Comprehensive Organic Synthesis - Selectivity, strategy and efficiency in modern organic chemistry in 9 Vol.Set [reprint 1991]

Front Matter......Page 988 Preface......Page 990 Contributors to Volume 2......Page 992 Table of Contents......Page 995 1.1.1 Introduction......Page 997 1.1.2.1 General Considerations......Page 999 1.1.2.2 Reactions of Type I Crotyl Metal Reagents with Achiral Aldehydes, Ketones and Imines......Page 1005 1.1.2.3 Reactions of Type III Crotyl Organometallics with Achiral Aldehydes and Ketones......Page 1015 1.1.3.1 Reactions with Chiral Aldehydes......Page 1020 59299_v02_01_01b.pdf......Page 1026 Cumulative Subject Index......Page 0 1.1.3.2 Reactions with Chiral C=N Electrophiles......Page 1028 1.1.4.1 Chiral Allyl Organometallics with Conventional Auxiliaries......Page 1029 1.1.4.2 Chiral Allyl Organometallics with Stereocenters at C-1 or C-4......Page 1034 1.1.5 Double Asymmetric Synthesis: Reactions of Chiral C=X Electrophiles and Chiral Allyl Organometallics......Page 1036 1.1.6 Summary......Page 1042 1.1.7 Addendum......Page 1043 1.1.8 References......Page 1045 1.2.1 Synthetic Utility......Page 1050 1.2.2 Boron-Substituted Allylic Anions......Page 1051 1.2.3 Silicon-Substituted Allylic Anions......Page 1052 1.2.4 Nitrogen-Substituted Allylic Anions......Page 1055 1.2.5 Phosphine-Substituted Allylic Anions......Page 1059 1.2.6 Oxygen-Substituted Allylic Anions......Page 1061 1.2.7 Sulfur-Substituted Allylic Anions......Page 1066 1.2.8 Selenium-Substituted Allylic Anions......Page 1071 1.2.9 Halogen-Substituted Allylic Anions......Page 1072 1.2.11 References......Page 1073 1.3.3 Structure and Physical Properties......Page 1075 1.3.4.1 Non-Heteroatom-Substituted Propargyl or Allenyl Organometallics......Page 1076 1.3.4.2 Heteroatom-Substituted Propargyl and Allenyl Organometallics......Page 1082 1.3.5 Diastereoselective Reactions......Page 1085 1.3.6 Enantioselective Reactions......Page 1090 1.3.7 References......Page 1091 1.4.1 Introduction......Page 1093 1.4.2.1 Alkali Metal Enolates by Deprotonation of Carbonyl Compounds......Page 1094 1.4.2.2 Alkali Metal Enolates by Addition to alpha,beta-Unsaturated Carbonyl Compounds......Page 1100 1.4.2.3 Alkali Metal Enolates from Ketenes......Page 1101 1.4.2.4 Alkali Metal Enolates from Enol Acetates and Silyl Enol Ethers......Page 1102 1.4.2.5 Alkali Metal Enolates by Miscellaneous Methods......Page 1103 1.4.3 Magnesium Enolates......Page 1104 1.4.4 Boron Enolates......Page 1105 1.4.5 Aluminum Enolates......Page 1108 1.4.6 Tin Enolates......Page 1110 1.4.7 Titanium Enolates......Page 1111 1.4.9 Copper Enolates and Enolates from Cuprates......Page 1113 1.4.10 Zinc Enolates......Page 1116 1.4.11 Other Transition Metal Enolates......Page 1119 1.4.12 References......Page 1122 1.5.1 Introduction......Page 1126 1.5.3 Reversibility of the Aldol Reaction......Page 1127 1.5.5 Self-Reactions of Aldehydes......Page 1129 1.5.6 Mixed Reactions of Aldehydes......Page 1132 1.5.7 Self-Reactions of Ketones......Page 1133 1.5.9 Reactions of Ketones with Aldehydes......Page 1135 1.5.9.1 Acyclic Ketones......Page 1136 1.5.9.2 Cyclic Ketones......Page 1140 1.5.9.3 Alkylaryl and Related Ketones......Page 1143 1.5.9.4 Vinylogous Enolates......Page 1145 1.5.9.5 Stereochemistry......Page 1146 1.5.10.1 Dialdehydes......Page 1149 1.5.10.2 Keto Aldehydes......Page 1151 59299_v02_01_05b.pdf......Page 1152 1.5.10.3 Diketones......Page 1154 1.5.10.4 Stereochemistry of Aldol Cyclizations......Page 1159 1.5.10.5 Transannular Cyclizations......Page 1162 1.5.10.6 Polyketides......Page 1163 1.5.11 References......Page 1169 1.6.1 Introduction......Page 1173 1.6.2.1 Stoichiometric Deprotonation of Carbonyl Compounds......Page 1174 1.6.2.2 Regioselective Deprotonation