Six-Membered Cyclic Nitroso Acetals: Synthesis and Studies of the Nitrogen Inversion Process of N-Silyloxy-3,6-dihydro-2H-1,2-oxazines

Article abstract of DOI:10.1002/ejoc.201600952

Silyl nitronates undergo rhodium-catalyzed formal [3+3]-cycloaddition with enol diazoacetates to form N-silyloxy-3,6-dihydro-2H-1,2-oxazines. The scope of the reaction and the extent of the major side process were evaluated. A mechanistic scheme was propo

Full text of DOI:10.1002/ejoc.201600952

A Journal of
Accepted Article
Title: New six-membered cyclic nitroso acetals - N-silyloxy-3,6-dihydro-2H-1,2-
oxazines: synthesis and studies of the nitrogen inversion process
Authors: Alexander Shved; Andrey Tabolin; Roman Novikov; Yulia Nelyubina; Vladi-
mir Timofeev; Sema Ioffe
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European Journal of Organic Chemistry
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New six-membered cyclic nitroso acetals - N-silyloxy-3,6-dihydro-
2H-1,2-oxazines: synthesis and studies of the nitrogen inversion
process.
Alexander S. Shved,*[a,b] Andrey A. Tabolin,*[a] Roman A. Novikov,[c] Yulia V. Nelyubina,[d] Vladimir P.
Timofeev,[c] and Sema L. Ioffe[a]
Abstract: Silyl nitronates undergo rhodium-catalyzed formal [3 + 3]-
cycloaddition with enol diazoacetates giving rise to N-silyloxy-3,6-
dihydro-2H-1,2-oxazines. Reaction scope and major side process
were evaluated. Mechanistic scheme was proposed. Nitrogen
inversion barrier in obtained nitroso acetals was estimated both by
means of quantum calculations and kinetic measurements.
Introduction
Nitroso acetals constitute
a interesting class of organic
compounds from both theoretical and practical aspects.[1]
Presence of two electronegative oxygens bonded to the central
nitrogen is known to increase nitrogen inversion barrier thus
encouraging investigations on asymmetric nitrogen atom.[2,3]
Synthetic potential of nitroso acetals mostly arise from the
presence of two relatively weak N-O bonds which rupture allows
synthesis of various amino alcohol derivatives, including
biologically
active
ones,
via
hydrogenolysis[4]
or
Scheme 1. Pathways for the synthesis of nitroso acetals from nitronates.
rearrangements.[5] The most common and convenient
precursors for nitroso acetal syntheses are nitronates (Scheme
1) with three main transformation pathways are: consecutive
electrophile and nucleophile addition (pathway a),[6] electrophile
addition with subsequent proton elimination (pathway b)[7] and
[3+2]-cycloaddition (pathway c).[1b,4,8] The latter possibility was
the most exploited, however this was nearly the only type of
cycloaddition investigated for nitronates. Consequently, only 5-
membered isoxazolidine ring was accessible.
Results and Discussion
Silyl nitronate 1a and enol diazoacetate 2a were chosen as
substrates for optimization experiments (Table 1). 2 mol % of
Rh2(OAc)4 in CH2Cl2 (Entry 1) gave the best results leading to
target 1,2-oxazine 3aa in 88% yield. Other tried metal (Cu, Ag)
catalysts failed to promote desired reaction (Entries 17-20).
Attempts to reduce the amount of catalyst gave increased
amounts of side-product 4 even for more active catalyst
Rh2(esp)2 (Entries 3-5).[12] Increase of reaction temperature also
did not suppress formation of 4 completely (Entry 5). Use of
more polar solvents also gave inferior results (Entries 6,7),
presumably due to solvent coordination to the catalyst. Low
yields obtained in aromatic solvents (toluene, p-fluorotoluene,
perfluorobenzene, Entries 8-10) can be ascribed to low solubility
of rhodium acetate in the reaction medium. Consequently, better
soluble rhodium octanoate gave high yields of target product
regardless of solvent used (cf. Entries 2, 11, 12). More Lewis
acidic rhodium trifluoroacetate gave lower yields of target [3+3]-
adduct 3aa (Entry 16). Chiral complex Rh2(S-PTA)4 was able of
catalyzing the reaction, but the asymmetric induction was low
(Entries 13-15). [13]
Expanding reactivity of nitronates to other cycloaddition
types may give access to other N,O-containing heterocycles.
Thus, [3+3]-cycloaddition can give access to such useful
products as 1,2-oxazine derivatives.[9] Recently we reported the
first examples of formal [3 + 3]-cycloaddition of nitronates with
donor-acceptor cyclopropanes.[10] Herein we report [3 + 3]-
cycloaddition of silyl nitronates 1 with rhodium enolcarbenoid
species,[11] generated in situ from corresponding enol
diazoacetates 2.
[a]
[b]
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of
Sciences, Leninsky prosp. 47, Moscow 119991, Russian Federation
E-mail: shvedalx@gmail.com; tabolin87@mail.ru
Higher Chemical College, D. I. Mendeleev University of Chemical
Technology of Russia, Miusskaya sq. 9, Moscow 125047, Russian
Federation
[c]
[d]
V. A. Engelhardt Institute of Molecular Biology, Russian Academy of
Sciences, Vavilov str. 32, Moscow, 119991, Russian Federation
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian
Academy of Sciences, Vavilov str. 28, Moscow 119991, Russian
Federation
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
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19
20
CuOTf∙PhH, 5 mol%, CH2Cl2, r.t., 1 d
0
0
0
0
AgOTf, 5 mol%, CH2Cl2, r.t., 2 h
[a] determined by 1H NMR with internal standard (1,4-dinitrobenzene). [b] esp
= α,α,α′,α′-tetramethyl-1,3-benzenedipropionate. [c] S-PTA = N-phthaloyl-(S)-
alaninate [d] ee value of 3aa is indicated in parentheses. Determined on
Chiralpak IA-3 column, eluent: Hexane-i-PrOH, 98:2, 1 mL/min.
Formation of product 4 deserves some additional attention
(Scheme 2, eq. 1). Metal enol carbenoids 5 are known to exist in
equilibrium with corresponding cyclopropenes 6.[11d,14] Therefore
competitive [3+2]-cycloaddition between nitronate 1a and
cyclopropene 6 might be expected leading to cyclopropane-
annelated isoxazolidine 7. However, obtained NMR-data was
inconsistent with the structure of 7 and evidenced about
occurred rearrangement and formation of aziridine 4.[5b,15] Such
cycloaddition-rearrangement process closely resembles reaction
course of nitronates with acetylenes (Scheme 3).[16] Isolation of
pure aziridine 4 was achieved after separation of steps of Rh-
catalyzed cyclopropene formation 2→6 and addition of nitronate
1a (Scheme 2, eq (2)). Filtration through a short plug of silica
eliminated Rh-catalyst from cyclopropene 6 suppressing [3+3]-
cycloaddition between 1a and 5. Addition of Rh-catalyst turned
the reaction again to the formation of oxazine 3aa.
Table 1. Optimization of the conditions for formal [3+3]-cycloaddition.
Entry
Conditions
Yield
Yield
3aa, % [a]
4, % [a]
1
2
3
4
5
Rh2(OAc)4, 2 mol%, CH2Cl2, r.t., 1 h
Rh2(Oct)4, 2 mol%, CH2Cl2, r.t., 1 h
Rh2(OAc)2, 0.5 mol%, CH2Cl2, r.t., 1 d
Rh2(esp)2,[b] 0.5 mol%, CH2Cl2, r.t., 1 h
88
85
17
78
40
0
0
45
6
Rh2(OAc)2, 0.5 mol%, ClCH2CH2Cl, 65 °C,
1 h
29
6
Rh2(OAc)4, 2 mol%, THF, r.t., 1 d
Rh2(OAc)4, 2 mol%, MeCN, r.t., 1 d
Rh2(OAc)4, 2 mol%, toluene, r.t., 1 d
Rh2(OAc)4, 2 mol%, C6F6, r.t., 1 d
20
0
33
34
23
34
23
Chemoselectivity of the reaction can be interpreted on the
basis of position of equilibrium between 5 and 6 (Scheme 2).[17]
Large Rh-catalyst loadings (e.g. 2 mol %, Table 1, Entries
1,2,11,12) shifted the equilibrium resulting in higher
7
8
24
24
27
9
concentration of
5
thus leading to [3 + 3]-cycloaddition
exclusively. Oppositely when the concentration of 5 was too low
for fast [3 + 3]-cycloaddition, competitive uncatalyzed [3 + 2]-
10
Rh2(OAc)4, 2 mol%, p-fluorotoluene, r.t., 1
d
cycloaddition of 1a with
6 became a significant process
11
12
13
14
15
16
17
18
Rh2(Oct)4, 2 mol%, toluene, r.t., 1 h
87
0
furnishing aziridine 4 (see Table 1, Entries 3-10,16). Lewis
bases LB (e.g. coordinating solvents: THF, MeCN, Entries 6,7)
were shown to decrease the activity of Rh-species presumably
through displacement of bound carbene in ligand sphere of
rhodium. This increases the rate of 5→6 transformation thus
also decreasing concentration of 5.[11d] Nitronates 1 should also
be considered as Lewis base due to N-oxide moiety. Thus they
are also able to deactivate Rh-species. The effect should be
more significant in the case of Lewis acidic Rh-catalysts and
was observed for rhodium trifluoroacetate (Entry 16).[11d] In
accordance with the equilibrium between 5 and 6 is the
formation of adduct 3aa in the Rh-catalyzed reaction between
nitronate 1 and preformed cyclopropene 6 (Scheme 2, eq (2)).
