Diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines

Article abstract of DOI:10.1016/j.tetlet.2017.03.067

The diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines is reported. These molecules are synthesized by formation of sulfinyl imine followed by diastereoselective addition of a diphenylphosphine sulfide. The product N-sulfinyl α-aminophosphine sulfides can be converted to phosphines through removal of the sulfur by reaction with Raney nickel. Hydrolysis of the sulfinyl group provides an amine that can then be attached to other ligands or structural scaffolds.

Full text of DOI:10.1016/j.tetlet.2017.03.067

Accepted Manuscript
Diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phos-
phines
Wei Zhang, Scott R. Gilbertson
PII:
S0040-4039(17)30370-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.03.067
TETL 48768
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
10 March 2017
21 March 2017
22 March 2017
Please cite this article as: Zhang, W., Gilbertson, S.R., Diastereoselective synthesis of N-sulfinyl α-aminophosphine
sulfides and phosphines, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.03.067
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Diastereoselective synthesis of N-sulfinyl α-
aminophosphine sulfides and phosphines
Wei Zhang, and Scott R. Gilbertson

1
Tetrahedron Letters
journal homepage: www.els evier.com
Diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines
Wei Zhang, Scott R. Gilbertson∗
Department of Chemistry, University of Houston, Houston TX 77204, United States
ARTICLE INFO
ABSTRACT
Article history:
Received
The diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines is
reported. These molecules are synthesized by formation of sulfinyl imine followed by
Received in revised form
Accepted
Available online
diastereoselective addition of a diphenylphosphine sulfide. The product N-sulfinyl α-
aminophosphine sulfides can be converted to phosphines through removal of the sulfur by
reaction with Raney nickel. Hydrolysis of the sulfinyl group provides an amine that can then be
attached to other ligands or structural scaffolds.
2009 Elsevier Ltd. All rights reserved.
Aminophosphine
Sulfinyl phosphine
Phosphine oxide
Phosphine sulfide
Phosphines have been used in catalysis as ligands on transition
metals for many years. In cases of asymmetric catalysis they have
been used as monovalent and bivalant ligands on their own or
with other metal ligands, such as oxazolines, alkenes and ether
oxygens.1-3 With very few exceptions, the chirality of the
transition metal complex is present in the phosphine’s partner or
the tether connecting the two ligands. Recently, the sulfinyl
group has been used in asymmetric catalysis as a bivalent ligand
on its own, or in combination with other groups including
phosphines or olefins (Figure 1).4-12 The use of a sulfinyl group
provides a chiral atom directly attached to the catalytic metal and
maybe an excellent complement to the more traditional
phosphine partners. In addition to transition metal catalysis, there
have been reports where N-sulfinyl α-aminophosphines, related
to α-aminophosphonates, have been used as nucleophilic
catalysts in reactions such as the cross Rauhut-Currier reaction.13
Sulfinamide phosphinates have also been used in organo-catalytic
reduction of imines.14 To date there have not been any reports of
phosphine based N-sulfinyl α-aminophosphine sulfides and
phosphines being used as ligands for transition metals in
reactions catalyzed by the metal.
Since both enantiomers of the tert-butyl amino sulfinyl group
are inexpensive and commercially available, a logical approach
to the desired chiral N-sulfinyl α-aminophosphine derivatives
was to synthesize the sulfinyl imine and then add a phosphide
anion, or the equivalent, to the imine using the sulfur chirality to
direct the addition. Such an approach has been used in the
synthesis of amino phosphates, which are then used as amino
acid mimics.16
Figure 1. Sulfinyl based ligands bidentate ligands
The stereoselective synthesis of various phosphine ligands has
been an ongoing program for us. We have recently begun to
explore the role of phosphines, phosphine oxides and phosphine
sulfides as transition metal ligands.15 N-sulfinyl α-
aminophosphines have not been extensively studied and may
offer ready access to a series of metal complexes useful in
catalysis. This paper reports a route to the synthesis of a series of
phosphine based N-sulfinyl α-aminophosphine sulfides, oxides
and phosphines (Figure 2).
Figure 2. N-sulfinyl aminophosphine based ligands
Reaction of the sulfinyl amine to form the necessary imines is
performed by the copper catalyzed addition of commercially
available optically active 2-methyl-2-propanesulfinamide to a
variety of aldehydes (Table 1).17-18 Both aromatic and aliphatic
aldehydes participate in the reaction at 60 ˚C in generally good
yields (12-24).
———
∗ Corresponding author. Tel.: +1-832-842-8821; fax: +1-713-743-2709; e-mail: srgilbertson@uh.edu (S.R. Gilbertson)

