Oligosaccharide Analogues of Polysaccharides. Part 3. A new protecting group for alkynes: Orthogonally protected dialkynes

Dialkynes of the type 3 (Scheme 1) are regioselectively deprotected by treating them either with base in a protic solvent (→ 4 ), or– after exposing the OH group– by catalytic amounts of base in an aprotic solvent (→ 5 and 8 ). The Me₃Si-protected 12 (Scheme 2) is inert to catalytic BuLi/THF which transformed 11 into 9 , while K₂CO₃/MeOH transformed both 10 into 9 , and 12 into 13 , evidencing the requirement for a more hindered (hydroxypropyl)silyl substituent. C-Silylation of the carbanions derived from 17–19 (Scheme 3) with 15 led to 20–22 , but only 22 was obtained in reasonable yields. The key intermediate 27 was, therefore, prepared by a retro-Brook rearrangement of 23 , made by silylating the hydroxysulfide 16 with 15 . The OH group of 27 was protected to yield the {dimethyl(oxy)propyl]dimethylsilyl}acetylenes (DOPSA's) 21, 28 , and 29 . The orthogonally protected acetylenes 20–22, 28 , and 29 were de-trimethylsilylated to the new monoprotected acetylene synthons 30–34 . The scope of the orthogonal protection was checked by regioselective deprotection of the dialkynes 39–42 (Scheme 4), prepared by alkylation of 35 (→ 39 ), or by Pd⁰/CuI-catalyzed cross-coupling with 36–38 (→40–42 ). The cross-coupling depended upon the solvent and proceeded best in N,N,N′,N′ -teramethylethylenediamine (TMEDA). Main by-product was the dimer 43 . On the one hand, K₂CO₃/MeOH removed the Me₃Si group and transformed 39–42 into the monoprotected 44–47 ; catalytic BuLi/THF, on the other hand, transformed the alcohols 48–51 , obtained by hydrolysis of 39–42 , into the monoprotected dialkynes 52–55 , all steps proceeding in high yields. Addition of the protected DOPSA groups to the lactones 56 (→57–59 ) and 62 (→63 ) (Schemes 5 and 6) gave the corresponding hemiketals. Reductive dehydroxylation of 57 and 58 failed; but similar treatment of 59 yielded the alcohol 61 . Similarly, 63 was transformed into 64 which was protected as the tetrahydropyranyl (Thp) ether 65 . In an optimized procedure, 62 was treated sequentially with lithiated 31 , BuLi, and Me₃SiCl (→ 66 ), followed by desilyloxylation to yield 60% of 67 , which was protected as the Thp ether 68 . Under basic, protic conditions, 68 yielded the monoprotected bisacetylene 69 ; under basic, aprotic conditions, 67 led to the monoprotected bisacetylene 70 . These procedures are compatible with the butadiynediyl function. The butadiyne 73 was prepared by cross-coupling the alkyne 69 and the iodoalkyne 71 (obtained from 70 , together with the triiodide 72 ) and either transformed to the monosilylated 76 or, via 77 , to the monosilylated 78 . Formation of the homodimers 74 and 75 was greatly reduced by optimizing the conditions of cross–coupling of alkynes.