Читать книгу Spiro Compounds - Группа авторов - Страница 4

1 Chapter 1Figure 1.1 Growing interest in spiro compounds in chemical literature.Figure 1.2 Dye sensitizer 9,9‐spirobifluorene.Figure 1.3 Donor–acceptor spiro compounds and colors displayed by them.Figure 1.4 Examples of naturally occurring compounds containing the spiro mo...Figure 1.5 Spiro functionality in nicotinic receptor antagonists.Figure 1.6 Examples of marketed spiro compound drugs.Figure 1.7 ACC inhibitors of pharmaceutical interest.Figure 1.8 Commercial spirocyclic insecticide/acaricide products.Figure 1.9 Recently patented spiro compound of agrochemical interest.Figure 1.10 Example of numbering of spirocyclic compounds.Figure 1.11 Example of naming chiral spiro compounds.

2 Chapter 2Figure 2.1 X‐ray crystal structure (pdb 2gfx¹²) of Platensimycin (2, sticks ...Scheme 2.1 Key enyne cycloisomerization step in Nicolaou’s total synthesis o...Figure 2.2 Schematic comparison of substituted biaryl and spiro[3,4]octane s...Figure 2.3 Examples of saturated spirocyclic ring systems frequently encount...Figure 2.4 Examples of lead optimization employing spirocycles.Scheme 2.2 Summary of common strategies for the synthesis of common four‐mem...Figure 2.5 Comparison between carbonyl, gem‐dimethyl, and oxetane groups, hi...Figure 2.6 (a) Spiro‐oxetane as a morpholine bioisostere. (b) comparison...Figure 2.7 Replacement of morpholine by 2‐oxa‐6‐azaspiro[3.3]heptane in BTK ...Figure 2.8 Top: Structure of thalidomide 34 and its oxetano analogue 35. Bot...Figure 2.9 Representative examples of spirocyclic bioactive lead molecules....Figure 2.10 Additional examples further illustrating the breadth of ring typ...Figure 2.11 Representative examples of (a) multifunctional spiro building bl...

3 Chapter 3Scheme 3.1 Scandium‐catalyzed enantioselective carboannulation between alkyl...Scheme 3.2 Copper‐catalyzed asymmetric [3+2] cycloaddition between alkyliden...Scheme 3.3 Copper‐catalyzed asymmetric construction of dispiropyrrolidine sk...Scheme 3.4 Magnesium‐catalyzed asymmetric [3+2] cycloaddition between methyl...Scheme 3.5 Rhodium‐catalyzed enantioselective [3+2] annulation to form spiro...Scheme 3.6 Palladium‐catalyzed stereoselective 1,6‐conjugate addition/annula...Scheme 3.7 Copper‐catalyzed asymmetric synthesis of spirocyclic β‐lactams th...Scheme 3.8 Bimetallic relay catalysis for the enantioselective synthesis of ...Scheme 3.9 Regio‐ and enantioselective aza‐Diels–Alder reactions of 3‐vinyli...Scheme 3.10 Ni‐catalyzed asymmetric Diels–Alder/[3,3]sigmatropic rearrangeme...Scheme 3.11 Scandium‐catalyzed asymmetric cycloaddition between ketenes and ...Scheme 3.12 Rhodium‐catalyzed [2+2+2] cycloadditions between alkynes and cyc...Scheme 3.13 Synergistic palladium/chiral secondary amine‐catalyzed formal ri...Scheme 3.14 Conjugate umpolung of β,β‐disubstituted enals and isatins promot...Scheme 3.15 Bifunctional squaramide‐catalyzed synthesis of enantioenriched s...Scheme 3.16 Chiral phosphoric acid‐catalyzed enantioselective 1,3‐dipolar cy...Scheme 3.17 Stereoselective synthesis of spiroindene via trienamine catalysi...Scheme 3.18 Organocatalytic [4+2] addition reactions via tetraenamine interm...Scheme 3.19 Chiral H‐bond donor‐catalyzed asymmetric Tamura [4+2]‐cycloaddit...Scheme 3.20 Enantioselective Diels–Alder cyclization for the synthesis of ca...Scheme 3.21 NHC‐catalyzed [4+3] annulation of oxotryptamines with enals to a...Scheme 3.22 Organocatalytic enamine‐activation of cyclopropanes for highly s...Scheme 3.23 Chiral primary amine‐catalyzed regiodivergent asymmetric cycload...Scheme 3.24 Organocatalytic asymmetric tandem Nazarov cyclization/semipinaco...Scheme 3.25 Chiral phosphoric acid‐catalyzed asymmetric synthesis of SPINOL ...

