Spurred by the desire to make chemistry a sustainable and "greener" technology, the field of organocatalysis has grown to become one of the most important areas in synthetic organic chemistry. Organic catalysts can often replace potentially toxic metal catalysts and allow reactions to proceed under mild reaction conditions, thereby saving energy costs and rendering chemical processes inherently safer. More importantly perhaps, organocatalysis offers a complementary reactivity in many instances leading to increased versatility. This Handbook describes 126 key reagents for organocatalytic reactions and will be especially useful for professionals in the area of sustainable chemistry, medicinal research, as well as synthetic organic chemists working in academia and the pharmaceutical industry.

All the information compiled in this volume is also available in electronic format on Wiley Online Library. The 126 reagents represented here are but a small fraction of the ca. 5,000 reagents available in the electronic Encyclopedia of Reagents for Organic Synthesis (e-EROS). e-EROS offers various search interfaces to locate reagents of interest, including chemical structure, substructure and reactions search modes. e-EROS is updated regularly with new and updated entries.

Tom Rovis holds the John K. Stille chair in Chemistry at the Colorado State University, Fort Collins (USA). He graduated from the University of Toronto (Canada) in 1998 and studied with David Evans at Harvard University, before joining the faculty of Colorado State. Among other scientific awards, he received the Roche Excellence in Chemistry Award in 2010. He is a Fellow of the AAAS, Excecutive Editor for the Encyclopedia of Reagents for Organic Synthesis, and Associate Editor for the journal Synlett.

Preface xi

Introduction xiii

Catalyst Finder xv

Recent Review Articles and Monographs xix

Short Note on InChIs and InChIKeys xxi

4-Acetamido-2,2,6,6-tetramethyl-1-piperidinyloxyl 1

4-Acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium Tetrafluoroborate 2

2[1]-Amino-[1,1[1]-binaphthalen]-2-ol 13

(9R)-9-Amino-9-deoxyquinidine 16

9(S)-Amino-9-deoxyquinine 24

(1R,2S)-1-Amino-2,3-dihydro-1H-inden-2-ol 35

(2S,4S)-2-(Anilinomethyl)-1-ethyl-4-hydroxypyrrolidine 50

(S)-2-(Anilinomethyl)pyrrolidine 51

9-Azabicyclo[3.3.1]nonane-N-oxyl 59

Benzoyl trimethylsilane 61

Benzyl 1,3-Butadiene-1-carbamate 66

3-Benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazolium Chloride 69

(S)-5-Benzyl-2-mesityl-6,6-dimethyl-6,8-dihydro-5H-[1,2,4]triazolo[3,4-C][1,4]-oxazin-2-ium Tetrafluoroborate 72

3-Benzyl-4-methyl-1,3-thiazolium Chloride 75

cis-4-Benzyloxy-α, α-bis-(3,5-dimethylphenyl)-L-prolinol (2S,4R)- 76

N-Benzylquininium Chloride 78

3-Benzylthiazolium Bromide 85

Benzyltriethylammonium Chloride 86

Bicyclo[2.2.1]heptan-2-one,7,7- Dimethyl-1-(1S,3S,4R)-2-thiabicyclo-[2.2.1]hept-3-yl-, (1S,4R) 88

[1,1[1]-Binaphthalene]-2,2[1]-diol, 3,3[1]-Bis[3,5-bis(trifluoromethyl)phenyl]-, (1R)- 95

N,N[1]-(1S)-[1,1[1]-Binaphthalene]-2,2[1]-diy lbis-(2S,2[1]S)-pyrrolidine-2-carboxamide 98

(R)-1,1[1]-Bi-2,2[1]-naphthol 101

1,1[1]-Binaphthyl-2,2[1]-disulfonic Acid 124

1,1[1]-Binaphthyl-2,2[1]-diyl Hydrogen Phosphate 129

N,N[1]-Bis[3,5-bis(trifluoromethyl)-phenyl]thiourea 133

1-[3,5-Bis(tert-butyl)phenyl]octahydro-3,6,6-trimethylcyclopenta[b]phosphole 137

1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene 139

1,3-Bis(2,6-diisopropylphenyl)imidazolidinium Chloride 146

1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene 149

(–)-(4R,5R)-4,5-Bis[hydroxy(diphenyl)-methyl]-2, 2-dimethyl-1,3-dioxolane(TADDOL) 152