of Ketones......Page 1175 1.6.2.4 Enolates from Conjugate Additions to alpha,beta-Unsaturated Carbonyl Compounds......Page 1176 1.6.2.5 Enolates from Reduction of alpha-Heteroatom-Substituted Carbonyl Compounds......Page 1178 1.6.2.6 Enolates of alpha,beta-Unsaturated Carbonyl Compounds......Page 1179 1.6.2.7 Dianions of Diketones and Keto Esters......Page 1181 1.6.3.1 General Overview......Page 1182 1.6.3.2 Ketone Enolates......Page 1184 1.6.3.3 Ester and Lactone Enolates......Page 1192 1.6.3.4 Carboxylic Acid Dianions (Ivanov Reaction)......Page 1202 1.6.3.5 Amide and Lactam Enolates......Page 1203 1.6.3.6 Thioester and Thioamide Enolates......Page 1206 1.6.4.1 Chiral Substrates......Page 1209 1.6.4.2 Chiral Enolates......Page 1215 1.6.4.4 Chiral Auxiliaries......Page 1224 1.6.5 Equilibration; Thermodynamic Control......Page 1226 1.6.6 References......Page 1227 1.7.1 Introduction......Page 1231 1.7.2.1 Preparation of Alkenyloxydialkylboranes......Page 1232 1.7.2.2 Diastereoselective Aldol Reactions (2,3-Stereochemistry)......Page 1236 1.7.2.3 Aldol Reactions Using Enantiomerically Homogeneous Alkenyloxydialkylboranes (3,4-Stereochemistry)......Page 1240 1.7.2.4 Aldol Reactions Mediated by Alkenyloxydialkoxyboranes......Page 1258 1.7.3.1 Preparation of Alkenyloxyalanes and Subsequent Aldol Reactions......Page 1260 1.7.3.2 Aldol Reactions Using Enantiomerically Homogeneous Alkenyloxydialkylalanes......Page 1263 1.7.4 References......Page 1265 1.8.1 Introduction......Page 1268 1.8.2.1 Isolation and Stability of Zinc Enolates......Page 1269 1.8.2.2 Structure of Zinc Enolates......Page 1271 1.8.3.1 Scope and Procedures......Page 1272 1.8.3.2 Chemoselectivity......Page 1274 1.8.3.3 Regioselectivity......Page 1276 1.8.3.4 Stereoselectivity......Page 1280 1.8.4 Reaction with Imines......Page 1285 1.8.5.1 Reaction with Esters and Acid Chlorides......Page 1287 1.8.5.2 Reaction with Nitriles, the Blaise Reaction......Page 1288 1.8.6 References......Page 1289 1.9.1 Introduction......Page 1291 1.9.2.1 Zirconium......Page 1292 1.9.2.2 Titanium......Page 1295 1.9.2.3 Rhodium......Page 1300 1.9.2.4 Cerium......Page 1301 1.9.3.1 Tungsten, Molybdenum and Rhenium......Page 1302 1.9.4.1 Cobalt......Page 1304 1.9.4.2 Iron......Page 1305 1.9.5 Other Asymmetric Aldol Reactions Involving Transition Metals......Page 1307 1.9.7 References......Page 1308 1.10.1 Introduction......Page 1310 1.10.2 General Considerations on the Nitroaldol Reaction and Its Utility in Organic Synthesis......Page 1311 1.10.3 Classical Nitroaldol Procedures and Their Limitations......Page 1314 1.10.3.1 Nitroaldol Reactions with Dialdehydes......Page 1315 1.10.3.2 Nitroaldol Reactions with Ketones......Page 1318 1.10.3.4 Regio- and Stereo-Selectivity in the Nitroaldol Reaction with alpha, beta-Unsaturated Aldehydes and Ketones......Page 1319 1.10.3.5 Significant Functionalized Nitroalkanes Used in Nitroaldol Reactions......Page 1320 1.10.4 Nitroaldol Reactions with Silyl Nitronates and with alpha, alpha Doubly Deprotonated Nitroalkanes......Page 1324 1.10.5 Addendum......Page 1327 1.10.6 References......Page 1328 1.11.1 Introduction......Page 1330 1.11.2.1 Reaction Conditions......Page 1332 1.11.2.2 Spectroscopy and Physical Properties......Page 1334 1.11.2.3 Mechanism......Page 1336 1.11.2.4 The Retro-Knoevenagel Reaction......Page 1338 1.11.2.5 Stereochemistry......Page 1339 1.11.2.6 Competitive Reactions......Page 1341 1.11.3.1 Variation of the Active Methylene Compound......Page 1343 1.11.3.2 Variation of the Carbonyl Compound......Page 1353 1.11.4 Sequential Reactions......Page 1358 1.11.5 Synthetic Applications......Page 1364 1.11.5.1 Carbocycles and Heterocycles......Page 1365 1.11.5.2 Natural Products and Biologically Active