Silyl ethers, protection with

Tetrabutylammonium fluoride (TBAF) is usually used in the form of the trihydrate or as a solution in tetrahydrofuran (THF). The pure form is difficult to isolate, owing to decomposition to FFF, tributylamine, and but-l-ene [18, 19] on dehydration. It has been used for a variety of reactions, including as a catalyst for various reactions with silicon compounds [20, 21]. One of its main uses is in the cleavage of silyl ether protecting groups [22]. 

Recognizing that l-(phenylsulfonyl)-3-lithioindole tends to isomerize to the corresponding 2-lithioindole derivative, Bosch et al. used a silyl ether protection to solve the problem. They prepared 3-indolylzinc reagent 36 from 3-bromo-l-(terr-butyldimethylsilyI)indole (35) and then coupled 36 with 2-halopyridine 33 to form 3-(2-pyridyl)indole 37. Finally, the Negishi adduct 37 was further manipulated to a naturally occurring indole alkaloid, ( )-nordasycarpidone (38) [23,27]. 

The thermal stability of silyl ethers (protected hydroxyl functions) is good. Hydrolytically, silylethers are less stable but the rate of hydrolysis of R3Si-OR changes with R, /.< ., ter. butyldimethylsilyl ethers hydrolyse about 10,000 times slower than trimethylsilyl ethers. 

Different strategies all including nucleophilic addition to acceptor-substituted allenes have been used for the synthesis of cyclic compounds, mostly heterocycles. Thus, it is obvious to release a nucleophile already existing within the allenic compound in a protected form. For example, treatment of silyl ethers 197 with tetrabu-tylammonium fluoride (TBAF) leads to the intermediates 198, which yield the dihy-drofurans 199 by nucleophilic addition (Scheme 7.32) [251]. 

With the non-C2-symmetrical dialdehyde 11, reductive cyclisation on treatment with Sml2 led to the preferential formation of the cyclic cz s-diol 12. The intervention of the transition state structure 13 was invoked to rationalise the uratz-selectivity observed with the bulky silyl ether-protected hydroxyl group. 

The Pd-catalyzed carbocyclization affects good control on the orientation of the newly formed OH group [192] (O Scheme 49). Thus, 225 and 227 afford the corresponding cyclitols with almost complete selectivity. In the rearrangement of 227, the stereoselectivity is controlled by the bulky silyl ether-protecting group, which effects the conformational change. 

The next steps in the synthesis include the multistep conversion of E)-15 into 16, subsequent cleavage of the silyl ether protecting group, and cyclization of 17, which cannot be isolated, to provide hexacyclic 18. With the reductive removal of the sulfonamide Magnus et al. arrived at their first goal, the total synthesis of the Wieland-Gumlich aldehyde (2). The conclusion of the total synthesis of strychnine is also within reach the authors succeed in converting 2 into the natural prod-... 

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