(2S,5S)-2-(Bis(4-methoxyphenyl)((trimethylsilyl)oxy) methyl)-5-(4-methoxy-3,5-dimethylphenyl)pyrrolidine 161

(3R,5R,8R)- 3,8-Bis(1-methylethyl)-2,2,7,7-tetrakis(4-methylphenyl)-1,4,6,9-tetraaza-5λ5-phosphaspiro[4,4] non-5-ene, Hydrochloride salt (1:1) 162

1,2-Bis(phenylsulfonyl)ethylene 163

3,3[1]-Bis(trifluoromethanesulfonyl)-2,2[1]-dihydroxy-1,1[1]-binaphthalene 172

1-[Bis(trifluoromethanesulfonyl)methyl]-2,3,4,5,6-pentafluorobenzene 174

3-[[3,5-Bis(trifluoromethyl)phenyl]-amino]-4-[[(1R,2R)-2-(dimethylamino)-cyclohexyl]amino]-3-cyclobutene-1,2-dione 180

N-[3,5-Bis(trifluoromethyl)phenyl]-N[1]-(9R)-cinchonan-9-yl-thiourea 183

N-[3,5-Bis(trifluoromethyl)phenyl]-N[1]-[(1R,2R)-2-(dimethylamino)cyclohexyl]-thiourea 186

1-[3,5-Bis(trifluoromethyl)phenyl]-3-{(2S)-3,3-dimethyl-1-[(triphenylphosphoranylidene)amino] butan-2-yl}thiourea 189

2-[Bis[3,5-bis(trifluoromethyl)phenyl][(trimethylsilyl) oxy]methyl]pyrrolidine 192

(1R)-3,3[1]-Bis(2,4,6-trimethylphenyl)-[1,1[1]-binaphthalene]-2,2[1]-dicarboxylic acid 199

Bromamine-T 202

Bromonitromethane 205

tert-Butyl 2-(tert-butyldimethylsilyl)-2-oxoacetate 210

(S)-5-((tert-Butyldimethylsilyloxy)-diphenylmethyl)-2-phenyl-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-2-ium Tetrafluoroborate 1a (and Related Reagents) 214

Chloramine-T 219

Cinchonanium, 1-(9-Anthracenylmethyl)-9-(propen-1-yloxy)-, Bromide(1:1), (8α,9R) 227

1,2-Cyclohexanediamine, N1,N2-Bis[4-(1-pyrrolidinyl)-2-quinolinyl]-, (1R,2R)- 235

1,4-Diazabicyclo[2.2.2]octane 241

1,3-Di-tert-butylimidazol-2-ylidene 247

Diethyl 1,4-Dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate 254

Diethyl Oxomalonate 261

1,3-Dihydro-1,3-bis(tricyclo[3.3.1.13,7]dec-1-yl)-2H-imidazol-2-ylidene 270

1,3-Dihydro-4,5-dimethyl-1,3-bis(1-methylethyl)-2H-imidazol-2-ylidene 273

4,5-Dihydro-4-phenyl-3H-dinaphtho[2,1-c:1[1],2[1]-e]phosphepin 277

2,3-Dihydro-2-phenylimidazo[2,1-b]benzothiazole 280

6,7-Dihydro-2-phenyl-5-(phenylmethyl)-5Hpyrrolo[2,1-c]-1,2,4-triazolium Chloride 286

(R)-2,2[1]-Dihydroxy-3,3[1]diphenyl-1,1[1]-binaphthyl 301

1,3-Dimesityl-4,5-dihydroimidazol-2-ylidene 304

1,3-Dimesityl-1H-imidazolium Salts and 1,3-Dimesitylimidazolylidene 306

4-Dimethylaminopyridine 309

2,2-Dimethyl-1,3-dioxan-5-one 315

Dimethyldioxirane 320

(11bR)-4-(1,1-Dimethylethyl)-4,5-dihydro-3Hdinaphtho[2,1-c:1[1],2[1]- e]phosphepin 327

[4S-(4α,5α)]-1-(1,3-Dimethyl-2-oxido-4,5-diphenyl-1,3,2-diazaphospholidine-2-yl)piperidine 330

(1R,2S,4R,5S)-2,5-Dimethyl-7-phenyl-7-phosphabicyclo[2.2.1]heptane 334

1,4-Dimethyl-1H-1,2,4-triazol-4-ium Iodide 335

(11bR)-Dinaphtho[2,1-d:1[1],2[1]-f][1,3,2]dioxaphosphepin,2,6-Bis[3,5-bis (trifluoromethyl)phenyl]-4-hydroxy-,