Compounds......Page 1370 1.11.5.3 Transformation of Sugars......Page 1374 1.11.5.4 Dyes and Polymers......Page 1376 1.11.7 References......Page 1377 1.12.1 Introduction......Page 1384 1.12.2 Mechanistic Considerations......Page 1385 1.12.3.1 Preparation of Cinnamic Acids and Related Aromatic Derivatives......Page 1388 1.12.3.2 Aliphatic Aldehydes and Ketones......Page 1389 1.12.3.3 Reparation of Coumarins......Page 1390 1.12.4.1 General and Mechanistic Considerations......Page 1391 1.12.4.2 Geometric Isomers of Oxazolone Products......Page 1392 1.12.4.3 Imines as Substrates......Page 1393 1.12.4.4 Rhodanine and Hydantoin Derivatives......Page 1395 1.12.5 References......Page 1396 1.13.1 Introduction......Page 1398 1.13.2 General and Mechanistic Considerations......Page 1400 1.13.3.1 Sulfur-Containing Groups......Page 1404 1.13.3.2 Nitriles......Page 1408 1.13.3.3 Lactones......Page 1409 1.13.3.4 Vinylogous Esters......Page 1410 1.13.3.6 Imines......Page 1411 1.13.3.7 Ketones......Page 1413 1.13.3.8 Carboxylic Acids......Page 1414 1.13.3.9 Silicon......Page 1415 1.13.4 Miscellaneous Modifications......Page 1416 1.13.5 Preparation of Aziridines......Page 1417 1.13.6.1 Phase-Transfer Conditions......Page 1418 1.13.6.2 Solid-Liquid Systems......Page 1423 1.13.7.1 Asymmetric Catalysis......Page 1424 1.13.7.2 Condensations Employing Asymmetric N-(alpha-Haloacetyl)Oxazolidinones......Page 1425 1.13.8 References......Page 1427 1.14.1 Introduction......Page 1429 1.14.3.1 Cyclopropane Ring Formation......Page 1431 1.14.3.2 Cyclopropane Ring Cleavage......Page 1432 1.14.5.1 Titanium Homoenolates......Page 1433 1.14.5.3 Other Metal Homoenolates......Page 1435 1.14.6.2 Zinc Homoenolates......Page 1436 1.14.7.1 Zinc Homoenolates......Page 1437 1.14.7.3 Silver Homoenolates......Page 1438 1.14.9 Synthetic Applications......Page 1439 1.14.9.3 Conjugate Addition......Page 1440 1.14.10 References......Page 1441 1.15.1 Introduction......Page 1443 1.15.3.1 Substrate Specificity......Page 1444 1.15.3.3 Enzyme Characteristics......Page 1449 1.15.3.4 Examples of FDP Aldolase in Organic Synthesis......Page 1450 1.15.4 N-Acetylneuraminic Acid Aldolase (E.C. 4.1.3.3)......Page 1451 1.15.5 Transketolase......Page 1452 1.15.6 KDO Synthetase......Page 1453 1.15.8 Conclusion and Future Perspectives......Page 1454 1.15.9 References......Page 1459 1.16.1 Introduction......Page 1462 1.16.2.1 Reactions of Imine Anions Derived from Aldimines......Page 1464 1.16.2.2 Reactions of Imine Anions Derived from 2-Azadienes......Page 1466 1.16.2.3 Reactions of Endocyclic Imine Anions Derived from Unsaturated Heterocycles......Page 1468 1.16.3.1 Phosphorus- and Silicon-Stabilized Imine Anions......Page 1469 1.16.4.2 Stabilized Oxime Anions......Page 1473 1.16.5.1 Acyclic Imidates......Page 1475 1.16.5.2 Metallated 2-Methyloxazolines......Page 1476 1.16.5.3 Metallated 2-Methyldihydro-1,3-Oxazines......Page 1479 1.16.5.5 Metallated 2-Methylimidazolines......Page 1481 1.16.6.1 2-Methyl Azaheteroaromatic Compounds......Page 1482 1.16.7.1 Asymmetric Synthesis of Amino Acids......Page 1485 1.16.8 References......Page 1488 1.17.1 Introduction......Page 1490 1.17.2 Preparation of Hydrazones from Aldehydes and Ketones......Page 1491 1.17.3 Formation of Azaallyl Metal Reagents from Hydrazones......Page 1493 1.17.4 Structures of Azaallyl Metal Reagents Derived from Hydrazones......Page 1494 1.17.5 Regiochemical and Stereochemical Control in Hydrazone Deprotonation......Page 1496 1.17.6 1,2-Additions to Aldehydes and Ketones......Page 1498 1.17.7 1,2-Additions to Carboxylic Acid Derivatives......Page 1503 1.17.8 1,4-Conjugate Additions to alpha,beta-Unsaturated Carbonyl Derivatives......Page 1504 1.17.9 Heterocycle Syntheses via 1,2- and 1,4-Additions of Hydrazone