Creativity from the Chiral Pool: Amino Acids

3.86 O 8.00 Me CO H CO2H HO CO2H CO2H CO2H 2 HS HO 4.07 NH2 NH2 O NH2 NH2 NH2 A C D E F

Ala Cys Asp Glu Phe

Me (S) CO2H CO2H Me CO2H CO2H Me CO2H N H NH2 NH NH2 NH2 NH2 NH2 Me NH2 6.10 10.53 G H I K L Gly His Ile Lys Leu

O MeS CO2H H2N CO2H CO H CO2H CO2H 2 HN H2N NH O NH NH NH 2 2 NH2 2 HN NH2 N M P Q 12.48 R Met Asn Pro Gln Arg

OH Me (R) CO2H CO2H CO2H CO2H CO2H HO Me H Me NH NH NH NH NH 2 2 2 HN 2 HO 2 S T V W 10.07 Y Ser Thr Val Trp Tyr Creativity from the Chiral Pool: Baran Lab Group Meeting Justine deGruyter Amino Acids 03.17.2017

Previously on Creativity from the Chiral Pool... Primary Uses of Chiral Pool Amino Acids: C H O "Total Synthesis of Thuggacin B" A = 6 13 Carvone, Rosen 2012.; Sugar Edition, Martinez 2014. (a) substrate control: chiral building block; stereocenter present Kirschning. Angew. Chem. Int. Ed. 2008, 47, 9134. H STrt Ph3P Some recent reviews: in target molecule and/or lends to generation of new stereocenters N (b) exogenous control: enantioselective agent; chiral catalyst or auxiliary CO Et "Recent Advances in Substrate-Controlled Asymmetric H OH L-Cys CHO 2 Induction Derived from Chiral Pool α-Amino Acids for Overview: Natural Product Synthesis" - interesting examples that utilize chiral pool AAs in total synthesis HS NHBoc Molecules. 2016, 21, 951. --> reviewed in alphabetical order by one-letter code cysteine " -Amino Acids with Electrically Charged and Polar Uncharged 1. A, , 94% α --> note: not all AAs are covered (lack of material) Me O Δ Side Chains as Chiral Synthon: Application to the Synthesis of - generation of enantiomerically pure heterocycles 2. TMSOTf, 2,6-lutidine, 79% HO Bioactive Alkaloids (1996–Dec, 2013)" - (very!) brief discussion of AAs as chiral catalysts/auxiliaries HO Me Tetrahedron. 2017, 10.1016/j.tet.2017.02.029 O HO 5 steps R N STrt "Total Synthesis of Dendrobate Alkaloid (+)-241D, Isosolenopsin and Isosolenopsin A: Application CO2Et O CO Et H of a Gold-Catalyzed Cyclization" Gouault. Org. Biomol. Chem. 2012, 10, 5541. N O Me 2 N Me S C H H OH O 6 13 Me O O Me Me Me TBSO OTBS NH C H 2 steps OMe undecyne, nBuLi S 2 6 13 Me D-Ala N C H Me HN 6 13 CO2H alanine Me thuggacin B Me NHBoc Boc C9H19 TBSO O O Me see: Biotin, Shenvi 2003. Me Me Gouault. Org. Lett. 2011, 13, 4371. PPh3AuCl (5 mol%), AgSbF (5 mol%) O 6 O "An Efficient Enantoselective Synthesis of the D1 Agonist (5aR, 11bS)-4,5,5a,6,7,11b,-Hexahydro- H 2-propyl-3-thia-5-azacyclopenta[c]penanthrene-9,10-diol (A-86929)" O OH 1a. ClCO2iBu, TEA, OMe N Ehrlich. J. Org. Chem. 1997, 62, 2782. 1b. CH2N2 N OH H OH O O MeO HO O R NH Me 1. HCl (3 N) MeO 2. AgNO3, TEA, R NH AlCl3 PG CH –OMe•HCl D-Asp H 3 PG O O H MeO Me N C H 2. 10% Pd/C, H2 85% MeO NHCOCF 9 18 Me N C9H19 aspartic acid 3 H Boc NHCOCF3 HO2C O 1. Pd/C, H2, 85% "A General Route for the Synthesis of Enantiopure Indolizidine Alkaloids from α-Amino Acids. Total Synthesis of 2. iBuO Cl (+)-Monomorine" Angle. Tet. Lett. 1993, 34, 3985. 2 OH 3. HN(OMe)Me•HCl OH O O quant. (over 2 steps) CO2Et BrCH2CO2Ph TIPSOTf HO S TEA Me NHBoc Me NHBn DIPEA Me N Me N CO2TIPS iPr Bn MeO MeO 64% Bn H H Br H LiAlH nBuLi MeO NHCOCF H 62% iPr H 3 MeO NHCOCF3 NH quant. (over 2 steps) S Me(MeO)N Pd/C, H 1. (ClOC) , DMSO, TEA O O 2 2 A-86929 iPr N Me N S 66% Bn 2. KH O O Me N nBu nBu Bn Me EtO P "The First Enantioselective Total Synthesis of the Anti-Helicobacter pylori agent (+)-spirolaxine methyl ester" OH Brimble. Chem. Commun. 2005, 1560. EtO nBu O 88% 1. NaNO2, KBr, H2SO4 Br 92% NaH; O 5 steps L-Asp OH HO O 2. BH SMe ; then MeOH then TBSPSCl 2 2 82% TBDPS 97% Creativity from the Chiral Pool: Baran Lab Group Meeting Justine deGruyter Amino Acids 03.17.2017

