Polyvalent Iodine in Synthesis (more than just Dess-Martin) Matthew M. Kreilein Wednesday, December 13 th, 2006

Transcription

1 Polyvalent odine in Synthesis (more than just Dess-Martin) Matthew M. Kreilein Wednesday, December 13 th, 2006

2 General otes: + A LT older than though originally. + Cl 2 was the first reported polyvalent iodine() compound prepared in 1886 by Willgerodt in Germany. 2 first iodine(v) compound, Willgerodt in Chemical properties similar to Hg(), Tl(), Pb(V), without the nastiness. Also similar to organometallics to a certain extent (ligand exchange, reductive elimination, etc.) + Four most useful forms in organic chemistry are as follows: -X-L system = no. of valence electrons X = heteroatom L = no. of ligands L L L L L L L L L L L L L L iodanes periodanes

3 General otes: + Further classified by number of carbon ligands. umber of carbon ligands affects the reactivity Derivatives of odine() with one carbon ligand: odosylarenes - Ar odoaryl halides - ArX 2 [Bis(acyloxy)iodo]arenes - Ar( 2 C) 2 Strong acid derivatives - ArX 2 (X = S 3, Cl 4, 3, etc.) Five-membered odine() heterocycles (benziodoxoles and benziodazoles) Derivatives with - bonds (amidodanes, iminiodanes, azidoiodanes) Derivatives with - element bonds odine() species with one sp 3 -carbon ligand Derivatives of odine() with two carbon ligands: Cyano-, alkynyl-, alkenyl-, aryl-, heteroaryl-, alkyl-, and fluroroalkyliodonium salts odonium ylides odonium imides Derivatives of odine() with three carbon ligands Derivatives of odine(v): odyl compounds Benziodoxole xides (BX, DMP)

4 Derivatives of odine() with one carbon ligand odosyl arenes - Ar + polymeric in solution with secondary - bonds Ar Ar Ar + but some have been isolated as monomers (intramolecular stabilization): S 2 t-bu 1. H 2 2, Ac 2 2. KH, H 2 S t-bu + reactions usually carried out with a catalyst (Lewis acid, hdroxylic solvent, and others) in order to depolymerize. + can also be activated in solid state by pulverization (mortar/pestle) with natural clays, cation-exchange clays, and HCl-activated silica gel

5 + Can be used as a precursor to a T of other iodine() reagents: + 2 TMS-X X 2 X = Cl, Ac, CCF 3, Ts Tf, 3, C, etc. TMS-S 2 + TMS-X (S 2 )X X = Ac, HAc, C, C = p-tol, CF 3, C 4 F 9 Tf 2 at 0 C Tf Tf Tf 2 or TfH at rt H Tf Tf 1/2 S 3-50 C + -S 3 - S 3, 50 C S 2

6 odosylbenzene - + α-methoxylation of silyl ketene acetals + oxidation of 1 0 alcohols to carboxylic acids, 2 0 alcohols to ketones, sulfides to sulfoxides + reaction tolerant of several functional groups 2 1 TMS 3 () n, MeH 57-74% Me 2 1 C =, 4-Me-C 6 H 4, 4-Me-C 6 H 4, 4-Cl-C 6 H 4 2 = H, Me; 3 = Me, Et S 1 () n, 10 mol% CTAB toluene:h 2 (500:1) %, 1 =, 2-Me-C 6 H 4, 2-Me-C 6 H 4, Bn, Me, Et S 1 CH 2 H () n (2.2 eq), KBr (0.2-1 eq) H 2, rt, 76-92% C 2 H H () n (2.2 eq), KBr (1 eq) H 2, rt, quant% KBr - K + Br H KBr H H H 2 n MeH, converted to (Me) 2, in water, converted to (H) 2

7 + ther oxidations can be accomplished (very substrate dependent), asymmetric variants also know using chiral Cr, Mn(), u()/() complexes CH 2 H 2, dry CH 2 Cl 2 rt, 3 d C H C 2 H (2.2 eq) CH 3 Cl, rt, 2 d H Cr H Me CF 3 F 3 C H, H 2, rt, 4 h H, 3 P, MeC, 0 C Me + n concert with 2, initiates radical chemistry H H ()/ 2 H H HC -1e H HC HC

