Stereochemical Control in Organic-Synthesis Using Silicon-Containing Compounds

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

Recent developments in the synthesis of prostaglandins and analogues.

The N,O-acetal and N,O-ketal derivatives (oxazolidinones) formed from proline, and aldehydes or ketones are well-known today, and they are detectable in reaction mixtures involving proline catalysis, where they have been considered ‘parasitic dead ends’. We disclose results of experiments performed in the early 1970's, and we describe more recent findings about the isolation, characterization, and reactions of the oxazolidinone derived from proline and cyclohexanone. This oxazolidinone reacts (THF, room temperature) with the electrophiles β-nitrostyrene and chloral (=trichloroacetaldehyde), to give the Michael and aldol adduct, respectively, after aqueous workup (Scheme 5). The reactions occur even at −75° when catalyzed with bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or EtN(i-Pr)2 (DIPEA) (10%; Table 1). It is shown by NMR (Figs. 1 and 3) and IR analysis (Figs. 2 and 4) that the primarily detectable product (before hydrolysis) of the reaction with the nitro-olefin is again an oxazolidinone. When dissolved in hydroxylic solvents such as MeOH, ‘hexafluoroisopropanol’ ((CF3)2CHOH; HFIP), AcOH, CF3COOH, or in LiBr-saturated THF, the ring of the oxazolidinone from cyclohexanone and proline opens up to the corresponding iminium ion (Tables 2–4), and when treated with strong bases such as DBU (in (D8)THF) the enamino-carboxylate derived from proline and cyclohexanone is formed (Scheme 8). Thus, the two hitherto putative participants (iminium ion and enamine) of the catalytic cycle (Scheme 9) have been characterized for the first time. The commonly accepted mechanism of the stereoselective C,C- or C,X-bond-forming step (i.e., A–D) of this cycle is discussed and challenged by thoughts about an alternative model with a pivotal role of oxazolidinones in the regio- and diastereoselective formation of the intermediate enamino acid (by elimination) and in the subsequent reaction with an electrophile (by trans-addition with lactonization; Schemes 11–14). The stereochemical bias between endo- and exo-space of the bicyclo[3.3.0]octane-type oxazolidinone structure (Figs. 5 and 6) is considered to possibly be decisive for the stereochemical course of events. Finally, the remarkable consistency, with which the diastereotopic Re-face of the double bond of pyrrolidino-enamines (derived from proline) is attacked by electrophiles (Schemes 1 and 15), and the likewise consistent reversal to the Si-face with bulky (Aryl)2C-substituents on the pyrrolidine ring (Scheme 16) are discussed by invoking stereoelectronic assistance from the lone pair of pyramidalized enamine N-atoms.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/hlca.200790050

Are Oxazolidinones Really Unproductive, Parasitic Species in Proline Catalysis? – Thoughts and Experiments Pointing to an Alternative View

3.2. Benzothiazoles 2933 3.3. Carbamates 2933 3.4. o-Diphenylphosphanylbenzoates 2935 3.4.1. Chemoand Regioselectivity 2936 3.4.2. Stereochemistry 2937 3.4.3. Stereodivergency 2939 3.4.4. Iterative Deoxypropionate Construction 2940 3.4.5. Natural Product Synthesis 2942 3.5. Chiral Reagent-Directing Groups 2944 3.5.1. Chiral Acetals 2944 3.5.2. Chiral Carbamates 2944 3.5.3. Chiral Oxazolines 2944 3.5.4. Chiral Esters 2944 4. Carbometalation of Alkynes 2945 4.1. Tethered Alkoxy and Sulfide Groups 2945 4.2. 2-Pyridylsilanes 2947 5. Allylation of Carbonyl Compounds 2947 6. Oxidation of Nonactivated C-H Bonds 2948 6.1. Directed Ortho Hydroxylation of Aromatic Carboxylic Acids 2948

Directed Reactions of Organocopper Reagents

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

The known ketone, 7-tert-butyldimethylsilyloxybicyclo[3.3.0]oct-8-en-2-one 11, was converted in five steps into 3-(4′-methoxycarbonylbutylidene)-7-tert-butyldimethylsilyloxy-8-cyanobicyclo[3.3.0]octan-2-one 13. Reduction gave the diastereoisomeric pair of allylic alcohols 14 and 15, both of which were converted into the allylsilane, 3-(1′-dimethylphenylsilyl-4′-methoxycarbonyl)butyl-7-tert-butyldimethylsilyloxy-8-cyanobicyclo[3.3.0]oct-2-ene 20. Protodesilylation of the allylsilane gave a high level of selectivity (>96∶4) in favour of the carbacyclin analogue, 5-(4′-methoxycarbonyl)butylidene-3-tert-butyldimethylsilyloxy-2-cyanobicyclo[3.3.0]octane 22, having the exocyclic double bond with the E-configuration.

Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of a (±)-carbacyclin analogue with the geometry of the exocyclic double bond controlled by the protodesilylation of an allylsilane

The stereospecific synthesis of a carbacyclin analogue using the protodesilylation of an allylsilane

Protodesilylation of the allylsilanes 5 and 6 is selective for the formation of the exocyclic double bond isomers 7 and 8, respectively, when the group R is isopropyl, but not when it is methyl.

Dick Higgins

Papers

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

Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of a (±)-carbacyclin analogue with the geometry of the exocyclic double bond controlled by the protodesilylation of an allylsilane

The stereospecific synthesis of a carbacyclin analogue using the protodesilylation of an allylsilane

Protodesilylation of allylsilanes for the control of double bond geometry exocyclic to a ring

Regioselective and Stereospecific Synthesis of Allylsilanes from Secondary Allylic Alcohol Derivatives.