Anions to Carbonyl Compounds and alpha,beta-Unsaturated Carbonyl Compounds......Page 1507 1.17.11 Cleavage of Hydrazones to Regenerate Carbonyl Groups......Page 1510 1.17.12 References......Page 1512 2.1.1 Introduction......Page 1514 2.1.2.1 Formaldehyde......Page 1515 2.1.2.2 Electron-Deficient Aldehydes......Page 1521 2.1.2.3 Aliphatic and Aromatic Aldehydes......Page 1524 2.1.2.4 Ketones......Page 1525 2.1.3.1 Type I Reactions......Page 1527 2.1.3.2 Type II Reactions......Page 1534 2.1.3.4 Type III Reactions and Other Reactions of Acetals......Page 1540 2.1.4 Thiocarbonyl Compounds......Page 1542 2.1.5 Addendum......Page 1543 2.1.6 References......Page 1545 2.2.1 Introduction......Page 1549 2.2.2 Mechanism......Page 1550 2.2.3.1 Allylsilanes......Page 1553 2.2.3.2 Allylstannanes......Page 1558 2.2.3.3 Allenyl-, Propargyl-, Vinyl- and Ethynyl-Silanes and -Stannanes......Page 1561 2.2.4.1 Allylsilanes......Page 1562 2.2.4.2 Allylstannanes......Page 1564 2.2.4.3 Allenyl-, Propargyl-, Vinyl- and Ethynyl-Silanes......Page 1565 2.2.5.1 Allylsilanes and Allylstannanes......Page 1566 2.2.5.2 Vinylsilanes and Ethynylstannanes......Page 1567 2.2.6.1 Allylsilanes......Page 1568 2.2.6.3 Allenyl- and Propargyl-Silanes and -Stannanes......Page 1573 2.2.6.4 Vinyl-Silanes and -Stannanes......Page 1574 2.2.7 References......Page 1576 2.3.1 Introduction......Page 1580 2.3.2.1 Formation of Alkyl Enol Ethers and Enol Esters......Page 1581 2.3.2.2 Formation of Enol Silyl Ethers and Silyl Ketene Acetals......Page 1584 2.3.2.3 Formation of Enol Stannyl Ethers......Page 1592 2.3.2.4 Other Enol Ethers......Page 1595 2.3.3.1 Uncatalyzed Aldol and Related Condensations......Page 1596 2.3.3.2 Catalyzed Addition to C-X pi-Bonds and Equivalents......Page 1597 2.3.5 References......Page 1610 2.4.1 Introduction......Page 1614 2.4.2.1 Lewis Acid Mediated Additions to Aldehydes......Page 1615 2.4.2.2 Fluoride Ion Mediated Additions to Aldehydes......Page 1618 2.4.2.4 Lewis Acid Mediated Additions to Imines......Page 1620 2.4.3.1 Diastereoselective Aldol Additions of Chiral Silyl Ketene Acetals and Chiral Silyl Enol Ethers......Page 1621 2.4.3.2 Diastereoselective Additions of Chiral Silyl Ketene Acetals to Imines......Page 1623 2.4.4 Chiral Electrophiles......Page 1624 2.4.4.1 Diastereoselective Additions to Chiral Carbonyl Compounds......Page 1625 2.4.4.2 Diastereoselective Addition to Chiral Imines, Nitrones and 4-Acetoxyazetidin-2-Ones......Page 1632 2.4.4.3 Diastereoselective Additions to Chiral Iminium, Oxonium and Thionium Ions......Page 1634 2.4.4.4 Diastereoselective Additions to Chiral Acetals......Page 1635 2.4.4.5 Intramolecular Diasteroselective Aldol-Type Additions......Page 1636 2.4.5.1 Diastereoselective Additions of Chiral Silyl Ketene Acetals to Chiral Aldehydes......Page 1637 2.4.6 Chiral Lewis Acids......Page 1639 2.4.7 Addendum......Page 1640 2.4.8 References......Page 1642 2.5 Reactions of Activated Dienes with Aldehydes......Page 1646 2.5.1.2 Aldehydes as Dienophiles......Page 1647 2.5.1.3 Lewis Acid Catalysis......Page 1648 2.5.2.1 Thermal and High-Pressure Reactions......Page 1649 2.5.2.2 Lewis Acid Catalyzed Reactions......Page 1650 2.5.2.3 Comparison of Lewis Acid Catalysis: Analysis of Reaction Conditions......Page 1658 2.5.3.1 Cram-Felkin and Anti Cram-Felkin Stereochemical Control......Page 1662 2.5.3.2 The Effect of Lewis Acids on Diastereofacial Selectivity......Page 1663 2.5.4 Methods to Control Absolute Stereochemistry......Page 1665 2.5.4.2 Chiral Catalysts......Page 1666 59299_v02_02_05b.pdf......Page 1671 2.5.5.1 Simple Monosaccharides......Page 1674 2.5.5.2 3-Deoxy-D-Manno-2-Octulopyranosate (KDO)......Page 1677 2.5.5.5 Hikosamine......Page 1679 2.5.5.7 Spectinomycin Analogs......Page 1681 