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Copper-Catalyzed Diastereoselective and Enantioselective Addition of 1,1-Diborylalkanes to Cyclic Ketimines and #-Imino Esters Jeongho Kim, Minkyeong Shin, and Seung Hwan Cho ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b02931 • Publication Date (Web): 15 Aug 2019 Downloaded from pubs.acs.org on August 15, 2019
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ACS Catalysis
Copper-Catalyzed Diastereoselective and Enantioselective Addition of 1,1-Diborylalkanes to Cyclic Ketimines and -Imino Esters Jeongho Kim, Minkyeong Shin and Seung Hwan Cho* Department of Chemistry, POSTECH, 37673, Pohang, Korea ABSTRACT: We report a broadly applicable copper catalytic conditions for the diastereoselective and enantioselective 1,2-addition of 1,1-diborylalkanes to cyclic ketimines and -imino esters. The developed method provides various -aminoboronate esters bearing adjacent stereocenters with high diastereo- and enantioselectivity. Synthetic applications for converting the resulting -aminoboronate esters to a diverse array of synthetically useful chiral molecules are demonstrated. KEYWORDS: copper catalysis, diastereoselectivity, enantioselectivity, -aminoboronate ester, boron The creation of contiguous stereocenters in a single catalytic reaction with controlling diastereo- and enantioselectivity is of considerable importance because such transformation enables the rapid synthesis of complex enantioenriched compounds.1 In particular, the stereoselective addition of prochiral nucleophiles to ketimines offers a potentially powerful approach for accessing sterically encumbered -tertiary amine and adjacent stereocenter, which exist in several pharmaceuticals, and biologically active compounds.2 Over the past decades, a strategy toward the stereoselective addition of carbonyl, nitro, and nitrile based nucleophiles to ketimines has been extensively explored.3 Nevertheless, the catalytic addition of prochiral organometallic reagents to ketimines with controlling diastereoand enantioselectivity has rarely been achieved. Trost and coworkers described a palladium-catalyzed cycloaddition of allylsilane derivatives to N-tosyl-protected ketimines with high diastereo- and enantioselectivity (Scheme 1a).4 Lam5a-c and Zhang5d reported the rhodium- or cobalt-catalyzed stereoselective addition of allylic potassium allyl trifluoroboronates to cyclic ketimines (Scheme 1b). Hoveyda et. al. disclosed a highly diastereoselective and enantioselective addition of allyl-Bpin reagents to various N-H ketimines catalyzed by chiral copper/NHC complex (Scheme 1c).6 Although these methods are very effective for the stereoselective addition of prochiral organometallic reagents to ketimines, all of reactions have been primarily focused on using allylsilanes or allylborons as coupling reagents.7,8 Thus, the development of stereoselective methods for the addition of prochiral alkylboron reagents to ketimines is still in demand and remains challenge. Recently, 1,1-diborylalkanes have been considered as useful prochiral nucleophiles in transition-metal-catalyzed coupling with prochiral electrophiles.9-11 These reagents enable the creation of two adjacent stereocenters derived from electrophiles and nucleophiles with high diastereo- and enantioselectvity. For example, Meek and coworkers reported a copper-catalyzed addition of 1,1-diborylalkanes to aldehydes10a and -ketoesters,10b affording enantioenriched -hydroxy-boronate esters. Our group also independently reported a copper catalyst ligated to a chiral phosphoramidite ligand was proved effective in the 1,2-addition of 1,1-diborylalkanes to aldimines, furnishing enantioenriched -aminoboronate esters with high