Rh2(Oct)4, 2 mol%, p-fluorotoluene, r.t., 1 h
Rh2(S-PTA)4,[c] 2 mol%, CH2Cl2, r.t., 1 h
Rh2(S-PTA)4, 2 mol%, toluene, r.t., 1 h
Rh2(S-PTA)4, 2 mol%, CH2Cl2, 0 °C, 2 h
Rh2(OOCCF3)4, 2 mol%, CH2Cl2, r.t., 1 d
Cu(MeCN)4PF6, 5 mol%, CH2Cl2, r.t., 1 d
78
0
77 (22)[d]
0
78 (12)[d]
0
80 (24)[d]
0
7
0
0
23
0
Cu(CF3C(O)CHC(O)CH3)2,
CH2Cl2, r.t., 1 d
5
mol%,
0
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European Journal of Organic Chemistry
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[a]
Scheme 2. Proposed mechanisms for the reactions of nitronate 1a and enol diazoacetate 2a.
Yield is based on nitronate 1a, determined by 1H NMR with
internal standard (1,4-dinitrobenzene)
Scheme 3. Tandem [3+2]-cycloaddition/rearrangement of nitronates and
alkynes.
After establishing the optimal conditions, the scope of nitronates
1 and enol diazoacetates 2 was tested (Scheme 4). All tried enol
diazoacetates 2a–d (R1 = Me, Et, benzyl, p-nitrobenzyl, Entries
1–4) gave desired oxazines 3 in good yields. Similarly various
silyl nitronates could be used (Entries 5-13). The reaction
tolerated such functionalities as acetal (Entries 6-8), carboxylate
(Entry 9) or aromatic ring (Entries 10,11) in initial silyl nitronate 1.
Silyl nitronates derived from both primary (Entries 1–11) and
secondary (Entries 12,13) nitro compounds could be used.
Structures of obtained dihydrooxazines 3 were supported by
NMR, HRMS and elemental analysis data. For adduct 3ha X-ray
analysis was performed (Figure 1).[18]
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All nitroso acetals 3 were isolated as single diastereomers.
While NOESY data were little informative for determination of
relative configuration, considering the similarity of 15N chemical
shifts of N–OTBS moiety for adducts 3aa-3ha (δ = 242-245
ppm) and X-ray data for 3ha their configuration may be
assumed as 2,3-cis. However, as was noted in the introduction,
slow nitrogen inversion should also be taken in consideration.
Indeed upon storage of adducts 3 in solution or neat in liquid
appearance of a second sets of signals in NMR spectra was
observed. To investigate the process the nitroso acetal 3ha was
chosen due to its X-ray analysis (vide supra) undoubtedly
providing relative configuration of stereocenters at N-2 and C-3.
Interestingly short heating of toluene solution of 3ha at 100 °C
gave complete conversion of starting material (Scheme 5)! NMR
spectra (1H, 13C, 29Si, 15N, COSY, NOESY, HSQC, HMBC) as
well as HRMS data were consistent with the occurrence of
nitrogen inversion and formation of diastereomer 3'ha. The most
dramatic change in NMR spectra was observed for CH2-C(3)
protons with two resolved doublets of doublets at 3.10 and 3.83
ppm turned into one multiplet at 2.92-2.98 ppm. One of the H-6
5
protons shifted from 3.98 to 3.75 ppm, while two JH,H coupling
constants between two H-6 and H-3 remained unchanged (≈1.5
Hz and 0 Hz) indicating that H-3 remained in pseudoequatorial
position. Of note is the change of 15N chemical shift of N–OTBS
moiety (δ (ppm) = 244 for 3ha; 226 for 3’ha). X-ray analysis of
desilylated product 9 proved its 2,3-trans configuration (Figure
2).[18]
Scheme 4. Formal [3+3]-cycloaddition of nitronates 1 and enol diaoacetates 2.
Scheme 5. Nitrogen inversion in oxazine 3ha.
Figure 1. Single-crystal ORTEP drawing for 3ha.
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Scheme 6. Rationale for stereochemical outcome of formal [3+3]-
cycloaddition.
Firstly nitrogen inversion barrier in
3 was estimated by
theoretical methods. Quantum chemical calculations were
performed in ORCA 3.0.3 package.[23] Geometry optimizations
were done at RIJCOSX-B3LYP/def2-TZVP level (briefly –
B3LYP). Frequency run was done at this point to acquire
thermochemical functions. Final single point energy was
acquired at DLPNO-CCSD(T)/def2-TZVPP level of theory (briefly
– CC)[24] at the geometries obtained from previous step (See
supporting information for details). Calculations were performed
for model oxazine derivatives 10-13 (Scheme 7, Figure 3).
Firstly simple 2-methyl-oxazinane 10 and its deutero-derivative
10’ were tested to verify the quality of calculations by
comparison with known experimental inversion barriers.[25]
Indeed calculated data fit well with the experimental results
(Scheme 7). After that variously 3-substituted N-silyloxy-3,6-
dihydro-2H-1,2-oxazines 11-13 were examined. All three cases
gave nearly the same nitrogen inversion barrier ≈115 kJ/mol
(Figure 3). A priori it was rather tricky to predict the dominant
conformation since preudoaxial position of OTBS-group allowed
anomeric stabilization in O-N-O moiety, while pseudoequatorial
position was considered to be less sterically demanded (see
above). Indeed, 3-unsubstituted (11) and 3,3-dimethyl- (13)
substituted derivatives showed negligible difference between
axial and equatorial positions of OSiH3 - group (# 1,3, Figure 3).
For 3-monomethyl-derivative 12 the difference in conformer
energies was more significant. Altogether four possible
isomers/conformers (12-2a3a, 12-2e3a, 12-2a3e, 12-2e3e)
should be taken into account for oxazine 12 (Scheme 7). The
preference of 2,3-diaxial isomer 12-2a3a is in agreement with
the structures of oxazines 3’ha and 9 (Scheme 5, Figure 3). All
four conformers of 12 are interconnected through ring and
nitrogen inversion processes. Considering the fast nature of ring
inversion conversion of 2,3-cis-isomer (cf. 3ha) to 2,3-trans-
isomer (cf. 3’ha) may occur either via 12-2e3a → 12-2a3a or 12-
2a3e → 12-2e3e pathway. Calculations indicated the former
pathway being more favorable (ΔG≠298 = 114.7 vs. 124.3 kJ/mol).
Figure 2. Single-crystal ORTEP drawing for 9.
Assuming the mechanism for [3+3]-cycloaddition nitroso acetals
3 should be considered as kinetic products as exemplified in
Scheme 6. Silyl nitronates are known to exist as equilibrating
mixtures of trans- (1-A) and cis- (1-B) isomers.[19] Trans-isomer
1-A is more stable than cis-isomer 1-B due to sterical reasons.
On the other hand approach to the N-oxide moiety in trans-
isomer is blocked by R-substituent so cis-isomer 1-B is
considered to be more reactive.[10b,20] Therefore interaction of 1-
B with enol carbenoid 5 give zwitter-ion 8 (see Scheme 2),
which ring-closure should occur in twist-like conformation 8-A
due to stereoelectronic effects. Finally fast ring inversion leads
to more stable conformation with bulky OTBS-group adopting a
pseudoequatorial position. However bulky substituents OTBS at
N-2 and R at C-3 are still in less sterically favoured cis-
arrangement. Heating the nitroso acetal 3 allows nitrogen
inversion leading to trans-arrangement of substituents at N-2
and C-3 in 3'. Preference of their (pseudo)axial positions may be
explained mainly by reduced sterical repulsion between these
two particular substituents.[21] Distances between C(25) and
Si(1) atoms (see Figures 1 and 2 for numbering) are 4.466 Å in
3ha (2-equatorial-3-axial isomer) and 4.635 Å in 9 (2,3-diaxial
isomer) thus supporting the thermodynamic preference of 2,3-
trans isomer. At the same time these atoms should be located at
only 4.044 Å distance in 2,3-diequatorial isomer (calculated data
for 12-2e3e, see Scheme 7) thus supporting the preference of
2,3-diaxial conformer over 2,3-diequatorial one. Additional
advantage of 2,3-diaxial conformer may arise from anomeric
effect in O–N–O system[22] and/or crystall packing.
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European Journal of Organic Chemistry
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Figure 3. Calculated (CC //B3LYP) energy diagrams for nitrogen inversion in
oxazines 11-13. ΔG298 are given in kJ/mol relatively to more stable conformer.
Possibility of isolation of diastereomerically pure 3ha and 3'ha
allowed to investigate nitrogen inversion barrier using kinetic
measurements. NMR monitoring of 3ha → 3'ha transformation
at different temperatures: 58 °C, 70 °C, 80 °C, 90 °C, 100 °C
(Table 2, see Supporting information for full experimental
Scheme 7. Oxazines used for quantum calculations of nitrogen inversion.
details)
– allowed to determine the rate constants and
consequently the thermodynamic parameters using Eyring
equation (Figure 4). Obtained inversion parameters (ΔH≠
=
111.2 kJ/mol, ΔS≠ = 0.6 J/(mol∙K), ΔG≠ = 111.0 kJ/mol) are in
298
good agreement with quantum calculation data (ΔG≠ = 114.7,
298
see above). From practical point such barrier value means that
exposure of the sample to elevated temperatures (including
those during evaporation) should be minimized if the isolation of
pure oxazine 3 is desired.