4 Chapter 4Figure 4.1 Natural and non‐natural products containing a spirocenter.Figure 4.2 List of ruthenium catalysts used in metathesis.Scheme 4.1 Synthesis of spirocyclic pyrazine.Scheme 4.2 Synthesis of chiral spiro‐connected cyclopentene.Scheme 4.3 Synthesis of spiro[4.5]–decanes.Scheme 4.4 Synthesis of spiro‐lactam.Scheme 4.5 Synthesis of spiro naphthalenone.Scheme 4.6 Synthesis of spiroketal 34.Scheme 4.7 Synthesis of spirocycles.Scheme 4.8 Efficient route to spiroannulated butanolide.Scheme 4.9 Synthesis of a spirocyclic amine 53.Scheme 4.10 Synthesis of spiro carba‐sugar using RCM.Scheme 4.11 Synthesis of novel spiro‐cyclohexene.Scheme 4.12 Synthesis of spiro‐heterocycle.Scheme 4.13 Synthesis of spiro‐center via an Ireland ester CR.Scheme 4.14 Synthesis of spirocyclic compounds through RCM.Scheme 4.15 Synthesis of spiro‐benzosultams.Scheme 4.16 Synthesis of spiro‐azetidine 91.Scheme 4.17 Synthesis of spiroannulated 3‐benzofuranone.Scheme 4.18 Asymmetric synthesis of spiroether.Scheme 4.19 Synthesis of spiro‐Meldrum’s acid derivative.Scheme 4.20 Synthesis of spiro‐lactone.Scheme 4.21 Synthesis of spirocycles starting with active methylene derivati...Scheme 4.22 Synthesis of spiro‐barbituric acid derivative.Scheme 4.23 Synthesis of spiroindolin‐2‐one derivatives.Scheme 4.24 Synthesis of spiro dibenzo[a,d]cycloheptene.Scheme 4.25 Synthesis of spiro‐carbohydrate 130.Scheme 4.26 Synthesis of sesquiterpenoid acorenone.Scheme 4.27 Synthesis of (+)‐spirocurcasone.Scheme 4.28 Synthesis of spiroindenes.Scheme 4.29 Synthesis of spiro‐bicyclo[2.2.2]octane 156.Scheme 4.30 Synthesis of oxaspirocyclic compound.Scheme 4.31 Synthesis of spiro‐fused compounds 165.Scheme 4.32 Synthesis of C‐spiro‐glycoconjugate 168.Scheme 4.33 Synthesis of spiro‐indole derivatives.Scheme 4.34 Synthesis of bis‐spirocycles.Scheme 4.35 Synthesis of bis‐spiro tetralone.Scheme 4.36 Synthesis of spiro‐bicyclic compound 189.Scheme 4.37 Synthesis of spirodione.Scheme 4.38 Synthesis of spiro‐polycyclic compounds.Scheme 4.39 Synthesis of spiro‐fluorene 204.Scheme 4.40 Synthesis of spiro‐truxene 208.Scheme 4.41 Efficient route to (+)‐perhydrohistrionicotoxin.Scheme 4.42 Synthesis of spirocyclic compound 218.Scheme 4.43 Synthesis of spiropiperidine‐3,3‐oxindole.Scheme 4.44 Construction of spiro‐mononitrogen heterocycle.Scheme 4.45 Synthesis of natural product nankakurine.Scheme 4.46 Synthesis of oxa‐aza spiro‐carbohydrate.Scheme 4.47 Synthesis of carbohydrate derivative 243.Scheme 4.48 Synthesis of spiro‐dihydropyran.Scheme 4.49 Synthesis of carbohydrate‐derived spiroacetal 252.Scheme 4.50 Synthesis of spirocyclic 3,6‐dihydro‐2H‐pyran 250.Scheme 4.51 Synthesis of spirocyclic oxindole 261.Scheme 4.52 Synthesis of spirocyclic ether 267.Scheme 4.53 Synthesis of spiroannulated carbanucleoside.Scheme 4.54 Synthesis of spirocyclic‐2‐azetidinone.Scheme 4.55 Synthesis of spirocyclic butenolide 280.Scheme 4.56 Synthesis of spiro‐2‐oxazolidinone.Scheme 4.57 Synthetic approach to (+)‐laurencin.Scheme 4.58 Synthesis of spiro oxacycles.Scheme 4.59 Synthesis of ABC ring of nortriterpenoid.Scheme 4.60 Synthesis of spiro‐C‐aryl glycoside.Scheme 4.61 Synthesis of cyclic phosphazene.Scheme 4.62 Synthesis of spiroketal 318.Scheme 4.63 Synthesis of anomeric spiroketal 325.Scheme 4.64 Synthesis of spiroketal 331.Scheme 4.65 RRM approach to azepine derivatives.Scheme 4.66 Synthesis of oxa‐spirocycle.Scheme 4.67 RCM of bisallyloxy cyclobutenone to oxa‐spirocycle.Scheme 4.68 Synthesis of spiro‐cage derivative.Scheme 4.69 Synthesis of bis‐oxaspirocycle.Scheme 4.70 Synthesis of oxaspirocycles.Scheme 4.71 Synthesis of spiro indene.Scheme 4.72 Synthesis of spirocycle containing silicon at spioro junction....

