IODONIUM DI-sym-COLLIDINE PERCHLORATE 1

Iodonium Di-sym-collidine Perchlorate

N

I+ ClO4–

2

[69417-67-0] C16H22ClIN2O4 (468.75)InChI = 1/2C8H11N.ClHO4.H2I/c2*1-6-4-7(2)9-8(3)5-6;2-

1(3,4)5;/h2*4-5H,1-3H3;(H,2,3,4,5);1H2/q;;;+1/p-1/f2C8H11N.ClO4.H2I/q;;-1;m

InChIKey = BYIWKLBXMKVCSV-XXHWELEDCY

(very reactive electrophile, superior source of I+,1 useful inthe synthesis of cis-β-hydroxy amines,2 activates glycosides forglycosylation;5,6 can be used for iodolactonization12,13 and

vicinal cis-diol14 preparation)

Alternate Name: IDCP.Solubility: soluble in chloroform; insoluble in ether.Form Supplied in: fine colorless crystalline powder.Drying: see Bromonium Di-sym-collidine Perchlorate.Handling, Storage, and Precaution: see Bromonium Di-sym-

collidine Perchlorate.

Original CommentaryTapan RaySandoz Research Institute, East Hanover, NJ, USA

cis-Oxyamination.2 IDCP (1) is useful in the synthesis ofcis-hydroxyamino sugars, e.g. methyl N-acetylristosaminide hasbeen obtained from an oxazoline which can be made by the re-action of a trichloromethyl imidate with IDCP. The imidate canbe prepared by reaction of the corresponding allylic alcohol withTrichloroacetonitrile in presence of Sodium Hydride (eq 1).

O

OMe

HO

OOCl3C

HN

ON

O

OMe

I

Cl3C

O

OMeCl3COCHN

HO(1)

NaH, CCl3CN

IDCP 1. 4.4 equiv Bu3SnH, AIBN

CH2Cl2

75% 2. py, TsOH, H2O 50%

The synthesis of methyl α,L-garosaminide,3 a key componentof aminocyclitol antibiotics, is complicated by the presence ofa cis-hydroxyamino group and by the tertiary character of thehydroxy group. The problems have been resolved by use of theallylic epoxide as starting material. This epoxide was converted inthree steps into an allylic amine. Treatment of iodonium salt gave

the iodooxazolidinone in 82% yield. The product was reduced andthe ethoxy ethyl group was removed and finally converted to thedesired product by hydrolysis (eq 2).

Similar methodology can convert an internal allylic amine into acis-β-hydroxyamine, as illustrated in a synthesis of holacosamin,a component of some glycosteroids (eq 3).4

ααα-Linked Disaccharides.5 The reagent functions as a superiorsource of I+, probably because of the nonnucleophilic counterion.Thus a pyranoid diene reacts with IDCP to give a planar ion towhich an alcohol adds in a 1,4-sense to give an α-glycoside. Thustetraacetylfructose reacts to give an α-disaccharide in 45% yield(eq 4). The β-isomer is not detected.

O

O

OMe O OMe

OCH(Me)OEt

NXMe

OO

NO

MeOMe

OCH(Me)OEt

CH2I O

O

NO OHMe

OMe

OHO OMe

NHMe

OH

(2)

1. MeNH22. EtOCOCl IDCP

X = CO2Et

1. H2, Pd/C KOH

3. EtOCH=CH2 65%

82%

2. pyH+ OTs– 82%

O

OEtN

Me

O

N

OO

I

OEt

Me

O

N

OOOEt

Me O

OEtMeHNOMe

+ (1)dioxane 1. NaI

EtO2C

(3)

OTs OTs

71% 2. Bu3SnH

OO OPh

O

AcOCH2OAc

OAc

AcOH2CHO

IDCP

OO

O

O

OAcO

OAcI

OAc

OAc

Ph

IH2C

O

ClO4–

+

(4)45%

Examples are known where this reagent has activated pent-4-enyl glycosides for glycosylation,6 but α- and β-glycosides wereobtained in various proportions regardless of the nature of donors

Avoid Skin Contact with All Reagents

2 IODONIUM DI-sym-COLLIDINE PERCHLORATE

or acceptors (primary or secondary hydroxyl groups). Glycosy-lations of 1,2:5,6-di-O-isopropylidene-α-D-galactopyranose andmethyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside were investigatedwith pent-4-enyl-2,3,4-tri-O-benzyl-β-D-glucopyranoside deriva-tives in which 6-OH was protected by a benzyl, a trityl, or aTBDMS group in order to assess the effect of the bulk of the6-substituents. The presence of a bulky 6-substituent (a) increasessignificantly the proportion of the α-product; (b) decreases theyield when a secondary hydroxy group is glycosylated, but the ef-fect is less or opposite when a primary hydroxy group is involved;(c) lowers the increase in yield of the α-product when a primaryhydroxy group is glycosylated; (d) gives a much better yield ofthe α-anomer when there is a higher proportion of ether in thesolvent.