Found inversion barrier is close to the values of five-membered
nitroso acetals 14 (ΔG≠ = 106-121 kJ/mol) (Figure 5).[2d-f,26]
Reasonably the barrier is higher than that of six-membered
nitroso acetals 15 (ΔG≠
= 56-60 kJ/mol),[7c] where barrier is
298
lowered due to the conjugation. Similarly higher barrier in nitroso
acetal 3ha compared to the data for nitroso acetals 16 (ΔG≠
=
298
84-103 kJ/mol),[2a-c] is in agreement with known regularity, that
ring strain in transition state raise the barrier of cyclic
compounds relatively to acyclic analogs.[3]
Table 2. Kinetic data for nitrogen inversion 3ha → 3’ha
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European Journal of Organic Chemistry
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Dirhodium (II) tetraacetate (0.02 equiv) and silyl nitronate 1 (1 equiv)
were mixed in dichloromethane (2 mL / 1 mmol of nitronate) in the
reaction vessel which was then purged with argon. A solution of
enoldiazoacetate 2 (1 equiv) in dichloromethane (3 mL / 1 mmol of
enoldiazoacetate) was added dropwise via syringe to the reaction vessel
at ambient temperature under stirring. Immediate dinitrogen evolution
was observed during the addition. The reaction was maintained for 1 h
(TLC monitoring), the solvent was removed in vacuo and the residue was
subjected to column chromatography (95:5 PE–EtOAc). Target
compounds 3 were obtained as colorless viscous oils. Some of them
could be recrystallized from methanol to afford crystalline adducts.
Entry
T, °C
k, h-1
t1/2
1
2
3
4
5
58
70
80
90
100
0.067
0.343
1.15
10 h
2 h
36 min
15 min
5 min
2.79
7.89
4-nitrobenzyl
2,5-bis((tert-butyldimethylsilyl)oxy)-3-methyl-3,6-
dihydro-2H-1,2-oxazine-4-carboxylate (3aa)
Obtained according to general procedure from nitronate 1a (284 mg, 1.5
mmol) and diazo compound 2a (566 mg, 1.5 mmol). Yield: 710 mg
1
(88 %), almost colorless viscous oil. Rf (SiO2, 10:1 PE–EtOAc): 0.36. H
NMR (400 MHz, CDCl3): δ = 8.21 (d, J = 8.9 Hz, 2 H, CH(pNB)), 7.51 (d,
J = 8.9 Hz, 2 H, CH(pNB)), 5.30 (d, J = 13.5 Hz, 1 H, CH2a(pNB)), 5.25 (d,
J = 13.6 Hz, 1 H, CH2b(pNB)), 4.30 (dd, J = 15.9, 1.6 Hz, 1 H, Ha-6), 4.06
(dd, J = 15.9, 0.8 Hz, 1 H, Hb-6), 3.98 (qdd, J = 6.2, 1.6, 0.8 Hz, 1 H, H-3),
1.33 (d, J = 6.3 Hz, 3 H, Me-3), 0.92 (s, 9 H, t-BuSi), 0.90 (s, 9 H, t-BuSi),
0.16 (s, 12 H, 2×Me2Si). 13C NMR (101 MHz, CDCl3): δ = 164.4 (C=O),
159.0 (C-5), 147.8 (C-NO2), 143.9 (C(pNB)), 128.6 (CH(pNB)), 123.9
(CH(pNB)), 109.8 (C-4), 67.9 (C-6), 64.3 (CH2(pNB)), 61.1 (C-3), 26.1
(Me3CSi), 25.7 (Me3CSi), 18.6 (Me3CSi), 18.0 (Me3CSi), 12.4 (Me-3), –
3.7 (Me2Si), –5.1 (Me2Si). 29Si INEPT (60 MHz, CDCl3): δ = 27.4, 24.2.
15N NMR (30 MHz, CDCl3, from {1H–15N}HMBC) δ = 242 (N–OTBS).
HRMS (ESI) m/z calcd. for [C25H42N2O7Si2 + Na+]: 561.2423, found:
561.2424.
Benzyl 2,5-bis((tert-butyldimethylsilyl)oxy)-3-methyl-3,6-dihydro-2H-
1,2-oxazine-4-carboxylate (3ab)
Figure 4. Eyring plot for nitrogen inversion 3ha → 3’ha.
Obtained according to general procedure from nitronate 1a (189 mg, 1.0
mmol) and diazo compound 2b (332 mg, 1.0 mmol). Yield: 400 mg
1
(81 %), colorless oil. Rf (SiO2, 5:1 PE–EtOAc): 0.60. H NMR (300 MHz,
CDCl3): δ = 7.43 – 7.26 (m, 5 H, Ph), 5.20 (s, 2 H, CH2(Bn)), 4.30 (dd, J =
15.8, 1.7 Hz, 1 H, Ha-6), 4.06 (dd, J = 15.8, 0.8 Hz, 1 H, Hb-6), 4.01 (qdd,
J = 6.2, 1.7, 0.8 Hz, 1 H, H-3), 1.35 (d, J = 6.3 Hz, 3 H, Me-3), 0.94 (s, 9
H, t-BuSi), 0.92 (s, 9 H, t-BuSi), 0.17 (s, 3 H, MeSi), 0.16 (s, 3 H, MeSi),
0.16 (s, 3 H, MeSi), 0.16 (s, 3 H, MeSi). 13C NMR (75 MHz, CDCl3): δ =
164.8 (C=O), 157.8 (C-5), 136.4 (CPh), 128.5, 128.4 and 128.2 (CHPh),
110.4 (C-4), 67.8 (C-6), 65.9 (CH2(Bn)), 61.1 (C-3), 26.1 (Me3CSi), 25.8
(Me3CSi), 18.6 (Me3CSi), 18.0 (Me3CSi), 12.3 (Me–11), –3.8 (MeSi), –3.8
(MeSi), –5.0 (MeSi), –5.1 (MeSi). 29Si NMR (60 MHz, CDCl3): δ = 27.2,
23.8. 15N NMR (30 MHz, CDCl3, from {1H–15N}HMBC) δ = 242 (N–OTBS).
HRMS (ESI): m/z calcd. for [C26H44N2O7Si2 + Na+]: 553.2760, found:
553.2760.
Figure 5. Nitroso acetals with known nitrogen inversion barriers.
Conclusions
Ethyl 2,5-bis((tert-butyldimethylsilyl)oxy)-3-methyl-3,6-dihydro-2H-
In conclusion
a new formal [3 + 3]-cycloaddition reaction
1,2-oxazine-4-carboxylate (3ac)
between silyl nitronates 1 and enol diazoacetates 2 was
discovered and its substrate scope was elaborated. Nitrogen
inversion barrier in target nitroso acetals 3 was estimated. The
investigation of chemistry of adducts 3 is currently underway.
Obtained according to general procedure from nitronate 1a (189 mg, 1.0
mmol) and diazo compound 2c (270 mg, 1.0 mmol). Yield: 418 mg
(97 %), colorless oil. Rf (SiO2, 5:1 PE–EtOAc): 0.56. H NMR (400 MHz,
1
CDCl3): δ = 4.26 (dd, J = 15.7, 1.6 Hz, 1 H, Ha-6), 4.17-4.23 (m, 2 H,
CH2(Et)), 4.03 (dd, J = 15.7, 0.8 Hz, 1 H, Hb-6), 3.95 (qdd, J = 6.3, 1.7,
0.8 Hz, 1 H, H-3), 1.32 (d, J = 6.3 Hz, 3 H, Me-3), 1.28 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 0.93 (s, 9 H, t-BuSi), 0.92 (s, 9 H, t-BuSi), 0.19 (s, 6 H,
Me2Si), 0.15 (s, 3 H, MeSi), 0.13 (s, 3 H, MeSi). 13C NMR (101 MHz,
CDCl3): δ = 165.1 (C=O), 157.0 (C-5), 110.9 (C-4), 67.8 (C-6), 61.2 (C-3),
Experimental Section
General procedure for dirhodium (II) catalyzed [3 + 3]-cycloadditions
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European Journal of Organic Chemistry
10.1002/ejoc.201600952
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60.1 (CH2(Et)), 26.1 (Me3CSi), 25.9 (Me3CSi), 18.6 (Me3CSi), 18.1
(Me3CSi), 14.6 (Me–3), 12.2 (OCH2CH3), –3.8 (MeSi), –5.0 (MeSi), –5.1
(MeSi). 29Si NMR (60 MHz, CDCl3): δ = 27.1, 23.6. 15N NMR (30 MHz,
CDCl3, from {1H–15N}HMBC) δ = 243 (N–OTBS). HRMS (ESI) m/z calcd.
for [C20H41NO5Si2 + Na+]: 454.2415, found: 454.2417.
18.0 (Me3CSi), –3.7 (Me2Si), –5.0 (Me2Si), –5.2 (Me2Si). 29Si NMR (60
MHz, CDCl3): δ = 27.9, 24.2. 15N NMR (30 MHz, CDCl3, from {1H–
15N}HMBC) δ = 371 (NO2), 243 (N–OTBS). HRMS (ESI) m/z calcd. for
[C29H50N2O9Si2 + Na+]: 649.2947, found: 649.2940.