5 Chapter 5Figure 5.1 Selected natural products and bioactive molecules containing a sp...Figure 5.2 Asymmetric synthesis of various spirooxindoles via organocatalyti...Scheme 5.1 Double Michael cascade reaction enabled by enamine/iminium sequen...Scheme 5.2 Asymmetric double Michael reactions involving isatylidene malonon...Scheme 5.3 Spirocyclobutaneoxindole synthesis by a stereoselective [2+2] cyc...Scheme 5.4 Three‐component reaction by enamine/iminium/enamine sequential ca...Scheme 5.5 Multicomponent domino reactions by quadruple iminium/enamine/imin...Scheme 5.6 Stereoselective Diels–Alder reaction enabled by trienamine cataly...Scheme 5.7 Asymmetric hetero‐Diels–Alder reaction of α,β‐unsaturated ketones...Scheme 5.8 Asymmetric Michael/Michael/aldol reaction of 3‐unsubsituted oxind...Scheme 5.9 Asymmetric vinylogous cascade reaction of 2,4‐dienals with 3‐hydr...Scheme 5.10 Michael/cyclization sequence of 3‐chlorooxindoles to spirocyclop...Scheme 5.11. Synthesis of spirocyclopentaneoxindoles with 3‐alkyloxindoles 4...Scheme 5.12 Stereoselective Michael/cyclization sequence of 3‐propargyl oxin...Scheme 5.13 Desymmetric intramolecular aldol condensation of 3,3′‐diacetonyl...Scheme 5.14 Chiral phosphine‐catalyzed [3+2] cycloaddition of allene and met...Scheme 5.15 [4+2] Annulation of isatylidene malononitriles and α‐substituted...Scheme 5.16 Asymmetric [3+2] cycloaddition of oxindole‐derived olefins with ...Scheme 5.17 Phosphine‐catalyzed [3+2] annulation of isatin‐derived MBH carbo...Scheme 5.18 Chiral tertiary amines‐catalyzed [3+2] annulation of isatin‐deri...Scheme 5.19 [4+2]‐Cycloaddition of α,β‐unsaturated acyl chlorides by nucleop...Scheme 5.20 Asymmetric [3+2]‐cycloaddition of brominated MBH adducts and ket...Scheme 5.21 Allylic alkylation–cyclization of 3‐hydroxyoxindoles with MBH ca...Scheme 5.22 Chiral NHC‐catalyzed asymmetric annulation involving isatins.Scheme 5.23 Spirooxindole‐δ‐lactones synthesis by NHC‐catalyzed formal [4+2]...Scheme 5.24 Spirooxindole lactams synthesis by NHC‐catalyzed annulation with...Scheme 5.25 Chiral NHC‐catalyzed annulation involving isatin‐derived enals....Scheme 5.26 Stereoselective annulation of isatin‐derived enals with α,β‐unsa...Scheme 5.27 Chiral NHC‐catalyzed asymmetric Michael/aldol/lactonization casc...Scheme 5.28. NHC‐catalyzed annulation with 3‐aminooxindoles or 3‐hydroxyoxin...Scheme 5.29. Tertiary amine‐H bond donor‐catalyzed asymmetric annulation inv...Scheme 5.30. Asymmetric intramolecular [1,5]‐electrocyclization of functiona...Scheme 5.31 Asymmetric annulation of isatin imine by tertiary amine‐H bondin...Scheme 5.32 Asymmetric annulation of methyleneindolinones via double Michael...Scheme 5.33 Asymmetric annulation of methyleneindolinones via Michael‐initia...Scheme 5.34 Asymmetric annulation using isatylidene malononitriles as C2 syn...Scheme 5.35 Asymmetric annulation using isatylidene malononitriles as C3 syn...Scheme 5.36 Asymmetric annulation involving isatin‐derived β,γ‐unsaturated α...Scheme 5.37 Asymmetric annulation involving C3 alkyl ester‐substituted oxind...Scheme 5.38 Asymmetric annulation involving 3‐allyloxindoles.Scheme 5.39 Asymmetric annulation involving 3‐isothiocyanato oxindoles.Scheme 5.40 Asymmetric [4+1] cyclization of 3‐chlorooxindoles with o‐QMs....Scheme 5.41 Asymmetric cyclopropanation of 3‐unsubstituted oxindoles with α‐...Scheme 5.42 One‐pot Michael/Michael/aldol tandem reaction involving 3‐unsubs...Scheme 5.43 Asymmetric desymmetrization of spiro cyclohexadienone oxindoles....Scheme 5.44 Enantioselective Diels–Alder reaction of methyleneindolinones wi...Scheme 5.45 Asymmetric [3+2] cycloaddition of methyleneindolinone and nitron...Scheme 5.46 Asymmetric MCR of diazooxindoles, nitrosoarenes, and nitroalkene...Scheme 5.47 Enantioselective cyclization reaction of isatin and 2‐aminobenza...Scheme 5.48 Asymmetric three‐component 1,3‐dipolar cycloaddition by phosphor...Scheme 5.49 Asymmetric three‐component 1,3‐dipolar cycloaddition.Scheme 5.50 Asymmetric three‐component 1,3‐dipolar cycloaddition.Scheme 5.51 Chiral phosphoric acid‐catalyzed cycloaddition with methyleneind...Scheme 5.52 [3+2] Cycloaddition of isatin‐derived 3‐indolylmethanols and 2‐v...Scheme 5.53 Chiral phosphoric acid‐catalyzed kinetic resolution of racemic s...Scheme 5.54 Asymmetric double Michael cascade reaction of 3‐alkenyloxindoles...Scheme 5.55 Enantioselective 1,3‐dipolar cycloaddition of 3‐alkenyloxindoles...Scheme 5.56 Intramolecular C‐acylation of 3‐substituted oxindoles 320 by PTC...Scheme 5.57 Enantioselective direct intramolecular C(sp²)–H/C(sp³)–H oxidati...Scheme 5.58 Chiral organoiodine‐catalyzed oxidative dearomatization of pheno...