OMe H O "Asymmetric Total Synthesis of ent-Cyclooroidin" Me O Lovely. Org. Lett. 2010, 12, 4940. HN O OH SO N(Me) OTBDMS OH O Me 2 2 O O H Cs CO , Δ MeO N N 2 3 O L-His (Me)2NO2S Me N O histidine N 52% N N OTBDPS HO O O OTBDMS N (+)-spirolaxine methyl ester Cl O HN For glutamic acid, see: Rapoport. J. Org. Chem. 1998, 63, 4069.; Henry Rapoport, Foo 2013. 5 steps

O "The Stereospecific Preparation of an Hydroxyethylene Isostere Precursor via a Novel Piperidine- H 2,5-dione Template" Plata and Morton. Tet. Lett. 1991, 32, 3623. O N O O H OH 1a. NaH HN HN HN 2 steps 5 steps 1b. CH3O2CCOCH(CH3)2 NHTrt L-Phe NHTrt (Me)2NO2S (Me) NO S (Me)2NO2S N 2 2 N N 2. LiOH, H2O N N N Br Br phenylalanine O CO2H N Br N Br N O H2N N3 PO(OMe3)2 Me Me ent-cyclooroidin 1. NHS, DCC 2. HCl; then NaHCO3 (aq.) O "Synthesis of Optically Active Piperidine and Pyrrolidine Alkaloids from L-Lysine, L-Ornithine, or H L-Proline Using Anodic Oxidation as Key Steps" N Shono. J. Org. Chem. 1986, 51, 2590. NH2 H OH O n = 4 O n = 4 1. -2 e-, MeOH CO2Me 6 N HCl, Δ HN Me 1. L-Selectride HN Me H2N HN MeO2C N OMe N nPr O Me lysine MeO C NHCO Me 2. MeOH, H+ 2. H , Pd/C 2 2 Me 2 Me 47% CO2Me CO2Me O Me HO O (+)-N-methylconiine