Scheme 1. Catalytic Stereoselective Addition of Prochiral Organometallics to Ketimines. a) Catalytic cycloaddition of functionalized allylsilane with ketimines (Trost4) N R1
Ts
Me3Si
+ Me
O O S N R
R1 Me CN
CN
and Zhang5d) O O S cat. [Rh],[Co]/L* NH 2 R * * 1 R R3 R4
b) Catalytic addition of allyl borons to ketimines (Lam
R
1
TsN
cat. [Pd]/L*
OAc
2
R3
+
BF3K R4
5a-c
c) Catalytic addition of allyl borons to N-H ketimines (Hoveyda6) N R1
H + R2
R2 NH2 Bpin
Bpin R
3
cat. [Cu]/L*
R1
Bpin
R3
d) This work: Copper-catalyzed addition of 1,1-diborylalkanes to ketimines N
PG
cat. [Cu]/L* LiOtBu
R2 +
pinB R1 Ar (R1 = aryl, vinyl, ester)
Bpin
via: L*/[Cu]
PGHN R1 Ar
rt - 50 oC
Bpin N
R2
R2
Ar
PG R1
Bpin
Creation of adjacent chiral -tertiary amine and secondary boronate ester Excellent diastereo- (up to >20:1) and enantioselectivity (up to 99% ee) Broad substrate scope
stereoselectivities.10d,e,12 The notable feature of these transformations was that the enantioselective transmetallation of 1,1-diborylalkanes with a chiral copper complex is expected to generate enantioenriched -boryl-alkyl-copper species that undergo addition reaction to prochiral electrophiles. With this consideration in mind, we envisaged that the reaction of the putative chiral -boryl-alkyl-copper species with ketimines would provide -aminoboronate esters containing contiguous tetrasubstituted and trisubstituted stereocenters. However, this strategy is challenging because ketimines proved to be intrinsically less reactive than aldimines. Herein, we report a
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Table 1. Optimization Study for the Copper-Catalyzed Addition of 2a to 1aa O
S
O
O
O N Ph
1 2
L
CuBr
L1
CuBr
L1
Table 2. Substrate Scope of Cyclic Ketimines and 1,1Diborylalkanesa–c
O NH Ph
O O S N
Me
Bpin
solvent 1,4-dioxane THF
yield (%)b
d.r.c
R1
ee (%)d
>20:1
76
O
S
CuBr
L1
toluene
78
>20:1
96
4
CuBr
L1
toluene/THF (1:1)
95
>20:1
98
6
CuCl
L1
CuI
L1
toluene/THF (1:1) toluene/THF (1:1)
97
>20:1
97
CuI
L2
toluene/THF (1:1)
88
>20:1
97
8
CuI
L3
toluene/THF (1:1)
97
>20:1
97
O
S
O
O O
Me
S
3d, 60% (81% ) (>20:1 d.r., 98% ee) O
S
O
Me
NH
O
NH Ph
O
CuI
L4
toluene/THF (1:1)
92
>20:1
91
10
CuI
L5
toluene/THF (1:1)
20:1
99
O
S
O
12e,f
CuI
L1
toluene/THF (1:1)
86
>20:1
S
O
Ar Ar O P R O
L1, R = NMe2 L2, R = NEt2 L3, R = N(CH2CH2)2O L4, R = N(Me)Bn
O
Me O
O Me P N Me O
O O Ph
Ar Ar L5, Ar = 4-(Me)C6H4
aThe
reaction was performed with 1a (0.20 mmol), 2a (1.5 equiv), [Cu] (5.0 mol %), ligand (10 mol %), and LiOtBu (2.0 equiv) in solvent (0.5 M) at room temperature for 24 h. b1H NMR yield using 1,1,2,2-tetrachloroethane as an internal standard. cDiastereomeric ratio was measured by 1H NMR of the crude reaction mixture. dEnantiomeric excess (% ee) was determined via. eCuI (3.0 mol %) and L1 (6.0 mol %) were used. fThe reaction was conducted at 50 oC for 12 h.
