ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19950780319
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