Brønsted Acids of Anionic Chiral Cobalt(III) Complexes as Catalysts for the Iodoglycosylation or Iodocarboxylation of Glycals

^◊ These authors contributed equally to this work.

Abstract

Brønsted acids of anionic chiral Co(III) complexes were found to act as efficient phase-transfer catalysts for the diastereoselective iodoglycosylation or iodocarboxylation of glycals with a variety of alcohols or carboxylic acids, respectively, with N-iodosuccinimide as the iodo cation source. The corresponding 2-deoxy-2-iodoglycosides, including monosaccharides and disaccharides, and 2-deoxy-2-iodoglycosyl carboxylates, which are of high synthetic and biological importance, were obtained in high yields (up to 88%) with good diastereoselectivities (up to 9:1 dr).

Key words

Brønsted acids - phase-transfer catalysis - iodoglycosylation - iodocarboxylation - glycals

Mono- and oligosaccharides are prevalent motifs in biologically active natural products such as glycopeptides, glycoproteins, proteoglycans, and glycolipids.[1] Deoxy sugars also constitute key intermediates with widespread applications in medicinal and pharmaceutical research.[2] Therefore, the development of efficient methods for the synthesis of these glycomolecules in high stereoselectivity and with broad structural diversity is undoubtedly appealing in chemistry, biology, and related fields.[2f] [3] Remarkable progress has been made, especially in transition-metal-catalyzed and organocatalyzed conventional glycosylations for the preparation of complex carbohydrates.[4] In this study, we focused on the iodoglycosylation and iodocarboxylation of glycals by using anionic chiral Co(III) complexes as phase-transfer catalysts, affording the corresponding 2-deoxy-2-iodoglycosides and 2-deoxy-2-iodoglycosyl carboxylates, which are of high synthetic and biological importance.[5] Although iodoglycosylations and iodoacetoxylations through stoichiometric glycosylations using glycals and alcohols or acetic acid in the presence of an electrophilic iodine reagent (NIS) or an iodate reagent such as NH₄I, NaI, I₂, or TMSI(OAc)₂ with an oxidant [for example, H₂O₂, CAN, Cu(OAc)₂, PhI(OAc)₂,[6] PPh_3, [6h] or TfOH[5d]] have been reported, the exploration of high-performance catalytic systems that are, in principle, distinct from previous ones remains essential for the development of mild and efficient stereoselective glycosylation methods. Furthermore, there are few reports on the catalytic stereocontrol of such reactions with chiral catalysts, due to the difficulty of asymmetric intermolecular halogenation[7] [8] or glycosylation.[4] [9]

The potential of the octahedral chiral-at-metal complexes, in which the metal center does not serve as a catalytic center to activate substrate by coordination but merely provides a rigid framework and an environment of centrochirality, is less well recognized.[10] We have recently developed Brønsted acids and sodium salts of anionic chiral Co(III) complexes as efficient catalysts for the highly enantioselective bromoaminocyclization of olefins and for the Povarov reaction of enol ethers with 2-azadienes.[11] More importantly, the chiral Co(III)-complex-templated Brønsted acids have been proved to function as bifunctional phase-transfer catalysts to shuttle N-bromosuccinimide (NBS) to the reaction solution and to control stereoselectivity.[11c] [d] We therefore speculated that such anionic chiral Co(III) complexes might also serve as alternative chiral-anion-mediated catalysts[12] with an iodo-cation source for the iodoglycosylation[4] [6a] [13] of glycals 2 [14] with alcohols 3 or carboxylic acids 5 (Scheme [1]).

Scheme 1 Chiral Co(III)-complex-templated phase-transfer catalysis

Here, we present our preliminary studies on catalytic iodoglycosylation and iodocarboxylation reactions for the preparation of 2-deoxy-2-iodoglycosides 4 and 2-deoxy-2-iodoglycosyl carboxylates 6 by using anionic chiral Co(III) complexes 1.

The diastereoselective iodoglycosylation of 3,4,6-tri-O-benzyl-d-glucal (2a) and benzyl alcohol (3a) with NIS at room temperature was initially tested, and the corresponding 2-deoxy-2-iodoglycoside 4aa was obtained in 69% yield with a 2:1 dr (α/β ratio) without a catalyst (Table [1], entry 1). As expected, the reaction occurred smoothly in the presence of various Lewis acids (entries 2–9), delivering the product in good yields (up to 86%), albeit with only up to 2.5:1 dr, even at a low temperature of –40 °C (entries 6 and 8).[5d] Several Brønsted acids, such as p-toluenesulfonic acid and the chiral phosphoric acids PA1 and PA2, were also tested, and the results suggested that the proton has no impact on the diastereoselectivity (entries 10–12). When DMAP and PPh₃ were employed as the catalysts, the α/β ratio of 4aa was only 3:1 (entries 13 and 14). A series of anionic chiral Co(III) complexes, either as sodium salts or Brønsted acids, were then screened (entries 15–21), Λ-(S,S)-1c afforded the best diastereomeric ratio of 4:1 in the highest yield of 86% (entry 18). The metal-centered chirality in the chiral Co(III)-complex-templated Brønsted acids had little effect on the stereochemical outcome of the iodoglycosylation (entries 16, 19, and 20). Several iodinating reagents, such as 1,3-diiodo-5,5-dimethylhydantoin (DIH) and N-iodosaccharine (NISC), were then tested, and NIS was found to be the optimal iodine source for this protocol (entries 18, 22, and 23). To our delight, changing the ratio of 2a, 3a, and NIS ratio slightly improved the diastereoselectivity (entry 24). Moreover, a screening of the reaction parameters, including the solvent, temperature, and additives, suggested that the reaction in CH₂Cl₂ at room temperature gave a higher α/β ratio of 5:1 with 4 Å MS (entries 24–34).

