Stereochemical Control in Organic-Synthesis Using Silicon-Containing Compounds

Directing groups have been widely used in recent years to achieve control over all aspects of reaction selectivity in a wide range of transformations involving transition-metal catalysis and organometallic reagents. In cases when the existing functional group within a substrate is unsuited to achieve efficient intramolecular delivery of a reagent or catalyst, the specific introduction of an appropriately designed removable reagent-directing group can be a solution to this problem. In this Review we give an overview of the state of the art in this area, including the stoichiometric and catalytic use of directing groups.

Removable Directing Groups in Organic Synthesis and Catalysis

Trimethylsilyl trifluoromethanesulfonate is an excellent catalyst for the acylation of alcohols with acid anhydrides. Highly functionalized primary, secondary, tertiary, and allylic alcohols, and phenols, were acylated cleanly and efficiently and in a fraction of the time used under the standard DMAP conditions.

An Extremely Powerful Acylation Reaction of Alcohols with Acid Anhydrides Catalyzed by Trimethylsilyl Trifluoromethanesulfonate

Synthesis of allenes with organometallic reagents

Allylsilanes in Organic Synthesis − Recent Developments

Primary and secondary allylic acetates and benzoates react with the dimethyl (phenyl)silyl-cuprate reagent to give allylsilanes, provided that the THF in which the cuprate is prepared is diluted with ether before addition of the allylic ester. The reaction is reasonably regioselective in some cases: (i) when the allylic system is more-substituted at one end than the other, as in the reactions 4→5 and 9→10; (ii) when the steric hindrance at one end is neopentyl-like, as in the reactions 15→16; and (iii) when the disubstituted double bond has the Z configuration, as in the reactions Z-19→E-21 or, better, because the silyl group is becoming attached to the less-sterically hindered end of the allylic system, Z-20→E-22. The regioselectivity is better if a phenyl carbamate is used in place of the ester, and a three-step protocol assembling the mixed cuprate on the leaving group is used, as in the reactions 23→24 and E- or Z-29→E-21, or, best of all, because the silyl group is again becoming attached to the less-sterically hindered end of the allylic system, E- or Z-30→E-22. This sequence works well to move the silyl group onto the more substituted end of an allyl system, but only when the move is from a secondary allylic carbamate to a tertiary allylsilane, as in the reaction 38→39. Allyl(trimethyl)silanes can be made using alkyl- or aryl-cuprates on trimethylsilyl-containing allylic esters and carbamates, as in the reactions 40→41, and 43→44. The reaction of the silyl-cuprate with allylic esters and the three-step sequence with the allylic carbamates are stereo-chemically complementary, the former being stereospecifically anti and the latter stereospecifically syn. Homochiral allylsilanes can be made by these methods with high levels of stereospecificity, as shown by the synthesis of the allylsilanes 54, 58 and 59.

A regioselective and stereospecific synthesis of allylsilanes from secondary allylic alcohol derivatives

Pent-3-yn-2-yl acetate (1) reacts with dimethyl(phenyl)silyl cuprate reagent to give a mixture of allenylsilane and propargylsilane. The corresponding N-phenylcarbamate (4) gives only the allenylsilane. Four other examples of this regioselective reaction are reported. The stereochemistry is largely syn.

Synthesis of allenylsilanes from propargyl carbamates

The stereochemistry of attack on an allylsilane is more selective when the substituent on the chiral centre carrying the silyl group is larger than a methyl group, as shown by the reactions of the allylsilanes (5) and (12) with osmium tetroxide, m-chloroperbenzoic acid, and Yamamoto's methylenation reagent.

The stereochemistry of osmylation, epoxidation, and methylenation of allylsilanes

The phenyldimethylsilyl-cuprate reagent reacts with secondary allyl acetates stereospecifically anti, and with secondary and tertiary allyl urethanes stereospecifically syn; these reactions can be used to synthesise either enantiomer of an optically active allylsilane from a single enantiomer of an optically active allyl alcohol.

A stereospecific synthesis of optically active allylsilanes

Unsymmetrical secondary allylic acetates and urethanes react with the dimethyl(phenyl)silylcuprate reagent to give allylsilanes with fair to good regioselectivity.

Andrew P. Thomas

Papers

A regioselective and stereospecific synthesis of allylsilanes from secondary allylic alcohol derivatives

Synthesis of allenylsilanes from propargyl carbamates

The stereochemistry of osmylation, epoxidation, and methylenation of allylsilanes

A stereospecific synthesis of optically active allylsilanes

Regiocontrolled allylsilane synthesis from secondary allylic alcohol derivatives