4-nitrobenzyl
2,5-bis((tert-butyldimethylsilyl)oxy)-3-(2,2-
Methyl 2,5-bis((tert-butyldimethylsilyl)oxy)-3-methyl-3,6-dihydro-2H-
dimethoxyethyl)-3,6-dihydro-2H-1,2-oxazine-4-carboxylate (3da)
1,2-oxazine-4-carboxylate (3ad)
Obtained according to general procedure from nitronate 1d (263 mg, 1.0
mmol) and diazo compound 2a (377 mg, 1.0 mmol). Yield: 462 mg
(75 %), almost colorless viscous oil. Rf (SiO2, 3:1 PE–EtOAc): 0.44. 1H
NMR (300 MHz, CDCl3): δ = 8.19 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.57 (d,
J = 8.8 Hz, 2 H, CH(pNB)), 5.33 (d, J = 13.7 Hz, 1 H, CH2a(pNB)), 5.20 (d,
J = 13.7 Hz, 1 H, CH2b(pNB)), 4.76 (dd, J = 7.4, 4.3 Hz, 1 H, CH(OMe)2),
4.32 (dd, J = 15.8, 1.6 Hz, 1 H, Ha-6), 4.16 (ddd, J = 6.3, 4.5, 1.4 Hz, 1 H,
H-3), 4.04 (d, J = 15.7 Hz, 1 H, Hb-6), 3.25 (s, 6 H, 2×OMe), 2.54 (ddd, J
= 14.6, 6.6, 4.3 Hz, 1 H, CH2a-C(3)), 1.87 (ddd, J = 14.7, 7.4, 4.4 Hz, 1 H,
CH2b-C(3)), 0.93 (s, 9 H, t-BuSi), 0.89 (s, 9 H, t-BuSi), 0.16 (s, 6 H,
Me2Si), 0.15 (s, 3 H, MeSi), 0.15 (s, 3 H, MeSi). 13C NMR (75 MHz,
CDCl3): δ = 164.2 (C=O), 158.2 (C-5), 147.7 (C-NO2), 143.8 (C(pNB)),
128.5 (CH(pNB)), 123.7 (CH(pNB)), 109.6 (C-4), 103.4 (C(OMe)2), 68.5
(C-6), 64.5 (CH2(pNB)), 61.8 (C-3), 53.3 (OMe), 52.7 (OMe), 32.1 (CH2-
C(3)), 26.1 (Me3CSi), 25.7 (Me3CSi), 18.5 (Me3CSi), 18.0 (Me3CSi), –3.8
(MeSi), –5.1 (MeSi), –5.2 (MeSi). 29Si NMR (60 MHz, CDCl3): δ = 27.9,
24.2. 15N NMR (30 MHz, CDCl3, from {1H–15N}HMBC) δ = 369 (NO2), 245
(N–OTBS). HRMS (ESI) m/z calcd. for [C28H48N2O9Si2 + Na+]: 635.2791,
found: 635.2786.
Obtained according to general procedure from nitronate 1a (189 mg, 1.0
mmol) and diazo compound 2d (256 mg, 1.0 mmol). Yield: 304 mg
(73 %), colorless oil. Rf (SiO2, 3:1 PE–EtOAc): 0.55. H NMR (400 MHz,
1
CDCl3): δ = 4.26 (dd, J = 15.8, 1.6 Hz, 1 H, Ha-6), 4.02 (dd, J = 15.8, 0.8
Hz, 1 H, Hb-6), 3.95 (qdd, J = 6.3, 1.7, 0.7 Hz, 1 H, H-3), 3.70 (s, 3 H,
OMe), 1.31 (d, J = 6.3 Hz, 3 H, Me-3), 0.93 (s, 9 H, t-BuSi), 0.91 (s, 9 H,
t-BuSi), 0.17 (s, 6 H, Me2Si), 0.14 (s, 3 H, MeSi), 0.13 (s, 3 H, MeSi). 13
C
NMR (101 MHz, CDCl3): δ = 165.6 (C=O), 157.4 (C-5), 110.6 (C-4), 67.8
(C-6), 61.2 (C-3), 51.2 (OMe), 26.1 (Me3CSi), 25.7 (Me3CSi), 18.5
(Me3CSi), 18.0 (Me3CSi), 12.2 (Me-3), –3.9 (MeSi), –5.04 (MeSi), –5.15
(MeSi). 29Si NMR (60 MHz, CDCl3): δ = 27.1, 23.6. 15N NMR (30 MHz,
CDCl3, from {1H–15N}HMBC) δ = 243 (N–OTBS). HRMS (ESI) m/z calcd.
for [C19H39NO5Si2 + H+]: 418.2440, found: 418.2421.
4-nitrobenzyl
2,5-bis((tert-butyldimethylsilyl)oxy)-3-ethyl-3,6-
dihydro-2H-1,2-oxazine-4-carboxylate (3ba)
Obtained according to general procedure from nitronate 1b (203 mg, 1.0
mmol) and diazo compound 2a (377 mg, 1.0 mmol). Yield: 475 mg
(86 %), almost colorless viscous oil. Rf (SiO2, 3:1 PE–EtOAc): 0.55. 1H
NMR (300 MHz, CDCl3): δ = 8.21 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.52 (d,
J = 9.0 Hz, 2 H, CH(pNB)), 5.32 (d, J = 13.4 Hz, 1 H, CH2a(pNB)), 5.21 (d,
J = 13.4 Hz, 1 H, CH2b(pNB)), 4.29 (dd, J = 15.9, 1.6 Hz, 1 H, Ha-6), 4.05
(dd, J = 15.9, 0.7 Hz, 1 H, Hb-6), 3.88 (dddd, J = 5.9, 4.7, 1.6, 0.7 Hz, 1 H,
H-3), 2.16 (dqd, J = 15.0, 7.5, 5.9 Hz, 1 H, Ha(Et-3)), 1.67 (dqd, J = 15.1,
7.6, 4.7 Hz, 1 H, Hb(Et-3)), 0.97 (t, J = 7.6 Hz, 3 H, Me), 0.93 (s, 9 H, t-
BuSi), 0.91 (s, 9 H, t-BuSi), 0.17 (s, 3 H, Me2Si), 0.16 (s, 6 H, Me2Si),
0.15 (s, 3H). 13C NMR (75 MHz, CDCl3): δ = 164.7 (C=O), 158.3 (C-5),
147.8 (C-NO2), 143.8 (C(pNB)), 128.7 (CH(pNB)), 123.9 (CH(pNB)),
109.3 (C-4), 68.0 (C-6), 66.7 (C-3), 64.5 (CH2(pNB)), 26.1 (Me3CSi), 25.8
(Me3CSi), 21.6 (CH2(Et)), 18.6 (Me3CSi), 18.03 (Me3CSi), 12.86
(CH3(Et)), –3.71 (Me2Si), –5.02 (Me2Si), –5.17 (Me2Si). 29Si NMR (60
MHz, CDCl3): δ = 27.3, 24.1. 15N NMR (30 MHz, CDCl3, from {1H–
15N}HMBC) δ = 369 (NO2), 245 (N–OTBS). HRMS (ESI) m/z calcd. for
[C26H44N2O7Si2 + Na+]: 575.2579, found: 575.2570.
4-nitrobenzyl
2,5-bis((tert-butyldimethylsilyl)oxy)-3-(2-((2-
methoxypropan-2-yl)oxy)ethyl)-3,6-dihydro-2H-1,2-oxazine-4-
carboxylate (3ea)
Obtained according to general procedure from nitronate 1e (291 mg, 1.0
mmol) and diazo compound 2a (377 mg, 1.0 mmol). Yield: 533 mg
(83 %), almost colorless viscous oil. Rf (SiO2, 3:1 PE–EtOAc): 0.51. 1H
NMR (300 MHz, CDCl3): δ = 8.19 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.52 (d,
J = 8.7 Hz, 2 H, CH(pNB)), 5.31 (d, J = 13.5 Hz, 1 H, CH2a(pNB)), 5.21 (d,
J = 13.5 Hz, 1 H, CH2b(pNB)), 4.30 (dd, J = 15.9, 1.6 Hz, 1 H, Ha-6), 4.03
(d, J = 15.9 Hz, 1 H, Hb-6), 3.97 (ddd, J = 6.0, 3.4, 1.2 Hz, 1 H, H-3), 3.64
(td, J = 9.6, 5.7 Hz, 1 H, CH2a–O), 3.55 – 3.42 (m, 1 H, CH2a–O), 3.11 (s,
3 H, OMe), 2.41 (ddt, J = 14.3, 9.8, 6.0 Hz, 1 H, CH2a–C(3)), 1.89 (dddd,
J = 13.7, 9.6, 5.8, 3.5 Hz, 1 H, CH2b–C(3)), 1.26 (s, 3 H, CH3), 1.26 (s, 3
H, CH3), 0.92 (s, 9 H, t-BuSi), 0.89 (s, 9 H, t-BuSi), 0.15 (s, 3 H, MeSi),
0.15 (s, 3 H, MeSi), 0.15 (s, 3 H, MeSi), 0.13 (s, 3 H, MeSi). 13C NMR (75
MHz, CDCl3): δ = 164.2 (C=O), 159.0 (C-5), 147.8 (C-NO2), 143.8
(C(pNB)), 128.6 (CH(pNB)), 123.8 (CH(pNB)), 109.1 (C-4), 99.9 (O-C-O),
68.3 (C-6), 64.4 (CH2(pNB)), 63.2 (C-3), 59.8 (CH2-O), 48.4 (OMe), 29.6
(CH2-C(3)), 26.0 (Me3CSi), 25.7 (Me3CSi), 24.6 (2×Me–14), 18.6
(Me3CSi), 17.9 (Me3CSi), –3.7 (MeSi), –5.1 (MeSi), –5.2 (MeSi). 29Si
NMR (60 MHz, CDCl3): δ = 27.8, 24.3. 15N NMR (30 MHz, CDCl3, from
{1H–15N}HMBC) δ = 369 (NO2), 244 (N–OTBS). HRMS (ESI) m/z calcd.
for [C30H52N2O9Si2 + Na+]: 663.3104, found: 663.3097.
