained from L-fucose169 using the Barton deoxygenation method for introduction of the 2-deoxy function. Another approach for the synthesis of L-oleosyl synthons started from the 3,4-di-D-acetyl L-fucal (71), readily converted into the corresponding chloride (Scheme 24).138 This method was used for the synthesis of dTDP-p-L-oliose, a glycosyl donor in the construction of aclacinomycin A (72). 

Scheme 6. Reaction conditions a, 3-chloroperoxybenzoic acid (MCPBA)/dichloromethane/aq. bicarbonate, then lithium diisopropylamide (LDA) b, diimide c, POCl3/pyridine d, LiAlH4, BuLi/PhCOCI e, MCPBA f, (PhSe)2/NaBH4/EtOH, then MCPBA/Pr2NH g, 0s04/pyridine h, acetonide formation, then Barton deoxygenation i, Ba(OH)2, then H +. ...

Barton deoxygenation, 548, 549 [Functionalized carbocycles] bicyclic compounds, 551 caiba-D-fructofuranose, 547 Corey lactone, 549 Cp2TiCl catalyst, 553, 563 cyclic transition state, 548, 549 cyclohexanes, 554 cyclopentanes, 546 1,2-dialkylcyclopentanes, 548 electron spin resonance, 552 eneynes, 556... 

The resulting alcohol then undergoes a Barton deoxygenation. Finally, the TMS group needs to be removed. 

Reduction of the ketone moiety in 24 with NaBH4 provides the corresponding alcohol as a 1 1 mixture of diastereoisomers, which is then transferred into the pentalene derivative by a Barton deoxygenation using thiocarbonyl diimidazole and tributyl tinhydride. Finally, desily-lation with AgNOs and KCN in EtOH provides the desired deprotected alkyne 25. 

The Barton deoxygenation (or Barton-McCombie deoxygenation) is a two-step reaction sequence for the reduction of an alcohol to an alkane. The alcohol is first converted to a methyl xanthate or thioimidazoyl carbamate. Then, the xanthate or ihioimidazoyl carbamate is reduced with a tin hydride reagent under radical conditions to afford the alkane. Trialkylsilanes have also been used as the hydride source. Reviews (a) McCombie, S. W. In Comprehensive Organic Synthesis Trost, B. M. Fleming, I., Eds. Pergamon Press Oxford, U. K., 1991 Vol. 8, Chapter 4.2 Reduction of Saturated Alcohols and Amines to Alkanes, pp. 818-824. (b) Crich, D. Quintero, L. Chem. Rev. 1989, 89, 1413-1432. 

The following example shows that the methoxybenzylidene acetal is not always an innocent bystander. During an attempted Barton deoxygenation the benzylidene acetal participated in a 1,5-hydrogen shift when the reaction was run under dilute conditions, but this could he obviated by running the reaction in neat BusSnH. ... 

Reductive radical elimination (Barton deoxygenation) of the 3, 4 -xanthate derivative of neamine (70) has been used to prepare the key intermediate 71 (compounds 70, 71) for the synthesis of the 3, 4 -dideoxyneamine analog gentamine Cia [52]. In this synthesis, a precursor possessing free hydroxyl groups at positions 3 and 4 was treated with a mixture of carbon disulfide, aqueous sodium hydroxide, and methyl iodide in DMSO to afford compound 70. Subsequent reduction of 70 with tributyltin hydride furnished the olefin 71, which affer cafalyfic hydrogenation and deprofecfion was converted to gentamine Cia. 

A related carbocycle is synthesized starting from carbohydrate precursors. The radicals are generated via Barton deoxygenation of the intermediate 5-heptenolsiei. The effect of 1-, 2-, 3-and 4-substituents on the stereoselectivity of the cyclization reaction has also been described 17-18. The formation of the 1,5-m-product is rationalized by the Beckwith modelThe 4,5-configuration of the main product is tram and is explained by the influence of allylic strain. 

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