6 Chapter 6Figure 6.1 Some representative examples of biologically active natural and s...Scheme 6.1 Overman’s approach to (−)‐spirotryprostratin B.Scheme 6.2 Catalytic asymmetric intramolecular Heck synthesis of a spirocycl...Scheme 6.3 Takemoto’s tandem cycloamidation of 2‐(butadienyl)phenylcarbamoyl...Scheme 6.4 Takemoto’s racemic synthesis of spirooxindole alkaloids elacomine...Scheme 6.5 Spirocyclization of α‐substituted tosylamines and proposed mechan...Scheme 6.6 Reductive Heck cyclization in Carreira’s synthesis of gelsemoxoni...Scheme 6.7 Pd(0)‐catalyzed spirooxindole synthesis from isatin‐derived Morit...Scheme 6.8 Enantioselective synthesis of 2‐oxindole spirofused lactones by a...Scheme 6.9 Enantioselective synthesis of 2‐oxindole spirofused lactams by a ...Scheme 6.10 Charette’s synthesis of spiro 3,3′‐cyclopropyloxindoles by silve...Scheme 6.11 Oxidation of N‐aryl‐2‐oxocycloalkane‐1‐carboxamides with Mn(OAc)Scheme 6.12 Aluminum‐promoted cyclization in Trost’s asymmetric synthesis of...Scheme 6.13 Córdova’s asymmetric synthesis of polysubstituted spirocyclic ox...Scheme 6.14 Proposed catalytic cycle for Córdova’s asymmetric synthesis of p...Scheme 6.15 Iron(II)‐catalyzed asymmetric intramolecular aminohydroxylation ...Scheme 6.16 Rhodium(II)‐catalyzed cyclopropanation of 3‐diazo‐2‐oxindole 38....Scheme 6.17 Rhodium(II)‐catalyzed cyclopropanation of 3‐diazo‐2‐oxindole 38....Scheme 6.18 Arai’s rhodium(II)‐catalyzed asymmetric cyclopropanation of 3‐di...Scheme 6.19 Zhou’s mercury(II)‐catalyzed asymmetric cyclopropanation of 3‐di...Scheme 6.20 Zhou’s gold(I)‐catalyzed asymmetric cyclopropanation of 3‐diazo‐...Scheme 6.21 Feng’s magnesium(II)‐catalyzed asymmetric cyclopropanation of al...Scheme 6.22 Feng’s scandium(III)‐catalyzed asymmetric cycloaddition of disub...Scheme 6.23 Carreira’s MgI₂‐catalyzed ring expansion of spiro(cyclopropane‐1...Scheme 6.24 Proposed mechanism for the MgI₂‐catalyzed reaction of spiro(cycl...Scheme 6.25 Ring expansion of a spiro(cyclopropane‐1,3′‐oxindole) in the syn...Scheme 6.26 Ring expansion of a spiro(cyclopropane‐1,3′‐oxindole) in Carreir...Scheme 6.27 Ring expansion of a spiro(cyclopropane‐1,3′‐oxindole) in Carreir...Scheme 6.28 Carboxylative Pd‐catalyzed TMM cycloaddition to an isopropyliden...Scheme 6.29 Enantioselective carboxylative Pd‐catalyzed TMM cycloaddition to...Scheme 6.30 Enantioselective Cu(I)‐catalyzed 1,3‐dipolar cycloaddition of az...Figure 6.2 Proposed structure of the tetrahedral complex formed by coordinat...Scheme 6.31 Enantioselective Ag(I)‐catalyzed 1,3‐dipolar cycloaddition of az...Scheme 6.32 Franz’s titanium(IV)‐catalyzed stereoselective synthesis of spir...Scheme 6.33 Franz’s scandium(III)‐catalyzed asymmetric [3+2] annulation of a...Scheme 6.34 Franz’s enantioselective allylsilane annulation and C–Si oxidati...Scheme 6.35 Franz’s titanium(IV)‐catalyzed diastereoselective synthesis of s...Scheme 6.36 Franz’s scandium(III)‐catalyzed enantioselective synthesis of a ...Scheme 6.37 Franz’s scandium(III)‐catalyzed enantioselective [3+2] carboannu...Scheme 6.38 Franz’s scandium(III)‐catalyzed enantioselective [3+2] carboannu...Scheme 6.39 Feng’s magnesium(II)‐catalyzed enantioselective [3+2] cycloaddit...Scheme 6.40 Lu’s palladium(0)‐catalyzed enantioselective [3+2] cycloaddition...Scheme 6.41 Proposed mechanism for the palladium(0)‐catalyzed enantioselecti...Scheme 6.42 Mei’s palladium(0)‐catalyzed enantioselective [3+2] cycloadditio...Scheme 6.43 Du’s rhodium(0)‐catalyzed enantioselective [3+2] cycloaddition o...Scheme 6.44 Asymmetric one‐pot sequential organo‐ and gold(I)‐catalyzed Mann...Scheme 6.45 Trost’s dinuclear zinc‐catalyzed asymmetric spiroannulation reac...Scheme 6.46 Kanai–Matsunaga’s strontium‐catalyzed asymmetric synthesis of 3‐...Scheme 6.47 Chen‐Xiao’s zinc(II)‐catalyzed enantioselective cascade Michael ...Scheme 6.48 Yan‐Zhou’s nickel(II)‐catalyzed diastereo‐ and enantioselective ...Scheme 6.49 Ashfeld’s rhodium‐catalyzed formal [4+1] cycloaddition route to ...Scheme 6.50 Ashfeld’s rhodium‐catalyzed formal [4+1] cycloaddition syntheses...Scheme 6.51 Lin‐Feng’s zinc‐catalyzed asymmetric Diels–Alder reaction of a B...Scheme 6.52 Kumar’s dysprosium‐catalyzed asymmetric hetero‐Diels–Alder react...Scheme 6.53 Kumar’s magnesium‐catalyzed asymmetric hetero‐Diels–Alder reacti...Scheme 6.54 Tanaka’s enantioselective synthesis of spirocyclic benzopyranone...Scheme 6.55 Shintani–Hayashi’s stereoselective synthesis of spirocyclic oxin...Scheme 6.56 Proposed catalytic cycle for the palladium‐catalyzed decarboxyla...Scheme 6.57 Liu–Feng’s nickel‐catalyzed asymmetric aza‐Diels–Alder reaction ...Scheme 6.58 Liebeskind’s enantioselective synthesis of spirooxindoles based ...Scheme 6.59 Feng’s cobalt‐catalyzed asymmetric Darzens reaction of phenacyl ...Scheme 6.60 Wang’s zinc‐catalyzed enantioselective desymmetrization/cyclizat...Scheme 6.61 Shanmugam’s copper(I)‐catalyzed one‐pot, three‐component diaster...Scheme 6.62 A plausible mechanism of the copper(I)‐catalyzed three‐component...