4-Oxide 339

(11bR)-Dinaphtho[2,1-d:1[1],2[1]-f][1,3,2]dioxaphosphepin,4-Hydroxy-2,6-di-2-naphthalenyl-, 4-Oxide 343

Dinaphtho[2,1-d:1[1],2[1]-f][1,3,2]dioxaphosphepin,4-Hydroxy-2,6-diphenyl-,4-Oxide, (11bR)-(Family of Reagents) 345

5,6-Dioxaspiro[2.4]heptane-4,7-dione 351

2,2[1]-Diphenyl-[3,3[1]-biphenanthrene]-4,4[1]- diol (VAPOL) and 3,3[1]-Diphenyl-[2,2[1]- binaphthrene]-1,1[1]-diol(VANOL) 353

α, α-Diphenyl-2-pyrrolidinemethanol 365

Dispiro[2H-pyran-2,4[1]-[4H-5,6,8b]-triazaacenaphthylene-7[1](5[1]H),2[1][1]-[2H]- pyran], 1[1],2[1],2[1]a,3,3[1],3[1][1], 4,4[1][1],5,5[1][1],6,6[1][1],8[1],8[1]a-tetradecahydro-1[1],2[1]-dimethoxy-6, 6[1][1]-dimethyl-, monohydrochloride,(1[1]S,2R,2[1]S,2[1][1]R,2[1]aS,6S,6[1][1]S,8[1]aS)- 372

N-[(4-Dodecylphenyl)sulfonyl]-2-pyrrolidinecarboxamide(Hua Cat) 373

Dodecyl 4-[[[(2S)-2-pyrrolidinylcarbonyl]-amino]sulfonyl]benzoate(Hua Cat II) 376

(11bR)-4-Hydroxy-2,6-bis[2,4,6-tris-(1-methylethyl)phenyl]-dinaphtho[2,1-d:1[1],2[1]-F][1,3,2]dioxaphosphepin-4-oxide,[(R)-TRIP] & (11bS)-4-Hydroxy-2,6-bis[2,4,6-tris(1-methylethyl)phenyl]- dinaphtho[2,1-d: 1[1],2[1]-f][1,3,2]dioxaphosphepin-4-oxide, [(S)-TRIP] 379

N-[(1S)-1-(Hydroxydiphenylmethyl)-3-methylbutyl]-2-pyrrolidinecarboxamide 393

trans-4-Hydroxy-l-proline 395

(4aR,9aS)-4-Hydroxy-4,4a,9,9a-tetrahydroindeno[2,1-b][1,4]oxazin-3(2H)-one 399

1H-Imidazolium, 1,3-Bis[2,6-bis-(1-methylethyl)phenyl],tetrafluoroborate(1-) 400

Iron(2+), tris(2,2[1]-bipyridine-N,N[1])-,Dibromide,(OC-6-11) 403

β-Isocupreidine (β-ICD) 406

1-Mesityl-3,4-dimethyl-4H-1,2,4-triazol-1-ium Tetrafluoroborate 411

9-Mesityl-10-methylacridinium Perchlorate 413

6[1]-Methoxy-(8S,9R)-cinchonan-9-yl N-tertbutoxycarbonyl-2-pyrrolidinecarboxylate 417

1-Methyl-2-azaadamantane N-Oxyl 420

(S)-1-Methyl-2-[(dihydroisoindol-2-yl)methyl]pyrrolidine 421

2-Methyltetrahydrofuran 422

Methyl(trifluoromethyl)dioxirane 428

Methyl Vinyl Ketone 438

d-2-Naphthylalanine, N,N[1]- [[(2S, 5S)-1-(4-pyridinyl)-2,5-pyrrolidinediyl]dicarbonyl]bis-, 3,3[1] - Dioctyl Ester1 and l-2-Naphthylalanine, N,N[1]-[[(2S,5S)-1-(4-pyridinyl)-2,5-pyrrolidinediyl]dicarbonyl]bis-, 3,3[1]-Dioctyl Ester 449

Nitroethane 451

4-Nitropyridine N-oxide 460

(2S)-N-(2,3,4,5,6-Pentafluorophenyl)-2-pyrrolidinecarboxamide 465

1,5-Pentanediamine, N,N[1]-Bis[(11bR)-3,5-dihydro-3,5-dimethyl-4-oxido-4H-dinaphtho[2,1-d:1[1],2[1]-f ]-[1,3,2]diazaphosphepin-4-yl]-N,N[1]-dimethyl 466