Table 1 Optimization of the Conditions for Iodoglycosylation^a

Entry	Catalyst	Solvent	I+ source	Yieldb (%)	drc (α/β)
1	–	CH2Cl2	NIS	69	2:1
2d	ZnBr2	CH2Cl2	NIS	76	1.5:1
3d	Sc(OTf)3	CH2Cl2	NIS	86	1:1
4d	Mg(OTf)2	CH2Cl2	NIS	85	1.6:1
5d	TMSOTf	CH2Cl2	NIS	78	1.5:1
6d,e	TMSOTf	CH2Cl2	NIS	55	2:1
7d	TfOH	CH2Cl2	NIS	59	1.8:1
8d,e	TfOH	CH2Cl2	NIS	45	2.5:1
9d	AgOTf	CH2Cl2	NIS	50	2.5:1
10d	TsOH·H2O	CH2Cl2	NIS	69	1.5:1
11	PA1	CH2Cl2	NIS	61	2:1
12	PA2	CH2Cl2	NIS	51	2:1
13d	DMAP	CH2Cl2	NIS	54	3:1
14d,e	PPh3	CH2Cl2	NIS	85	3:1
15	Λ-(S,S)-1a	CH2Cl2	NIS	82	3:1
16	Δ-(R,R)-1a	CH2Cl2	NIS	85	3.5:1
17	Λ-(S,S)-1b	CH2Cl2	NIS	56	3.8:1
18	Λ-(S,S)-1c	CH2Cl2	NIS	86	4:1
19	Δ-(R,R)-1c	CH2Cl2	NIS	78	3.5:1
20	Δ-(S,S)-1c	CH2Cl2	NIS	50	2:1
21	Λ-(S,S)-1d	CH2Cl2	NIS	79	3:1
22	Λ-(S,S)-1c	CH2Cl2	DIH	40	3:1
23	Λ-(S,S)-1c	CH2Cl2	NISC	12	3:1
24f	Λ-(S,S)-1c	CH2Cl2	NIS	82	5:1
25f	Λ-(S,S)-1c	CCl4	NIS	74	3.5:1
26f	Λ-(S,S)-1c	CHCl3	NIS	85	3.8:1
27f	Λ-(S,S)-1c	DCE	NIS	79	4.5:1
28f	Λ-(S,S)-1c	toluene	NIS	76	3:1
29f,g	Λ-(S,S)-1c	CH2Cl2	NIS	51	4:1
30f,h	Λ-(S,S)-1c	CH2Cl2	NIS	74	4.5:1
31f,i	Λ-(S,S)-1c	CH2Cl2	NIS	60	3:1
32f,j	Λ-(S,S)-1c	CH2Cl2	NIS	80	4:1
33f,k	Λ-(S,S)-1c	CH2Cl2	NIS	79	4:1
34f,l	Λ-(S,S)-1c	CH2Cl2	NIS	64	4:1

^a Unless otherwise noted, the reaction was performed with glycal 2a (0.1 mmol), 3a (0.15 mmol), NIS (0.12 mmol), catalyst (0.01 mmol), 4 Å MS (100 mg) in the solvent (1 mL) at r.t. under N₂ in the absence of light for 24 h.

^b Yield of isolated product 4aa.

^c Determined by ¹H NMR.

^d Catalyst (20 mmol%) was used.

^e The reaction was carried out at –40 °C.

^f The 2a/3a/NIS ratio was 1:1.2:1.1.

^g The reaction was carried out at 35 °C.

^h The reaction was carried out at 0 °C.

ⁱ The reaction was carried out at –20 °C.

^j 3 Å MS (100 mg) was used instead of 4 Å MS.

^k 5 Å MS (100 mg) was used instead of 4 Å MS.

^l No additive was used.