"Synthetic Approach to Quinocarcin" O "Synthesis of Hydroxyethylene Dipeptide Isosteres That Mimic A Cyclic Amino Acid at the P1' Hirata. Tet. Lett. 1987, 28, 4065. OH H Subsite" Rich. Tet. Lett. 1991, 32, 5857. H N TMS 3 steps [L-Glu] 1. Swern ox. H OH iBu iBu OH NR CO2Me L-Phe H 5 steps NH H N 2. TiCl4, py. L-Leu HN BocHN * CO2Me leucine SnCl O 4 HO R = Cbz O Boc 60% from Leu iBu CO H E E Preparation of Amino Aldehydes 2 E E Org. Lett. 2003, 5, 737. H H H H H * H 1. H , Pd/C BocN NMe 2 PGHN R PGHN R PGHN R HO H NMe NR O Me H N N 2. 27% HCHO N iBu N Me CO2H H H NaBH3CN * O N(OMe)Me O H I CN O O quinocarcin derivative Creativity from the Chiral Pool: Baran Lab Group Meeting Justine deGruyter Amino Acids 03.17.2017 HO CO2tBu "Total Synthesis and Isolation of Citrinalin and Cyclopiamine Congeners" CO tBu n = 4 n = 4 Sarpong. Nature 2014, 509, 318. 2 i. TFA N O Me OH O i. A, SnCl4, –78 °C NaOEt, EtOH Me N O N OH cat. [Ru], L ii. I2, DMAP, py., Me ii. BOP, DIPEA, N OH H 6 steps NC NC CCl O O N 4 n = 4 MoC/DKR Me then NaBH4 Me D-Pro N proline 98% 68% Me O 86% O (over 2 steps) (over 2 steps) H (–)-penibruguieramine A H see: Memory of Chirality, Voica 2008 H MeO O Me MeO O O Me O O O "Asymmetric Syntheses of 1-Deoxy-6,8a-di-epi-castanospermine and 1-Deoxy-6-epi-castanospermine" C HN NC Suh. J. Org. Chem. 2012, 77, 5389. HN I dppfPdCl (10 mol%) I N 2 N 1. B (20 mol%) N O TBSCl, DBU NBoc 1. TBSOTf, 2,6-lutidine N H O O2N K PO 2. PIFA, MeOH D-Pro-al LHMDS O 3 4 O H O N H H H 88%, > 20:1 2. A, EDCI, HOBt, NMM OTBS H 95% Me Me 70% H OTBS Me Me (over 2 steps) (over 2 steps) Me Me 60% (over 2 steps) OTBS 0 1. Zn , NH4Cl, HCO2NH4, p-TsOH, MeOH OTBS OTBS 2. NaCNBH3, 1 N HCl, 82% (over 2 steps) A = HO2C OTBS 3. Pd(OAc)2, benzoquinone, H2SO4, 71% LDA, mw 4. Me2S, methanesulfphonic acid, 96% Me Me O O OTBS O OTBS H2N OH O Me O 1. Oxone®, Me CO, NaHCO , 56%, 4:1 d.r. N N H O TBS N 2 3 H 66% O2N Me O OH OTBS 21% N N 2. Me OBF , 4 Å m.s. N H 3 4 H H H HN OH O Me Me 3. NaCNBH3, 66% (over 2 steps) H 1-deoxy-6-epi- O H OMe Me Me castanospermine [Ru] = [Ru(Cp)(MeCN)L2]PF6 A = MeO L = ent-citrinalin B O PPh2 O O TBSO NH H O 1. Ac2O H N Me O N i. NaH OH OH N TIPSO 2 N py., 71% N Oxone® ii. MeI, K CO , 60 °C OTBS N 2 3 H H tBu Me N 63% Me OH 2. LiAlH, 86% OH 78% H H OTBS B = C = Me O Me H O OTBS Me Me O Me H (over 2 steps) OH OH H Me Me H P Me O Me 1-deoxy-6,8a- P cyclopiamine B di-epi-castanospermine O Pt P Me Bpin H Me H OH NO 2 "A Facile Approach to the Synthesis of Securinega Alkaloids: Stereoselective Total Synthesis of (–)-allonorsecurinine" Srihari. Tet. Lett. 2012, 53, 5926. O O "Biomimetic Total Synthesis of (–)-Penibruguieramine A Using Memory of Chirality and Dynamic Kinetic Resolution" O Kim. Angew. Chem. Int. Ed. 2015, 54, 10875. O O 1. TFA O HO 5 steps HO O EtO Me L-Pro H Me O O H 2. K2CO3 L-Pro N N H i. NaH, nBuLi, 0 °C to rt (76%) Boc N H 65% (over Br Me Me Boc N 4-hexen-1-ol HO Boc Br 2 steps) ii. KOH (97%) n = 4 (–)-allonorsecurinine Me Creativity from the Chiral Pool: Baran Lab Group Meeting Justine deGruyter Amino Acids 03.17.2017