2.5.5.8 Tunicaminyluracil......Page 1682 2.5.5.9 Vineomycinone B_2......Page 1683 2.5.5.11 Lantin......Page 1684 2.5.5.13 6-Deoxyerythronolide B......Page 1685 2.5.5.15 Monensin Lactone......Page 1686 2.5.5.16 Tirandamycin......Page 1687 2.5.5.17 Rifamycin S......Page 1688 2.5.5.18 Zincophorin......Page 1689 2.5.6 References......Page 1690 3.1.1 Introduction......Page 1692 3.1.2.1 Mechanistic Aspects......Page 1693 3.1.3.1 Intermolecular Acylations......Page 1694 3.1.3.2 The Formation of Cyclic Ketones......Page 1695 3.1.3.3 The Use of Protic Acid......Page 1696 3.1.4.2 Alkenylsilanes......Page 1697 3.1.4.3 Allylsilanes......Page 1701 3.1.4.4 Acylations of Other Unsaturated Silanes......Page 1704 3.1.5.1 Simple Dienes......Page 1705 3.1.5.2 Diene Complexes......Page 1706 3.1.6.1 Simple Alkynes......Page 1708 3.1.6.2 Alkynylsilanes......Page 1710 3.1.7.1 Lewis Acid Catalyzed Acylations of Stannanes......Page 1711 3.1.8 Acylations of Alkanes......Page 1712 3.1.9 Aliphatic Formylation......Page 1713 3.1.10 References......Page 1714 3.2.1 Introduction......Page 1717 3.2.2 Mechanisms......Page 1718 3.2.3.1 Catalysts......Page 1719 3.2.3.3 The Sequence of Addition of the Reagents......Page 1722 3.2.4.1 Reactions Carried out in the Absence of Catalysts......Page 1723 3.2.4.2 Reactions Using Lewis Acid Catalysts......Page 1724 3.2.5 Fries Reactions......Page 1729 3.2.6 Reactions Using Nitriles - The Houben-Hoesch Synthesis......Page 1731 3.2.7 Vilsmeier and Related Ketone Syntheses......Page 1732 3.2.9 Gattermann and Related Formylation Reactions......Page 1733 3.2.10 References......Page 1734 3.3.1 Introduction......Page 1737 3.3.2 Electron Density Considerations......Page 1738 3.3.3 The Size of the Ring......Page 1739 3.3.3.1 Reactions Leading to the Formation of Five-Membered Rings......Page 1740 3.3.3.2 Reactions Leading to the Formation of Six-Membered Rings......Page 1742 3.3.3.3 Reactions Leading to the Formation of Seven-Membered Rings......Page 1747 3.3.5 References......Page 1750 3.4.2 The Normal Reaction......Page 1753 3.4.3 Scope and Limitations......Page 1754 3.4.4.1 Regioselectivity......Page 1755 3.4.4.2 Industrial Applications......Page 1756 3.4.5 The 'Abnormal' Reimer-Tiemann Reaction......Page 1757 3.4.6 The Mechanism of the Reaction......Page 1758 3.4.8 References......Page 1759 3.5.1 Introduction......Page 1760 3.5.3.1 Carbocyclic Compounds......Page 1762 3.5.3.2 Heterocyclic Compounds......Page 1763 3.5.4.1 Alkene Derivatives without Electron-Releasing Substituents......Page 1764 3.5.4.2 Alkene Derivatives with Electron-Releasing Substituents and Their Equivalents......Page 1766 3.5.5.1 Aldehydes and Ketones......Page 1768 3.5.5.3 Amides, Lactams and Lactones......Page 1769 3.5.5.5 Benzylic Methyl and Methylene Groups......Page 1772 3.5.6.1 Oxygen Nucleophiles......Page 1773 3.5.7.1 Hydrazones and Semicarbazones......Page 1774 3.5.8 References......Page 1775 3.6 Acylation of Esters, Ketones and Nitriles......Page 1778 3.6.1 Introduction......Page 1779 3.6.2 Mechanism......Page 1780 3.6.3.2 Mixed Esters and Unsymmetrical Diesters......Page 1782 3.6.3.3 The Dieckmann Reaction......Page 1789 3.6.3.4 Application to Synthesis......Page 1800 3.6.4.1 Introduction......Page 1812 3.6.4.2 Generation and Use of Enolates and Enol Ethers......Page 1813 3.6.4.3 Ketones as Enols: Acid Catalysis of Acylation......Page 1815 59299_v02_03_06b.pdf......Page 1816 3.6.4.4 Regiochemistry of Acylation......Page 1818 3.6.4.5 Synthetic Applications of Intermolecular Acylation of Ketones......Page 1820 3.6.4.6 Intramolecular Acylation of Ketones......Page 1826 3.6.4.7 Intramolecular Acyl Transfer......Page 1828 3.6.5.1 Chiral beta-Dicarbonyl Synthons......Page 1829 3.6.6.1 Mechanism......Page 1831 3.6.6.3 Scope