Visible Light Mediated Photocatalytic N-Radical Cascade Reactivity of O,δ-Unsaturated N-Arylsulfonylhydrazones: A General Approach to Structurally Diverse Tetrahydropyridazines

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Visible Light Mediated Photocatalytic N‑Radical Cascade Reactivity

of γ,δ-Unsaturated N‑Arylsulfonylhydrazones: A General Approach

to Structurally Diverse Tetrahydropyridazines

Emanuele Azzi, Giovanni Ghigo, Stefano Parisotto, Francesco Pellegrino, Emanuele Priola,

Polyssena Renzi, and Annamaria Deagostino *

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ABSTRACT: Tetrahydropyridazines are of particular interest for

their versatility as intermediates in organic synthesis and display

pharmacological activity in several domains. Here, we describe the

photocatalytic synthesis of diﬀerent tetrahydropyridazines starting

from γ,δ-unsaturated N-arylsulfonylhydrazones. Simple structural

changes of substrates result into three diﬀerent pathways beginning

from a common N-hydrazonyl radical, which evolves through a

domino carboamination/dearomatization, a HAT process, or a

photoinduced radical Smiles rearrangement to aﬀord diverse

tetrahydropyridazines. All reactions are carried out in very mild conditions, and the quite inexpensive [Ru(bpy)₃]Cl₂is used as

the catalyst. Preliminary mechanism studies are presented, among them luminescence and electrochemical characterization of the

involved species. Computational studies allow to rationalize the mechanism in accord with the experimental ﬁndings.

with several functional groups has been the driving force for

the use of other cyclization strategies. In this context,

hydrazones represent an appealing alternative,²¹⁻²⁴being

easy to prepare and displaying a very peculiar reactivity.²⁵⁻³⁰

Many synthetic approaches exploiting them have been

reported, like palladium^31,32and copper mediated cycliza-

tions,^33,34but especially visible light-mediated processes.

Photocatalytic transformations have, indeed, attracted huge

interest in the past years, disclosing alternative routes to

functionalized molecules under mild reaction conditions and

with high functional group tolerance.³⁵⁻³⁹In particular, visible

light-mediated generation of N-centered radicals^40,41has

rapidly become one of the most eﬃcient approaches in the

synthesis of N-heterocycles (Scheme 1).⁴²⁻⁴⁴Thus far, the

pioneering work by Xiao and co-workers has emerged as a

milestone, giving access to 4,5-dihydropyrazoles in good yields

from β,γ-unsaturated hydrazones through a photocatalytic N-

radical hydroamination.⁴⁵Similar strategies aﬀorded pyrazo-

lines, pyridazines, and isoxazolines under oxidative condi-

tions,^46,47or by a radical mediated cyclization/allylation.⁴⁸

Moreover, the light-induced N-radical 5-exo-cyclization/

INTRODUCTION

■

The synthesis of nitrogen-containing heterocycles represents a

major focus in organic synthesis.^1,2Among them, tetrahy-

dropyridazines are of particular interest since they are

frequently found in natural products and pharmacologically

active compounds. Their activity as lipoxygenase inhibitors,^3,4

cardiotonics,^5,6antibacterials,⁷cannabinoid receptor antago-

nists,⁸and inﬂuenza neuraminidase inhibitors⁹has been

reported (Figure 1), in addition to studies correlated to their

herbicidal properties.¹⁰Moreover, they are versatile inter-

mediates in organic synthesis.¹¹

Figure 1. Biologically active 1,4,5,6-tetrahydropyridazines.