4-nitrobenzyl
2,5-bis((tert-butyldimethylsilyl)oxy)-3-(((2-
methoxypropan-2-yl)oxy)methyl)-3,6-dihydro-2H-1,2-oxazine-4-
carboxylate (3ca)
Obtained according to general procedure from nitronate 1c (277 mg, 1.0
mmol) and diazo compound 2a (377 mg, 1.0 mmol). Yield: 492 mg
(79 %), almost colorless viscous oil. Rf (SiO2, 3:1 PE–EtOAc): 0.60. 1H
NMR (300 MHz, CDCl3): δ = 8.21 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.56 (d,
J = 8.8 Hz, 2 H, CH(pNB)), 5.34 (d, J = 13.7 Hz, 1 H, CH2a(pNB)), 5.18 (d,
J = 13.8 Hz, 1 H, CH2b(pNB)), 4.31 (dd, J = 15.8, 1.6 Hz, 1 H, Ha-6), 4.22
4-nitrobenzyl
2,5-bis((tert-butyldimethylsilyl)oxy)-3-(3-methoxy-3-
oxopropyl)-3,6-dihydro-2H-1,2-oxazine-4-carboxylate (3fa)
(ddd, J = 6.5, 5.5, 1.3 Hz, 1 H, H-3), 4.10 (dd, J = 9.5, 5.2 Hz, 1 H, CH2a
–
C(3)), 4.06 (d, J = 16.1 Hz, 1 H, Hb-6), 3.71 (dd, J = 9.5, 6.1 Hz, 1 H,
CH2b–C(3)), 3.12 (s, 3 H, OMe), 1.26 (s, 3 H, CH3), 1.23 (s, 3 H, CH3),
0.93 (s, 9 H, t-BuSi), 0.90 (s, 9 H, t-BuSi), 0.16 (s, 12 H, 2×Me2Si). 13C
NMR (75 MHz, CDCl3): δ = 164.7 (C=O), 157.5 (C-5), 147.8 (C-NO2),
143.9 (C(pNB)), 128.5 (CH(pNB)), 123.8 (CH(pNB)), 108.1 (C-4), 100.2
(O-C-O), 68.2 (C-6), 65.0 (C-3), 64.5 (CH2(pNB)), 58.9 (CH2-C(3)), 48.6
(OMe), 26.1 (Me3CSi), 25.7 (Me3CSi), 24.4 (2×Me-C), 18.5 (Me3CSi),
Obtained according to general procedure from nitronate 1f (261 mg, 1.0
mmol) and diazo compound 2a (377 mg, 1.0 mmol). Title compound was
recrystallized from methanol. Yield: 415 mg (68 %), off-white prisms. mp
76–77 °C (methanol). Rf (SiO2, 3:1 PE–EtOAc): 0.51. 1H NMR (400 MHz,
CDCl3): δ = 8.20 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.53 (d, J = 8.8 Hz, 2 H,
CH(pNB)), 5.30 (d, J = 13.3 Hz, 1 H, CH2a(pNB)), 5.23 (d, J = 13.3 Hz, 1
H, CH2b(pNB)), 4.30 (dd, J = 15.9, 1.6 Hz, 1 H, Ha-6), 4.03 (d, J = 15.9
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European Journal of Organic Chemistry
10.1002/ejoc.201600952
FULL PAPER
Hz, 1 H, Hb-6), 3.97 (ddd, J = 5.3, 3.8, 1.3 Hz, 1 H, H-3), 3.61 (s, 3 H,
OMe), 2.70 – 2.31 (m, 3 H, CH2-CO2Me + CH2a-C(3)), 2.16 – 1.94 (m, 1
H, CH2b-C(3)), 0.92 (s, 9 H, t-BuSi), 0.90 (s, 9H t-BuSi), 0.16 (s, 3 H,
MeSi), 0.16 (s, 3 H, MeSi), 0.15 (s, 3 H, MeSi), 0.14 (s, 3 H, MeSi). 13C
NMR (101 MHz, CDCl3): δ = 174.0 (C–13), 164.3 (C=O), 159.6 (C-5),
147.8 (C-NO2), 143.7 (C(pNB)), 128.7 (CH(pNB)), 123.9 (CH(pNB)),
108.4 (C-4), 68.3 (C-6), 64.5 (CH2(pNB)), 64.5 (C-3), 51.5 (OMe), 32.9
(CH2-CO2Me), 26.1 (Me3CSi), 25.7 (Me3CSi), 23.9 (CH2-C(3)), 18.6
(Me3CSi), 18.0 (Me3CSi), –3.6 (Me2Si), –5.2 (Me2Si). 29Si NMR (60 MHz,
CDCl3): δ = 28.03, 24.43. 15N NMR (30 MHz, CDCl3, from {1H–
15N}HMBC) δ = 369 (NO2), 245 (N–OTBS). Elem. anal. calcd. for
C28H46N2O9Si2: C, 55.06; H, 7.59; N, 4.59; Si, 9.20. Found: C, 55.08; H,
7.56; N, 4.60; Si, 9.18.
Hz, 1 H, CH2a(pNB)), 4.47-4.53 (m, 1 H, H-3), 4.42 (dd, J = 15.9, 1.4 Hz,
1 H, Ha-6), 4.39 (d, J = 13.5, 1 H, CH2b(pNB)), 3.98 (d, J = 15.9 Hz, 1 H,
Hb-6), 3.83 (dd, J = 14.0, 4.6 Hz, 1 H, CH2a–C(3)), 3.33 (s, 3 H, OMe),
3.10 (dd, J = 14.0, 6.5 Hz, 1 H, CH2b–C(3)), 0.97 (s, 9 H, t-BuSi), 0.86 (s,
9 H, t-BuSi), 0.25 (s, 3 H, MeSi), 0.19 (s, 3 H, MeSi), 0.13 (s, 3 H, MeSi),
0.09 (s, 3 H, MeSi). 13C NMR (50 MHz, toluene-d8): δ = 163.3 (C=O),
158.2 and 158.0 (C-5 and C(PMP)), 147.4 (C-NO2), 142.9 (C(pNB)),
132.0 (C(PMP)), 130.7 (CH(PMP)), 128.1 (CH(pNB)), 127.9 (CH(pNB)),
123.0 (CH(PMP)), 110.0 (C-4), 68.7, 67.2 and 63.9 (C-3, C-6 and
CH2(pNB)), 54.3 (OMe), 33.9 (CH2-C(3)), 25.7 (Me3CSi), 25.4 (Me3CSi),
18.2 (Me3CSi), 17.8 (Me3CSi), -4.2 (MeSi), -4.3 (MeSi), –5.3 (MeSi), –5.5
(MeSi). 15N NMR (30 MHz, toluene-d8, from {1H–15N}HMBC) δ = 244 (N–
OTBS). Signal of NO2 was not observed due to broadening and low
intensity. Elem. anal. calcd. for C32H48N2O8Si2: C, 59.60; H, 7.50; N, 4.34;
Si, 8.71. Found: C, 59.85; H, 7.51; N, 4.28; Si, 8.52.
4-nitrobenzyl
2,5-bis((tert-butyldimethylsilyl)oxy)-3-phenethyl-3,6-
dihydro-2H-1,2-oxazine-4-carboxylate (3ga)
4-nitrobenzyl 2,5-bis((tert-butyldimethylsilyl)oxy)-3,3-dimethyl-3,6-
dihydro-2H-1,2-oxazine-4-carboxylate (3ia)
Obtained according to general procedure from nitronate 1g (276 mg, 1.0
mmol) and diazo compound 2a (377 mg, 1.0 mmol). Yield: 461 mg
(73 %), colorless oil. Rf (SiO2, 3:1 PE–EtOAc): 0.51. H NMR (300 MHz,
1
Obtained according to general procedure from nitronate 1i (203 mg, 1.0
mmol) and diazo compound 2a (377 mg, 1.0 mmol). Yield: 375 mg
(68 %), colorless oil. Crystallized spontaneously upon storage at 4 °C.
mp 50–53 °C (not recrystallized). Rf (SiO2, 3:1 PE–EtOAc): 0.60. 1H NMR
(400 MHz, CDCl3): δ = 8.21 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.53 (d, J =
8.8 Hz, 2 H, CH(pNB)), 5.30 (d, J = 13.5 Hz, 1 H, CH2a(pNB)), 5.23 (d, J
= 13.4 Hz, 1 H, CH2b(pNB)), 4.21 (d, J = 15.5 Hz, 1 H, Ha-6), 3.91 (br d, J
= 15.6 Hz, 1 H, Hb-6), 1.36 (s, 3 H, Me-3), 1.23 (s, 3 H, Me-3), 0.92 (s, 9
H, t-BuSi), 0.89 (s, 9 H, t-BuSi), 0.19 (s, 6 H, Me2Si), 0.15 (s, 6 H, Me2Si).