copper-catalyzed 1,2-addition of 1,1-diborylalkanes to cyclic ketimines and -imino esters that proceeds with high diastereoselectivity and enantioselectivity (Scheme 1d). Further transformations that convert the obtained -aminoboronate esters to synthetically beneficial chiral building blocks are also demonstrated. We initiated our study by choosing 4-phenyl-1,2,3benzoxathiazine-2,2-dioxide (1a) as a prochiral electrophile13 and 1,1-diborylethane (2a) as a coupling reagent (Table 1). When 1a and 2a were subjected in the presence of catalytic amounts of CuBr (5.0 mol %) and phosphoramidite ligand L1 (10 mol %), and LiOtBu in 1,4-dioxane at room temperature (Table 1, entry 1), the β-aminoboronate ester 3a was obtained in 79% yield. Notably, the product 3a was obtained with a diastereoselectivity (d.r.) greater than 20:1 and 93% enantioselectivity (% ee). The use of THF or toluene as a solvent yielded 3a with similar efficiency and higher % ee than
O
S
O NH CO2tBu Me Bpin
S
3i, 65%d (64%)e (>20:1 d.r., 95% ee)
O
O
NH Ph
O
S
O
OTBS
NH Ph
O
Bpin
Ph
3l, 79%f ,g (>20:1 d.r., 99% ee) O O S NH
F
Me
Me Bpin 3p, 77% (>20:1 d.r., 96% ee)
Bpin
3n, 70% (>20:1 d.r., 97% ee) O O S NH
Me
Me
Bpin
3m, 52%f ,g (>20:1 d.r., 98% ee) O O S NH
Bpin
3k, 71%f ,g (>20:1 d.r., 99% ee) O O S NH
NH Ph
O O
Bpin
3j, 65%f ,g (>20:1 d.r., 99% ee)
O
S
Bpin
Bpin
Me
O
Br
3h, 60% (88%)d (>20:1 d.r., 98% ee)
NH Ph
99
3f, 89% (>20:1 d.r., 99% ee)
Me
O
Me
Bpin
NH
Bpin
O
NH Ph
MeO
3e, 66% (>20:1 d.r., 98% ee)
O
3g, 80% (>20:1 d.r., 99% ee)
O
Me
O
S
Bpin
Me
9
3c, 79% (>20:1 d.r., 97% ee)
O
Cl
F
Me
Bpin OMe
Bpin
O
NH Ph
Me
3b, 89% (>20:1 d.r., 99% ee)
O NH Ph
O
S
Bpin
d
7
O
NH Ph
Me
99
Bpin
O
Me
3a, 97% (>20:1 d.r., 99% ee)
98
>20:1
S
O
Bpin
O
5
O
NH Ph
R3
3
O
98
3
R1
toluene/THF (1:1) rt, 24 h
2
93
>20:1
O O S NH 2 R
cat. CuI/L1 LiOtBu (2.0 equiv)
3
Bpin
pinB
1
O
79
R +
R2
3a
2a
[Cu]
S
solvent, rt, 24 h
Bpin
pinB
1a
entry
cat. [Cu]/ligand LiOtBu (2.0 equiv)
Me +
O
Page 2 of 7
3o, 71% (>20:1 d.r., 98% ee) O
Ph Bpin
3q, 46%f ,g (>20:1 d.r., 99% ee)
O Ph
S
O NH Me Me Bpin
3r, 20:1 d.r. and 98% ee. When CuBr was replaced by CuCl, the yield was improved slightly (entry 5), and the highest yield was obtained when CuI was employed as the catalyst (entry 6) with >20:1 d.r. and 99% ee. Reactions conducted in the presence of other phosphoramidite ligands (L2-L4) also afforded the product 3a in good yields, albeit with
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ACS Catalysis diminished efficiencies (entries 7–9). No reaction occurred when L5 was used as a ligand (entry 10). The catalyst loadings could be reduced to 3.0 mol % while maintaining the yields and stereoselectivities (entry 11).14,15 Increasing the reaction temperature to 50 oC shortened the reaction time to 12 h in a slightly low yield without compromising stereoselectivity (entry 12). Under optimized conditions, we investigated the scope of cyclic ketimines at room temperature (Table 2). Reactions of cyclic ketimines bearing an electron-donating substituent (3b, 3c, and 3f) with 2a provided the desired products in good yields (79%–89%) with stereoselectivities (>20:1 d.r. and >97% ee). Substrates bearing fluoride and chloride groups readily reacted with 2a, giving 3d and 3e in 60% and 66% yields, respectively, with >20:1 d.r. and 98% ee. Cyclic ketimines containing 4-tolyl, 4-bromopheyl, and ester group as the R2 substituent