As a consequence, many eﬀorts have been dedicated to new

strategies for the construction of these nitrogen heterocycles:

among those are [4 + 2] cycloaddition of azoalkenes,¹²⁻¹⁵1,2-

diaza-1,3-dienes,^9,16or diazenes,¹⁷and [3 + 3] formal

cycloadditions¹⁸exploiting cyclopropyl derivatives and hydra-

zones.^19,20Nevertheless, the need for available starting

materials and a good compatibility of reaction conditions

Received: November 10, 2020

Published: February 1, 2021

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Scheme 1. N-Radical-Centred Reactivity of Unsaturated

Aryl Hydrazones to Aﬀord Diﬀerent N-

Tetrahydropyridazine Scaﬀolds

Scheme 2. Photocatalyzed Cyclization of Phenylbut-3-enyl-

N-tosylhydrazone (1)

could be further involved in alternative reaction pathways

leading to byproducts or product degradation. Therefore, we

turned our attention to phenyl-2,2-dimethylbut-3-enyl-N-

tosylhydrazone (10a), where the presence of two geminal

CH₃at the β-C avoids the undesired 1,5-HAT. When 10a was

reacted under the optimized reaction conditions for 1 (entry 1,

Table 1), we witnessed the total conversion of the reagent

yielding an unexpectedly diﬀerent product. NMR analysis

suggested structure 13a containing a 1,4-dienic moiety

corroborated by a broad singlet at 5.35 and a multiplet at

6.75 ppm pertinent to alkenyl sp₂protons and three signals

related to methylenes in the DEPT-135 spectrum (31.4, 31.5,

and 34.6 ppm). This structure was eventually conﬁrmed by

single crystal X-ray diﬀraction (Table 1, top right). Most

importantly, we observed the formation of a single

diastereoisomer. This new outcome delighted us, mostly

because the introduction of two geminal methyl groups

aﬀorded, with complete diastereoselectivity, a tricyclic

structure containing a 1,4-diene moiety as the result of an

arene dearomatization. This was probably the consequence of

a cascade process involving two consecutive exo-trig-cycliza-

tions, a very diﬀerent result from the cyclization/addition/

aromatization cascade of β,γ-unsaturated-N-tosylhydrazones

reported by Xiao et al. where the dienic portion spontaneously

evolved to an aromatic ring.⁴⁹1,4-(Skipped) dienes are

ubiquitous structural units in natural products such as polyenic

macrolides,⁵²⁻⁵⁴macrolactames,⁵⁵and alkaloids⁵⁶and also in

functional materials.⁵⁷⁻⁵⁹Their synthesis is not trivial, and in

the past years the dearomatization approach has emerged as a

powerful strategy to access this motif.⁶⁰Optimization of

reaction conditions for 10a is reported in Table 1. When a 40

W blue light was utilized (entry 2), the yield of 13a increased

to 52%. The use of K₂CO₃in CHCl₃aﬀorded the product in

40% yield (entry 3), and 73% yield was obtained switching the

solvent to CH₃CN (entry 10). A mixture of degradation

products was recovered using both KOH and NaOH as the

bases in CH₃CN (entries 4, 5, and 6), whereas Cs₂CO₃

demonstrated a complete ineﬃcacy; in fact, starting material

10a was fully recovered (entry 7). The base was essential for

the success of the reaction as demonstrated by entry 17. 1.5

equiv of the base in respect to 10a was optimal for the reaction.

The eﬀect of the light source power was evident as well, since

the reaction carried out using a 9 W blue lamp did not reach

completion after 72 h (85% conversion, 50% yield, entry 9).

Diﬀerent photocatalysts were also tested: 3% mol [Ru(bpy)₃]-

Cl₂·6H₂O was optimal (entry 10), since lower loadings gave a

total conversion but lower yields (58 and 55% respectively,

entries 11 and 12). Anyway, its performances were superior to

[Ir(ppy)₂(dtbpy)][PF₆] and [Ir{dFCF₃ppy₂(bpy)]PF₆(entries

14 and 15) and Eosin Y, the latter being completely ineﬃcient

(entry 13). Experiments in the absence of photosensitizer

(entry 18) or light (entry 19) aﬀorded no product, conﬁrming

the photocatalytic nature of the process.