Chemospecific glycosidation of partially benzoylated thiogly-cosides (‘disarmed’ acceptors) with perbenzylated thioglycosides(‘armed’ donors) can be realized in the presence of the promotorIDCP (eq 5).7

(5)OSEt

OBn

OBz

OBn

BnO

OSEt

OBz

OBz

OBz

HO O

OBn

OBz

OBn

BnO

O

O

OBz

OBz

OBz

SEt+IDCP

Reaction of IDCP with unsaturated alcohols and carboxylicacids in dichloromethane at ambient temperature has affordedthree- to seven-membered ring iodoethers and four- to seven-membered ring iodolactones, respectively, in moderate yields andgenerally with high regioselectivity. The reaction has particularutility for synthesis of 2-(1-iodoalkyl)oxiranes and -oxetanes.11

Glycosylation has also been achieved by electrophile-induced ac-tivation of anomeric O-glycosyl N-allyl carbamates (eq 6).8

(6)

O

OR1

OR1

R1OR1O OH

OO N

H

O

OR1

OOR2

OR1

i-Pr2NEt, CH2Cl2

OCN

IDCP, R2OH

R1 = Bn, CO2-t-Bu

Treatment of fully benzylated 1-methylene-D-glucose withIDCP gives easy access to 1-iodoheptuloses or a 1-iodomethylenederivative.9 The latter compound is, in turn, further amenable tosimilar IDCP-mediated addition reaction. In the synthesis of ci-clamycin O the required trisaccharide glycol was assembled bysubstituent-directed iodinative coupling of glycals as shown in(eq 7).10

O

OHOBz

OBnO

O

O

O

XBnO

O

OHOBz

O

OOBz

OH

OH

O

O OH

CO2Me

O

O

O

O

XOR

OR

OH

OH O

O

OH

CO2Me

OH

O

O

O

O

O

O

O

OH

ORH

HH

IDCP +

(7)

+

IDCP + OH

OH

IDCP

Iodolactonization of heptadienoic acid derivatives havingoxazolidin-2-ones or a sultam12 as chiral auxiliary gave the chiraliodolactone with moderate to excellent enantioselectivity.13

Vicinal cis-Diols.14 An allylic alcohol is converted into its pri-mary urethane derivative, which is then subjected to iodonium ioninduced cyclization to give a single iodocarbonate. The carbon-ate is then deiodinated reductively and hydrolyzed to afford thevicinal diol.

First UpdateAlexei V. DemchenkoUniversity of Missouri, St. Louis, MO, USA

Iodosulfonamidation. Danishefsky has developed a glycaliodosulfonamidation approach to the diastereoselective synthe-sis of N-, O-, or S-linked glycosides. According to this technique,D-glycal derivatives are treated with the combination of IDCP andbenzenesulfonamide in the presence of molecular sieves (4Å) indichloromethane to afford 2-iodo-1-sulfonamido derivatives withthe α-D-manno configuration.15 These derivatives could be effi-ciently applied in glycoside synthesis by reaction with an appro-priate nucleophile in the presence of AgOTf and a strong base(lithium tetramethylpiperidide). This technique was found to besuitable for the synthesis of a range of O-linked di- and oligosac-charides, of 1-azido derivatives,16 and of S-ethyl thioglycosides(eq 8).15 The 1-azido derivatives were subsequently transformedinto N-linked glycopeptides.16 This method was extended to thesynthesis of a variety of oligosaccharides and glycoconjugates.17

A list of General Abbreviations appears on the front Endpapers

IODONIUM DI-sym-COLLIDINE PERCHLORATE 3

Acetal Cleavage and Cyclic Ether Formation. The activa-tion of a suitably placed alkene in the side chain of a glycoside

O

O

O

O

IDCP

O OO

O

I

O

O

O

O

I

O

OH

OH

O

I

H2O

NaBH4

Zn

O OO

O

I

OH OO

O

O

O

O

O

I

OH

O

OH

O

O

I

H+

(9)

+

anhydr.

