Stereospecificity acetylides

Potassium or lithium derivatives of ethyl acetate, dimethyl acetamide, acetonitrile, acetophenone, pinacolone and (trimethylsilyl)acetylene are known to undergo conjugate addition to 3-(t-butyldimethylsiloxy)-1 -cyclohexenyl t-butyl sulfone 328. The resulting a-sulfonyl carbanions 329 can be trapped stereospecifically by electrophiles such as water and methyl iodide417. When the nucleophile was an sp3-hybridized primary anion (Nu = CH2Y), the resulting product was mainly 330, while in the reaction with (trimethylsilyl)acetylide anion the main product was 331. 

The stereospecific reduction of a 2-butyne-l, 4-diol derivative and silver( I)-mediated cyclization of the resulting allene were successively applied to a short total synthesis of (+)-furanomycin 165 (Scheme 4.42) [68], Stereoselective addition of lithium acetylide 161 to Garner s aldehyde in the presence of zinc bromide afforded 162 in 77% yield. The hydroxyl group-directed reduction of 162 with LiAlH4 in Et20 produced the allene 163 stereospecifically. Cyclization followed by subsequent functional group manipulations afforded (+)-furanomycin 165. 

A stereospecific synthesis for cw-3-hexen-l-ol starts with the ethylation of sodium acetylide to 1 -butyne, which is reacted with ethylene oxide to give 3-hexyn-l-ol. Selective hydrogenation of the triple bond in the presence of palladium catalysts yields cw-3-hexen-l-ol. Biotechnological processes have been developed for its synthesis as a natural flavor compound, e.g., [12]. 

Absorption of orally administered, relatively lipophilic compounds, such as estrone or estradiol, occurs mainly in the intestine. The bacteria that colonize the gut are, however, particularly adept at converting those compounds by attack at the 17 position to very water-soluble derivatives that defy absorption. Alkylation of that position avoids this catabolic pathway and consequently enhances bioavailability on oral administration. The reaction of 17-keto steroids with nucleophiles illustrates the high degree of stereospecifity that is maintained in many steroid reactions approach of that carbonyl group from the (3 face is virtually forbidden by the presence of the adjacent 18 methyl. The reaction products consequently consist of almost pure isomers from attack at the a face. Reaction of estradiol with lithium acetylide thus gives ethynylestradiol (9-2) [9] the corresponding alkylation of estradiol 3-methyl ether (9-1) leads to mestranol (9-3) [10]. Both compounds are potent orally active... 

Fig. 16.31. Stereoselective and stereospecific Pd(0)-cata-lyzed alkenylations of copper acetylides with iodoalkenes at the beginning of a two-step...

Mechanistically, this new insertion-CI-Diels-Alder hetero domino sequence can be rationalized as follows (Scheme 64) After the oxidative addition of the aryl halide 115 or 118 to the in situ generated Pd(0) species the arylpalladium halide 120 intramolecularly coordinates and inserts into the tethered triple bond via a syn-carbopaUadation to furnish cyclized vinylpalladium species 121 with a p-acceptor substitution in a stereospecific fashion. Transmetallation of the in situ generated copper acetylide 122 gives rise to the diorganylpalladium complex 123 that readily undergoes a reductive elimination and liberates the electron poor vinylpropargylallyl ether 124. The triethylamine catalyzed propargyl-allene isomerization furnishes the... 

Other Reactions.—A review on the preparative methods of acetal formation contains steroidal examples.62 Periodic acid was reported to be useful for regeneration of ketones from thioacetals.63 The reaction of lithium acetylide with the 14p-hydroxy-17-ketone (47) gave stereospecifically the 17 (3-hydroxy-compound (48) whereas the... 

Protonation of the acetylide complexes (76) (R = Me, Ph, l-C.oH,) with CFjSOjH at low temperature (-78 °C) has been shown > from H NMR analysis to proceed with high stereoselectivity, giving preferentially (>98% de) the anticlinal diastereomeric vinylidene complexes (77a) (Scheme 11). Analogous Cp methyla-t ons of (76) are similarly stereospecific. This high 1,3 asymmetric induction was... 

By the judicious choice of reaction conditions, it is possible to control the regioselectivity and stereoselectivity of acetylide addition to a keto group. For instance, the reaction of the diketone 14 with lithium acetylide in THF at low temperatures gives the C(9)-acetylenic alcohol 75 (Scheme 4) [10], and a stereospecific synthesis of the acetylenic triol 16 is achieved by the condensation of the lithium reagent 77 derived from the isopropenylmethyl (IPM) ether of ( j-3-methylpent-2-en-4-yn-l-ol (18) with the optically active ketone 19, followed by acid-catalysed removal of the protecting groups [11]. Only 3% of the C(6)-diastereoisomer of 16 was detected (Scheme 5). The preparation of 16 is described in Worked Example 2. Table 1 lists a selection of a-hydroxyalkynes that have been prepared from metal acetylides. 

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