13C NMR (101 MHz, CDCl3): δ = 166.0 (C=O), 151.2 (C-5), 147.8 (C-
NO2), 143.6 (C(pNB)), 128.6 (CH(pNB)), 123.9 (CH(pNB)), 112.6 (br, C-
4), 65.2 (C-3), 64.6 (CH2(pNB)), 61.5 (br, C-6), 27.3 (Me-3), 26.1
(Me3CSi), 25.7 (Me3CSi), 22.5 (Me-3), 18.4 (Me3CSi), 18.0 (Me3CSi), –
3.83 (Me2Si), –4.77 (Me2Si). 29Si NMR (60 MHz, CDCl3): δ = 27.1, 23.7.
15N NMR (30 MHz, CDCl3, from {1H–15N}HMBC) δ = 240 (N–OTBS).
HRMS (ESI) m/z calcd. for [C26H44N2O7Si2 + H+]: 553.2760, found:
553.2760.
CDCl3): δ = 8.18 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.49 (d, J = 8.8 Hz, 2 H,
CH(pNB)), 7.25 – 7.06 (m, 5 H, Ph), 5.30 (d, J = 13.3 Hz, 1 H,
CH2a(pNB)), 5.21 (d, J = 13.3 Hz, 1 H, CH2b(pNB)), 4.33 (dd, J = 15.9,
1.6 Hz, 1 H, Ha-6), 4.07 (dd, J = 15.9, 0.7 Hz, 1 H, Hb-6), 4.05 – 4.00 (m,
1 H, H-3), 2.87 (ddd, J = 13.5, 11.5, 5.3 Hz, 1 H, CH2a–Ph), 2.77 – 2.63
(m, 1 H, CH2a–Ph), 2.51 (ddt, J = 14.2, 11.4, 5.7 Hz, 1 H, CH2a–C(3)),
1.88 (dddd, J = 14.2, 11.6, 5.4, 3.8 Hz, 1 H, CH2b–C(3)), 0.96 (s, 9 H, t-
BuSi), 0.93 (s, 9 H, t-BuSi), 0.20 (s, 3 H, MeSi), 0.19 (s, 3 H, MeSi), 0.18
(s, 3 H, MeSi), 0.18 (s, 3 H, MeSi). 13C NMR (75 MHz, CDCl3): δ = 164.5
(C=O), 158.8 (C-5), 147.8 (C-NO2), 143.7 (C(pNB)), 142.8 (CPh), 128.9
(CH(pNB)), 128.8 (CHm-Ph), 128.6 (CHp-Ph), 125.8 (CHo-Ph), 123.9
(CH(pNB)), 109.3 (C-4), 68.1 (C-6), 65.2 (C-3), 64.4 (CH2(pNB)), 34.9
(CH2–Ph), 30.8 (CH2–C(3)), 26.2 (Me3CSi), 25.8 (Me3CSi), 18.6 (Me3CSi),
18.0 (Me3CSi), –3.69 (MeSi), –4.97 (MeSi), –5.09 (MeSi). 29Si NMR (60
MHz, CDCl3): δ = 27.7, 24.3. 15N NMR (30 MHz, CDCl3, from {1H–
15N}HMBC) δ = 369 (NO2), 245 (N–OTBS). HRMS (ESI) m/z calcd. for
C32H49N2O7Si2: 629.3073, found: 629.3071.
4-nitrobenzyl
1,4-bis((tert-butyldimethylsilyl)oxy)-2-oxa-1-
4-nitrobenzyl
rel-(2R,3R)-2,5-bis((tert-butyldimethylsilyl)oxy)-3-(4-
azaspiro[5.5]undec-4-ene-5-carboxylate (3ja)
methoxybenzyl)-3,6-dihydro-2H-1,2-oxazine-4-carboxylate (3ha)
Obtained according to general procedure from nitronate 1j (243 mg, 1.0
mmol) and diazo compound 2a (377 mg, 1.0 mmol). Title compound
crystallized spontaneously upon storage. Yield: 400 mg (67 %), white
solid. mp 51–53 °C (not recrystallized). Rf (SiO2, 3:1 PE–EtOAc): 0.57.
1H NMR (300 MHz, CDCl3): δ = 8.21 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.54
(d, J = 8.7 Hz, 2 H, CH(pNB)), 5.32 (d, J = 13.6 Hz, 1 H, CH2a(pNB)),
5.20 (d, J = 13.6 Hz, 1 H, CH2b(pNB)), 4.18 (d, J = 15.4 Hz, 1 H, Ha-6),
3.73 (d, J = 15.4 Hz, 1 H, Hb-6), 1.97 – 1.02 (m, 10 H, CH2(c-Hex)), 0.92
(s, 9 H, t-BuSi), 0.87 (s, 9 H, t-BuSi), 0.24 (s, 3 H, MeSi), 0.21 (s, 3 H,
MeSi), 0.13 (s, 3H, MeSi), 0.13 (s, 3H, MeSi). 13C NMR (75 MHz, CDCl3):
δ = 167.0 (C=O), 147.8 (C-5), 147.7 (C-NO2), 143.5 (C(pNB)), 128.5
(CH(pNB)), 123.8 (CH(pNB)), 113.0 (C-4), 66.7 (C-3), 64.8 (CH2(pNB)),
59.0 (C-6), 36.6 (CH2-C(3)), 31.4 (CH2-C(3)), 26.1 (Me3CSi), 25.7
(Me3CSi), 21.8 (CH2), 21.4 (CH2), 18.2 (Me3CSi), –3.8 (MeSi), –4.1
(MeSi), –4.9 (MeSi). 29Si NMR (60 MHz, CDCl3): δ = 27.8, 23.3. 15N NMR
(30 MHz, CDCl3, from {1H–15N}HMBC) δ = 235 (N–OTBS). Elem. anal.
calcd. for C29H48N2O7Si2: C, 58.75; H, 8.16; N, 4.73; Si, 9.47. Found: C,
58.70; H, 8.17; N, 4.72; Si, 9.36.
Obtained by a modified general procedure: solution of nitronate 1h (590
mg, 2.0 mmol) and diazo compound 2a (1131 mg, 3.0 mmol) in CH2Cl2 (4
mL) was added dropwise during 15 min. to the stirring suspension of
Rh2(OAc)4 (18 mg, 0.04 mmol) in CH2Cl2 (1 mL). Title compound was
recrystallized from methanol (10 mL). Yield: 897 mg (70 %), off-white
prisms. mp 95–97 °C (methanol). Rf (SiO2, 3:1 PE–EtOAc): 0.50. 1H
NMR (400 MHz, CDCl3): δ = 8.15 (d, J = 8.7 Hz, 2 H, CH(pNB)), 7.32 (d,
J = 8.7 Hz, 2 H, CH(pNB)), 7.08 (d, J = 8.5 Hz, 2 H, CH(PMP)), 6.68 (d, J
= 8.6 Hz, 2 H, CH(PMP)), 5.04 (d, J = 13.6 Hz, 1 H, CH2a(pNB)), 4.66 (d,
J = 13.6 Hz, 1 H, CH2b(pNB)), 4.37 (dd, J = 15.9, 1.5 Hz, 1 H, Ha-6), 4.20
(ddd, J = 6.6, 4.8, 1.4 Hz, 1 H, H-3), 4.08 (d, J = 15.9 Hz, 1 H, Hb-6), 3.71
(s, 3 H, OMe), 3.57 (dd, J = 13.9, 4.8 Hz, 1 H, CH2a–C(3)), 2.85 (dd, J =
13.9, 7.0 Hz, 1 H, CH2b–C(3)), 0.91 (s, 9 H, t-BuSi), 0.90 (s, 9 H, t-BuSi),
0.16 (s, 6 H, Me2Si), 0.15 (s, 3 H, MeSi), 0.14 (s, 3 H, MeSi). 13C NMR
(101 MHz, CDCl3): δ = 164.1 (C=O), 158.4 (C-5), 157.9 (C(PMP)), 147.7
(C-NO2), 143.6 (C(pNB)), 132.2 (C(PMP)), 130.7 (CH(PMP)), 128.4
(CH(pNB)), 123.7 (CH(pNB)), 113.6 (CH(PMP)), 109.9 (C-4), 68.9 (C-6),
67.1 (C-3), 64.4 (CH2(pNB)), 55.3 (OMe), 33.6 (CH2-C(3)), 26.1 (Me3CSi),
25.7 (Me3CSi), 18.5 (Me3CSi), 18.0 (Me3CSi), –3.7 (MeSi), –5.0 (MeSi), –
5.2 (MeSi). 29Si NMR (60 MHz, CDCl3): δ = 27.8, 24.4. 15N NMR (30 MHz,
CDCl3, from {1H–15N}HMBC) δ = 369 (NO2), 244 (N–OTBS). 1H NMR
(200 MHz, toluene-d8): δ = 7.73 (d, J = 8.5 Hz, 2 H), 7.15 (d, J = 8.3 Hz,
2 H), 6.72 (d, J = 8.5 Hz, 2 H), 6.62 (d, J = 8.2 Hz, 2 H), 4.94 (d, J = 13.5
4-nitrobenzyl
(2R*,3S*)-1-((tert-butyldimethylsilyl)oxy)-2-(2-((tert-
butyldimethylsilyl)oxy)-2-oxoethyl)-3-methylaziridine-2-carboxylate
(4)
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European Journal of Organic Chemistry
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FULL PAPER
Dirhodium (II) tetraacetate (2.2 mg, 0.005 mmol) was added to a solution
of diazo compound 2a (377 mg, 1.0 mmol) in dichloromethane (1 mL) at
ambient temperature. The mixture was maintained until full conversion of
2a (completion of nitrogen evolution, ca. 30 min) and was filtered through
a short plug of silica. Then nitronate 1a (208 mg, 1.1 mmol) was added.