7 Chapter 7Scheme 7.1 Synthesis of spiropyrrolidines by Mikami.Scheme 7.2 Asymmetric construction of a dispiropyrrolidine by Yu and Deng....Scheme 7.3 Silver phosphate‐catalyzed asymmetric intramolecular dearomatizat...Scheme 7.4 Enantioselective [4+1] spiroannulation catalyzed by Rh.Scheme 7.5 Chiral phosphine‐catalyzed synthesis of spiropyrrolidines reporte...Scheme 7.6 Organocatalyzed asymmetric formal [3+2] cycloaddition of isocyano...Scheme 7.7 The combination photoredox and primary amine catalysis used at th...Scheme 7.8 Enantioselective synthesis of spiroindolenines reported by You....Scheme 7.9 Enantioselective construction of spiroindolenines catalyzed by Pd...Scheme 7.10 Enantioselective synthesis of spiroindolines by intramolecular d...Scheme 7.11 Enantioselective organocatalyzed cascade reactions to spiroindol...Scheme 7.12 Application of chiral phosphoric acid for the preparation of spi...Scheme 7.13 Oxidative N‐heterocyclic carbene catalyzed dearomatization of in...Scheme 7.14 Enantioselective access to gem‐difluorinated spiroindolines.Scheme 7.15 Enantioselective synthesis of spiroindolines via cascade reactio...Scheme 7.16 Enantioselective synthesis of spirobilactams reported by Cai....Scheme 7.17 Enantio‐ and diastereoselective Pd‐catalyzed carbocyclization ca...Scheme 7.18 Pd‐catalyzed asymmetric intramolecular arylative dearomatization...Scheme 7.19 Iridium‐catalyzed intramolecular asymmetric allylic dearomatizat...Scheme 7.20 Enantioselective organocatalyzed formal [3+3] spiroannulation re...Scheme 7.21 NHC‐catalyzed enantioselective synthesis of spiropiperidinones r...Scheme 7.22 Asymmetric dearomative formal [4+2] cycloadditions published by ...Scheme 7.23 Enantioselective ene‐type spirocyclization developed by Mikami....Scheme 7.24 Enantioselective 1,6‐conjugate addition/annulation of para‐quino...Scheme 7.25 Enantioselective synthesis of spirodihydrofuranes developed by S...Scheme 7.26 The enantioselective synthesis of spirolactones reported by Gade...Scheme 7.27 Asymmetric copper‐catalyzed preparation of spirotetrahydropyrane...Scheme 7.28 Enantioselective dearomatization of phenols using chiral hyperva...Scheme 7.29 Chiral hypervalent organoiodine‐catalyzed enantioselective oxida...Scheme 7.30 Enantioselective oxidative dearomatization of arenols using chir...Scheme 7.31 Asymmetric synthesis of spiro‐2(3H)‐furanones via phase‐transfer...Scheme 7.32 Enantioselective construction of spirocyclic benzofuranone cyclo...Scheme 7.33 Asymmetric tandem synthesis of spirocyclic (2H)‐dihydrobenzofura...Scheme 7.34 The enantioselective synthesis of spirobenzofuranones reported b...Scheme 7.35 The catalytic asymmetric one‐pot [3+2] cyclization/semipinacol r...Scheme 7.36 Reaction mechanism.Scheme 7.37 Organocatalytic synthesis of spirobenzofuranones via cascade Mic...Scheme 7.38 Two approaches to chiral spirocyclic benzofuranones by using ami...Scheme 7.39 The enantioselective approaches leading to spirocyclic compounds...Scheme 7.40 Organocatalytic asymmetric double Michael addition and Michael/a...Scheme 7.41 Asymmetric construction of spirocyclopentenebenzofuranone core s...Scheme 7.42 Application of trienamine catalysis for the construction of spir...Scheme 7.43 Asymmetric synthesis of pyrrolidine‐ and tetrahydrothiophene‐fus...Scheme 7.44 Catalytic asymmetric brominative or chlorinative dearomatization...Scheme 7.45 The synthesis of spiro‐heterocycles by the NHC‐catalyzed annulat...Scheme 7.46 The enantioselective formal [2+1+3] annulation forming spirocycl...Scheme 7.47 Enantioselective ring expansion of vinyl cyclopropanes combining...Scheme 7.48 Catalytic enantioselective synthesis of spirocycles 13.Scheme 7.49 Enantioselective synthesis of spirocyclic benzopyranones by rhod...Scheme 7.50 Enantioselective organometallic approach to chiral spirobenzopyr...Scheme 7.51 Enantioselective synthesis of a‐spirocyclopropyl lactones.Scheme 7.52 Asymmetric synthesis of 3,4‐dihydrocoumarin motif in spirocycle ...Scheme 7.53 Synthesis of highly substituted chiral spirodihydrocoumarins....Scheme 7.54 Organocatalytic tandem Morita–Baylis–Hillman–Michael reaction fo...Scheme 7.55 A chiral squaramide‐catalyzed approach constructing spiro‐3,4‐di...Scheme 7.56 Construction of spiro‐bridged polyheterocyclic compounds.Scheme 7.57 The synthesis of spirocycle compounds via enantioselective organ...Scheme 7.58 Catalytic desymmetrizing dehydrogenation of 4‐substituted cycloh...Scheme 7.59 Enantioselective synthesis of spirocyclic compounds containing b...Scheme 7.60 Asymmetric synthesis of spirocyclic tetrahydrothiophene‐chromano...Scheme 7.61 Enantioselective synthesis of spiro compounds containing tetrahy...Scheme 7.62 Enantioselective construction of polyfunctionalized spiroannulat...Scheme 7.63 A chiral fluoride‐catalyzed asymmetric cascade sulfa‐Michael/ald...Scheme 7.64 Enantioselective synthesis of spirocyclic compounds containing b...Scheme 7.65 Enantioselective synthesis of spirocyclic compounds containing b...Scheme 7.66 The enantioselective approach provides chiral spiro[thiopyranoin...Scheme 7.67 NHC‐catalyzed enantioselective dearomatizing hydroacylation of b...Scheme 7.68 Asymmetric synthesis of spiropyrazolones by complex of rhodium‐c...Scheme 7.69 Enantioselective vinylogous Michael/aldol reaction to synthesize...Scheme 7.70 Highly stereoselective synthesis of spiropyrazolones reported by...Scheme 7.71 The synthesis of unsymmetrical diaryl‐substituted spirocyclohexa...Scheme 7.72 The synthesis of spiropyrazolones via organocatalytic Michael/Mi...Scheme 7.73 