2
Tetrahedron
The isolated N-tert-butanesulfinyl imines were then reacted
removal of the sulfinyl group could be coupled to amino acids
(47).
with diphenylphosphine sulfide in the presence of potassium
phosphate at room temperature. In most cases the products were
obtained in greater than 95:5 diastereomeric ratio. The
stereochemistry was established by x-ray crystal structure of 27.
The stereochemistry of the other products from the reaction were
assigned by correlation to the x-ray structure. In the case of the
major product, the coupling constant between the NH and the H on
the carbon bearing phosphorus is smaller (approx. 2.5 -3.0 Hz)
than in the minor product (approx. 10-11 Hz). The reaction
proceeded with both aliphatic and aromatic sulfinyl imines. The
reaction tolerates a variety of different substitutions on the
aromatic ring with only electron withdrawing groups in the para
position reducing the selectivity (26, 27 and 29). In all cases the
diastereomers are easily separated by silica gel chromatography.
Table 1. Synthesis of tert-butylsulfinyl imines.
Figure 3. X-ray structure of 27 major diastereomer
Scheme 1. Phosphine sulfide addition
Cpd Aldehyde
12
Yield Cpd Aldehyde Yield
O
S
O
S
81%
81%
83%
69%
19
20
21
99%
99%
56%
93%
1.5 eq. HSPPh2
DCM, rt
NH
PPh2
N
K3PO4 H2O 1 eq.
overnight
R
R
H
S
13
14
15
O
S
O
S
O
S
tBu
NH
PPh2
tBu
NH
tBu
NH
PPh2
PPh2
S
S
S
Cl
F
27 76%
dr 64:36
26 87%
dr 32:68
25 73%
dr >95:5
22
O
O
O
S
S
S
tBu
NH
tBu
NH
tBu
NH
PPh2
PPh2
PPh2
16
92%
23
24
82%
80%
S
S
S
O
O2N
28 79%
dr >95:5
29 78%
dr 49:51
30 93%
dr >95:5
17
18
96%
91%
O
O
S
O
S
S
tBu
NH
tBu
NH
PPh2
tBu
NH
PPh2
PPh2
S
S
S
Br
32 74%
dr >95:5
33 77%
dr >95:5
31 95%
dr 11:89
O
O
S
O
S
A number of transformations have been performed on the N-
sulfinyl α-aminophosphine sulfides. The N-sulfinyl group can be
hydrolyzed to the amine by reaction with HCl (38, 40). The free
amine can then be converted to a carbamoyl group by reaction
with Boc anhydride in the presence of triethylamine (41).
Reaction with acetyl chloride provides the N-acetyl protected
phosphine sulfide. The phosphine sulfide can be converted to the
free phosphine by reaction with Raney nickel (44, 45). We have a
long-standing program of using amino acid building blocks as
potential chiral templates for asymmetric catalysts. With the
correct ligand building blocks they allow for the ready
construction of chiral ligands by amide coupling reactions. With
this use in mind, it was demonstrated that the free amine after
S
tBu
NH
tBu
NH
PPh2
tBu
NH
PPh2
PPh2
S
S
S
O
34 80%
dr >95:5
35 76%
dr >95:5
36 96%
dr 6:94
O
S
tBu
NH
PPh2
S
N
37 62%
dr >95:5

3
References and notes
Scheme 2. Modification of the N-sulfinyl α-aminophosphine
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4.
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diethylzinc to acyclic enones with chiral sulfoxide-phosphine
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Li, Y.-G.; Li, L.; Yang, M.-Y.; Qin, H.-L.; Kantchev, E. A.
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additions. Tetrahedron 2012, 68 (15), 3220-3224.
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The approach presented here provides a route to molecules
possessing a number of potential applications. We are currently
investigating the use of N-sulfinyl α-aminophosphines and
phosphine sulfides as ligands for transition metals. These types of
molecules have potential as nucleophilic catalysts. After removal
of sulfur these types of these molecules can be used to
incorporate phosphine groups into any number of structures by
amide formation.
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Acknowledgments
Synthesis of α-Amino- and α-Alkyl- α-aminophosphonic Acids
Using N-tert-Butylsulfinyl Imines as Chiral Auxiliaries. Synthesis
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This work was supported in part by NSF CHE-0953083.
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4
Tetrahedron
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5
Highlights
Simple
aminophosphine sulfides and phosphines.
approach
to
N-sulfinyl
α-
Access to chiral ligands from readily available
starting materials,
A number of potential uses;
Transition metal ligands
Nucleolophilic catalysts
Amino acid surrogates.