8 odoaryl halides - X 2 + Very powerful yet selective halogenating agents; however, they aren t that widely used due to - difficult preparation (unless you like working with XeF 2, F 2, HF/Hg, etc. for example) - instability - F 2 for example is VEY hygroscopic so using any aqueous methods is VEY clunky, bromides are unstable to the point that they can t be isolated as individual compounds. + Sometimes though, may be the best way to go TMS Cl 2, Pb(SC) 2, CH 2 Cl 2, 0 to 25 C presumably via... (SC) 2 SC S Bn F 2, CH 2 Cl 2, 12 h, 0 C S F Bn Tol F F S Bn Tol F + S H F - Bn + S F - Bn

9 [Bis(acyloxy)iodo]arenes - Ar( 2 C) 2 + Probably the most well-known and well studied of the polyvalent iodine() compounds + Two are commercially available - (diacetoxyiodo)benzene - DB - (Ac) 2-100g ~$100 - [bis(trifluoroacetoxy)iodo]benzene - BT - (CCF 3 ) 2-50g ~$150 + Also can be used to make a TALAD of other [bis(acyloxy)iodo]arenes (WAY too many to partially list). + Attachment to make polymer-supported variations has also been detailed. + Most useful as an oxidant for alkenes, heteroatoms, oxidative halogenation, phenols, phenolic ethers as well as a radical initiator at carbon, oxygen, and nitrogen. + Quite LW reactivity for the oxidation of alcohols to aldehydes and ketones. xidation can be carried out under µw or with addition of TEMP. Useful if you need to oxidize another functional group with an alcohol or aldehyde present as oxidations with Ar( 2 C) 2 do not give overoxidation to the acid. 'CHH DB, TEMP (0.1 eq), CH 2 Cl 2, rt, 6 min-15 h 55-95% 'C=

10 [Bis(acyloxy)iodo]arenes - Ar( 2 C) 2 + α-hydroxylation of enolizable carbonyls 1 2 ( 2 CCF 3 ) 2 CF 3 C 2 H, MeC H 2, 30-94% 1 H 2 1. (Ac) 2 KH/MeH 2. hydrolysis H - K + Ac Ac - Me - Me Ac Ac Me - Me Me Me H hydrolysis 18 H 18 label ends up here if 18 labelled acetophenone is used

11 + several fragmentations and rearrangements catalyzed by DB and BT especially at electron-deficient centers. Et Et H DB Et Et Ac Et Et Et Et - Ac Et Et Ac + Also possible to oxidize sulfides to thiosulfonic S-esters or to arylsulfinic esters. + otable use in sulfur oxidation is formation of carbonyls from monothioacetals or dithianes CH 2 Cl 2, rt Ar-SS-Ar + BT or ArS X H, reflux X = S or depending on condition S S 1 2 DB, acetone/h 2 rt, 1-3 min, 64-92% 1 2

12 + oxidation of phenols can be carried out using both DB and BT H 5 1 BT, MeC, H H 2 H DB, H Me Me

13 Strong acid Derivatives - Ar(H)X + Most common is [hydroxy(tosyloxy)iodo]benzene - (H)Ts - HTB also called Koser s eagent + The mesylate form of HTB is also available (H)Ms as is the phosphoryl (H)P() 2 and nosyl flavor (H)s + n solution, these tend to be fully dissociated into + H - Ts (for example). + Many uses for these, but the primary use is for the functionalization of carbonyl compounds by addition of the X group to the α-carbon, which is VEY handy for one step functionalization of carbonyls. Boc (H)Ts CH 2 Cl 2, rt 17 h, 68% Boc Ts Boc H H Ts Boc H Boc + - Ts

14 + Functionalization of carbonyls in this manner can be followed by conversion to other functional groups. Very handy and some are one-pot two-step processes. 2 HB, MeC, reflux then 3 H or Sm 2 or a 3 X 2 X = 3,, or 3 + Always looking for improvements though P (Ac) 2 TsH H 2, CH 3 Cl rt, 24 h P (H)Ts H 2 CH 3 Cl, reflux, 16 h 2 Ts + + H Me - Ts -30 C Ts up to 30% ee