Three‐component Michael/Michael/aldol reaction cascade reported ...Scheme 7.74 Asymmetric synthesis of spiropyrazolones through phosphine‐catal...Scheme 7.75 Asymmetric, three‐component, and one‐pot synthesis of spiropyraz...Scheme 7.76 Mechanism of asymmetric, three‐component, one‐pot synthesis of s...Scheme 7.77 Diastereo‐ and enantioselective construction of cyclohexanone‐fu...Scheme 7.78 Lewis‐base‐catalyzed asymmetric [3+3] annulation reaction of Mor...Scheme 7.79 Asymmetric synthesis of spirocyclohexene pyrazolones via formal ...Scheme 7.80 Enantioselective synthesis of pyrazolone‐fused spirocyclohexenol...Scheme 7.81 Diastereodivergent and enantioselective access to spiroepoxides....Scheme 7.82 Synthesis of chiral pyrazolone and spiropyrazolone derivatives t...Scheme 7.83 NHC‐catalyzed asymmetric formal [4+2] annulation to construct sp...Scheme 7.84 Asymmetric synthesis of spiropyrazolones by sequential organo‐ a...Scheme 7.85 Michael/Conia‐ene cascade reaction under synergistic catalysis p...Scheme 7.86 Diastereoselective and enantioselective synthesis of barbiturate...Scheme 7.87 The enantioselective approaches to spirobarbiturates by using ch...Scheme 7.88 Isothiocyanate strategy for the synthesis of spirocyclic barbitu...Scheme 7.89 Palladium‐catalyzed enantioselective synthesis of spirocyclic az...Scheme 7.90 Application of chiral phosphine in organocatalytic synthesis of ...Scheme 7.91 Anderson’s synthesis of spirocyclic azlactones.Scheme 7.92 Formal [3+2] cycloaddition of vinylcyclopropane azlactones to en...Scheme 7.93 Enantioselective access to spirocyclic sultams by chiral Cp^x–rho...Scheme 7.94 The synthesis of chiral spirosultams by multi sequential reactio...Scheme 7.95 Asymmetric construction of spirocyclic pyrrolidine‐thiazolidined...Scheme 7.96 The enantioselective cycloaddition of cyclic enones with sultams...Scheme 7.97 Asymmetric construction of spiro thiopyrano‐indole‐benzoisothiaz...Scheme 7.98 Enantioselective synthesis of chiral spirocycles containing rhod...Scheme 7.99 Asymmetric synthesis of highly functionalized spirothiazolidinon...Scheme 7.100 Enantioselective construction of spiro chroman‐thiazolones.Scheme 7.101 Catalytic asymmetric synthesis of aromatic spiroketals.Scheme 7.102 Enantio‐ and diastereoselective spiroketalization catalyzed by ...Scheme 7.103 Asymmetric synthesis of spiroketals and spiroaminals.Scheme 7.104 Chiral phosphoric acid‐catalyzed enantioselective and diastereo...Scheme 7.105 Organohalogenite‐catalyzed spiroketalization.Scheme 7.106 Stereoselective three‐component reaction of salicylaldehydes, a...Scheme 7.107 The enantioselective synthesis spiropyrrolidines containing dih...Scheme 7.108 Asymmetric synthesis of spirocyclic β‐lactams through copper‐ca...Scheme 7.109 Hetero‐Diels−Alder process used for the synthesis of spiropyrro...Scheme 7.110 The enantioselective fluorocyclization catalyzed by chiral BINO...Scheme 7.111 Enantioselective cycloaddition to trisubstituted nitroolefins t...Scheme 7.112 Enantioselective access to dispirooxindoles from furfurylcyclob...Scheme 7.113 The enantioselective synthesis of bis‐spiroketals.Scheme 7.114 Highly efficient enantioselective synthesis of bispiro benzofur...

8 Chapter 8Figure 8.1 Common strategies for the synthesis of spirocycles: (a) alkylatio...Scheme 8.1 Spirocyclizations reported by Gade.Scheme 8.2 Spirocyclization reported by Takisawa.Scheme 8.3 Spirocyclization reported by Smith.Scheme 8.4 Synthesis of spirocycles reported by Hashimoto et al.Scheme 8.5 Synthesis of spirofuranes and spiropyrrolidines reported by Mikam...Scheme 8.6 Nicolaou synthesis of platensimycin.Figure 8.2 Proposed mechanism for the Rh‐catalyzed synthesis of spirocycles ...Scheme 8.7 Rh–catalyzed synthesis of spirocycles reported by Shintani and Ha...Scheme 8.8 First asymmetric palladium‐catalyzed synthesis of spirocycles.Scheme 8.9 Pd‐catalyzed synthesis of spirocycles reported by Mikami.Scheme 8.10 Pd‐catalyzed spirocyclization of allyl propargyl ethers.Scheme 8.11 Pd‐catalyzed spirocyclization reported by Toste.Scheme 8.12 Spirocyclization reported by Cai.Scheme 8.13 Spirocyclization reported by Dixon.Scheme 8.14 Spirocyclization reported by Luan.Scheme 8.15 [2+2+2] Cycloaddition reported by Shibata et al.Scheme 8.16 [2+2+2] Cycloaddition with unsymmetrical dialkynes.Scheme 8.17 Synthesis of spirocyclanes via a [2+2+2] cycloaddition reported ...Figure 8.3 Proposed mechanism by Tanaka.Scheme 8.18 [2+2+2] Spirocyclization reported by Tanaka.Scheme 8.19 Copper‐catalyzed enantioselective Diels–Alder reaction.Scheme 8.20 [3+2] Cycloaddition reported by C.‐J. Wang.Scheme 8.21 Spirocyclization reported by Deng.Scheme 8.22 Spirocyclizations reported by Trost and Zhao.Scheme 8.23 Spirocyclization reported by Liu.Scheme 8.24 Spirocyclization reported by Rios.Scheme 8.25 Spirocyclization reported by Liu.Scheme 8.26 Enantioselective PET reaction developed by Bach.Scheme 8.27 Synthesis of spirocyclic β‐lactones developed by Romo.Scheme 8.28 Cascade reaction reported by Wang.Scheme 8.29 Spirocyclization reported by Xie.Scheme 8.30 Spirocyclization reported by Chen.Scheme 8.31 Spirocyclization reported by Jørgensen.Scheme 8.32 Spirocyclopropanation of benzofulvenes.Scheme 8.33 Spirocyclization reported by Lin.Scheme 8.34 Spirocyclization reported by Rodriguez and Bonne.Scheme 8.35 Spirocyclization reported by Li.Scheme 8.36 α‐ketol rearrangement reported by Tu.Scheme 8.37 Ring expansion reported by Takisawa.Scheme 8.38 Spirocyclization reported by Zhang.Scheme 8.39 Spirocyclization reported by Zhang.