addition/aromatization cascade by dual Ru/Co cocatalysis was

reported, aﬀording various dihydropyrazole-fused benzosul-

tams from β,γ-unsaturated hydrazones.⁴⁹Dihydropyrazoles

were also obtained starting from aldehyde hydrazones with

halo-1,3-dicarbonyls⁴⁴or α-halohydrazones with β-ketocar-

bonyls.⁵⁰In 2017 our research group reported the ﬁrst example

of a visible light driven transformation of α,β-unsaturated

sulfonylhydrazones to allylic sulfones by the generation of

highly delocalized radicals, crucial in promoting nitrogen loss

instead of the commonly observed intramolecular hydro-

amination.⁵¹A 1,5-rearrangement of the sulfonyl group with

loss of nitrogen was hypothesized via a six member ring

transition state, moreover the formation of a vinyl radical was

demonstrated (Scheme 1). To our knowledge, no studies on

visible-light mediated reactivity of γ,δ-unsaturated derivatives

are reported in literature, so we decided to explore such

substrates as possible precursors for tetrahydropyridazines

synthesis and compare them to α,β and β,γ-analogues (Scheme

1).

RESULTS AND DISCUSSION

■

Reaction Optimization and Scope. First attempts were

carried out using phenylbut-3-enyl-N-tosylhydrazone (1). The

eﬀect of the light source, solvent, photocatalyst, and base was

studied and the complete optimization is reported in

Supporting Information (Table S1 in SI). Under the best

reaction conditions, KOH was used as the base, [Ru(bpy)₃]-

Cl₂·6H₂O as the catalyst in CHCl₃, and a 9W blue lamp as the

light source, to aﬀord 2 in 24% yield (Scheme 2).

Despite the reaction selectively aﬀording product 2 deriving

from the originally designed 6-exo-trig cyclization (Scheme 2),

any attempt to enhance the yield was unsuccessful, even when

a more powerful light source was used (40 W). In light of these

results, we speculated a competition between the desired

cyclization and the formation of a stable allylic radical which

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a

Table 1. Optimization for Photocatalyzed Cyclization of Phenylprop-3-enyl-N-tosylhydrazone (10a)

b

entry

base

photosensitizer

solvent

time [h]

conversion [%]

yield [%]

d

c

1

KOH (1.2 equiv)

K₂CO₃(1.5 equiv)

KOH (1.2 equiv)

KOH (1.5 equiv)

NaOH (1.5 equiv)

Cs₂CO₃(1.5 equiv)

K₂CO₃(1.5 equiv)

−

[Ru(bpy)₃]Cl₂·6H₂O (3%)

[Ru(bpy)₃]Cl₂·6H₂O(3%)

[Ru(bpy)₃]Cl₂·6H₂O (3%)

[Ru(bpy)₃]Cl₂·6H₂O (2%)

[Ru(bpy)₃]Cl₂·6H₂O (1%)

Eosyn Y

CHCl₃

16

72

16

72

16

100

0

35 (22)

52 (45)

g

c

2

g

c

3

40 (35)

g

h

4

CH₃CN

0

g

h

5

d

6

0

43

50

d

7

d

8

45

85

d

9

g

c

10

11

12

13

14

15

16

17

100

0

100

0

73 (70)

g

58

55

0

37

42 (36)

0

g

e

f

[Ir(ppy)₂(dtbpy)][PF₆] (3%)

[Ir{dFCF₃ppy}₂(bpy)]PF₆(3%)

[Ru(bpz)₃][PF₆]₂·6H₂O (3%)

[Ru(bpy)₃]Cl₂·6H₂O (3%)

−

f

c

g

0

g

18

19

K₂CO₃(1.5 equiv)

i

[Ru(bpy)₃]Cl₂·6H₂O (3%)

traces

a

b

Reaction conditions: tosylhydrazone 10a (0.3 mmol), anhydrous solvent (5 mL) [reagent concentration: 0.06 M], base, catalyst. Determined by

NMR spectroscopy using nitromethane as internal standard. Yields determined on isolated product. 450 nm light source, blue light. 9 W. 550

nm light source, green light. 365 nm light source, purple light. 450 nm light source, blue light, 40 W. A mixture of degradation products was

recovered. Reaction performed in the dark.