With the optimized reaction conditions in hand,[15] we next explored the scope of the iodoglycosylation with respect to the alcohol 3. As shown in Table [2], various substituents on the aryl moiety of the benzyl alcohols 3b–f were tolerated, affording the corresponding 2-deoxy-2-iodoglycosides 4 in up to 73% yield with up to 4.5:1 dr (Table [2], entries 1–5). The electronic nature of the substrates had no evident influence on the reactivity. In addition, 1-naphthylmethanol was also well tolerated and provided the product 4ag with 4:1 dr (entry 6). Nonbenzylic aliphatic alcohols 3h–n were also suitable substrates, giving the desired glycosides 4ah–an in high yields and up to 6.5:1 dr (entries 7–13). Sterically hindered alcohols 3j and 3k readily participated in the reaction with up to 6.5:1 dr (entries 9 and 10). The Z-alkene in 3n was also well tolerated (4:1 dr; entry 13). More importantly, the iodoglycosylation proceeded under mild conditions with monosaccharides such as the primary alcohol 3o and the secondary alcohol 3p, giving the corresponding disaccharides with up to 9:1 dr (entries 14 and 15).

The scope of the iodoglycosylation using Brønsted acid of anionic chiral Co(III)-complexes 1 with regard to the glycals 2 was also evaluated (Table [3]). Glycals with other hydroxy-protecting groups, such as 2b and 2c, were good substrates for the iodoglycosylation reaction, giving the corresponding products in moderate to high yields and with up to 8:1 dr (entries 1–8). Moreover, tri-O-benzyl-d-galactal (2d), the C4-epimer of 2a, afforded the corresponding products in moderate yields with similar diastereoselectivities (up to 6.5:1 dr; entries 9 and 10).[16]

Table 2 Scope of the Alcohols 3 for the Iodoglycosylation^a

Entry	Alcohol	Product	Yieldb (%)	drc (α/β)	drd (Lit.)
1	(3b)	4ab	72	4:1	–
2	(3c)	4ac	62	4.5:1	–
3	(3d)	4ad	73	4:1	–
4	(3e)	4ae	56	4:1	–
5	(3f)	4af	66	4.5:1	–
6	CyOH (3g)	4ag	75	4:1	–
7	Ph(CH2)2OH (3h)	4ah	84	4.5:1	–
8	(3i)	4ai	78	4.5:1	4.8:1[6h]
9	i-PrOH (3j)	4aj	73	5:1	2:1[6h]
10	t-BuOH (3k)	4ak	72	6.5:1	–
11	Me(CH2)7OH (3l)	4al	78	4:1	2.3:1[6h]
12	(3m)	4am	78	4:1	–
13	(3n)	4an	76	4:1	–
14e	(3o)	4ao	88	6.5:1	2.5:1[6h]
15e	(3p)	4ap	53	9:1	–

a Unless otherwise noted, the reaction was performed with glycal 2a (0.1 mmol), alcohol 3 (0.12 mmol), NIS (0.11 mmol), Λ-(S,S)-1c (0.01 mmol), and 4 Å MS (100 mg) in CH₂Cl₂ (1 mL) at r.t., under N₂ in the absence of light for 24 h.

b Yield of isolated product.

c Determined by ¹H NMR.

d Anomer ratios reported in the literature.

e The reaction was carried out on a 0.1 mmol scale for 72 h with a 2a/3/NIS ratio of 2:1:2.4.

Table 3 The Scope of Glycals for the Iodoglycosylation^a

Entry	Glycal	Alcohol	Product	Yieldb (%)	drc (α/β)	drd (Lit.)
1		3a	4ba	80	8:1	5:1[6d] 9:1[6e]
2		3c	4bc	54	5:1	–
3		3f	4bf	55	4:1	6:1[6d] 11:1[6e]
4		3g	4bg	70	5:1	–
5		3h	4bh	63	4.5:1	–
6		3a	4ca	60	4:1	–
7		3c	4cc	66	5:1	–
8		3j	4cj	61	5:1	–
9		3c	4dc	47	4:1	–
10		3k	4dk	52	6.5:1	–

^a Unless otherwise noted, the reaction was performed with glycal 2 (0.1 mmol), alcohol 3 (0.2 mmol), NIS (0.15 mmol), Λ-(S,S)-1c (0.01 mmol), and 4 Å MS (100 mg) in CH₂Cl₂ (1 mL) at r.t. under N₂ in the absence of light for 48 h.

^b Yield of isolated product.

^c Determined by ¹H NMR.

^d Anomer ratios reported in the literature.

Encouraged by these results, we next studied the iodocarboxylation of glycal 2a with carboxylic acids and sodium salts 5 to give the corresponding 2-deoxy-2-iodoglycosyl carboxylates 6 (Table [4]).[17] The reaction of the sodium salts 5a and 5c and the acids 5b and 5d in the absence of the chiral-Co(III)-complex-templated Brønsted acid were first tested, and products 6a and 6b were obtained with low diastereoselectivities (Table [4], entries 1-4). Interestingly, the presence of the Brønsted acid of a chiral Co(III) complex Λ-1c resulted in enhanced diastereoselectivity (up to 6.5:1 dr; entries 5–8), but the sodium salts of the acids still gave low yields (entries 5 and 6). It is suggested that the presence of an acidic proton might promote the reaction and that the bulky chiral Co(III) complexes influence the stereocontrol. The protocol also tolerated other carboxylic acids, and the corresponding glycosyl carboxylates 6c–e were obtained with good diastereoselectivities (up to 7.5:1 dr; entries 9–11).