+

with IDCP leads to cleavage of the acetal and formation of a cycliciodomethylether. This methodology, initially designed for acetalcleavage under neutral conditions, was extended to a number ofother applications (eq 9). Thus, it was demonstrated that the in-termediate oxacarbenium ion could be quenched intermolecularlywith an incoming nucleophile, for example, water.18 The productof this trapping reaction could be either reduced to obtain a polyolderivative or subjected to the isopropylidene acetal cleavage.19

Alternatively, the key oxacarbenium ion intermediate could betrapped intramolecularly by a further alkene in a highly diastereo-selective C–C bond forming process leading to a tetrahydropyranring, juxtaposed with an iodomethyltetrahydrofuran.20 Thelatter could then be reductively cleaved to give overall a pyranosederivative,20 thereby demonstrating the versatility of the approachand its potential applicability to the synthesis of a range of naturalcompounds (eq 9).21

OBnO

BnOBnO

NHSO2Ph

Nu

OOBn

BnOBnO

OBnO

BnOBnO

I

NHSO2Ph

PhSO2NH2

IDCP, CH2Cl2 Nu

Nu = ROH, HSEt, –N3 78%

18–64%

(8)

Synthesis of C-aryl Glycosides. A protected O-pentenyl gly-coside was used as a glycosyl donor in an IDCP-mediated

intramolecular C-arylation.22 It was noted that the resulting prod-uct was kinetically favored, however, the thermodynamic trans-fused product could be obtained by subsequent treatment with aLewis acid (BF3·Et2O) (eq 10).

OOBn

BnOBnO

O

O

OMe

OMeMeO

BnO

BnO

OBn

O

OMe

OMe

O

IDCP

BF3 · Et2O

OOBn

BnOBnO

O

O

OMe

OMeMeO

I

OBnO

BnOBnO

O

OMe

OMe

+

(10)

OMe

OMe

Electrophilic Additions. In electrophilic additions to alkenes,it was reported that higher diastereoselectivities could be ob-tained when bulky electrophilic reagents were used (IDCP or Ph-SeBr) (eq 11). This was rationalized via steric interactions in the

Avoid Skin Contact with All Reagents

4 IODONIUM DI-sym-COLLIDINE PERCHLORATE

transition state.23 The steric effect of the neighboring group R inthese transformations was also highlighted.

O

O

R

O

O

R

IDCPO

O

R

I

O

O

R

I

Nu

+

Nu

R=H, Me, TMSNu = ROH

74–76%

E+

E+

(11)

1. Lemieux, R. U.; Morgan, A. R., Can. J. Chem. 1965, 43, 2190.

2. Pauls, H. W.; Fraser-Reid, B., J. Org. Chem. 1983, 48, 1392.

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4. George, M.; Fraser-Reid, B., Tetrahedron Lett. 1981, 22, 4635.

5. Fraser-Reid, B.; Iley, D. E., Can. J. Chem. 1979, 57, 645.

6. Houdier, S.; Voltero, P. J. A., Carbohydr. Res. 1992, 232, 349.

7. (a) Veeneman, G. H.; Van Boom, J. H., Tetrahedron Lett. 1990, 31, 275.(b) Veeneman G. H.; Van Leeuwen, S. H.; Van Boom, J. H., TetrahedronLett. 1990, 31, 1331.

8. Kuns, H.; Simmer, J., Tetrahedron Lett. 1993, 34, 2907.

9. Noort, D.; Veeneman, G. H.; Boons, G. P. H.; Vander Marel, G. A.;Mulder, G. J.; Van Boom, J. H., Synlett 1990, 205.

10. Susuki, K.; Sulikowski, G. A.; Friesen, R. W.; Danishefsky, S. J., J. Am.Chem. Soc. 1990, 112, 8895.

11. Evans, R. D.; Magee, J. W.; Schauble, J. H., Synthesis 1988, 862.

12. Oppolser, W.; Chapuis, C.; Bernardielli, G., Helv. Chim. Acta 1984, 67,1397.

13. Yokomatsu, T.; Iwasawa, H.; Shibuya, S., Chem. Commun. 1992, 510.

14. Pauls, H. W.; Fraser-Reid, B., J. Carbohydr. Chem. 1985, 4, 1.

15. Griffith, D. A.; Danishefsky, S. J., J. Am. Chem. Soc. 1990, 112, 5811.

16. McDonald, F. E.; Danishefsky, S. J., J. Org. Chem. 1992, 57, 7001.

17. (a) Roberge, J. Y.; Beebe, X.; Danishefsky, S. J., J. Am. Chem. Soc. 1998,120, 3915. (b) Kwon, O.; Danishefsky, S. J., J. Am. Chem. Soc. 1998,120, 1588.

18. Elvey, S. P.; Mootoo, D. R., J. Am. Chem. Soc. 1992, 114, 9685.

19. Shan, W.; Wilson, P.; Liang, W.; Mootoo, D. R., J. Org. Chem. 1994, 59,7986.

20. Khan, N.; Xiao, H.; Zhang, B.; Cheng, X.; Mootoo, D. R., Tetrahedron1999, 55, 8303.

21. Zhao, H.; Hans, S.; Cheng, X.; Mootoo, D. R., J. Org. Chem. 2001, 66,1761.

22. Rousseau, C.; Martin, O. R., Tetrahedron: Asymmetry 2000, 11, 409.

23. Dalla, V.; Pale, P., Tetrahedron Lett. 1996, 37, 2777.

A list of General Abbreviations appears on the front Endpapers