Azides reductions

A novel method for preparing amino heterocycles is illustrated by the preparation of 2-amino-5-methylthiophene (159). In this approach vinyl azides act as NH2 equivalents in reaction with aromatic or heteroaromatic lithium derivatives (82TL699). A further variant for the preparation of amino heterocycles is by azide reduction the latter compounds are obtained by reaction of lithio derivatives with p- toluenesulfonyl azide and decomposition of the resulting lithium salt with tetrasodium pyrophosphate (Scheme 66) (82JOC3177). 

The azido mesylate may also be reduced with lithium aluminum hydride in the same manner as previously described for iodo azide reductions. The sodium borohydride/cobalt(II)tris(a,a -dipyridyl)bromide reagent may be used, but it does not seem to offer any advantages over the more facile lithium aluminum hydride or hydrazine/Raney nickel procedures. 

The pyrrolidine derivative 314, a skeletal analog of the antitumor antibiotic anisomycin, was synthesized from the acetal derivative 16b. The 5-OH group of 16b was tosylated and then substituted with sodium azide. Reduction (sodium borohydride) of the lactone group afforded an open-chain derivative, which was selectively protected to give 313. Hydrogenation of the azide function, followed by p-toluenesulfonylation, led to 314 by an intramolecular nucleophilic displacement (284). 

Warren and associates (18) have prepared a glycosyl azide derivative (15) of a heptasaccharide. This glycosyl azide was obtained from O-a-D-manno-pyranosyl-( 1 — 6)-0-[a-D-mannopyranosyl-( 1 — 3)-(9-a-D-mannopyrano syl-(l— 6)-0-a-D - mannopyranosyl - (1 — 3)] - O-fi- d - mannopyranosyl -(1 — 4) - O - (2 - acetamido - 2 - deoxy-/ -d-glucopyranosyl) - (1 — 4) - 2 -acetamido-2-deoxy-D-glucopyranose (12) by treatment of its peracetylated derivative 13 with trimethylsilyl trifuoromethanesulfonate, followed by reaction of the intermediary oxazoline 14 with trimethylsilyl azide. Reduction of the glycosyl azide 15 in the presence of Lindlar catalyst gave the glycosyla-mine derivative 16. The condensation of 16 with 1-tert-butyl N-(9-fluoren-... 

With both building blocks 103 and 109 in hand, the total synthesis of lb was completed as shown in Scheme 17. Coupling of acid 103 and alcohol 109 under Yamaguchi conditions to give ester 110 and subsequent desilylation followed by chemoselective oxidation provided hydroxy acid 111. Lactonization of the 2-thiopyridyl ester derived from 111 in the presence of cupric bromide produced the macrodiolide 112 in 62% yield, which was finally converted to pamamycin-607 (lb) via one-pot azide reduction/double reductive AT-methylation. In summary, 36 steps were necessary to accomplish the synthesis of lb from alcohols 88 and 104, sulfone 91, ketone 93, and iodide rac-97. 

One-Pot Azide Reduction and Acetylation Using Zn/Ac20 General Procedure 12961... 

Simultaneous Dts and Azide Reduction in Solution Using DTT General Procedure 1431... 

The first total synthesis of the potent cytotoxic marine natural product makaluvamine F (5) involved the preparation of 2,3-dihydrobenzothiophene 2 <99CC143>. Debenzylation and subsequent acid-catalyzed cyclization of thioether 1 gave 2 which was converted in four steps to 2-azido-2,3-dihydrobenzothiophene 3 using a combination of Phl=0 and McjSiNj for installation of the azide. Reduction of the azide followed by coupling the resultant amine with pyrroloiminoquinone 4 then gave makaluvamine F (5). 

Azides may be converted to amines by hydrogenation, but another possibility is the Staudinger Reaction, which is a very mild azide reduction. As there are a variety of methods for preparing azides readily, the Staudinger Reaction makes it possible to use "N3 as an" NH2 synthon. 

Step 11 Azide reduction to the amine hydrogenolysis of the benzyl ethers intramolecular displacement of the mesylate to construct the piperidine ring. 

The key [4+2] glycosylation followed by desilylation of the two phosphorylation sites resulted in a moderate 39% yield over two steps (Scheme 13.23). Phosphoramidite 153 was used to phosphorylate both of the resulting free hydroxy groups. A three-step protocol was applied for final deprotection, starting with azide reduction with Zn and acetic acid, then removal of cyanoethoxy phosphate protection with DBU, and finally... 

Problem 18.7 Synthesize 2-phenylethanamine, PhCH2CH2NH2, from styrene, PhCH=CH2, by the azide reduction method. ... 

Treatment of the azido diacetal 256 with benzyl bromide and sodium hydride yielded the ether 257 quantitatively (Scheme 33).106,107 And this was subjected to azide reduction to give amine 258, and subsequent deacetonation gave 259. 

A recent report by Evans14 of azide reduction by SnCl2 in aqueous dioxane and in situ amine protection by addition of B0C2O has demonstrated that other methods of reduction of azides may be feasible if catalytic reduction of the azide is precluded because of the presence of protective groups sensitive to hydrogenolysis. 

Azides are converted into amines by the Staudinger reaction. It is a very mild azide reduction with triphenylphosphine. ... 

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