"Total Synthesis of (+)-3-Demethoxyerythratidinone and (+)-Erysotramidine via the Oxidative "Total Synthesis of (–)-( )-Kainic Acid via a Diastereoselective Intramolecular [3+2] Cycloaddition Reaction of an Aryl H O Amidation of a Phenol" Ciufolini. Org. Lett. 2015, 17, 3422. Cyclopropyl Ketone with an Alkyne." Zhou and Li. Org. Lett. 2012, 14, 2540. HN OMe MeO Ph OH OMe MeO 1. 1% Pd(PPh ) , aq. Na CO 1. TsCl, TEA TsHN CO2Me 1. DIBAl-H 1. Me3SOI, NaH 3 4 2 3 D-Ser•HCl O HO 2. aq. LiOH Bpin 2. TBSCl, imid. 2. PhCOCH=PPh TsHN 2. 1-Br-2-butyne, (76% over 2 steps) 87% (over 2 steps) OTBS 3 serine HO 94% NaH Br CO Me 3. L-Ser-Me ester•HCl 79% (over 2 steps) 2 OTBS DCC, DMAP, TEA OC N H CO Me OBn BnO 2 O O Ph Ph Me Ph 1. Burgess reagent 54% (over 2 steps) O 2. H , Pd(OH) /C Me DBU Me SmI2 2 2 TsN 86% OTBS OTBS OMe OMe 95% 81%, d.r. = 4:1 MeO OMe MeO MeO N N OTBS Ts Ts 1. O3 TsOH•H2O PhI(OCOCF ) * N N 3 2 2. H2O2, NaOH O H O O O 3. CH3I, K2CO3 90% 62% 78% (over 3 steps) CO2Me CO2Me O O N CO2H OH CO2Me CO Me 2 1. Jones ox. Me O CO2Me HO Tebbe reagent, py. 2. 3 N LiOH Me OTBS CO H OTBS 2 72% 3. Li/NH N N 3 H H2, Pd/C 83% (over 3 steps) OMe N Ts HO 89% Ts MeO (–)-(α)-kainic acid MeO MeO O N H CO2Me "Total Synthesis of the Marine Alkaloid Halichlorine: Development and Use of a General Route to Chiral Piperidines" HO Clive. J. Org. Chem. 2009, 74, 7417. H N HO O N MeO OMe O O E E O 4 steps H O TBDMSO HO H Cs2CO3, Δ HO θ ≈ 90 ° θ ≈ 0 ° O O O N N N H MeOH N Cbz H O H stereoselective formation O I 80% O PMBO PMBO PMBO MeO O MeO "Investigations of a Nucleophilic Alaninol Synthon Derived from MeO O Serine" Sibi. J. Am. Chem. Soc. 1999, 121, 7509. N NH O MeO O N MeO OH N 1. NaBH4, 90% O O MeO triphosgene TEA 2. TsCl, py., 82% L-Ser O NH O NH 3. NaI, Me CO, 83% H O O MeO 95% 2 O Cl Me CO2Me I (+)-3-demethoxy-erythratidinone (+)-erysotramidine HO halichlorine Creativity from the Chiral Pool: Baran Lab Group Meeting Justine deGruyter Amino Acids 03.17.2017

