Toward the Synthesis of Modified Carbohydrates by Conjugate Addition of Propane‐1,3‐dithiol to α,β‐Unsaturated Ketones

Abstract

Selected 5‐substituted derivatives 4 of 1,1‐diethoxy‐5‐hydroxypent‐3‐yn‐2‐one were treated with propane‐1,3‐dithiol under various conditions. The unprotected hydroxy ketones underwent cyclization during the dithiol addition and gave the corresponding 3‐(diethoxymethyl)‐2‐oxa‐6,10‐dithiaspiro[4.5]decan‐3‐ols 5 in 80–90% yield as the only products (Scheme 3 and Table 1). These products can be regarded as partly modified carbohydrates in the furanose form. When the benzyl‐protected analogues 10‐Bn of the 1,1‐diethoxy‐5‐hydroxypent‐3‐yn‐2‐one derivatives were treated with the same dithiol, however, no cyclization occurred; instead the corresponding 3‐{2‐[(benzyloxy)methyl]‐1,3‐dithian‐2‐yl}‐1,1‐diethoxypropan‐2‐one derivatives 11‐Bn were formed in good yield (up to 99%; Table 4). These 1,3‐dithianes were and are in the process of being converted to a number of new carbohydrate analogues, and here are reported high‐yield syntheses of functionalized molecules 17 belonging to the 5,5‐diethoxy‐1,4‐dihydroxypentan‐2‐one family of compounds (Table 7), via 15‐Bn (Table 5) and 16‐Bn (Table 6 and Scheme 8).

Conjugated Ynones in Organic Synthesis

“…Nucleophiles centered at S, Se, and Te have been reacted with few ynones, and among these nucleophiles, the sulfur-centered have been used the most. The most common reaction involves thiolates generated in situ by adding a base to a solution of a thiol and ynones, − ,− but some reactions have also been carried out under neutral conditions. ,, A few alkanethiols and dithiols − ,,− have been applied, but also some thiophenols. ,, Furthermore, most reactions have been carried out at room temperature or below, − ,, but heating as high as 80 °C has also been reported. , …”

“…Hemiacetalization similar to that completing the synthesis of tetrahydropyran 513 was also observed by Sydnes and co-workers treating derivatives of 1,1-diethoxy-5-hydroxyalk-3-yn-2-one 375 with propan-1,3-dithiol under standard conditions . The resulting functionalized 2-oxa-6,10-dithiaspiro[4.5]­decanes 514 were obtained in excellent yield except when R = Ph when it dropped to 44% (Scheme ).…”

“…When ynones 71 are treated with propane-1,3-dithiol in a 1:1 molar ratio, the corresponding 1,3-dithiane was obtained. This reaction, developed by Ley and his group, is in general clean and gives the products ( 502 ) in excellent yields, − ,, but if the ynone contains a second electrophilic site, such as a formyl group ( 503 ), 1,3-dithiane formation may be followed by cyclization, which is the case when 503 is converted to spirocompound 504 (Scheme ). …”

Formation of an Isomeric Mixture of Dienynes Instead of a Diallene

“…Since the synthesis of 3,3,4,4-tetraethoxybutyne (TEB) was reported some 15 years ago [1][2][3], many of its chemical properties have been uncovered and used to prepare a range of chemical compounds with rich structural diversity [4][5][6][7][8][9][10][11][12][13][14][15]. Among the most densely functionalized molecules made is 1,1,2,2,7,7,8,8-octaethoxyocta-3,5-diyne (1), which has one ketal moiety in propargylic position to each of the triple bonds [16].…”

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].…”