ASYMMETRIC SYNTHESIS THROUGH C– H ACTIVATION - Catalytic Asymmetric Synthesis - page 208

[68,265-268]. To highlight the synthetic potential of C-H amination, some examples will
be discussed here although they are not enantioselective reactions.
3-Amino glycol derivatives are important synthetic intermediates for the syntheses
of 2-oxygenated sugars, 2-deoxy sugars, glycosylated peptides, and antibiotics [66]. Pre-
vious syntheses of such structures were based on the modifi cation of simpler glycosides.
However, more recently, dirhodium(II)-catalyzed nitrene transfer has been used as a
key step in elegant syntheses of carbamate-protected 3-aminoglycols [269]. For example,
carbamate 198 was selectively transformed into oxazolidinone 199 in 86% yield (Scheme
4.53 ). Oxazolidinone 199 could be converted to L-vancosamine ( 200 ) [269] . Protected
glycals of L - daunosamine, D - saccharosamine, L - ristosamine, and methyl - L - callipeltose
have been prepared by this methodology [269,270]. The latter is a fragment of the anti-
tumor natural product callipeltoside A.

Me

Me Me

Rh 2 (OAc) 4
(10 mol %)

O

O

HO

O

O

O

O

O

H 2 N

PhI(OAc) 2
MgO, CH 2 Cl 2

H 2 N

H
199

OH

Me

Me

Me

198 200

86% yield L-vancosamine

Scheme 4.53. Synthesis of L-vancosamine using nitrene insertion.

Two rhodium(II) - catalyzed C -H insertion steps were elegantly applied to the total
synthesis of the highly toxic natural product (−)-tetrodotoxin to install the two tetrasu-
bstituted centers C6 and C8a (Scheme 4.54) [68]. Du Bois and coworkers converted
diazoketone 201 to cyclic ketone 202 via a carbenoid insertion in high yield without
purifi cation. The remarkably complex intermediate 203 was converted to 204 via a
nitrenoid insertion in 77% yield using Rh 2 (HNCOCF 3 ) 4 (10 mol %), demonstrating the
tolerance of both the steric and functional group environment for these transformations.
The latter intermediate 204 was converted to (− ) - tetrodotoxin in seven steps [68] . These
examples highlight the synthetic utility of both carbenoid- and nitrenoid-mediated C- H
insertions. A highly diastereoselective carbamate cyclization has also been applied to
the synthesis of bromopyrrole alkaloid manzacidin A [268].
The fi rst enantioselective intramolecular C-H amination of prochiral sulfonamides
was reported by Che and coworkers (Scheme 4.55) [256,271]. The chiral Ru(II) porphy-
rin complex 187 was employed as catalyst. A variety of cyclic sulfamidates were con-
structed, both fi ve- and six-membered rings, in 70-89% yield and in 77-88% ee [256,271].
These cyclic sulfamidates are very important intermediates in synthesis [272,273]. An
enantioselective intramolecular amination protocol via Lebel's nitrene precursor ( 210 ,
Scheme 4.56) has been achieved with Rh 2 ( S - TCPTAD) 4 , which afforded the correspond-
ing cyclic carbamates 211 in 62 - 75% yield and in 78 - 82% ee [274] .
Enantioselective cyclizations of sulfonamides catalyzed by dirhodium carboxylates
have previously been achieved only with poor enantiomeric induction (< 21% ee) [264] .
Recently, Du Bois and others reported the development of Rh 2 ( S - nap) 4 , which is an
effective chiral catalyst for oxidations with sulfonamides 212 (Scheme 4.57 ) [264] . Simple
p -substituted phenyl substituents gave 50-89% yield and 56-92% ee, but the reactions