Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with commercially available chiral cyclic secondary amines as catalysts Structure-based catalyst screening identified l-proline and 5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) as the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding aldol products with high regio-, diastereo-, and enantioselectivities Reactions employing hydroxyacetone as an aldol donor provide anti-1,2-diols as the major product with ee values up to >99% The reactions are assumed to proceed via a metal-free Zimmerman−Traxler-type transition state and involve an enamine intermediate The observed stereochemistry of the products is in accordance with the proposed transition state Further supporting evidence is provided by the lack of nonlinear effects The reactions tolerate a small amount o

https://www.scripps.edu/barbas/pdf/Sakthivel01JACS.pdf

Amino Acid Catalyzed Direct Asymmetric Aldol Reactions: A Bioorganic Approach to Catalytic Asymmetric Carbon-Carbon Bond-Forming Reactions

Proline-catalyzed asymmetric reactions

2.1.8. Michael Reaction 2245 2.1.9. Others 2247 2.2. Cyclization Reactions 2248 2.2.1. Carbon Diels−Alder Reactions 2248 2.2.2. Aza-Diels−Alder Reactions 2252 2.2.3. Other Hetero-Diels−Alder Reactions 2255 2.2.4. Ionic Diels−Alder Reaction 2256 2.2.5. 1,3-Dipolar Cycloadditions 2256 2.2.6. Other Cycloaddition Reactions 2258 2.2.7. Prins-type Cyclization 2259 2.3. Friedel−Crafts Acylation and Alkylation 2259 2.4. Baylis−Hillman Reaction 2263 2.5. Radical Addition 2264 2.6. Heterocycle Synthesis 2267 2.7. Diazocarbonyl Insertion 2270 3. C−X (X ) N, O, P, Etc.) Bond Formation 2271 3.1. Aromatic Nitration and Sulfonylation 2271 3.2. Michael Reaction 2272 3.3. Glycosylation 2273 3.4. Aziridination 2275 3.5. Diazocarbonyl Insertion 2276 3.6. Ring-Opening Reactions 2277 3.7. Other C−X Bond Formations 2280 4. Oxidation and Reduction 2280 4.1. Oxidation 2280 4.2. Reduction 2281 5. Rearrangement 2283 6. Protection and Deprotection 2285 6.1. Protection 2285 6.2. Deprotection 2288 7. Polymerization 2291 8. Miscellaneous Reactions 2291 9. Lanthanide(II) Triflates in Organic Synthesis 2295 10. Conclusion 2295 11. Acknowledgment 2295 12. References 2295

Rare-earth metal triflates in organic synthesis

Applications of NMR Spectroscopy in Organic Chemistry.

Organocatalytic Asymmetric Mannich Reactions: New Methodology, Catalyst Design, and Synthetic Applications

Enamines: recent advances in synthetic, spectroscopic, mechanistic, and stereochemical aspects—I

Reaction of α,β-unsaturated acid chlorides with enamines—I

Enamines derived from isoxazolidine and 1,3-dioxa-5-azacyclohexane have been prepared. The effect of the addition a α- or β-heteroatoms is to decrease the pπ-conjugation between the nitrogen lone pair of electrons and the π-electrons of the double bond, as reflected in the spectral properties of the enamines and their reactivity with electrophiles. The reasons for this are discussed.

Enamine chemistry. Part 27. The effect of additional α- and β-heteroatoms on the pπ-conjugation and reactivity of enamines. Sub or super-enamines

Chemical, spectroscopic and X-ray crystallographic evidence has confirmed that the three isomers of 6-hydroxy-7,9-dimethyl-6-phenyladamantane-2,4-dione, obtained by the reaction of crotonoyl chloride with the pyrrolidine enamine of 4-benzoyl-4-methylcyclohexanone, have the 9α-methyl-6α-phenyl (4), 9β-methyl-6α-phenyl (2), and 9β-methyl-6β-phenyl (3) configurations. The mechanism of their formation has been investigated and the evidence available indicates that the stereochemistry of the C-6 and C-9 chiral centres is determined largely by the stereochemistry of the [3,3] sigmatropic rearrangement leading to them. A chair-like transition state for the rearrangement, occurring from the same side of the cyclohexene ring as the benzoyl group (chair-syn) in the intermediate N-acylated enamine (9a) must lead to the 9α-Me,6α-Ph configuration as in (4), whereas the same process from the opposite side (chair-anti) followed by inversion of the substituted ring carbon could lead to the 9β-Me,6β-Ph configuration as in (2) and the 9β-Me,6α-Ph configuration as in (3). However, the main isomer (3), having the more crowded 9β-Me,6β-Ph configuration, is more likely to be derived by a [3,3] sigmatropic rearrangement having a boat-like transition state, but again occurring from the same side of the cyclohexene ring as the benzoyl group (boat-syn). An X-ray crystallographic analysis of 6β- hydroxy-7,9α-dimethyl-6α-phenyladamantane-2,4-dione (4) and of 3-(5-benzoyl-5-methyl-2-oxocyclohexyl)-butanoic acid (34), isolated at an intermediate stage in the above reaction, has been carried out. The corresponding reaction of αβ-unsaturated acid chlorides with enamines of 4-benzoyl-4-phenyl-cyclohexanone (9c) and ethyl 1 -benzoyl-4-oxocyclohexane-1 -carboxylate (9b) has been carried out and shown to lead to 6-hydroxy-6,7-diphenyladamantane-2,4-diones and ethyl 2-hydroxy-4,6-dioxo-2-phenyladamantane-1 -carboxylates respectively, as a mixture of stereoisomers. A similar multiplicity in the stereochemistry of the transition state of the [3,3] sigmatropic rearrangement is evident from the structures of the adamantane derivatives produced.

Enamine chemistry. Part 29. Synthesis of adamantane derivatives from α,β-unsaturated acid chlorides and 4,4-disubstituted cyclohexanone enamines. Multiple [3,3] sigmatropic rearrangement transition state stereochemistry. X-Ray analysis

Reaction of αβ-unsaturated acid chlorides with the morpholine or pyrrolidine enamines derived from 4-benzoyl-4-methylcyclohexanone gives the corresponding 6-hydroxy-7-methyl-6-phenyladamantane-2, 4-dione in moderate to good yield Enamines from 4-acetyl-4-phenyl (or 4-ethoxycarbonyl) cyclohexanone could not be isolated owing to their preferential cyclisation into 1 -phenyl (or 1 -ethoxycarbonyl) 4-substituted aminobicyclo[222]octan-2-ones

Peter W. Hickmott

Papers

Enamines: recent advances in synthetic, spectroscopic, mechanistic, and stereochemical aspects—I

Reaction of α,β-unsaturated acid chlorides with enamines—I

Enamine chemistry. Part 27. The effect of additional α- and β-heteroatoms on the pπ-conjugation and reactivity of enamines. Sub or super-enamines

Enamine chemistry. Part 29. Synthesis of adamantane derivatives from α,β-unsaturated acid chlorides and 4,4-disubstituted cyclohexanone enamines. Multiple [3,3] sigmatropic rearrangement transition state stereochemistry. X-Ray analysis

Enamine chemistry. Part 26. Preparation of substituted adamantane-2,4-diones and bicyclo[2.2.2]octan-2-ones