of the Reaction......Page 1832 3.6.6.5 Application to Synthesis......Page 1834 3.6.7 Tandem Reactions......Page 1835 3.6.8.2 Cleavage of beta-Diketones......Page 1838 3.6.9 Conclusions......Page 1840 3.6.10 References......Page 1842 3.7.1 Introduction......Page 1847 3.7.2.1 alpha-Thioiminium Salt Formation......Page 1849 3.7.2.2 Sulfide Contraction and Carbon-Carbon Bond Formation......Page 1851 3.7.3.1 Knoevenagel-Based Modification......Page 1855 3.7.3.2 Thio-Wittig Modification......Page 1856 3.7.3.3 Preparation of beta-Dicarbonyl Compounds......Page 1857 3.7.4.1 Dendrobatid and Other Neurotoxic Alkaloids......Page 1858 3.7.4.2 Pyrrolidine Alkaloids......Page 1863 3.7.4.3 Quinolizidine, Pyrrolizidine and Related Alkaloids......Page 1864 3.7.4.4 Phosphodiesterase Inhibitor Analogs......Page 1867 3.7.4.5 Antibiotics......Page 1869 3.7.4.6 Nucleoside Analogs......Page 1871 3.7.4.7 Macrocycles......Page 1872 3.7.5 References......Page 1874 4.1.1.1 Introduction......Page 1875 4.1.1.2 Earlier Reviews and Scope of this Chapter......Page 1876 4.1.1.3 Mechanism......Page 1877 4.1.1.4 Scope and Limitations......Page 1878 4.1.1.5 New Modifications......Page 1879 4.1.2.2 Acyclic N,N-Dialkyliminium Salts......Page 1880 4.1.2.3 Cyclic Iminium Salts......Page 1894 4.1.2.4 N-Silyl- and N,N-Disilyl-Iminium Salts......Page 1895 4.1.3.1 Introduction......Page 1897 4.1.3.2 Acyclic N-Aryl- and N-Alkyl-Imines......Page 1898 59299_v02_04_01b.pdf......Page 1908 4.1.3.3 N-Heterosubstituted Imines......Page 1916 4.1.3.4 In Situ Methods......Page 1923 4.1.3.5 Cyclic Imines......Page 1924 4.1.5 References......Page 1930 4.2.1 Introduction......Page 1934 4.2.2 Mechanisms......Page 1935 4.2.3.1 Aminoalkylation Reactions of Phenols......Page 1937 4.2.3.3 Aminoalkylation Reactions of Other Carbocyclic Compounds......Page 1942 4.2.3.4 Reactions with Electron-Rich Heterocyclic Systems......Page 1943 4.2.4.2 Reactions Leading to Cyclic Products and Their Reactions......Page 1949 4.2.5 Reactions Using Imines......Page 1951 4.2.6 Amidoalkylation Reactions......Page 1952 4.2.7 References......Page 1953 4.3.1.1 Reactivity and Structure......Page 1955 4.3.1.2 Regio- and Stereo-Chemistry......Page 1958 4.3.2.1 Using Allyl Organometallic Reagents......Page 1960 4.3.2.2 Using Crotyl Organometallic Reagents......Page 1968 4.3.2.3 Using Propargyl/Allenic Organometallics......Page 1972 4.3.3.2 Oximes and Oxime Ethers......Page 1974 4.3.3.3 Sulfenimines......Page 1978 4.3.3.5 Sulfonylimines......Page 1979 4.3.4.1 Using Preformed Iminium Salts......Page 1980 4.3.4.2 Using Iminium Salts Generated In Situ......Page 1982 4.3.5 Reactions with gem-Amino Ethers......Page 1983 4.3.6 References......Page 1986 4.4.1 Introduction......Page 1987 4.4.2 Cyclization with pi-Nucleophiles......Page 1989 4.4.2.1 Carbonyl Compounds......Page 1990 4.4.2.2 Acetals and Enol Ethers......Page 1993 4.4.2.3 Arenes......Page 1996 4.4.2.4 Alkenes......Page 2003 4.4.2.5 Alkynes......Page 2008 4.4.2.6 Organosilanes......Page 2010 4.4.2.7 Relative Reactivities of Intramolecular pi-Nucleophiles......Page 2016 4.4.3 Electron Transfer Induced Photocyclizations......Page 2017 4.4.4 Molecular Rearrangements Terminated by Mannich Cyclizations......Page 2020 4.4.5 References......Page 2024 4.5.1 Introduction......Page 2027 4.5.2.1 Methods to Generate N-Acyliminium Ions......Page 2028 4.5.2.3 Reaction Behavior......Page 2033 4.5.2.4 Reactivity Compared with Other Electrophilic Species......Page 2036 4.5.3.1 Intermolecular Reactions......Page 2037 4.5.3.2 Intramolecular Reactions......Page 2042 4.5.4.1 Intermolecular Reactions......Page 2046 4.5.4.2 Intramolecular Reactions......Page 2049 4.5.5.1 Intermolecular Reactions......Page 2050 4.5.5.2 Intramolecular Reactions......Page 