"The Four-Step Total Synthesis of (–)-Caetominine" Me OH "Total Synthesis of Legionaminic Acid as Basis for Serological Studies" Seeberger. J. Am. Chem. Soc. 2015, 137, 2848. H O Huang. Chem. Commun. 2014, 50, 1986. HO HN NO2 H OH Me CHO Me N nBuLi, furan, MgBr •OEt OH O H H D-Thr 2 2 O O O NTs L-Ala-OMe•HCl 80% syn, d.r. = 5:1 O NTs HN NH threonine D-Trp O NO2 Me Me Me Me NH ClCO2iBu, NMM NH O O ; 3 O OH then PPh , TMSCHN 59% CO2H OH 3 2, tryptophan N Me OMe Me H LiBH4 R' = CHO, R = CO2Me N AcHN O CO H 2 R' = H, R = CH2OH H HC(OMe)3, AcHN HO NaOCl, cat. TEMPO, R' = H, R = CHO Zn/TiCl KBr 4 legionaminic acid O R'O N Me Me O 1. LiBH4, THF, 0 °C to rt, 92% OH N O OH 2. NaOCl, cat. TEMPO, KBr Me R OH Me O Ph sat. NaHCO3, quant. CO Me Me N 2 O NTs O Me N N Ts NTs NR 3. (E)-styrylboronic acid, HNR H H O N Me 2 2 O N AcHN d.r. > 19:1 (anti/syn) Me Me MeO Me N DMDO; N OH O then dry DMSO O O NH O NH O "Total Synthesis of (–)-L-755,807: Establishment of Relative and Absolute Configurations N O O H O OH N Kobayashi and Kogen. Org. Lett. 2016, 18, 1920. N Me OMe N Me OMe H H HN Me Me OH 1. SO •py., DMSO, DIPEA O epoxidation; 4 steps 3 CO tBu N N O ring-opening cyclization; D-Val 2 Me OH Me H (–)-chaetominine lactamization Me Me 2. BrCH(CO tBu) , LHMDS 2 2 TBDPSO CO tBu valine TBDPSO 94% (over 2 steps) 2 O Me

1. HCO2H "Ir-Catalyzed Reverse Prenylation of 3-Substituted Indoles: Total Synthesis of (+)-Aszonalenin and 2. NH(OMe)Me•HCl, (–)-Brevicompanine B" Carreira. J. Am. Chem. Soc. 2014, 136, 16756. PyBOP, DIPEA O R = H Me Me cond. = 84% (over 2 steps) Me 1. 2-aminobenzoic acid NH n = 3 CO2Me Me OBoc Me Me Me cond. Me TEA, HATU N Me O O NBoc Me Me O O O 2. AlMe3 N H O OMe H 0.50 mol% [{Ir(cod)Cl} ] O 1. NH N H 85% (over 2 steps) H O 2 HO R P 3 N H KHMDS Me Me OMe 2. TESOTf, 2,6-lutidine Me Me (+)-aszonalenin D-Trp (+)-exo 9-BBN-n-C H O OMe O 6 13 N TESO O L-Trp O 58% Me H O NH2 3. SiO2, 86% (over 3 steps) Me Me Me H CO2Me 4. (OMe)2P(O)Me, nBuLi, 89% Me Me NH Me O L-755,807 1. Fmoc-Leu, TEA, HATU P N NBoc 82% N O cond. Me N H N H H 2. Et2NH H O (1 mol%) (–)-exo 83% (–)-brevicompanine B see also: Baran. J. Am. Chem. Soc. 2015, 137, 10160; Reisman. J. Am. Chem. Soc. 2013, 135, 5557. Creativity from the Chiral Pool: Baran Lab Group Meeting Justine deGruyter Amino Acids 03.17.2017