Table 4 The scope of the Iodocarboxylation^a

Entry	Acid or Na Salt	Product	Catalyst	Yieldb (%)	drc
1	BzONa (5a)	6a	–	14	3.5:1
2	BzOH (5b)	6a	–	82	2:1
3	AcONa (5c)	6b	–	29	2.5:1
4	AcOH (5d)	6b	–	70	1.8:1
5	BzONa (5a)	6a	Λ-(S,S)-1c	28	3.8:1
6	AcONa (5c)	6b	Λ-(S,S)-1c	28	5.5:1
7	BzOH (5b)	6a	Λ-(S,S)-1c	74	6.5:1
8	AcOH (5d)	6b	Λ-(S,S)-1c	65	5.5:1 d
9	4-F3CC6H4CO2H (5e)	6c	Λ-(S,S)-1c	67	6:1
10	(5f)	6d	Λ-(S,S)-1c	62	6:1
11	2,6-Cl2C6H4CO2H (5g)	6e	Λ-(S,S)-1c	75	7.5:1

^a Unless otherwise noted, the reaction was performed with glycal 2a (0.1 mmol), 5 (0.15 mmol), NIS (0.12 mmol), Λ-(S,S)-1c (0.01 mmol), and 4 Å MS (100 mg) in CH₂Cl₂ (1 mL) at r.t. under N₂ in the absence of light for 12 h.

^b Yield of isolated product.

^c Determined by ¹H NMR.

^d The reported anomer ratio of 5d was 4:1.[6f]

Next, we performed a ¹H NMR spectral analysis of mixtures of NIS with Brønsted acid Λ-(S,S)-1c or benzoic acid (5b) in CDCl₃ at room temperature. The presence of succinimide in the former mixture clearly revealed that Λ-(S,S)-1c reacted with NIS to produce a new complex,[11c] [d] thereby leading to the formation of succinimide, while no evidence was found to show that there is an interaction between benzoic acid (5b) and NIS in the latter mixture (Figure [1]).

Figure 1 ¹H NMR analysis of mixtures of NIS with Brønsted acid Λ-(S,S)-1c or benzoic acid (5b) in CDCl₃.

On the basis of the interesting experimental results and our previous work,[11c] [d] we propose a plausible mechanism for these reaction of a chiral-Co(III)-templated Brønsted acid in combination with NIS. As shown in Scheme [2], the Brønsted acid 1 might undergo an exchange reaction with NIS to generate a reactive chiral iodinating reagent 7, as suggested by the ¹H NMR spectral analysis. The chiral ion-pair 7 might then undergo diastereoselective reaction with the glycal 2 to afford the 2-deoxy-2-iodoglycoside 4 or a 2-deoxy-2-iodoglycosyl carboxylate 6 through nucleophilic addition of the alcohol 3 or carboxylic acid 5, respectively, with regeneration of Brønsted acid 1. The stereochemical outcomes were not good enough to have been caused by the competition of the rapid noncatalytic reaction of NIS.

Scheme 2 Proposed mechanism

In summary, we have developed a diastereoselective iodoglycosylation or iodocarboxylation of glycals with NIS mediated by a chiral-Co(III)-complex-templated Brønsted acid. The catalytic reaction proceeds under mild conditions, providing convenient access to 2-deoxy-2-iodoglycosides or 2-deoxy-2-iodoglycosyl carboxylates in up to 88% yield and with up to 9:1 dr. The anionic chiral Co(III) complexes also function as bifunctional phase-transfer catalysts to shuttle the N-iodosuccinimide to the reaction solution. Further studies will focus on the development of stereoselective halogenations catalyzed by Brønsted acids of anionic chiral Co(III) complexes.

Acknowledgment

We sincerely thank Prof. Zheng-Zhu Zhang and Dr. Chuan-Zhi Yao (AHAU) for their support.

• References and Notes

• 1a Varki A. Glycobiology 1993; 3: 97
• 1b Carbohydrates in Chemistry and Biology, Vols. 1–4. Ernst B, Hart GW, Sinaÿ P. Wiley-VCH; Weinheim: 2000
• 1c Glycoscience, Chemistry and Chemical Biology, Vols. 1–3. Fraser-Reid BO, Tatsuta K, Thiem J. Springer; Berlin: 2001
• 1d Bertozzi CR, Kiessling LL. Science 2001; 291: 2357
• 2a Deoxy Sugars . Gould RF. ACS; Washington: 1968
• 2b Kirschning A, Bechthold AF.-W, Rohr J. Top. Curr. Chem. 1997; 188: 1
• 2c Weymouth-Wilson AC. Nat. Prod. Rep. 1997; 14: 99
• 2d Kren V, Martínková L. Curr. Med. Chem. 2001; 8: 1303
• 2e De Lederkremer RM, Marino C. Adv. Carbohydr. Chem. Biochem. 2008; 61: 143
• 2f Hou D, Lowary TL. Carbohydr. Res. 2009; 344: 1911
• 3a Demchenko AV. In Handbook of Chemical Glycosylation: Advances in Stereoselectivity and Therapeutic Relevance. Demchenko AV. Wiley-VCH; Weinheim: 2008. 1