c

d

e

f

g

h

i

Conditions listed in entry 10 resulted to be the best, so we

extended the scope of the reaction to the β-hindered-γ,δ-

unsaturated hydrazones listed in Scheme 3. Tosyl, phenyl-

sulfonyl (10 and 11), and mesitylsulfonyl-hydrazones (12)

were prepared in order to evaluate the inﬂuence of the

substituent on the hydrazonyl moiety (Scheme 3) starting

from the suitable α,β-unsaturated aldehyde 3 which was

reacted with a Grignard reagent 4. The so-formed alcohol 5,

after oxidation with MnO₂, aﬀorded the γ,δ-unsaturated ketone

8 and, after reaction with the arylsulfonyl hydrazide, the

corresponding hydrazone (10, 11, or 12). Acetone and

acetophenone derivatives were used as starting materials for

the preparation of both terminal and internal γ,δ-unsaturated

hydrazones. Moreover, natural terpene pulegone was exploited

(10l and 12g). As reported in Table 2, best results were

obtained with tosylhydrazones 10a and 10i and aﬀorded

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine-10,10-diox-

ide 13a and 13i in 70% and 73% yields, respectively, thus

demonstrating that an aromatic group is not compulsory and

the reaction can be successfully applied to aliphatic

arylsulfonylhydrazones. The reaction demonstrated to be

totally diastereoselective; X-ray diﬀraction-derived molecular

structure of 13a are reported in Table 1 (see SI Tables S5, S6,

and S7). In the case of methyl derivative 10i the reaction was

scaled up to 2 mmol, and product 13i was obtained in 51%

yield after 72 h. When phenylsulfonylhydrazones 11a and 11b

were subjected to irradiation, products 13j and 13k were

recovered in lower yields with respect to those obtained with

tosylhydrazones 10a and 10i (40% and 55% yield,

respectively). Electron-rich aromatic rings can also be

introduced: 2-naphthyl (13b, 43%), 3-methoxyphenyl (13f,

50%), and tolyl substituents. In the last case meta, para, and

ortho derivatives (10c, 10d, and 10e) were used in order to

evaluate both electronic and steric eﬀects. O-tolyl derivative

aﬀorded the product 13e in lower yield with respect to meta

13c and para 13d, which are comparable, thus demonstrating

an inﬂuence of steric eﬀects. The electron-poor 2-pyridinyl

derivative 10g aﬀorded product 13g in 37% yield, slightly

worse than electron rich substrates. The reaction was also

successfully extended to the unsaturated hydrazone 10l

deriving from pulegone, a monoterpene ketone found in the

leaves and ﬂowering tops of several members of the mint

family Lamiaceae, aﬀording the corresponding tetrahydropyr-

idazine 13l in 35% yield.

Finally, also the geminal substituents in the bridge were

changed, and the tosylhydrazone 10j, where a phenyl group

was introduced in place of one of the two methyl groups,

successfully aﬀorded the cyclization product 13h in 34% yield.

Furthermore, we tested the reactivity of mesitylhydrazones

(mesityl = 2,4,6-trimethylphenyl) 12a−12g and a completely

diﬀerent outcome was observed (Table 3). Two products were

recovered in high yields: the ﬁrst (14a) derived from the

photocatalyzed cyclization of the N-hydrazonyl radical, and the

second due to a photoradical promoted carboamination/

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Scheme 3. Synthesis and List of the β-Hindered γ,δ-Unsaturated Hydrazones

