Topics in Current Chemistry (2020) 378:16
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Ir-phosphoramidite catalyst, this reaction can be rendered stereodivergent [36]
whereby the BTM and iridium catalyst each independently control one of the two
vicinal stereocenters in the products, via C1-ammonium enolate and π(allyl)Ir
+
intermediates. Overall, 17 branched products were prepared in excellent yield and
with high levels of diastereoselectivity and enantioselectivity.
In an extension to their work with Pd (Scheme 24), Snaddon et al. exploited this
Ir-catalyzed method to prepare branched homoallylic amines [33]. Using a slightly
modified experimental procedure, this protocol could also be paired with in situ
ammonolysis/Hofmann rearrangement to provide a stereodivergent synthesis of
branched homoallylic amines (Scheme 28). Overall, 17 enantioenriched carbamateprotected branched amines were prepared in good yields and with good-to-excellent levels of diastereoselectivity and excellent enantioselectivity (94 to > 99% ee).
N
O
BocO
CO 2 Me
R 2
R 4
NHCO 2 R 3
OBoc
R 1
N
O
R 2
R 1
N
CO 2 R 3
R 4
CO 2 Me
O
O P
N
Ph Ph
Ir
Ph
[Ir-1]OTf:
+ – OTf
PhMe, rt, 12 h
18 Examples
[Ir-1]OTf (4 mol%)
DABCO (20 mol%)
1.0 eq
1.6 eq
N
O
Me
N
CO 2 Me
CO 2 Me
74%
92% ee
16:1 d.r.
N
O
Me
N
CO 2
i Pr
CO 2 Me
77%
90% ee
>19:1 d.r.
N
O
Bn
N
CO 2
i Pr
CO 2 Me
75%
91% ee
>19:1 d.r.
MeO
MeO
N
O
BocO
CO 2 Me
Me
1.0 eq
R
N
O
0.9 eq
O
CO 2 Me
N
O
Me
N
CO 2 Me
CO 2 Me
THF, rt, 24 h
2 Examples
5 mol% [Ir-1]BF 4
20 mol% LB,
R
LB:
N
N
R = H
48%
92% ee
>19:1 dr
R = OMe
51%
91% ee
>19:1 dr
Selected Examples:
Non-benzannulated, Cyclic Carbamates:
N
O
BocO
CO 2 Me
NHCO 2 Me
OBoc
Me
N
O
CO 2 Me
Me
NHCO 2 Me
[Ir]
LB
N
O
Me
N
CO 2 Me
CO 2 Me
Mechanistic Proposal:
N
O
CO 2 Me
Me
LB
[Ir]
LB
t BuO –
t BuO – + CO 2
t BuOH
[Ir]
Ylide Formation
π(allyl)Ir Formation /
[4+3] Annulation
N
O
Me
N
CO 2 Me
CO 2 Me
MeO
Scheme 29 Application of iridium complexes in asymmetric [4+3] annulations
Reprinted from the journal
124
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Ir-phosphoramidite catalyst, this reaction can be rendered stereodivergent [36]
whereby the BTM and iridium catalyst each independently control one of the two
vicinal stereocenters in the products, via C1-ammonium enolate and π(allyl)Ir
+
intermediates. Overall, 17 branched products were prepared in excellent yield and
with high levels of diastereoselectivity and enantioselectivity.
In an extension to their work with Pd (Scheme 24), Snaddon et al. exploited this
Ir-catalyzed method to prepare branched homoallylic amines [33]. Using a slightly
modified experimental procedure, this protocol could also be paired with in situ
ammonolysis/Hofmann rearrangement to provide a stereodivergent synthesis of
branched homoallylic amines (Scheme 28). Overall, 17 enantioenriched carbamateprotected branched amines were prepared in good yields and with good-to-excellent levels of diastereoselectivity and excellent enantioselectivity (94 to > 99% ee).
N
O
BocO
CO 2 Me
R 2
R 4
NHCO 2 R 3
OBoc
R 1
N
O
R 2
R 1
N
CO 2 R 3
R 4
CO 2 Me
O
O P
N
Ph Ph
Ir
Ph
[Ir-1]OTf:
+ – OTf
PhMe, rt, 12 h
18 Examples
[Ir-1]OTf (4 mol%)
DABCO (20 mol%)
1.0 eq
1.6 eq
N
O
Me
N
CO 2 Me
CO 2 Me
74%
92% ee
16:1 d.r.
N
O
Me
N
CO 2
i Pr
CO 2 Me
77%
90% ee
>19:1 d.r.
N
O
Bn
N
CO 2
i Pr
CO 2 Me
75%
91% ee
>19:1 d.r.
MeO
MeO
N
O
BocO
CO 2 Me
Me
1.0 eq
R
N
O
0.9 eq
O
CO 2 Me
N
O
Me
N
CO 2 Me
CO 2 Me
THF, rt, 24 h
2 Examples
5 mol% [Ir-1]BF 4
20 mol% LB,
R
LB:
N
N
R = H
48%
92% ee
>19:1 dr
R = OMe
51%
91% ee
>19:1 dr
Selected Examples:
Non-benzannulated, Cyclic Carbamates:
N
O
BocO
CO 2 Me
NHCO 2 Me
OBoc
Me
N
O
CO 2 Me
Me
NHCO 2 Me
[Ir]
LB
N
O
Me
N
CO 2 Me
CO 2 Me
Mechanistic Proposal:
N
O
CO 2 Me
Me
LB
[Ir]
LB
t BuO –
t BuO – + CO 2
t BuOH
[Ir]
Ylide Formation
π(allyl)Ir Formation /
[4+3] Annulation
N
O
Me
N
CO 2 Me
CO 2 Me
MeO
Scheme 29 Application of iridium complexes in asymmetric [4+3] annulations
Reprinted from the journal
124