proved to be facile electrophiles, affording the corresponding products 3g-3i in good-to-moderate yields (64%–88%), with high diastereo- (>20:1) and enanantioselectivity (95–99% ee). Of note. the product 3i was isolated after oxidation of Bpin because of the instability on silica gel. Next, we examined the scope of 1,1-diborylalkanes. However, when 1a 1,1-diboryl-3-phenylpropane were subjected in the presence of 3.0 mol % of CuI and 6.0 mol % of L1, the product 3j was obtained in rather low yield (31%). To improve the yield, we conducted a re-optimization study and found that increasing the loading of the copper catalyst to 10 mol % in the presence of 2.0 equivalents of 1,1-diboryl-3phenylpropane afforded 3j in an acceptable yield (65%) with high diastereo- (>20:1) and enantioselectivity (99% ee) after 48 h.14 This re-optimized catalytic condition was immediately applied to reactions involving other 1,1-diborylalkanes. Reactions of a TBS-protected alcohol (3k), an acetal protected aldehyde (3l), and an olefin (3m) containing 1,1-diborylalkanes delivered the desired products in good yields (52%-79%) with high diastereo- (>20:1) and enantioselectivity (>98% ee). Intriguingly, five-membered cyclic ketimines also amenable to the 1,2-addition of 1,1-diborylalkanes. Reactions of fivemembered cyclic ketimines that bear phenyl, 4-tolyl, and 4fluorophenyl as a R2 substituent with 2a, providing the corresponding -aminoboronate esters 3n-3p (71-77%, >20:1 d.r., 96-98% ee).15 Phenyl-containing 1,1- diborylalkane smoothly reacted with a five-membered cyclic ketimine, resulting in the formation of 3q in moderate yields (46%) with good stereoselectivities (>20:1 d.r., 99% ee). Unfortunately, no reaction took place when methyl-containing cyclic ketimine (3r) was subjected to the reaction conditions. Since cyclic ketimine that bear enolizable -proton exhibited poor reactivity under the reaction conditions, we envisioned to develop two step sequences involving the 1,2-addition of 1,1diborylalkane to ,-unsaturated cyclic ketimine and subsequent hydrogenation (eq 1). However, this strategy should overcome the challenge associated with competitive 1,4addition of 1,1-diborylalkane to ,-unsaturated cyclic ketimine.16 Gratifyingly, when 1m was treated with 2a under the developed catalytic conditions at 50 oC, the desired 1,2addition product was solely obtained. Subsequent hydrogenation of the obtained product afforded the O O
S
O N
Me Ph
1m
+
pinB 2a
1) CuI (3.0 mol %) L1 (6.0 mol %) LiOtBu (2.0 equiv) toluene/THF (1:1) 50 oC, 24 h
Bpin 2) Pd/C (5.0 mol %) H2 (1 atm) MeOH, rt, 2 h
O O
S
O
Ph
NH Me Bpin
3s, 60% (2 steps) (>20:1 d.r., 99% ee)
(1)
Table 3. Evaluation of the N-Protecting Group (PG) of 4a likely via: Me
cat. CuBr/L1 PGNH CO2tBu PG Me N LiOtBu (2.0 equiv) Me + Ph 1,4-dioxane Bpin Ph CO2tBu pinB Bpin rt, 24 h 4aa-4ad
2a
PG N
5aa-5ad
entry
PG
yield (%)b
1
SO2Ph (4aa)
2
Ts (4ab)
3 4
Bpin [Cu]/L*
Ph
O OtBu
product
d.r.c
ee (%)d
94
5aa
15:1
96
93
5ab
15:1
93
SO2NMe2 (4ac)
94
5ac
>20:1
96
Boc (4ad)