Smiles rearrangement (15a).⁶¹⁻⁶⁴Best results were obtained

with 2,2-dimethylbut-3-enylphenylmesitylhydrazone (12a) and

2,2-dimethylbut-3-enylmethylmesitylhydrazone (12e) with a

total yield of 95% and a ratio of 53:47 and 61:39 between

products 14a/15a and 14e/15e, respectively, again demon-

strating no diﬀerence between aromatic and aliphatic

derivatives (Table 3). When 2-naphthyl (12b) was introduced

as the substituent, 72% yield was obtained and a ratio of 58:42

between the cyclization product 14b and the Smiles rearrange-

ment 15b. Also in this case, steric hindrance of o-tolyl

derivative 12d decreased the eﬃciency of the process

compared to p-substituted 12c (87% versus 62% yield; Table

3). Pulegone hydrazone 12g was subjected to irradiation, as

well. In such case only product 14f was recovered in 35% yield,

while only traces of the corresponding Smiles rearrangement

product were observed. We reasoned that the steric hindrance

and the rigidity of the pulegone cyclic structure make the

attack of the so-formed alkyl radical to the aromatic ring more

diﬃcult.

Then we moved on testing tosylhydrazones 10j, 10k, and

12f where an internal double bond was introduced. Again, this

modiﬁcation imposed a diﬀerent reaction outcome because

only the Smiles rearrangement product was recovered in all

cases, not only with mesitylsulfonyl hydrazone 12f (product

15h, 72%), but also when tosyl derivatives 10j and 10k were

involved (72 and 70% for 15h and 15g, respectively). We

supposed that the presence of the methyl makes diﬃcult the

interaction with the ortho H of the aromatic ring. Finally, the

reaction demonstrated to be diastereoselective; in fact, only a

diastereoisomer was recovered.

Reaction Mechanism Studies. To verify if a C-centered

radical is involved as a key intermediate during the process, a

trapping experiment with TEMPO was realized. The model

reaction was carried out in the presence of TEMPO (2.0

equiv) aﬀording 1-phenyl-N-tosyl-6-(2,2,6,6-tetramethyl-N-

methylenoxy)1,4,5,6-tetrahydropyridazine 16 in 30% yield

(Scheme 4). The structure of TEMPO adduct was conﬁrmed

by HRMS, NMR spectroscopy, and single crystal X-ray

diﬀraction (Figure 2).

To exclude the possibility of a chain radical mechanism,

experiments with 10a were also carried out in the presence of

radical initiators: no reaction was induced when AIBN was

used, whereas the more reactive benzoyl peroxide produced a

mixture of degradation byproducts (see SI).

Then, the Stern−Volmer luminescence quenching studies

were performed (Figure 3, left). The interaction mechanism

between the K⁺salt of the model substrate K⁺-10a and

[Ru(bpy)₃]²⁺was investigated (see details in SI). The

nonlinearity of the trend is due to both static and dynamic

quenching, in agreement with the formation of an ion pair

between the tosylhydrazone anion K⁺-10a and the [Ru-

(bpy)₃]²⁺, as already observed in previous studies.^51,65The

model reaction has been also studied from an electrochemical

point of view. The cyclovoltammetries (CVs) of 2,2-

dimethylbut-3-enylphenone-N-tosylhydrazone-K+ salt (K⁺-

10a) and the corresponding isolated reaction product (13a)

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Table 2. Scope of the Synthesis of Tetrahydropyridazines by Photocatalyzed Cyclization of γ,δ-Unsaturated-N-

a b c

, ,

Arylsulfonylhydrazones (10a−l, 11a−b)

a

Reaction conditions: arylsulfonylhydrazone 10a−l and 11a,b 0.3 mmol, K₂CO₃0.45 mmol, anhydrous CH₃CN 5 mL, [Ru(bpy)₃]Cl₂·6H₂O 0.09

b

c

mmol (3%), Kessil blue lamp 40W, 16 h, inert atm. Yields determined on isolated product. Relative conﬁgurations of products were assigned by

analogy to 13a. Reaction scaled to 2 mmol of 13i (51%, 72 h).

d

show that K⁺-10a can be irreversibly oxidized, aﬀording 13a

that, conversely, is stable in the employed reaction conditions.