2051 4.5.6.1 Intermolecular Reactions......Page 2054 4.5.6.2 Intramolecular Reactions......Page 2057 4.5.7 References......Page 2060 4.6.1 Introduction and Brief History of Isocyanide Chemistry......Page 2063 4.6.2.1 alpha-Acyloxycarboxamides......Page 2064 4.6.2.3 alpha-Hydroxyalkyltetrazoles......Page 2066 4.6.3.1 General Features, Scope and Limitations......Page 2067 4.6.3.3 Preparative Advantages......Page 2069 4.6.3.5 Stereochemical Course and Reaction Mechanism......Page 2070 4.6.3.6 Side Reactions......Page 2072 4.6.4.1 Peptide Coupling......Page 2074 4.6.4.2 alpha-Amino Acid Derivatives from Achiral Amines......Page 2075 4.6.4.3 Asymmetric Syntheses of alpha-Amino Acid and Peptide Derivatives......Page 2078 4.6.4.4 beta-Lactams......Page 2080 4.6.4.5 Macromolecules......Page 2084 4.6.6 References......Page 2086 Abbreviations......Page 2090 A......Page 2093 B......Page 2095 C......Page 2099 D......Page 2102 E......Page 2105 F......Page 2106 G......Page 2108 H......Page 2110 I......Page 2114 J......Page 2116 K......Page 2117 L......Page 2121 M......Page 2123 N......Page 2128 O......Page 2130 P......Page 2131 R......Page 2134 59299_v02_aindxc.pdf......Page 2135 S......Page 2136 T......Page 2143 U......Page 2145 V......Page 2146 W......Page 2147 Y......Page 2150 Z......Page 2151 A......Page 2152 B......Page 2162 C......Page 2167 D......Page 2173 E......Page 2175 F......Page 2179 G......Page 2180 H......Page 2181 I......Page 2183 59299_v02_sindxb.pdf......Page 2185 K......Page 2187 L......Page 2189 M......Page 2191 N......Page 2194 O......Page 2195 P......Page 2196 R......Page 2203 S......Page 2204 T......Page 2208 V......Page 2212 Z......Page 2213 Front Matter......Page 2215 Table of Contents......Page 2217 Preface......Page 2219 Contributors to Volume 3......Page 2221 Abbreviations......Page 2223 1.1.1 Introduction......Page 2226 1.1.2.1 Regiospecific Alkylations of Unsymmetrical Acyclic and Cyclic Ketones......Page 2228 1.1.2.2 Stereochemistry of Enolate Alkylations......Page 2237 1.1.2.3 Cycloalkylation Reactions of Saturated Ketones......Page 2243 1.1.2.4 Alkylations of Metal Enolates of Saturated Aldehydes......Page 2245 1.1.3 Alkylations of Metal Dienolates of alpha,beta-Unsaturated Ketones......Page 2246 1.1.4 Alkylations via Silyl Enol Ethers and Other Enol Derivatives......Page 2250 1.1.5.1 Regiochemistry and Stereochemistry of Alkylations of Nitrogen Derivatives of Carbonyl Compounds......Page 2253 59299_v03_01_01b.pdf......Page 2258 1.1.5.2 Enantioselective Syntheses via Alkylations......Page 2260 1.1.6.2 Diasteroselective Alkylations of Exocyclic and Endocyclic Enolates of Carboxylic Acid Derivatives......Page 2264 1.1.6.3 Diastereoselective Alkylations of Acyclic Enolates of Carboxylic Acid Derivatives......Page 2267 1.1.6.4 Diastereoselective Alkylations of Acyclic Carboxylic Acid Derivatives Containing Chiral Auxiliary Groups......Page 2269 1.1.6.5 Cycloalkylations of Enolates of Carboxylic Acid Derivatives......Page 2273 1.1.6.6 Alkylations of Dienolates of alpha,beta-Unsaturated Carboxylic Acid Derivatives......Page 2275 1.1.6.7 Asymmetric Synthesis via Alkylations of Anions of Masked Carboxylic Acid Derivatives......Page 2278 1.1.7.1 Alkylations of Monoanions of beta-Dicarbonyl and Related Compounds......Page 2279 1.1.8 References......Page 2283 1.2.1 Introduction......Page 2289 1.2.2.1 Acyclic Systems......Page 2292 1.2.2.2 Heterocyclic Systems......Page 2293 1.2.3.1 Mechanistic Aspects......Page 2296 1.2.3.2 Acyclic Systems......Page 2299 1.2.3.3 Heterocyclic Systems......Page 2300 1.2.4 References......Page 2306 1.3 Alkylations of Sulfur- and Selenium-Containing Carbanions......Page 2308 1.3.1 Introduction......Page 2309 1.3.2.1 Alkylation......Page 2311 1.3.2.2 Synthetically