20:1 d.r. and 99% ee). After achieving the 1,2-addition of 1,1-diborylalkanes to cyclic ketimines, we attempted to explore N-protected acyclic ketimines as electrophiles. To begin this study, we chose imino esters as electrophiles because the coordination of chiral copper species with nitrogen and oxygen atoms of the imino and ester group could facilitate the transfer of the -boryl-alkyl moiety to the adjacent electrophilic C=N bond.17 Furthermore, the reaction provided -boryl--amino acid derivatives, which can be used as versatile synthons in the preparation of unnatural peptide. To test the 1,2-addition reaction of 1,1-diborylalkanes to imino esters, we examined the reaction of various N-protected -imino ester (4) with 2a under the reaction conditions (Table 3). When phenylsulfonyl-protected -imino ester (4aa) and 2a were treated in the presence of 5.0 mol % of CuBr, 10 mol % of L1, and LiOtBu in 1,4-dioxane at room temperature, the corresponding -boryl--amino acid derivative 5aa was obtained in 94% yield with 15:1 d.r. and 96% ee (Table 3, entry 1). An analogous reaction of N-Ts-protected -imino ester (4ab) with 2a afforded 5ab in good yield and diastereoselectivity, albeit with slightly lower enantioselectivity (entry 2). The introduction of the N,N-dimethylsulfamoyl moiety (4ac) as the N-protecting group of -imino ester (entry 3) yielded the product 5ac in good yield (94%) with >20:1 d.r. and 96% ee.15 The use of Boc-protected -imino ester did not provide the coupled product (entry 4). Encouraged by these results, we examined the scope and limitations of the developed protocol (Table 4). We found that -imino esters bearing electron-donating (5b, 5c, and 5f) and electron-withdrawing (5d and 5e) substituents on the arene ring were well tolerated, giving the -boryl--amino acid derivatives products in good yields (80-95%) with high d.r. (>20:1) and enantioselectivity (92%-97% ee). A naphthylgroup-containing -imino ester also participated in the reaction, leading to the product 5g in 89% yield (>20:1 d.r. and 90% ee). In contrast, the reaction of 4ac with 1,1-diboryl-3phenylpropane afforded 5h in 61% yield with 18:1 d.r. and 60% ee,14 indicating the current limitation of the Cu/L1 catalyst system. The synthetic usefulness of the developed 1,2-addition process was demonstrated by conducting the developed
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Table 4. Substrate Scope of -Imino Esters and 1,1Diborylalkanesa–c O O S N NMe2 Ar
Bpin
pinB
CO2tBu 4
Bpin
5b, 95% (>20:1 d.r., 93% ee)
O O S NMe2
Bpin
MeO
5c, 93% (>20:1 d.r., 92% ee)
Bpin
HN CO2tBu Me
5d, 80% (>20:1 d.r., 97% ee)
5e, 80% (16:1 d.r., 93% ee)
5f, 75% (18:1 d.r., 97% ee)
O O S NMe2 HN CO2tBu Me Bpin 5g, 89% >20:1 d.r., 90% ee
O O S NMe2
Me
Me
HN CO2tBu Me
Me
Ph
Bpin
Bpin
3o, 62% (1.28 g) >20:1 d.r. 98% ee
5ac, 84% (1.97 g) >20:1 d.r. 96% ee
with CuI/L1 in toluene/THF
with CuI/L1 in toluene/THF
with CuBr/L1 in 1,4-dioxane
S
O
O
NH Ph
HN CO2tBu Me Bpin
O O S NH
3a, 72% (1.50 g) >20:1 d.r. 99% ee
O
Bpin
Cl
NH Ph
b) Further transformations of 3a, 3o, and 5ac
O O S NMe2 Me
Bpin
Bpin
HN CO2tBu Me
O O S NMe2
HN CO2tBu Me
O
O O S NMe2
HN CO2tBu Me Me
S
O
Me
OH
a
a,d
(f rom 3a)
(f rom 3o)
6, 99% >20:1 d.r., 99% ee
O
O S N
e
O
3a, 3o, or 5ac
O
Bpin
(4-tolyl) Me Ph 9, 40% >20:1 d.r., 98% ee
(f rom 5ac) f
7, 89% >20:1 d.r., 99% ee
5h, 61%d,e (18:1 d.r., 60% ee)
O O S NMe2 HN
a
The reaction was performed with 1 (0.20 mmol), 2 (1.5 equiv), CuBr (5.0 mol %), L1 (10 mol %), LiOtBu (2.0 equiv) in 1,4dioxane (0.5 M) at rt for 24 h. bDiastereomeric ratio was measured by 1H NMR of the crude reaction mixture. cThe enantiomeric excess (% ee) was determined via HPLC. dCuBr (10 mol %), L1 (20 mol %), and 2 (2.0 equiv) were used. eThe reaction was performed for 48 h.