Given the electrochemical characterization of these species, we

followed the whole reaction by CV. Therefore, a 0.1 mM

Ru(bpy)₃Cl₂·6H₂O and 3 mM K⁺-10a solution in acetonitrile

was irradiated for 20 h, under nitrogen atmosphere. In Figure 3

right, we observed, immediately after the beginning of the

irradiation, only the peak of K⁺-10a (+0.52 V). The low

concentration of the catalyst does not allow to detect it as its

peaks are covered by those of the substrate K⁺-10a. After 4 h

under irradiation, as the reaction proceeds, the peak of the

substrate K⁺-10a located at +0.52 V begins to decrease in

intensity while the signal of product 13a, at +1.23 V, grows

(red line). Finally, after 20 h of irradiation, the reaction goes to

completeness showing an intense peak at +1.23 V due to the

complete conversion of the substrate K⁺-10a, and the signal of

tosylhydrazone salt disappeared K⁺-10a (blue line).

COMPUTATIONAL STUDIES

■

The experimental results have been ﬂanked by the computa-

tional DFT study of the reaction mechanism in CH₃CN (the

details on the method and the full data are reported in the SI).

Given the experimental results and the computational data

recovered so far, a general reaction mechanism is hypothesized

in Scheme 5. Here we only focus on the key steps of the

reaction mechanism; the complete scheme, discussion, and

energy proﬁles are reported in the SI. The computational study

is focused on the fate of the radicals A and performed for the

reaction of tosylhydrazones 10i (R′, R″ = H) and 10k (R′=

Me, R″ = H), and mesitylsulfonylhydrazone 12e (R′ = H, R″ =

Me). The energy values commented here are Gibbs free

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Table 3. Alternative Reactivity with γ,δ-Unsaturated Mesitylsulfonylhydrazones (12a−12f) and 2.2-Dimethylpent-3-enone

a b c

, ,

Arylhydrazones (10j−k)

a

Reaction conditions: arylsulfonylhydrazone 0.3 mmol, K₂CO₃0.45 mmol, anhydrous CH₃CN 5 mL, [Ru(bpy)₃]Cl₂·6H₂O 0.09 mmol (3%),

b

c

Kessil blue lamp 40W, 16 h, inert atm. Determined on isolated product. Mes (mesityl) = 2,4,6-trimethylphenyl.

the anions 10′ in accordance with electrochemical measure-

Scheme 4. TEMPO Trapping Experiment

ments on K⁺-10a. Their single-electron oxidation by the

excited state of the photocatalyst (*[Ru(bpy)₃]²⁺) gives the N-

centered radicals A⁵¹and, following an exo-closure, the radicals

B. Actually, this step takes place through several conformations

of TS^Ayielding the same number of radical intermediates B.

The lowest activation energies are quite similar for the three

hydrazones: ΔG^‡= 10.8 and 9.2 kcal mol⁻¹for the tolyl

derivatives 10i and 10k and 12.2 kcal mol⁻¹for the mesityl

derivative 12e. This step is monomolecular, so we can easily

apply the Eyring equation that furnishes (taking into account

all conformations) an estimation of the rate constants, which

are 2 × 10⁵(10i), 1 × 10⁶(10k), and 1 × 10⁴(12e) s⁻¹. This

fast formation of radicals B is irreversible, being exoergic in all

energies at room temperature (ΔG, in kcal mol⁻¹). The

experimental data and the comparison with the previous

study⁵¹allow us to deduce that the deprotonation of

arylhydrazones 10 occurs under basic conditions to aﬀord

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when, in the γ,δ-unsaturated hydrazones containing the

