From 3,3,4,4-tetraethoxybutyne to carbohydrate mimics

Abstract

3,3,4,4-Tetraethoxy-1-butyne, available in high yield in four simple steps from ethyl vinyl ether, is a highly functionalized alkyne, which appears to be a versatile starting material for the synthesis of a range of alkylated, more-or-less deoxygenated carbohydrate mimics. However, many of the reactions used to achieve extension and subsequent structural modification of the carbon chain as well as removal of the protecting groups turn out to be rather sensitive to the substituents' steric and electronic influence. As a result, the reactivity pattern that emerges is somewhat complex.

Synthesis of (E)‐1,1‐Diethoxy‐3‐(3‐hydroxy‐3‐arylfuro[2,3‐b]quinoxalin‐2(3H)‐ylidene)propan‐2‐ones via Acid‐Catalyzed, Stereoselective 5‐Exo‐Dig Cyclization

“…The synthesis of alcohols 2 from ketones 1 was carried out by applying the procedure developed for coupling of TEB with simple aldehydes and ketones viz . treating TEB with butyllithium at −78 °C followed by reacting the resulting acetylide with the ketones at 0 °C to room temperature . When the ketones were reacted with the lithium acetylide of TEB in a 1:1 ratio (M = H; Method 1), the reaction mixture turned out to contain many unreacted ketone and TEB, and the alcohols were obtained in 40–50% yield only (Scheme ).…”

“…Alcohols 2 are propargylic alcohols that constitute an important class of compounds for the synthesis of a variety of functionalized heterocycles, often under protic or Lewis‐acid conditions . The alcohols also contain the TEB unit, which has been used to synthesize a variety of five‐ and six‐membered heterocycles in high yields under both acidic and basic conditions . And with the quinoxalyl fragment in sort of a benzylic position to the hydroxylated carbon, the prospects for formation of some new polycyclic structures under acidic conditions seemed to be promising .…”

“…On the basis of the results presented previously, the following reaction mechanism is proposed (Scheme ). The first step is acid‐catalyzed deketalization of 2 , a robust and reliable transformation, which affords the corresponding α,β‐unsaturated ketone A . This unsaturated ketone is ideally set for Michael addition in a 5‐ exo‐dig fashion, which is favored according to Baldwin's rules , has precedence from the literature , and leads to ring closure and formation of enol B .…”

“…With the aim of extending the range of chemical structures obtained from 1 , we decided to attach an acid‐sensitive, functionalized substituent to the heterocycle by using the keto function as connecting point and investigate what happened at elevated temperature under acidic conditions. An interesting substituent to introduce for this purpose was 3,3,4,4‐tetraethoxybut‐1‐yne (TEB), which is easy to make in high yield in a four‐step synthesis from ethyl vinyl ether , is labile under acidic conditions , and whose acetylide is known to give alcohols in high yields from aldehydes and ketones . And indeed, when a selection of 3‐aroylquinoxalin‐2(1 H )‐ones were reacted with TEB acetylide, the corresponding 3‐(4,4,5,5‐tetraethoxy‐1‐hydroxy‐1‐arylpent‐2‐ynyl)quinoxalin‐2(1 H )‐ones ( 2 ) were obtained and used to investigate the reactivity under acidic, aqueous conditions.…”

1,1,2,2,7,7,8,8-Octaethoxyocta-3,5-diyne

“…3,3,4,4-tetraethoxybut-1-yne (TEB) (1) [8], toward a number of reagents under a variety of conditions. This has eventually led to the synthesis of a range of different products including functionalized allylic and homoallylic alcohols [9,10], highly substituted furans [11,12], amino-substituted furfurals [13], functionalized triazoles [14], deoxygenated carbohydrate analogues [9,[15][16][17], various heterocycles [18][19][20], and functionalized 1,3-dithianes [17,21].…”