b
OH Me
Ph
O
HN
Me
Ph
Me
8, 67% >20:1 d.r., 98% ee
H2N Ph
HN CO2tBu
O
(4-tolyl)
b,c
O O S NMe2
reaction on a gram scale. We were able to obtain the desired aminoboronate esters 3a, 3o, and 5ac in good yields while preserving the optical purity (Scheme 2a). Next, we focused on exploring further transformations of compounds 3a, 3o, and 5ac, as depicted in Scheme 2b. Oxidation of the Bpin group of 3a with H2O2 and NaHCO3 in THF/H2O produced the -amino alcohol 6 in an almost quantitative yield (>20:1 d.r., 99% ee). Subsequent deprotection of the sulfonyl group upon treatment with LiAlH4 and intramolecular Mitsunobu cyclization with triphenylphosphine and diethyl azodicarboxylate yielded the enantioenriched dibenzofuranamine derivative 7 in 89% yield in two steps (>20:1 d.r., 99% ee). After oxidation of Bpin moiety of 3o, the addition of trichloromethyl chloroformate with trimethylamine furnished the compound 8 in 67% yield in two steps. The compound 8 was readily converted into the oxazolidinone 9 by the removal of the sulfonyl group (40%, >20:1 d.r., 97% ee). The -boryl--amino acid derivative 5ac could also be transformed into other synthetically important enantioenriched molecules. Oxidation of the Bpin group of 5ac with H2O2 delivered -hydroxy-- amino acid derivative 10 in 94% yield (>20:1 d.r., 99% ee), which can be further manipulated by the reduction of ester group of 10 with LiAlH4 to yield the corresponding 2-amino- 1,3-diol 11 in 84% yield (18:1 d.r., 96% ee). Following acetal protection of 11 to give 12 (87%, 18:1 d.r., 96% ee), removal of N,N-dimethylsulfamoyl group with 1,3-diaminopropane gave the free amine 13 in 99% yield without racemization (18:1 d.r., 96% ee). Finally, the
Me
Ar
2a
(5.0 mmol)
O
PGHN R1
solvent, rt, 24 h
Bpin
pinB
R1
O
cat. [Cu]/L1 LiOtBu (2.0 equiv)
Me +
Ar
Bpin
O O S NMe2
HN CO2tBu Me
F3C
1,4-dioxane rt, 24 h
PG
N
5
O O S NMe2
5ac, 94% (>20:1 d.r., 96% ee)
a) Gram-scale reaction
HN CO2tBu R Ar
2
Bpin
Scheme 2. Synthetic Utility
O O S NMe2
cat. CuBr/L1 LiOtBu (2.0 equiv)
R +
Page 4 of 7
O O S NMe2
i
HN CO2tBu Me
OH
N tBuO2C Ph
Ph
OH
11, 84% 18:1 d.r., 96% ee
O O S NMe2
10, 94% >20:1 d.r., 96% ee
Me
14, 55% >20:1 d.r., 96% ee
g O O S NH
Me2N
Ph
Me
Me O O
12, 87%, 18:1 d.r. 96% ee
Me
NH2
h Ph
Me
Me O O
Me
13, 99% 18:1 d.r., 96% ee
aH
b 2O2, NaHCO3, THF/H2O, room temperature (rt). LiAlH4, THF, reflux, then H2O. cPPh3, diethyl azodicarboxylate (DEAD), CH2Cl2, 0 °C to rt. dTrichloromethyl chloroformate, Et3N, THF, 0 °C. eSodium naphthalide, DME, rt. fH2O2, NaHCO3, THF/H2O, 0 °C. g2,2-dimethoxypropane, p-TsOH·H2O, acetone, rt. h1,3diaminopropane, 140 °C. iPPh3, diisopropyl azodicarboxylate (DIAD), THF, 0 °C to rt.
reaction of 10 with diisopropyl azodicarboxylate and triphenylphosphine gave the 1,1,2-trisubstituted aziridine 14 in moderate yield (55%) with preservation of enantiopurity (>20:1 d.r., 96% ee). In summary, we have developed an efficient copper-catalytic condition for the diastereoselective and enantioselective addition of 1,1- diborylalkanes to various cyclic ketimines and -imino esters. The developed reaction provides aminoboronate esters bearing adjacent -tertiary amine and secondary boronate ester in good yields, with high diastereoand enantioselectiviy. The reaction can be conducted on gram scale and the synthetic utility of the obtained -aminoboronate esters was demonstrated by performing additional transformations, thus providing methods to afford various chiral libraries. Further studies are ongoing to understand the origin of
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ACS Catalysis this stereocontrol and develop new transformations of 1,1-diborylalkanes.
copper-catalyzed
ASSOCIATED CONTENT Supporting Information. Experimental procedures, characterization data, NMR, X-ray structures of 3a, 3n, and 5d, and HPLC spectra for new compounds. CCDC 1909710 (3a), 1909709 (3n), and 1909711 (5d) contain the supplementary crystallographic data for this paper. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION Corresponding Author *
[email protected] Notes The authors declare no competing financial interest.
ACKNOWLEDGMENT This work was supported by the National Research Foundation of Korea (NRF-2019M1A2A2067940 and NRF2019R1A2C2004925).