Useful Transformations of Alkylated Sulfides and Selenides......Page 2329 1.3.3.1 Alkylations of 1-Metallo-1,1-Dithioalkanes Bearing Hydrogen and/or Alkyl Groups on Their Carbanionic Center and Their Synthetic Applications......Page 2344 59299_v03_01_03b.pdf......Page 2349 1.3.3.2 Alkylations of 1,1-(Dithio)Allyl- and 1,1-(Dithio)Propargyl-Metals and Their Synthetic Uses......Page 2354 1.3.3.3 Alkylations of Acyl Anion Equivalents Containing at Least One Sulfur or Selenium on Their Carbanionic Center......Page 2357 1.3.4 alpha-Metalloorthothio- and alpha-Metalloorthoseleno-Formates, as Precursors of Esters......Page 2367 1.3.5.1 Reactions Involving Sulfoxides......Page 2370 1.3.5.2 Alkylations of alpha-Metallo-Alkyl and -Vinyl Selenoxides......Page 2380 1.3.6.1 Reactions Involving alpha-Metalloalkyl Sulfones......Page 2381 59299_v03_01_03c.pdf......Page 2388 1.3.6.2 Reactions Involving alpha-Metalloallyl Sulfones......Page 2391 1.3.6.3 Reactions Involving alpha-Metallovinyl Sulfones......Page 2396 1.3.6.4 Reactions Involving alpha-Metallo-alpha-Heterosubstituted Alkyl Sulfones......Page 2397 1.3.7 Alkylation of Sulfur Ylides......Page 2401 1.3.8 Alkylation of Alkyl Sulfonates, Sultones and Sulfonamides......Page 2403 1.3.9 References......Page 2405 1.4.2 Carbanions Stabilized by Oxygen......Page 2415 1.4.2.2 Preparation by Halogen-Metal Exchange......Page 2416 1.4.2.3 Preparation by Tin-Lithium Exchange......Page 2417 1.4.3.1 Allylic and Benzylic alpha-Alkoxy Carbanions......Page 2418 1.4.3.2 alpha-Alkoxy Carbanions from Protected Cyanohydrins......Page 2419 1.4.3.3 alpha-Alkoxy Carbanions Stabilized by Silicon......Page 2420 1.4.4 Carbanions Stabilized by Boron......Page 2421 1.4.6 Carbanions Stabilized by Phosphorus......Page 2422 1.4.7 Carbanions Stabilized by the Halogens......Page 2424 1.4.8 Carbanions Stabilized by Arsenic, Germanium, Tin, Antimony, Lead and Bismuth......Page 2425 1.4.9 References......Page 2426 1.5.1 Introduction......Page 2428 1.5.2.1 Preparation of the Reagents......Page 2429 1.5.2.2 Nature of the Reagents......Page 2431 1.5.2.3 Mechanism of the Reaction......Page 2434 1.5.2.4 Reactions with Organic Substrates......Page 2436 59299_v03_01_05b.pdf......Page 2447 1.5.3 Nickel and Palladium Catalysts......Page 2448 1.5.3.1 Organonickel Catalysis......Page 2449 1.5.3.2 Organopalladium Catalysis......Page 2451 1.5.4 References......Page 2454 1.6.1 Introduction......Page 2461 1.6.2.1 Alkylations of Vinyl and Aryl Grignard Reagents......Page 2462 1.6.2.2 Alkylations of Vinyl- and Aryl-Lithium Species......Page 2467 1.6.2.3 Alkylations of Heteroatom-Substituted Vinyl Carbanions......Page 2472 1.6.2.4 Alkylations of Allene Carbanions......Page 2476 1.6.2.5 Alkylations by an S_N 2' Process......Page 2477 1.6.3 Alkylations with Less Conventional Electrophiles......Page 2478 1.6.4 Alkylations of Vinyl and Aryl Carbanions, RM, Where M is not equal to Li, Mg or Cu......Page 2479 1.6.5 Alkylations of Heteroaromatic Carbanions......Page 2480 1.6.6 Alkylations at sp^2 -Centers Using Epoxides......Page 2482 1.6.7 References......Page 2486 1.7.2 Metallations of Alkynes......Page 2491 1.7.3.1 Alkylations with Alkyl Halides and Sulfates......Page 2492 1.7.3.2 Alkylations with Epoxides......Page 2497 1.7.3.3 Other Alkylation Reactions......Page 2501 1.7.4 Electrophilic Substitution of Haloalkynes......Page 2504 1.7.5.1 Macrolides......Page 2506 1.7.5.2 Sesquiterpenes......Page 2508 1.7.5.3 Leukotrienes and Prostaglandins......Page 2509 1.7.5.4 Non-Natural Products......Page 2510 1.7.6 References......Page 2511 1.8.1 Introduction......Page 2513 1.8.2.1 Alkylating Agents......Page 2514 1.8.2.2 Catalysts......Page 2515 1.8.3 Alkylation of Arenes......Page 2518 1.8.3.1 Alkylation with Alkyl Hal