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pure amines effectively. The fluoride-promoted addi-
tion of allyltrimethylsilane to racemic sulfinyl imines
has been previously reported.[4e]
Table 4. Benzyl group addition to N-tert-butanesulfinyl imines.[a]
For this study, trimethyl(phenylethynyl)silane 4, al-
lyltrimethylsilane 5a, and trimethyl(2-methylallyl)si-
lane 5b were chosen as pro-nucleophile substrates.
The generality of the reaction with respect to imine
substrates was challenged with 12 derivatives
1a,b,d–h,l,–o,k,q, which included alkyl, aryl, heteroar-
yl and ferrocenyl aldimines and the activated keti-
mine 1q. In all cases, the desired propargylic (15a–h)
and homoallylic (16a–i) sulfinyl amines were ob-
tained in moderate to very good yields (Table 3). In
general, the d.r. values for phenylethynyl additions
(ranging from 99:1 to 89:11) were consistently higher
and better than those of the allyl additions (ranging
from 94:6 to 75:25). The absolute configuration of
the major isomer of sulfinamides 15e and 16a were
determined to be (1S,RS) and (1R,RS), respectively, by
comparison with reported literature data.[15e,18b]
Synthetic routes to substituted chiral homobenzyl
amines have been a subject of interest over the past
decade owing to the presences of this structural
motif in many pharmaceuticals and biologically
active compounds.[19] A valuable method to prepare
chiral amine compounds containing such a subunit is
the addition of benzyl organometallic reagents to
chiral sulfinyl imines. To date, the use of mixed Mg/
Zn organometallics have been successfully utilised
for benzyl additions.[7,20] The fluoride-promoted addi-
tion of unsubstituted benzylsilane 6a to racemic
imines has been previously reported.[4f]
Our primary interest was to determine the level of
generality for highly selective additions for an exten-
sive series of substituted benzyltrimethylsilanes. As
such, the electronically and structurally diverse si-
lanes 6a–j were chosen as nucleophilic substrates
and were tested against a wide range of aryl-, hetero-
1
[a] Yield after chromatography; d.r. determined by H NMR spectroscopy and HPLC.
aryl- and ferrocenyl-substituted N-tert-butanesulfinyl aldimines
and an activated ketimine (Table 4).
azole substrates and aliphatic imines. Thiazole additions are
useful as one-carbon homologating procedures as their con-
version to a formyl group is readily achievable.[22] Thiazole ad-
ditions performed very well to produce the desired aryl thi-
azole sulfonamides 17a–c each with excellent 99:1 diastereo-
selectivity (Table 5). Pleasingly, addition of other aromatic and
non-aromatic heterocycles to cyclohexyl-, isopropyl- and 3-
phenylpropane-substituted imines also gave products 17d, f
and g, respectively, with high d.r. values (Table 5).
Diastereoselective addition of aryl organometallics to chiral
imines, as a route to diarylmethyl amines, has been explored
for several nucleophilic substrates.[3b] To date, the organometal-
lics of choice for diastereoselective aryl addition reactions have
been either Li, Mg or B.[23] Although more recently, the silylox-
ide-promoted addition of ortho-substituted aryltrimethylsilanes
to N-tert-butanesulfinyl imines has been communicated.[6] The
substrate breadth for these additions has now been expanded
to ortho-, meta- and para-substituted aryltrimethylsilanes. We
were delighted to find that, in most cases, the desired diaryl-
Remarkably, all reactions were successful under the one set
of reaction conditions with all the desired products 11 b–r ob-
tained. Of note is the predominately high d.r. values with over
75% of sulfinyl amides obtained with diastereomeric ratios of
90:10 or above (Table 4). Product 11 g, obtained with a d.r. of
96:4, is of particular relevance as a precursor to a-amino acids
with quaternary stereogenic centres. The absolute configura-
tion of the major isomer of sulfinamide 11 b was determined
to be (1R,RS) by analytical correlation with the literature data[7]
and, by analogy, the other examples have been assigned iden-
tical stereochemistry.
Diastereoselective nucleophilic addition of heteroaryls to N-
tert-butanesulfinyl imines has been previously examined in the
literature by utilising lithium and magnesium reagents.[21] Re-
cently, we have reported the selective addition of heterocyclic
trimethylsilanes to aryl N-tert-butanesulfinyl imines.[6] This initial
study has now been expanded to include 2-(trimethylsilyl)thi-
Chem. Eur. J. 2015, 21, 18717 – 18723
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