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(8) The steoselective addition of enantioenriched allyl boron reagents to ketimines was reported. Chen, J. L. Y.; Aggarwal, V. K. Highly Diastereoselective and Enantiospecific Allylation of Ketones and Imines Using Borinic Esters: Contiguous Quaternary Stereogenic Centers. Angew. Chem., Int. Ed. 2014, 53, 10992–10996. (9) For recent reviews, see: (a) Miralles, N.; Maza, R. J.; Fernández, E. Synthesis and Reactivity of 1,1-Diborylalkanes towards C-C Bond Formation and Related Mechanisms. Adv. Synth. Cat. 2018, 360, 1306– 1327; (b) Nallagonda, R.; Padala, K.; Masarwa, A. gem-Diborylalkanes: Recent Advances in Their Preparation, Transformation and Application. Org. Biomol. Chem. 2018, 16, 1050–1064; (c) Wu, C.; Wang, J. Geminal Bis(boron) Compounds: Their Peparation and Synthetic Applications. Tetrahedron Lett. 2018, 59, 2128–2140. (10) (a) Joannou, M. V.; Moyer, B. S.; Meek, S. J. Enantio- and Diastereoselective Synthesis of 1,2-Hydroxyboronates through CuCatalyzed Additions of Alkylboronates to Aldehydes. J. Am. Chem. Soc. 2015, 137, 6176–6179; (b) Murray, S. A.; Green, J. C.; Tailor, S. B.; Meek, S. J. Enantio‐ and Diastereoselective 1,2‐Additions to ‐Ketoesters with Diborylmethane and Substituted 1,1‐Diborylalkanes. Angew. Chem., Int. Ed. 2016, 55, 9065–9069; (c) Park, J.; Lee, Y.; Kim, J.; Cho, S. H. Copper-Catalyzed Diastereoselective Addition of Diborylmethane to N-tert-Butanesulfinyl Aldimines: Synthesis of βAminoboronates. Org. Lett. 2016, 18, 1210–1213; (d) Kim, J.; Ko, K.; Cho, S. H. Diastereo- and Enantioselective Synthesis of βAminoboronate Esters by Copper(I)-Catalyzed 1,2-Addition of 1,1Bis[(pinacolato)boryl]alkanes to Imines. Angew. Chem., Int. Ed. 2017, 56, 11584–11588. (e) Kim, J.; Hwang, C.; Kim, Y.; Cho, S. H. Improved Synthesis of -Aminoboronate Esters via Copper-Catalyzed Diastereo- and Enantioselective Addition of 1,1-Diborylalkanes to Acyclic Arylaldimines. Org. Process Res. Dev. 2019, DOI: 10.1021/acs.oprd.9b00179. (11) (a) Potter, B.; Szymaniak, A. A.; Edelstein, E. K.; Morken, J. P. Nonracemic Allylic Boronates through Enantiotopic-Group-Selective Cross-Coupling of Geminal Bis(boronates) and Vinyl Halides. J. Am. Chem. Soc. 2014, 136, 17918–17921; (b) Sun, C.; Potter, B.; Morken, J. P. A Catalytic Enantiotopic-Group-Selective Suzuki Reaction for the Construction of Chiral Organoboronates. J. Am. Chem. Soc. 2014, 136, 6534–6537; (c) Sun, H.-Y.; Kubota, K.; Hall, D. G. Reaction Optimization, Scalability, and Mechanistic Insight on the Catalytic Enantioselective Desymmetrization of 1,1-Diborylalkanes via Suzuki– Miyaura Cross-Coupling. Chem. Eur. J. 2015, 21, 19186–19194; (d) Kim, J.; Cho, S. H. Access to Enantioenriched Benzylic 1,1Silylboronate Esters by Palladium-Catalyzed Enantiotopic-Group Selective Suzuki–Miyaura Coupling of (Diborylmethyl)silanes with Aryl Iodides. ACS Catal. 2019, 9, 230–235. (12) Hall and coworkers reported diastereoselective monoprotodeboronation of -sulfinimido 1,1-diboronate esters for the synthesis of -aminoboronate esters, see: Li, X.; Hall, D. G. Diastereocontrolled Monoprotodeboronation of -Sulfinimido gem-
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ACS Catalysis
Table of Contents (TOC) N
PG
cat. [Cu]/L* LiOtBu
R2 +
pinB R1 Ar (R1 = aryl, vinyl, ester)
Bpin
via: L*/[Cu]
PGHN R1 Ar
rt - 50 oC
Bpin N
R2
R2
Ar
PG R1
Bpin
Creation of adjacent chiral -tertiary amine and secondary boronate ester Excellent diastereo- (up to >20:1) and enantioselectivity (up to 99% ee) Broad substrate scope
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