9 Chapter 9Scheme 9.1 Intramolecular dearomative reaction of para‐substituted phenol.Scheme 9.2 Proposed dearomative reaction pathway.Scheme 9.3 Preliminary enantioselective construction of all‐carbon spirocent...Scheme 9.4 Synthesis of spiro[4.5]decane core architecture via dearomative s...Scheme 9.5 Iridium‐catalyzed asymmetric allylic dearomatization of phenols....Scheme 9.6 C‐alkylation for ortho‐substituted naphthols.Scheme 9.7 Intramolecular dearomative reaction of alkyne‐substituted phenol....Scheme 9.8 Intermolecular dearomative spiroannulation of phenol and iodobenz...Scheme 9.9 Strategy for dearomative arylation of phenols.Scheme 9.10 Preliminary results of asymmetric dearomative arylation of pheno...Figure 9.1 Natural erythrina alkaloids.Scheme 9.11 Pd(0)‐catalyzed intramolecular arylative coupling of 5‐hydroxyl ...Scheme 9.12 Preliminary asymmetric studies for constructing erythrinane skel...Scheme 9.13 Proposed one‐step construction of spirocarbocycles and potential...Scheme 9.14 A DYKAT of phenolic derivative via axial‐to‐central chirality tr...Scheme 9.15 Palladium‐catalyzed dynamic kinetic asymmetric transformation.Scheme 9.16 [3+2] Spiroannulation of phenol‐derived biaryls and diynes.Scheme 9.17 Formal [2+2+1] cycloaddition routes to new tricycles.Scheme 9.18 Ru^II‐catalyzed dearomative spiroannulation of naphthols via C(spFigure 9.2 Proposed mechanism of C–H bond activation/dearomative reaction.Scheme 9.19 Spiroannulation of 2‐arylphenols via C–H activation/dearomative ...Scheme 9.20 Pd‐catalyzed oxidative dearomatization of free naphthols.Scheme 9.21 [2+2+1] Spiroannulation of unsymmetrical alkynes.Scheme 9.22 Spirocyclopentadienes of 2‐alkenylphenols and alkynes.Scheme 9.23 Spirocyclopentadienes of 2‐alkenylphenols and conjugated enynes....Scheme 9.24 Three‐component dearomatizing [2+2+1] spiroannulation.Scheme 9.25 Preliminary studies on the synthetic application of dearomatizin...Scheme 9.26 Pd/NBE‐catalyzed C–H activation/arene dearomatization reaction....Scheme 9.27 [4+1] Spiroannulation by C(sp³)‐H activation and naphthol dearom...Scheme 9.28 Ir‐catalyzed asymmetric allylic alkylation for constructing spir...Scheme 9.29 Allylic dearomatization for the synthesis of spiro cyclopentene‐...Figure 9.3 The energetic barrier of transition states.Scheme 9.30 Dearomative arylation of indoles for spiroindolenine derivatives...Scheme 9.31 Dearomatization of C2‐substitued indoles for spirooxindoles.Scheme 9.32 Synthesis of the core structure of phalarine.Scheme 9.33 Process of gold‐catalyzed intramolecular alkyne hydroarylation....Scheme 9.34 Dearomatization of aromatic ynones for spirocyclic scaffolds.Scheme 9.35 One‐pot spirocyclization/trapping to form tetracycles.Scheme 9.36 Scaffolds for the synthesis of spirocyclic indole derivatives.Scheme 9.37 Intermolecular spirocyclization of indoles and propargyl carbona...Figure 9.4 Novel spiroindolenine products.Scheme 9.38 Stepwise synthesis spirocyclic indolines of indoles with allyl a...Scheme 9.39 Pd/NBE‐catalyzed intermolecular dearomative spiroannulation of i...Figure 9.5 Proposed reaction mechanism for palladium‐catalyzed dearomatizati...Scheme 9.40 Asymmetric cycloadditions of vinylcyclopropanes with indoles.Scheme 9.41 Allylic dearomatization of pyrroles for six‐membered spiro‐2H‐py...Scheme 9.42 Arylative dearomatization of pyrroles for six‐membered spiro‐2H‐...Figure 9.6 Selected bioactive compounds bearing spironaphthalene‐pyrrolidine...Scheme 9.43 Allylic dearomatization of pyrroles for five‐membered spiro‐2H‐p...Figure 9.7 Quantitative formation of spirocycles from 3‐pyrroles.Scheme 9.44 Intramolecular nucleophilic dearomatization of furans.Scheme 9.45 Dearomatizing 2,5‐alkoxyarylation of furan rings for spirooxindo...Scheme 9.46 Three possible pathways for the formation of 142a.Scheme 9.47 Mechanistic experiments for dearomatizing 2,5‐alkoxyarylation of...Scheme 9.48 Further transformations of spiro π‐allyl palladium.Scheme 9.49 Synthesis of spiroacetals from boronic acids and hydroxyalkylfur...Scheme 9.50 Synthesis of thiophene‐containing spirocyclic products via C–H a...Scheme 9.51 Cu(II)‐promoted transformations of α‐thienylcarbinols into spiro...Scheme 9.52 Synthesis of halogenated spirothienooxindoles from 159a and 158aScheme 9.53 Intermolecular Heck‐type dearomative [2+2+1] spiroannulation of ...Scheme 9.54 Palladium‐catalyzed aryne insertion/arene dearomatization to spi...Scheme 9.55 Mechanism studies for the 5‐exo‐trig spiroannulation...Scheme 9.56 Intramolecular asymmetric allylic dearomatization of benzene der...Scheme 9.57 A Cu‐catalyzed Sommelet–Hauser dearomatization of dihydrophenant...Scheme 9.58 Substituent effects.