"Total Synthesis of (–)-Acetylaranotin" "Studies on the Synthesis of Stemona Alkaloids; Stereoselective Preparation of the Hydroindole Ring System by O H Tokuyama. Angew. Chem. Int. Ed. 2012, 51, 13062. Oxidative Cyclization of Tyrosine" Wipf. Tet. Lett. 1992, 33, 5477. N O O H OH 1. cat. DBU O OH O O NaHCO OH 3 steps quant. 3 NaHCO3 L-Tyr-CBz PIDA, MeOH 0 °C CO Me H rt 2 tyrosine H 2. H O , cat. NaOH H 68% H 2 2 82% 70% O N HO CbzN 97% CbzN H O HO H R CO H CO2Me CO2Me CO2Me 2 RHN O 1. NH2NH2•H2O, AcOH NHR H NHR 55% R = Boc, Cbz 2. DMP, 97% PIDA, NaHCO3 1. TMSOTf, iPr2NEt, DCM, rt 2. DMDO; evaporation; 54% O O O acidic silica gel O H TFAA, UHP H 56% (over 2 steps) "Asymmetric Total Synthesis of the Stemona Alkaloid (–)-Stenine" TBSO H Wipf. J. Am. Chem. Soc. 1995, 117 , 11106. TBSO H H H O O CbzN 53%* CbzN 3. TBSOTf, 2,6-lutidine CbzN OH HO CO Me MeO C CO Me CO Me 2 O O 2 2 2 CO2Me H E H OH HO H O N R N O 1. KHMDS, PhNTf2 R N N H R E H R H 77% H H 2. cat. Pd(OAc) , PPh HCO H > 98:2 2 3, 2 O A1,3-strain nBu3N, 94% "First Total Synthesis of Epicoccarine A via O- to C-Acyl Rearrangement Strategy" cat. Pd(OAc)2, ca. TEA Yoda. Org. Lett. 2012, 14, 5142. CO Me O O N 2 91% H H N TBSO CO2Me HO O BOPCl, TEA Me OH CBz O Me TBSO N OTBS Me Me H H H I N KOH O TBSO N Br LDA, HMPA CbzN 83% Me O Me Me Me 45% Me Me H CO2Me O quant. CO2H N O 41% LiEt3BH, Δ H Cbz (over 5 steps) TBSO 1. Et SiH, cat. Pd(OAc) , 72% 3 2 HN O cat. TEA, 78% L-Tyr O 1. TPAP, NMO 2. TBAF Me Me HO HO 3. nor-AZADO, PIDA, 93% 2. Pinnick ox. O EDCI Me Me Me 62%, 2S/2R = 94/6 Me Me Me TBSO DMAP O O O HS SH 1. NaBH , O O OH 4 H 1.TEA, DMAP, CaCl N OAc TEA O CeCl •7 H O, 69% O 2 Me H S S H N 3 2 O AcO N H OAc N O HN HN AcO S4 H H H Me 2. TBAF O then O N 2. NaHMDS, S , 31% O N Me Me Me 2 8 O 59% (over 2 steps) 40% O 3. AcCl, DMAP, 44% O O Me Me Me O H HO (–)-acetylaranotin O O TBSO epicoccarine A Creativity from the Chiral Pool: Baran Lab Group Meeting Justine deGruyter Amino Acids 03.17.2017