For some reviews on the methods for the synthesis of 2-deoxyglycosides, see:
• 3b Thiem J, Klaffke W. Top. Curr. Chem. 1990; 154: 285
• 3c Marzabadi CH, Franck RW. Tetrahedron 2000; 56: 8385
• 3d Borovika A, Nagorny P. J. Carbohydr. Chem. 2012; 31: 255
• 3e Zeng J, Xu Y, Wang H, Meng L, Wan Q. Sci. China: Chem. 2017; 60: 1162
• 3f Bennett CS, Galan MC. Chem. Rev. 2018; 118: 7931

For recent reviews, see:
• 4a Li X, Zhu J. Eur. J. Org. Chem. 2016; 2016: 4724 ; and references cited therein
• 4b Williams R, Galan MC. Eur. J. Org. Chem. 2017; 2017: 6247 ; and references cited therein

For selected examples of glycosylations controlled by chiral Brønsted acids, see:
• 4c Cox DJ, Smith MD, Fairbanks AJ. Org. Lett. 2010; 12: 1452
• 4d Balmond EI, Coe DM, Galan MC, McGarrigle EM. Angew. Chem. Int. Ed. 2012; 51: 9152
• 4e Kimura T, Sekine M, Takahashi D, Toshima K. Angew. Chem. Int. Ed. 2013; 52: 12131
• 4f Gould ND, Allen CL, Nam BC, Schepartz A, Miller SJ. Carbohydr. Res. 2013; 382: 36
• 4g Balmond EI, Benito-Alifonso D, Coe DM, Alder RW, McGarrigle EM, Galan MC. Angew. Chem. Int. Ed. 2014; 53: 8190
• 4h Liu D, Sarrafpour S, Guo W, Goulart B, Bennett CS. J. Carbohydr. Chem. 2014; 33: 423
• 4i Kuroda Y, Harada S, Oonishi A, Kiyama H, Yamaoka Y, Yamada K.-i, Takasu K. Angew. Chem. Int. Ed. 2016; 55: 13137
• 4j Park Y, Harper KC, Kuhl N, Kwan EE, Liu RY, Jacobsen EN. Science 2017; 355: 162
• 5a Friesen RW, Danishefsky SJ. J. Am. Chem. Soc. 1989; 111: 6656
• 5b Suzuki K, Sulikowski GA, Friesen RW, Danishefsky SJ. J. Am. Chem. Soc. 1990; 112: 8895
• 5c Sebesta DP, Roush WR. J. Org. Chem. 1992; 57: 4799
• 5d Tanaka H, Takahashi D, Takahashi T. Angew. Chem. Int. Ed. 2006; 45: 770
• 5e Perret P, Slimani L, Briat A, Villemain D, Halimi S, Demongeot J, Fagret D, Ghezzi C. Eur. J. Nucl. Med. Mol. Imaging 2007; 34: 734
• 5f Wang H, Tao J, Cai X, Chen W, Zhao Y, Xu Y, Yao W, Zheng J, Wan Q. Chem. Eur. J. 2014; 20: 17319
• 5g Pradhan TK, Lin CC, Mong K.-KT. Org. Lett. 2014; 16: 1474
• 6a Thiem J, Karl H, Schwentner J. Synthesis 1978; 696
• 6b Gammon DW, Kinfe HH, De Vos DE, Jacobs PA, Sels BF. Tetrahedron Lett. 2004; 45: 9533
• 6c Roush WR, Narayan S, Bennett CE, Briner K. Org. Lett. 1999; 1: 895
• 6d Saeeng R, Sirion U, Sirichan Y, Trakulsujaritchok T, Sahakitpichan P. Heterocycles 2010; 81: 2569
• 6e Sirion U, Purintawarrakun S, Sahakitpicchan P, Saeeng R. Carbohydr. Res. 2010; 345: 2401
• 6f Reddy TR, Rao DS, Babachary K, Kashyap S. Eur. J. Org. Chem. 2016; 2016: 291
• 6g Yuan W, Liu Y, Li C. Synlett 2017; 28: 1975
• 6h Kimura T, Takahashi D, Toshima K. J. Org. Chem. 2015; 80: 9552

A similar reaction using 3,4-O -isopropylidene-6-O-(tert -butyldiphenyl)silyl-protected glycosyl donors that favor the β-anomer was recently reported, see:
• 6i Yang D.-M, Chen Y, Sweeney RP, Lowary TL, Liang X.-Y. Org. Lett. 2018; 20: 2287

For leading reviews on asymmetric intermolecular halogenation, see:
• 7a Chen J, Zhou L. Synthesis 2014; 46: 586 ; and references cited therein
• 7b Cheng YA, Yu WZ, Yeung Y.-Y. Org. Biomol. Chem. 2014; 12: 2333