15 + Can also catalyze the Hofmann earrangement: Br H 2 BT, MeC/H 2 rt, 24 h, 83% Br H 2 Br Tf H 2 Tf H Tf Br Br C

16 Two carbon ligand derivatives - translation salts 2 + X - + These seem to have caught fire in a random manner. + o real set scale of stability, utility, etc. as it is all VEY dependent on the identity of the and X groups. For example, several X = C variants decompose at rt in 2-5 min and explode when exposed to air; however, other X = C types (mainly the cyclic forms) are stable indefinately. + Probably the most important research being done on them (synthetic organic chemist speaking) are couplings with palladium and other metals with amines, benzotraizoles, amidoximes, organoboron compounds, organostannanes, silanes, leads, zirconium compounds, phosphites, mercaptans, alcohols, allenes, substituted α,β-enones, Grignards, alkenes, alkynes, etc. 2 + X - + Y Pd(P 3 ) 2 Cl 2, Cu K 2 C 3,, DMF/H 2 Y rt, 2-3 h, 65-99% + ucleophilic substitutions are also known as well + X - u - u 2 S + BF 4 - S 2 a 2 S S 2

17 odonium ylides and imides ( 1 = 2 and Ar=S 2 ) + Again, getting a bit more attention. + Synthetically speaking, they have found application in epoxidations, aziridinations, Wittig olefination, amidation, and heteroatom imidation. + Again, asymmetric variations have been explored somewhat. Ac ()X EtLi Et Me - ()X -EtAc 1 CH + 1 CH= CH + Ac ()X Et 3, P 3 MeH, rt to 60 C via conversion of iodonium ylide to phosphonium ylide 1 1 (Et) 2 P Ar Ts, CuTf MeC, rt (Et) 2 P Ts Ar 1 2 Ts chiral u() or Mn()-porphyrin HTs 1 2 up to 53% ee t-bu t-bu Ts, Cu() or Cu() t-bu t-bu S S Ts

18 BX and DMP + Varied applications in synthesis. Usually, what one can do the other can too (oxidize alcohols, C-H to C-H, etc.) + ne notable difference, BX can oxidized diols to diketones or α-hydroxy ketones where as DMP usually leads to cleavage of the C-C diol bond. This has been studied by M and shown to result from the ability of the diol to bond twice with the iodine in DMP but not BX. + BX has also been show oxidize carbonyl compounds to α,β unsaturated and cross-conjugated ketones. H 2-idoxybenzoic acid (BX) Ac Ac Ac Dess-Martin periodinane (DMP) Does BX go BM!?!?! don t know 100%, but if had heard of it happening, this is probably the LAST thing d do CAUT Compound 1 was reported to be explosive by Meyer and more recently by J. B. Plumb and D. J. Harper, C armaceuticals Group, in Chemical and Engineering ews to be explosive similar to trinitrotoluene. The C preparation of 1, found to be explosive, had 43.5% iodine by elemental analysis (calculated 45.32% for 1) although none of the samples of 1 prepared by our method had any unexpected decrease in the percentage of iodine. They also had some bromine (4%) in 1 after washing with only water. We washed with water and ethanol to form a nonexplosive sample of 1. Although we have been unable to induce an explosion of 1 that would break the glass container or an explosion upon hard impact of a steel hammer, we suggest that the synthesis of 1 be handled with care. t is possible that some bromate or other impurity may be included in the samples found to be explosive Dess and Martin, JACS, 1991, 113,

19 The Bottom Line (if there is one) + Polyvalent iodine compounds are more than just DMP + Have a wide array of synthetic utility + Drawbacks seem to be the need to prepare and instability of some of the reagents in storage Leading eferences Stang, P.J.; Zhdankin, V.V. Chem. ev. 1996, 96, (564 references cited) Zhdankin, V.V.; Stang, P.J. Chem. ev. 2002, 102, (690 references cited)