10 Chapter 10Figure 10.1 Fenestrane motifs and their multifariousness. Top: (a) A stylist...Figure 10.2 From spiranes to fenestranes and beyond. Top: Spiro[4.4]nonane (Scheme 10.1 Retrosynthetic approach to the [5.5.5.5]fenestrane skeleton from...Figure 10.3 Systematic extensions of Keese’s parent all‐cis‐[5.5.5.5]fenestr...Scheme 10.2 Keese’s first synthesis of all‐cis‐[5.5.5.5]fenestrane (2).Scheme 10.3 Cook’s first‐reported synthesis of all‐cis‐[5.5.5.5]fenestra‐2,5...Scheme 10.4 Three hypothetical functionalized spiro structures as starting p...Scheme 10.5 Synthesis of 1,3‐indanediol 24 and [2,2′]spirobiindane‐1,1′‐diol...Scheme 10.6 Attempted construction of the benzoannelated [5.6.6.6]fenestrane...Scheme 10.7 Synthesis of the benzoannelated [5.5.5.6]fenestranes with cis,ci...Scheme 10.8 Unsuccessful attempts to synthesize fenestrindane 7 along the fu...Scheme 10.9 Naphthoannelated all‐cis‐[5.5.5.6]fenestranones 51 and 53‐55 acc...Figure 10.4 The first benzoannelated [5.5.5.6]fenestranones bearing two (56)...Scheme 10.10 Construction of extended benzoannelated fenestrane derivatives ...Scheme 10.11 Top: Both the stereoisomeric tetramethyl‐substituted [5.5.5.6]f...Scheme 10.12 Synthesis of the bis‐(pentaarylphenyl)fenestrindane 82 from the...Scheme 10.13 Synthesis of saddle‐shaped fourfold bay‐bridged fenestrindane 9...Figure 10.5 The parent fenestrindane saddle 10 and its octamethoxy derivativ...Figure 10.6 Solid‐state structure of the fourfold bay‐bridged fenestrindane Scheme 10.14 Access to centrohexaindanes via the “broken fenestrane route” a...Figure 10.7 Solid‐state molecular structure of tetramethoxycentrohexaindane Figure 10.8 Selected derivatives of centrohexaindane (9) in a perspective pr...Figure 10.9 The four constitutional isomers of hexanitrocentrohexaindane, 10...Figure 10.10 Dodecafunctionalized centrohexaindanes 105–107, synthesized by ...Figure 10.11 Solid‐state molecular structure of dodecaphenylcentrohexaindane...Figure 10.12 Two hypothetical extensions of the centrohexaindane core, model...

11 Chapter 11Figure 11.1 The different synthesized natural products discussed in this cha...Figure 11.2 The structure of (+)‐calafianin.Figure 11.3 The proposed retrosynthesis for (+)‐calafianin.Scheme 11.1 The synthesis of exocyclic vinyl epoxide 7.Scheme 11.2 The 1,3 dipolar cycloaddition leading to compounds 6 and 11.Scheme 11.3 The synthesis of (+)‐calafianin (1).Figure 11.4 The structure of pseurotin A.Figure 11.5 The retrosynthesis of pseurotin A.Scheme 11.4 The synthesis of 16.Scheme 11.5 The synthesis of pseurotin A.Figure 11.6 The structure of (−)ushikulide A.Figure 11.7 The retrosynthesis of (−)ushikulide A.Scheme 11.6 The synthesis of compounds 33, 34, and 35.Scheme 11.7 The synthesis of compound 30.Scheme 11.8 The synthesis of compound 31.Scheme 11.9 The synthesis of (−)ushikulide A.Figure 11.8 The structure of (−)‐acutamine.Figure 11.9 The proposed retrosynthesis procedure.Scheme 11.10 The synthesis of compounds 60 and 61.Scheme 11.11 The synthesis of compound 59.Scheme 11.12 The synthesis of 58.Scheme 11.13 The synthesis of 77.Scheme 11.14 The synthesis of compound 80.Scheme 11.15 The synthesis of (−)‐acutumine.Figure 11.10 Herzon’s retrosynthesis of (−)‐acutumine.Scheme 11.16 The synthesis of compound 87.Scheme 11.17 The synthesis of compound 95.Scheme 11.18 The synthesis of (−)‐acutumine.Figure 11.11 The structure of spirotryprostatin B.Figure 11.12 The proposed retrosynthesis.Scheme 11.19 The synthesis of compound 101.Scheme 11.20 The synthesis of compounds 109 and 110.Scheme 11.21 The synthesis of (−)‐spirotryprostatin B.Figure 11.13 The retrosynthesis proposed by Carreira.Scheme 11.22 The synthesis of compound 116.Scheme 11.23 The synthesis of compound 115.Scheme 11.24 The synthesis of (−)‐spirotryprostatin B.