2-Phenyl-6,10b-dihydro-4H,5aH-5-oxa-3,10c-diaza-2-azonia-cyclopenta[c] fluorene tetrafluoroborate; 2-Pentafluorophenyl-6,10b-dihydro-4H, 5aH-5-oxa-3,10c-diaza-2-azoniacyclopenta[c]fluorine tetrafluoroborate; 6,7-Dihydro-2-phenyl-5-(phenylmethyl)-5H-pyrrolo[2,1-c]-1,2,4-triazolium chloride 474

(8α,9R)-(8[1][1]α,9[1][1]R)-1,1[1][1]-[1,3-Phenylenebis(methylene)]bis[9-hydroxy-cinchonanium]Dibromide and (9S)-(9[1][1]S)-1,1[1][1]-[1,3-Phenylenebis(methylene)]bis[9-hydroxy-cinchonanium]Dibromide 486

2-(Phenylmethoxy)acetaldehyde 489

(S)-Proline 494

(2S)-2-Pyrrolidinemethanol-α,α-bis(3,5-dimethylphenyl)and (2R)-2-Pyrrolidinemethanol-α, α-bis(3,5-dimethylphenyl) 517

1-(2-Pyrrolidinylmethyl)pyrrolidine 520

4-(1-Pyrrolidinyl)pyridine 525

5H-Pyrrolo[2,1-c]-1,2,4-triazolium, 7-Fluoro-6,7-dihydro-5-(1-methylethyl)-2-(2,3,4,5,6-pentafluorophenyl)-, (5R,7R)-, Tetrafluoroborate(1-) 528

Quinine 531

3-Quinuclidinol 547

Ruthenium (II), Tris(2,2[1]-bipyrazine-κN1, κN1[1]),1(OC-6-11)- 551

Ruthenium(II), Tris(2,2[1]-bipyridine-κN1,κN1[1])-,(OC-6-11)- 554

Ruthenium(II), Tris(1,10-phenanthroline-κN1,κN10)-,(OC-6-11)- 559

4,4[1]-Spirobi[4H-dinaphth[2,1-c:1[1],2[1]-e]-azepinium],3,3[1],5,5[1]-tetrahydro- 2,6-bis(3,4,5-trifluorophenyl), bromide 561

Spiro[6H-1,3-dioxolo[4,5-c]pyran-6,5[1]-oxazolidine]-3[1]-carboxylic acid, tetrahydro-2,2-dimethyl-2[1],7-dioxo-, 2-methyl-2-propyl ester, (3aR, 5[1]S, 7aR)- 567

Squaramide 571

Tetrachlorosilane 575

2,3,5,6-Tetrahydro-2,6-bis(phenylmethyl)-1H-imidazo[1,2-a] imidazole 582

2,2,6,6-Tetramethylpiperidin-1-oxyl 583

(S)-2-(5-1H-Tetrazolyl)pyrrolidine and (R)-2-(5-1H-Tetrazolyl)pyrrolidine 595

1,2,4-Triazolo[4,3-α]pyridinium, 5,6,7,8-tetrahydro-2-(2,3,4,5,6-pentafluorophenyl)-, Tetrafluoroborate 603

Triflimide 604

N-[4-(Trifluoromethyl)benzyl]-cinchoninium Bromide 612

3-(2,4,6-Trimethylphenyl)-1-methyl-1Hbenzo[d]imidazol-3-ium Iodide 614

(5S)-2,2,3-Trimethyl-5-(phenylmethyl)-4-imidazolidinone 616

1,5,7-Trimethyl-7-(5,6,7,8-tetrahydronaphth[2,3-d ]oxazol-2-yl)-3-azabicyclo-[3.3.1]nonan-2-one 621

2-Triphenylmethylpyrrolidine 624

Tris[(trifluoromethyl)sulfonyl]methane and Related Salts 625

l-Tryptophan, N,N[1]-[[(2S,5S)-1-(4-pyridinyl)-2,5-pyrrolidinediyl]-dicarbonyl]bis-, 3,3[1]-dioctyl Ester 628

Urea, N-[3,5-Bis(trifluoromethyl)phenyl]-N[1]-[(8a,9S)-6[1]-methoxycinchonan-9-yl]-; Urea, N-[3,5-Bis(trifluoromethyl)phenyl]-N[1]-(9R)-cinchonan-9-yl- 633

List of Contributors 639

Reagent Formula Index 655