For recent examples of asymmetric intermolecular halogenations, see:
• 8a Li L, Su C, Liu X, Tian H, Shi Y. Org. Lett. 2014; 16: 3728
• 8b Qi J, Fan G.-T, Chen J, Sun M.-H, Dong Y.-T, Zhou L. Chem. Commun. 2014; 50: 13841
• 8c Hu DX, Seidl FJ, Bucher C, Burns NZ. J. Am. Chem. Soc. 2015; 137: 3795
• 8d Soltanzadeh B, Jaganathan A, Staples RJ, Borhan B. Angew. Chem. Int. Ed. 2015; 54: 9517
• 8e Denmark SE, Carson N. Org. Lett. 2015; 17: 5728
• 8f Landry ML, Hu DX, McKenna GM, Burns NZ. J. Am. Chem. Soc. 2016; 138: 5150
• 8g Zhou P, Cai Y, Zhong X, Luo W, Kang T, Li J, Liu X, Lin L, Feng X. ACS Catal. 2016; 6: 7778
• 8h Wang Z, Lin L, Zhou P, Liu X, Feng X. Chem. Commun. 2017; 53: 3462
• 8i Zhou P, Lin L, Chen L, Zhong X, Liu X, Feng X. J. Am. Chem. Soc. 2017; 139: 13414
• 8j Burckle AJ, Gál B, Seidl FJ, Vasilev VH, Burns NZ. J. Am. Chem. Soc. 2017; 139: 13562
• 8k Guo S, Cong F, Guo R, Wang L, Tang P. Nat. Chem. 2017; 9: 546
• 8l Horibe T, Tsuji Y, Ishihara K. ACS Catal. 2018; 8: 6362

For selected reviews, see:
• 9a Toshima K, Tatsuta K. Chem. Rev. 1993; 93: 1503
• 9b Seeberger PH, Werz DB. Nature 2007; 446: 1046
• 9c Boltje TJ, Buskas T, Boons G.-J. Nat. Chem. 2009; 1: 611
• 9d Zhu X, Schmidt RR. Angew. Chem. Int. Ed. 2009; 48: 1900
• 9e Yu B, Sun J, Yang X. Acc. Chem. Res. 2012; 45: 1227
• 9f Ranade SC, Demchenko AV. J. Carbohydr. Chem. 2013; 32: 1
• 9g Nigudkar SS, Demchenko AV. Chem. Sci. 2015; 6: 2687
• 9h Yang Y, Zhang XH, Yu B. Nat. Prod. Rep. 2015; 32: 1331

For reviews on chiral-at-metal complexes in catalysis, see:
• 10a Brunner H. Angew. Chem. Int. Ed. 1999; 38: 1194
• 10b Knight PD, Scott P. Coord. Chem. Rev. 2003; 242: 125
• 10c Fontecave M, Hamelin O, Ménage S. Top. Organomet. Chem. 2005; 15: 271
• 10d Bauer EB. Chem. Soc. Rev. 2012; 41: 3153
• 10e Gong L, Chen L.-A, Meggers E. Angew. Chem. Int. Ed. 2014; 53: 10868
• 10f Cao Z.-Y, Brittain WD. G, Fossey JS, Zhou F. Catal. Sci. Technol. 2015; 5: 3441
• 11a Yu J, Jiang H.-J, Zhou Y, Luo S.-W, Gong L.-Z. Angew. Chem. Int. Ed. 2015; 54: 11209
• 11b Jiang H.-J, Liu K, Wang J, Li N, Yu J. Org. Biomol. Chem. 2017; 15: 9077
• 11c Jiang H.-J, Liu K, Yu J, Zhang L, Gong L.-Z. Angew. Chem. Int. Ed. 2017; 56: 11931
• 11d Liu K, Jiang H.-J, Li N, Li H, Wang J, Zhang Z.-Z, Yu J. J. Org. Chem. 2018; 83: 6815
• 11e Li N, Yu H, Wang R, Shen J, Wu W.-Q, Liu K, Sun T.-T, Zhang Z.-Z, Yao C.-Z, Yu J. Tetrahedron Lett. 2018; 59: 3605
• 11f Jiang H.-J, Zhong X.-M, Yu J, Zhang Y, Zhang X, Wu Y.-D, Gong L.-Z. Angew. Chem. Int. Ed. 2019; 58: 1803

For selected reviews on catalysis by chiral anions, see:
• 12a Lacour J, Hebbe-Viton V. Chem. Soc. Rev. 2003; 32: 373
• 12b Lacour J, Moraleda D. Chem. Commun. 2009; 7073
• 12c Zhang Z, Schreiner PR. Chem. Soc. Rev. 2009; 38: 1187
• 12d Wenzel M, Hiscock JR, Gale PA. Chem. Soc. Rev. 2012; 41: 480
• 12e Phipps RJ, Hamilton GL, Toste FD. Nat. Chem. 2012; 4: 603
• 12f Mahlau M, List B. Angew. Chem. Int. Ed. 2013; 52: 518
• 12g Brak K, Jacobsen EN. Angew. Chem. Int. Ed. 2013; 52: 534

