Acyl tosylates ester synthesis

Although introduced over 40 years ago, Hurd and Mori s synthesis of 1,2,3-thiadiazoles remains the most widely used for the synthesis of 1,2,3-thiadiazoles. The simplicity of the method has contributed to its popularity. A variety of ketones and aldehydes have been converted into their corresponding hydrazones (tosyl and acyl), and thioamides have been converted into thio-carbazonate esters. The carbonyl derivatives are then treated with thionyl chloride to yield 1,2,3-thiadiazoles in high yields. When one is faced with the task of synthesizing new 1,2,3-thiadiazoles, Hurd and Mori s method should always receive attention. 

Under the same basic conditions /ra . -l-acetoxymethyl-1-methyl-2-tosylcyclopropane generated an a-sulfonyl anion, which attacked the ester group intramolecularly and afforded 2,5-dimethyl-l-tosyl-3-oxabicyclo[3.1.0]hexan-2-ol (22) in 50% yield.Stereoselective synthesis with a chiral cyclopropyl sulfoxide was experienced when ( )-4-tolylsulfinylcyclopropane was reacted first with butyllithium and then with methyl benzoate and gave 1-benzoyl-1-[(5)-4-tolylsulfinyl]cyclopropane (23a) in 62% yield. A useful reaction took place when 2-(hy-droxymethyl)cyclopropyl phenyl sulfide was treated first with an excess of butyllithium and then with dimethylformamide and gave 2-hydroxy-l-phenylsulfanyl-3-oxabicyclo[3.1.0]hexane (24), a lactol which has been used to carry out various useful synthetic transformations. Another useful reaction occurred when cyclopropyl phenyl sulfones were treated with butyllithium followed by an acyl imidazole to give acyl cyclopropanes in decent yield. 

Proline benzyl ester 3 is the starting material for a variety of A -substituted derivatives formed by A-acylation with unsaturated acids, which are useful chiral dienophiles for enantioselective Diels-Alder reactions (Section D. 1.6.1.1.1.). The synthesis of these derivatives, e.g., (S)-6 or (S)-7 is conveniently achieved by A-acylation of the hydrochloride or tosylate of the benzyl ester (the allyl ester may also be used) of proline with triethylamine/4-(dimethyl-amino)pyridine5. 

As noted above, alkyne anions are very useful in Sn2 reactions with alkyl halides, and in acyl addition reactions to a carbonyl.46 Alkyl halides and sulfonate esters (tosylates and mesylates primarily) serve as electrophilic substrates for acetylides. A simple example is taken from Kaiser s synthesis of niphatoxin B, in which propargyl alcohol (36) is treated with butyllithium and then the OTHP derivative of 8-bromo-1-octanol to give a 47% yield of 37.48... 

A soln. of tosyl-a-methylalanyl-a-methylalanine in acetic anhydride heated 15 min. at 110-120° -> 4,4-dimethyl-2-(r-methyl-r-tosylamino)ethyloxazolone (Y 94%) dissolved with a-methylalanine methyl ester in acetonitrile, and heated 4 hrs. at 100° tosyl-a-methylalanyl-a-methylalanyl-a-methylalanine methyl ester (Y 95%).—Most of the conventional methods of peptide synthesis are not suitable for the joining of a-methylalanyl residues. The absence of a H-atom from the a-position favors the oxazolone method because there can be neither racemization nor acylation at the a-G-atom. F. e., methods, and limitation by ring opening to amidine derivatives, s. M. T. Leplawy et al., Tetrahedron n, 39 (1960). 

---