Some interesting/potentially usefully heterocycles There exists enough literature on the use of amino acids as chiral auxiliaries or catalysts to constitute their own group "A Convenient Method for the Preparation of Enantiomerically "Stereospecific Synthesis of 4-Fluoroglutamic Acids" meeting. Below are examples that I consider to be seminal advances in the field... Pure 2-Substituted N-Tosylaziridines" Craig. Synlett. 1992, 41. Young. Tet. Lett. 1992, 33, 1509. Chiral Auxiliaries Some reviews/communications by reaction type (non-aldol): O R L-Pro HO CO H O R "Natural Amino Acids as Chiral Auxiliaries in Asymmetric Diels–Alder R CO2H LiAlH R CH2OH TsCl 2 der. Me OMe Reactions" DMAP N 1.DAST F O N N Can. J. Chem. 1988, 66, 2826. NHTs NHTs Ts "Asymmetric control in the Pictet-Spengler Reaction by Means of N- O N CO2Bn N R = Me, iPr, iBu, TBSOCH , MeS(CH ) + Protected Amino Acids as Chiral Auxiliary Groups" 2 2 2 2. H3O H N CO H R MeO Boc 2 2 Chem. Eur. J. 1996, 2, 1566. ca. 30% 1 Evans' oxazolidinones R "Amino Acid Esters as Chiral Auxiliaries in Barbier-type Reactions in S O Schollkopf Aqueous Solution" "Stereospecific Synthesis of N-Protected Statine and Its Analogues via Chiral Tetramic Acid" synthesis of chiral Lieb. Anna. Chem. 1991, 1317. Jouin. J. Chem. Soc. Perkins Trans. 1. 1987, 1177. Me S N amino acids "Amino Acid Esters as Chiral Auxiliaries in Asymmetric Cycloadditions" OH O Gazzetta Chimica Italiana. 1991, 121, 277. HO R CO H Meldrum's HO "Chiral Auxiliaries in Polymer-Supported Organic Synthesis" 2 acid R R O Δ H2 or Tet. Asymm. 2004, 15, 387. BocHN Me thiazolidinethiones IPCF, DMAP BocHN R N O R O O O NaBH4 N Me Boc Boc Asymmetric Catalysts R = iBu, Me, iPr, Bn, BnOCH2, MeS(CH2)2, CbzHN(CH2)4, indol-3-yl-CH2, BOM-imidazole-CH2 "Amino Acid Catalyzed Direct Asymmetric Aldol Reactions: A Bioorganic Approach to Catalytic Asymmetric Carbon– Carbon Bond-Formation Reactions" Barbas. J. Am. Chem. Soc. 2001, 123, 5260. "Asymmetric Synthesis of a Homochiral -Isoxazoline Amino Acid Derivative" O + Savage. Heterocycles. 1994, 37, 529. L-Pro O H2 DMTC O OH N SO2Me O N O R H DMTC = O- 1. PhCHO Ar O O DBU O 2. (EtCO)2O ArCNO Me R S L-mCys O Me Me O N O O 3. Oxone® N O N O Et O Ph Et O Et Ph Ph O O NH O "Photochemistry of N-Phthaloyl Derivatives of Methionine" "A Potential Cabapenem Intermediate from L-Glutamic O Griesbeck. Tet. Lett. 1993, 34, 453. Acid" Somfai. Tet. Lett. 1991, 32, 283. H N N O N OH O H Me H L-Met L-Glu O Me Me S Me H Me O HO Et Me Me O O CH OH n = 2 S hυ Et 2 N N OTBS Me 80% O NH O O H CO H N O OH 2 O O O O Ts O H H R R N "Decarboxylative Cyclization of Allylic Cyclic Carbamates: Applications to the Total Synthesis of (–)-Codonopsine" N OH H O O H N OH Wang. J. Org. Chem. 1991, 56, 4341. O Ar HO OH CO H Me R 2 OH Me R re-facial attack 1. mCPBA N O H Me 1. NaBH4 1. BF3•Et2O 2. H SO L-Ala Me Ar 2 4 O N Me N Ar 2. NaH Me An oldie but goodie: "The Chiral Pool as a Source of Enantioselective Catalysts and Auxiliaries" Chem. Rev. 1992, 92, 935. 2. ClCO2Me, TEA 3. LiAlH EtO CHN Ar CO2Me Me 2 73% N 60% 12% H O cis/trans = 2:1 cis/trans = 1:1.3 e.r. not reported