For selected examples, see:
• 12h Hamilton GL, Kanai T, Toste FD. J. Am. Chem. Soc. 2008; 130: 14984
• 12i Mayer S, List B. Angew. Chem. Int. Ed. 2006; 45: 4193
• 12j Hamilton GL, Kang EJ, Mba M, Toste FD. Science 2007; 317: 496
• 12k Sigman MS, Jacobsen EN. J. Am. Chem. Soc. 1998; 120: 4901
• 12l Sigman MS, Vachal P, Jacobsen EN. Angew. Chem. Int. Ed. 2000; 39: 1279
• 12m Llewellyn DB, Adamson D, Arndtsen BA. Org. Lett. 2000; 2: 4165
• 12n Carter C, Fletcher S, Nelson A. Tetrahedron: Asymmetry 2003; 14: 1995

For some reviews, see:
• 13a Lemieux RU, Levine S. Can. J. Chem. 1964; 42: 1473
• 13b De Castro M, Marzabadi CH. Tetrahedron 2010; 66: 3395

For selected examples of syntheses of 2-deoxy-2-iodoglycosides, see:
• 13c Rodríguez M. Á, Boutureira O, Arnés X, Matheu MI, Díaz Y, Castillón S. J. Org. Chem. 2005; 70: 10297
• 13d Kövér A, Boutureira O, Matheu MI, Díaz Y, Castillón S. J. Org. Chem. 2014; 79: 3060
• 13e Battina SK, Kashyap S. Tetrahedron Lett. 2016; 57: 811

For a review, see:
• 14a Danishefsky SJ, Bilodeau MT. Angew. Chem. Int. Ed. 1996; 35: 1380