The reaction was maintained for 24 hours, then evaporated and
subjected to column chromatography on silica to give 206 mg (40 %) of
title compound 4 as colorless oil. Rf (SiO2, 3:1 PE–EtOAc): 0.53. 1H NMR
(300 MHz, CDCl3): δ = 8.19 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.48 (d, J =
8.8 Hz, 2 H, CH(pNB)), 5.30 (d, J = 13.6 Hz, 1 H, CH2a(pNB)), 5.16 (d, J
= 13.8 Hz, 1 H, CH2b(pNB)), 3.02 (d, J = 18.1 Hz, 1 H, CH2a–CO2TBS),
2.81 (d, J = 18.2 Hz, 1 H, CH2b–CO2TBS), 2.79 (q, J = 6.3 Hz, 1 H, CH–
N), 1.27 (d, J = 6.2 Hz, 3 H, Me–C), 0.89 (s, 18 H, 2×t-BuSi), 0.24 (s, 3 H,
MeSi), 0.23 (s, 3 H, MeSi), 0.13 (s, 3 H, MeSi), 0.10 (s, 2 H, MeSi).
Characteristic NOESY-interactions: CH2–CO2TBS / Me–C, CH–N / Me–C.
13C NMR (75 MHz, CDCl3): δ = 171.2 (C=O), 170.4 (C=O), 147.8 (C-
NO2), 143.2 (C(pNB)), 128.0 (CH(pNB)), 123.9 (CH(pNB)), 65.3
(CH2(pNB)), 45.8 (CH-N), 45.3 (C-N), 29.9 (CH2–CO2TBS), 26.3
(Me3CSi), 25.63 (Me3CSi), 18.3 (Me3CSi), 17.7 (Me3CSi), 6.7 (Me–C), –
3.5 (MeSi), –4.7 (MeSi), –5.1 (MeSi), –5.2 (MeSi). 15N NMR (30 MHz,
CDCl3, from {1H–15N} HMBC) δ = 369 (NO2), 135 (N–OTBS). HRMS
(ESI) m/z calcd. for [C25H42N2O7Si2 + Na+]: 561.2423, found: 561.2412.
(C-3), 64.9 (CH2(pNB)), 57.3 (C-6), 55.3 (OMe), 40.2 (CH2-C(3)), 25.8
(Me3CSi), 17.9 (Me3CSi),–5.5 (MeSi), –5.7 (MeSi). 29Si NMR (60 MHz,
CDCl3): δ = 27.4. 15N NMR (30 MHz, CDCl3, from {1H–15N}HMBC) δ =
228 (N–OTBS) Signal of NO2 was not observed due to broadening and
low intensity. HRMS (ESI) m/z calcd. for [C26H34N2O8Si + H+]: 531.2157,
found: 531.2150.
Acknowledgements
Research was supported by Russian Science Foundation (grant
14-50-00126).
Keywords: nitroso acetals • cycloaddition • nitrogen
heterocycles • nitrogen inversion • diazo compounds
[1]
a) V. F. Rudchenko, Chem. Rev. 1993, 93, 725-739; b) S. L. Ioffe in
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synthesis, 2nd ed. (Ed.: H. Feuer), John Wiley & Sons: Hoboken, New
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Dilman, A. A. Tishkov, Izv. Akad. Nauk, Ser. Khim. 2001, 1850-1861;
Russ. Chem. Bull. 2001, 50, 1936-1948.
4-nitrobenzyl
rel-(2S,3R)-2,5-bis((tert-butyldimethylsilyl)oxy)-3-(4-
methoxybenzyl)-3,6-dihydro-2H-1,2-oxazine-4-carboxylate (3’ha)
[2]
a) G. V. Shustov, A. B. Zolotoi, R. G. Kostyanovsky, Tetrahedron 1982,
38, 2319-2326; b) R. G. Kostyanovsky, V. F. Rudchenko, V. G.
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Org.Chem. 2011, 76, 9757-9763.
Solution of oxazine 3ha (89 mg, 0.14 mmol) in toluene (1.1 mL) was
maintained at 100 °C for 1 h and evaporated to give 89 mg (ca. 100%) of
oxazine 3’ha as colorless oil. 1H NMR (400 MHz, toluene-d8): δ = 7.77 (d,
J = 8.8 Hz, 2 H, CH(pNB)), 7.20 (d, J = 8.6 Hz, 2 H, CH(PMP)), 6.90 (d, J
= 8.8 Hz, 2 H, CH(pNB)), 6.75 (d, J = 8.7 Hz, 2 H, CH(PMP)), 4.86 (d, J =
13.4 Hz, 1 H, CH2a(pNB)), 4.76 (d, J = 13.4 Hz, 1 H, CH2b(pNB)), 4.40
(dd, J = 16.3, 1.7 Hz, 1 H, Ha-6), 4.16 (ddd, J = 7.9, 5.5, 1.4 Hz, 1 H, H-3),
3.74 (d, J = 16.3 Hz, 1 H, Hb-6), 3.37 (s, 3 H, OMe), 2.92-2.98 (m, 2 H,
CH2–C(3)), 0.92 (s, 9 H, t-BuSi), 0.88 (s, 9 H, t-BuSi), 0.18 (s, 3 H,
Me2Si), 0.14 (s, 3 H, MeSi), 0.08 (s, 3 H, MeSi), -0.09 (s, 3 H, MeSi). 13
C
NMR (101 MHz, toluene-d8): δ = 163.9 (C=O), 158.6 (C(PMP)), 157.5 (C-
5), 147.6 (C-NO2), 143.1 (C(pNB)), 131.2 (C(PMP)), 130.7 (CH(PMP)),
128.1 (CH(pNB)), 123.2 (CH(pNB)), 113.5 (CH(PMP)), 105.0 (C-4), 69.1
(C-3), 63.8 (CH2(pNB)), 59.8 (C-6), 54.4 (OMe), 40.1 (CH2-C(3)), 25.7
(Me3CSi), 25.5 (Me3CSi), 18.3 (Me3CSi), 17.8 (Me3CSi), –4.2 (MeSi), –
4.4 (MeSi), –5.7 (MeSi), –5.9 (MeSi). 29Si NMR (60 MHz, CDCl3): δ =
26.7, 23.7. 15N NMR (30 MHz, CDCl3, from {1H–15N}HMBC) δ = 369
(NO2), 226 (N–OTBS). HRMS (ESI) m/z calcd. for [C32H48N2O8Si2 + Na+]:
667.2841, found: 667.2841.
[3]
[4]
J.-M. Lehn, Top. Curr. Chem. 1970, 15, 311-377.
Reviews: a) R. Y. Baiazitov, S. E. Denmark in Methods and
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(rel)-(2S,3R)-4-nitrobenzyl 2(tert-butyldimethylsilyloxy)-5-hydroxy-3-
(4-methoxybenzyl)-3,6-dihydro-2H-1,2-oxazine-4-carboxylate (9)
Water (0.75 mL) was added to the solution of oxazine 3’ha (97 mg, 0.15
mmol) in acetone (3 mL). The reaction mixture was refluxed for 5 h,
evaporated and recrystallized from EtOH to give 51 mg (64%) of oxazine
9 as slightly beige powder. Alternatively: Crystalls of 9 were obtained
during attempted crystallization of 3’ha for X-ray analysis from the
MeOH/toluene, ca. 10:1, at open air. mp 109–111 °C. 1H NMR (400 MHz,
CDCl3): δ = 11.66 (br s, 1 H, OH), 8.26 (d, J = 8.8 Hz, 2 H, CH(pNB)),
7.52 (d, J = 8.8 Hz, 2 H, CH(pNB)), 7.05 (d, J = 8.7 Hz, 2 H, CH(PMP)),
6.76 (d, J = 8.7 Hz, 2 H, CH(PMP)), 5.31 (s, 2 H, CH2(pNB)), 4.49 (dd, J
= 16.9, 1.1 Hz, 1 H, Ha-6), 3.99 (d, J = 16.9 Hz, 1 H, Hb-6), 3.78 (s, 3 H,
OMe), 3.69 (td, J = 6.9, 1.1 Hz, 1 H, H-3), 2.79 (d, J = 6.9 Hz, 2 H, CH2–
[5]
Reviews: a) A. A. Tabolin, S. L. Ioffe, Chem. Rev. 2014, 114, 5426-
5476; b) A. A. Tabolin, S. L. Ioffe, Isr. J. Chem. 2016, 56, 385-398.
Selected seminal publications: c) Ya. A. Naumovich, V. E. Buckland, D.
A. Sen’ko, Yu. A. Nelyubina, Yu. A. Khoroshutina, A. Yu. Sukhorukov,
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Zhmurov, A. Yu. Sukhorukov, V. I. Chupakhin, Yu. V. Khomutova, S. L.
Ioffe, V. A. Tartakovsky, Org. Biomol. Chem. 2013, 11, 8082-8091; e) P.