For recent examples of syntheses of deoxyglycosides from glycals, see:
• 14b Sau A, Williams R, Palo-Nieto C, Franconetti A, Medina S, Galan MC. Angew. Chem. Int. Ed. 2017; 56: 3640
• 14c Palo-Nieto C, Sau A, Galan MC. J. Am. Chem. Soc. 2017; 139: 14041
• 14d Sau A, Galan MC. Org. Lett. 2017; 19: 2857
• 14e Palo-Nieto C, Sau A, Williams R, Galan MC. J. Org. Chem. 2017; 82: 407
• 14f Zhao G, Wang T. Angew. Chem. Int. Ed. 2018; 57: 6120
• 15 2-Deoxy-2-Iodoglycoside 4aa; Typical Procedure A 10-mL oven-dried vial was charged with catalyst Λ-1c (7.2 mg, 0.01 mmol), NIS (24.8 mg, 0.11 mmol), activated 4 Å MS (100 mg), glycal 2a (41.6 mg, 0.10 mmol), and distilled CH₂Cl₂ (1 mL) at r.t. in the absence of light. Alcohol 3a (0.12 mmol) was added and the resulting solution was stirred vigorously under N₂ for 24 h. The reaction was then quenched with Et₃N (140 μL, 1.0 mmol) and sat. aq Na₂S₂O₃ (0.2 mL). The mixture was purified by flash column chromatography to give the 2-deoxy-2-iodoglycosides 4aa as an α/β mixture. 4aaα Colorless oil; yield: 43.9 mg (67%); R_f = 0.43 (PE–EtOAc, 10:1); [α]_D ²⁰ +3.45 (c 1.27, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 7.48–7.35 (m, 4 H), 7.35–7.19 (m, 14 H), 7.16 (d, J = 6.2 Hz, 2 H), 5.30 (s, 1 H), 4.84 (d, J = 10.8 Hz, 1 H), 4.72–4.66 (m, 3 H), 4.52–4.46 (m, 5 H), 3.92–3.91 (m, 2 H), 3.80–3.75 (m, 1 H), 3.69 (d, J = 10.8 Hz, 1 H), 3.37–3.34 (m, 1 H). ¹³C NMR (151 MHz, CDCl₃): δ = 138.46, 138.29, 137.80, 136.98, 128.51, 128.44, 128.35, 128.10, 128.08, 128.05, 127.82, 127.69, 127.52, 100.85, 100.80, 76.05, 75.31, 73.47, 72.51, 71.04, 69.54, 69.00, 33.58, 33.55. HRMS (ESI): m/z [M + Na]⁺ calcd for C₃₄H₃₅NaIO₅: 673.1427; found: 673.1420. 4aaβ White solid; yield: 9.5 mg (15%); mp 101–103 °C; R_f = 0.38 (PE–EtOAc, 10:1); [α]_D ²⁰ +4.91 (c 0.55, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 7.47–7.36 (m, 4 H), 7.36–7.26 (m, 14 H), 7.19 (d, J = 6.9 Hz, 2 H), 4.97 (d, J = 10.2 Hz, 1 H), 4.92 (d, J = 11.7 Hz, 1 H), 4.85 (d, J = 10.1 Hz, 1 H), 4.80 (d, J = 10.9 Hz, 1 H), 4.68 (d, J = 11.8 Hz, 1 H), 4.62 (t, J = 9.6 Hz, 2 H), 4.57 (t, J = 12.5 Hz, 2 H), 4.01–3.94 (m, 1 H), 3.77–3.70 (m, 3 H), 3.64 (t, J = 9.2 Hz, 1 H), 3.49 (d, J = 7.6 Hz, 1 H). ¹³C NMR (151 MHz, CDCl₃): δ = 138.17, 137.90, 137.85, 136.88, 128.55, 128.48, 128.42, 128.33, 128.18, 127.98, 127.89, 127.83, 127.76, 101.98, 86.01, 79.79, 75.62, 75.42, 75.03, 73.65, 71.39, 68.72, 32.68. HRMS (ESI): m/z [M + Na]⁺ calcd for C₃₄H₃₅NaIO₅: 673.1427; found: 673.1422. (see Supporting Information for further information).
• 16 Iodoglycosylations of either glucal (2b) or galactal (2d) with alcohol 3c in the absence of the chiral-Co^III-complex-templated Brønsted acid were also tested, affording the desired 2-deoxy-2-iodoglycosides in yields of 52% and 24% with 2.5:1 and 1.8:1 dr, respectively.
• 17 2-Deoxy-2-Iodoglycosyl Carboxylate 6a; Typical Procedure A 10-mL oven-dried vial was charged with catalyst Λ-1c (7.2 mg, 0.01 mmol), NIS (27.0 mg, 0.12 mmol), activated 4 Å MS (100 mg), glycal 2a (41.6 mg, 0.10 mmol), and distilled CH₂Cl₂ (1 mL) at r.t. in the absence of light. BzOH (5a; 0.15 mmol) was added and the resulting solution was stirred vigorously under N₂ for 12 h. The reaction was then quenched with Et₃N (140 μL, 1.0 mmol) and sat. aq Na₂S₂O₃ (0.2 mL). The mixture was purified by flash column chromatography to give the glycosyl carboxylate 6a as a α/β mixture. 6aα Colorless oil; yield: 42.7 mg (64%); R_f = 0.4 (PE–EtOAc, 8:1); [α]_D ²⁰ +3.78 (c 0.82, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 7.93 (d, J = 7.0 Hz, 2 H), 7.59 (t, J = 7.4 Hz, 1 H), 7.43 (t, J = 7.8 Hz, 2 H), 7.41–7.35 (m, 4 H), 7.34–7.24 (m, 9 H), 7.22–7.16 (m, 2 H), 6.66 (s, 1 H), 4.90 (d, J = 10.5 Hz, 1 H), 4.76–4.72 (m, 2 H), 4.58–4.52 (m, 4 H), 4.13–4.09 (m, 1 H), 4.07–4.03 (m, 1 H), 3.83 (dd, J = 11.3, 4.0 Hz, 1 H), 3.71 (dd, J = 11.3, 1.6 Hz, 1 H), 3.33 (dd, J = 8.7, 4.1 Hz, 1 H). ¹³C NMR (151 MHz, CDCl₃): δ = 164.07, 138.37, 138.08, 137.26, 133.75, 129.92, 129.12, 128.62, 128.57, 128.49, 128.38, 128.34, 128.32, 128.11, 127.94, 127.81, 127.59, 96.17, 76.20, 75.63, 75.31, 73.67, 71.22, 68.65, 31.20. HRMS (ESI): m/z [M+Na]⁺ calcd for C₃₄H₃₃INaO₆: 687.1220; found: 687.1215. 6aβ Colorless oil; yield: 6.5 mg (10%); R_f = 0.4 (PE–EtOAc, 8:1); [α]_D ²⁰ +65.61 (c 0.22, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 8.11 (d, J = 7.7 Hz, 2 H), 7.60 (t, J = 7.3 Hz, 1 H), 7.47 (t, J = 7.7 Hz, 2 H), 7.43 (d, J = 7.4 Hz, 2 H), 7.36 (t, J = 7.3 Hz, 2 H), 7.34–7.23 (m, 9 H), 7.17 (d, J = 7.4 Hz, 2 H), 6.05 (d, J = 9.5 Hz, 1 H), 5.00 (d, J = 10.2 Hz, 1 H), 4.91 (d, J = 10.2 Hz, 1 H), 4.82 (d, J = 10.8 Hz, 1 H), 4.60 (dd, J = 15.7, 11.5 Hz, 2 H), 4.48 (d, J = 12.1 Hz, 1 H), 4.19 (t, J = 9.8 Hz, 1 H), 3.87–3.69 (m, 5 H). ¹³C NMR (151 MHz, CDCl₃): δ = 164.67, 137.76, 133.75, 130.34, 128.56, 128.51, 128.45, 128.16, 128.01, 127.98, 127.86, 127.80, 95.09, 85.65, 79.07, 76.17, 75.76, 75.10, 73.71, 68.02, 30.23. HRMS (ESI): m/z [M+Na]⁺ calcd for C₃₄H₃₃INaO₆: 687.1220; found: 687.1217. (See Supporting Information for further information).