A. Zhmurov, A. A. Tabolin, A. Yu. Sukhorukov, A. V. Lesiv, M. S.
Klenov, Yu. A. Khomutova, S. L. Ioffe, V. A. Tartakovsky, Izv. Akad.
Nauk, Ser. Khim. 2011, 2343-2348; Russ. Chem. Bull. 2011, 60, 2390-
2395.
C(3)), 0.80 (s, 9 H, t-BuSi), -0.05 (s, 3 H, Me2Si), -0.15 (s, 3 H, MeSi). 13
C
NMR (101 MHz, CDCl3): δ = 170.2 (C=O), 168.3 (C-5), 158.2 (C(PMP)),
148.0 (C-NO2), 142.7 (C(pNB)), 131.2 (C(PMP)), 130.5 (CH(PMP)),
128.5 (CH(pNB)), 124.0 (CH(pNB)), 113.6 (CH(PMP)), 95.0 (C-4), 66.8
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European Journal of Organic Chemistry
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FULL PAPER
[6]
a) V. O. Smirnov, S. L. Ioffe, A. A. Tishkov, Yu. A. Khomutova, I. D.
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Dilman, Yu. A. Khomutova, D. E. Arkhipov, A. A. Korlyukov, S. L. Ioffe,
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[15] For similar rearrangements, see: a) X. Xu, D. Shabashov, P. Y. Zavalij,
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publications: b) V. A. Tartakovskii, O. A. Luk’yanov, S. S. Novikov, S. S.
Dokl. Akad Nauk, 1968, 178, 123-126; Dokl. Chem., 1968, 178, 21-24;
c) I. E. Chlenov, I. L. Sokolova, S. S. Novikov, V. A. Tartakovskii, Izv.
Akad. Nauk SSSR, Ser. Khim. 1973, 473-474; Bull. Acad. Sci. USSR.
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[17] For detailed investigation on equilibrium between enol carbenoid and
cyclopropene and its influence on competitive [3+3]- and [3+2]-
cycloadditions between isoquinolinium methylides and enol
diazoacetates, see Ref.[11d]
[7]
[8]
a) H. Feger, G. Simchen, Liebigs Ann. Chem. 1986, 1456-1465; b) A. D.
Dilman, A. A. Tishkov, I. M. Lyapkalo, S.L. Ioffe, Yu. A. Strelenko, V. A.
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A. Khomutova, Yu. A. Strelenko, I. D. Nesterov, M. Yu. Antipin, S. L.
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Selected seminal publications: a) V. A. Tartakovskii, I. E. Chlenov, S. S.
Smagin, S. S. Novikov, Izv. Akad. Nauk SSSR, Ser. Khim. 1964, 583-
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Chlenov, V. I. Khudak, L. N. Kolymagina, N. S. Morozova, V. A.
Tartakovskii, Izv. Akad. Nauk SSSR, Ser. Khim. 1970, 1867-1871; Bull.
Acad. Sci. USSR. Div. Chem. Sci. 1970, 19, 1757-1761; d) S. E.
Denmark, C. B. W. Senanayake, G.-D. Ho, Tetrahedron 1990, 13/14,
4857-4876.
[18] Single-crystal X-Ray diffraction data for 3ha and 9 was deposited at
Cambridge Crystallographic Data Centre (CCDC-1460807 and CCDC-
1496258 respectively). These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif.
[19] a) S. L. Ioffe, V. M. Shitkin, B. N. Khasapov, M. V. Kashutina, V. A.
Tartakovskii, M. Ya. Myagi, E. T. Lippmaa, Izv. Akad. Nauk SSSR, Ser.
Khim. 1973, 2146-2148; Bull. Acad. Sci. USSR. Div. Chem. Sci. 1973,
22, 2100-2102; b) E. W. Colvin, A. K. Beck, B. Bastani, D. Seebach, Y.
Kai, J. D. Dunitz, Helv. Chim. Acta 1980, 63, 697-710; c) R. E. Marti, J.
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[9]
a) M. Brasholz, H.-U. Reissig, R. Zimmer, Acc. Chem. Res. 2009, 42,
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557; c) B. S. Bodnar, M. J. Miller, Angew. Chem. 2011, 123, 5746-
5764; Angew. Chem. Int. Ed. 2011, 50, 5630-5647; d) Y. Yamamoto, H.
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[20] About greater reactivity of cis-nitronates in comparison to their trans-
isomers in [3+2]-cycloaddition, see: a) R. Gree, R. Carrie, Tetrahedron
Lett, 1971, 4117-4120; b) V. M. Shitkin, S. L. Ioffe, M. V. Kashutina, V.
A. Tartakovskii, Izv. Akad. Nauk SSSR, Ser. Khim. 1977, 2266-2273;
Bull. Acad. Sci. USSR. Div. Chem. Sci. 1977, 26, 2101-2108.
[21] Existed X-ray data evidence that preferred pseudoaxial position of
substituent at C-3 in various substituted 3,6-dihydro-2H-1,2-oxazines is
a general trend. For representative examples see, a) L. Bollans, J.
Bacsa, D. A. O'Farrell, S. Waterson, A. V. Stachulski, Tetrahedron Lett.
2010, 51, 2160-2163; b) Q.-Q. Cheng, J. Yedoyan, H. Arman, M. P.
Doyle, J. Am. Chem. Soc. 2016, 138, 44-47; c) M. Jasinski, D. Lentz,
H.-U. Reissig, Beilstein J. Org. Chem. 2012, 8, 662-674; d) J.-M Chen,
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Ref.[11g] f) Y. Yamamoto, H. Yamamoto, Angew. Chem. 2005, 117,
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N. W. Isaacs, G. W. Kirby, P. Snedden, S. G. T. Tierney, J. Chem. Res.
(S) 1996, 2, 80-81; h) To the best of our knowledge the only
counterexample with 3-pseudoequatorial substituent is described in: M.
A. Chowdhury, I. Brudgam, H. Hartl, H.-U. Reissig, Z. Kristallogr. NCS
2006, 221, 213-214.
[10] a) E. O. Gorbacheva, A. A. Tabolin, R. A. Novikov, Yu. A. Khomutova,
Yu. V. Nelyubina, Yu. V. Tomilov, S. L. Ioffe, Org. Lett. 2013, 15, 350-
353; b) A. A. Mikhaylov, R. A. Novikov, Yu. A. Khomutova, D. E.
Arkhipov, A. A. Korlyukov, A. A. Tabolin, Yu. V. Tomilov, S. L. Ioffe,
Synlett 2014, 25, 2275-2280; c) A. A. Tabolin, R. A. Novikov, Yu. A.
Khomutova, A. A. Zharov, G. A. Stashina, Yu. V. Nelyubina, Yu. V.
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Mikhaylov, A. D. Dilman, R. A. Novikov, Yu. A. Khoroshutina, M. I.
Struchkova, D. E. Arkhipov, Yu. V. Nelyubina, A. A. Tabolin, S. L. Ioffe,
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[11] Reviews: a) Y. Deng, M. P. Doyle, Isr. J. Chem. 2016, 56, 399-408; b)
X. Xu, M. P. Doyle, Acc. Chem. Res. 2014, 47, 1396-1405; c) X. Xu, M.
P. Doyle, Aust. J. Chem. 2014, 67, 365-373. Selected seminal
publications: d) X. Xu, P. Y. Zavalij, M. P. Doyle, J. Am. Chem. Soc.
2013, 135, 12439-12447; e) P. E. Guzman, Y. Lian, H. M. L. Davies,
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Denton, Y. Lian, H. M. L. Davies, C. M. Williams, J. Am. Chem. Soc.
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[22] About anomeric effect in O–N–O moiety, see: Yu. V. Nelyubina, K. A.
Lyssenko, J. Phys. Chem. A 2013, 117, 3084-3092.
[23] F. Neese, WIREs Comput. Mol. Sci. 2012, 2, 73-78.
[24] a) C. Riplinger, F. Neese, J. Chem. Phys. 2013, 138, 034106; b) D. G.
Liakos, M. Sparta, M. K. Kesharwani, J. M. L. Martin, F. Neese, J.
Chem. Theory Comput. 2015, 11, 1525–1539.
[25] a) F. G. Riddell, J.-M. Lehn, J. Wagner, Chem. Commun. (London)
1968, 1403; b) F. G. Riddell, E. S. Turner, A. Boyd, Tetrahedron 1979,
20, 259-261.
[12] F. Gonzalez-Bobes, M. D. B. Fenster, S. Kiau, L. Kolla, S. Kolotuchin,
M. Soumeillant, Adv. Synth. Cat. 2008, 350, 813-816.
[13] About successful use of this catalyst in asymmetric formal cycloaddition
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European Journal of Organic Chemistry
10.1002/ejoc.201600952
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N,O-heterocycles
Alexander S. Shved,* Andrey A.
Tabolin,* Roman A. Novikov, Yulia V.
Nelyubina, Vladimir P. Timofeev, and
Sema L. Ioffe
Page No. – Page No.
The reaction of silyl nitronates and enol diazoacetates afforded new type of nitroso
acetals - N-silyloxy-3,6-dihydro-2H-1,2-oxazines. Reaction scope was determined.
Quantum chemical calculations and kinetic data allowed determination of nitrogen
inversion barrier in target nitroso acetals.
New six-membered cyclic nitroso
acetals - N-silyloxy-3,6-dihydro-2H-
1,2-oxazines: synthesis and studies
of the nitrogen inversion process.
This article is protected by copyright. All rights reserved