terminal double bond, the aryl is the tolyl (10i) or the mesityl

(12e). Comparing the last two pathways, we can observe that

for the tolyl derivative 10i, the attack to the ortho positions

(TS^B, Figure 4, left) is favored. The rate constant that we can

estimate by the Eyring equation is 4 × 10²s⁻¹, 20 times larger

than that for TS^C(2 × 10¹s⁻¹). For the mesityl derivative 12e,

it is the attack to the ipso positions (TS^C, Figure 4, right) to be

favored. The rate constant is 2 × 10²s⁻¹, and has to be

compared to 3 s⁻¹for TS^B. Therefore, our calculations indicate

that for the tolyl derivative 10i, the formation of the condensed

three-rings 13 (i.e., 13i), is preferred. While, for the mesityl

derivative 12e, the formation of the radical Smiles rearrange-

ment product 15 (i.e., 15e) is preferred. As said above, here we

are not conﬁdent in using the calculated rate constant for

pathway i, but we have an indication that it can be around 10²

s⁻¹. This value is just of the same order as the one calculated

for the other two pathways. We can also observe that the

reaction constant for the formation of product 13 (i.e., 13i)

from 10i is twice the one of product 15 (i.e., 15e) from 12e.

This is in a semiquantitative agreement with the experimental

ﬁnding: 13i is the only product obtained from the tolyl

derivative 10i, while in the reaction of the mesityl derivative

12e, 15e (39%), being that its rate constant is lower, is

generated along with 14 (i.e., 14e, 61%).

The reason the intramolecular attack of the primary radical

centers to the ortho positions of the aromatics (TS^B) in the

mesityl derivative (ΔG^‡= 17.1 kcal mol⁻¹) is more diﬃcult

than that in the tolyl case (ΔG^‡= 14.4 kcal mol⁻¹) is

presumably the steric hindrance of the ortho methyl groups in

the ﬁrst case. This eﬀect is absent in the cases of the attack to

the ipso positions. By contrast, the same methyl groups in the

mesityl derivative concur to stabilize the incipient delocalized

aromatic radicals formed in TS^C, which, in fact, presents a

lower barrier (ΔG^‡= 14.7 kcal mol⁻¹) that in the case of the

tolyl derivative (ΔG^‡= 16.0 kcal mol⁻¹). These results are

qualitatively applicable to all other cases with the terminal γ,δ-

unsaturated hydrazone. When Ar is a phenyl or a tolyl (see

Table 3), the lack of the para-methyl does not change the

choice between pathways ii and iii: all arylhydrazones follow

the same pathway as 10i yielding 13a−n. The presence of an

Figure 2. ORTEP plot of the asymmetric unit of TEMPO adduct 16

in the crystal structure (color code: gray, carbon; navy blue, nitrogen;

red, oxygen; yellow, sulfur; 50% of probability represented).

cases (ΔG = −9.7, −11.1, and −7.6 kcal mol⁻¹), giving rise to

three possible pathways:

i. The hydrogen atom transfer (HAT) from the solvent

CH₃CN generating products 14.

ii. The intramolecular attack of the radical centers to the

ortho (with respect to the sulfur) position of the

aromatic yielding, after the HAT from CH₃CN, products

13.

iii. The intramolecular attack of the primary radical centers

to the ipso positions of the aromatic yielding a sort of

radical Smiles rearrangement and the ﬁnal HAT from the

solvent, products 15.

Process i is bimolecular and involves a molecule taken from

the solvent, while pathways ii and iii are monomolecular.

Therefore, we cannot conﬁdentially compare the rate constant

calculated for pathway i with those calculated for the other two

pathways. However, the rate constant for the HAT of triplet

benzophenone with CH₃CN reaction has been measured,⁶⁶

and the value is 10²s⁻¹. The pathway ii, passing through TS^B,

is required to overcome a barrier of 14.4, 17.2, and 17.1 kcal

mol⁻¹(lowest values of all conformations for each TS) for the

tolyl 10i and 10m and for the mesityl 12e, respectively. For

pathway iii, passing through TS^C, the ΔG^‡are, respectively,

16.0, 15.8, and 14.7 kcal mol⁻¹for the tolyl 10i and 10m and

for the mesityl 12e. We ﬁrst focus on the diﬀerent outcomes

Figure 3. Left: Stern−Volmer plot for the [Ru(bpy)₃]²⁺luminescence quenching in the presence of 2,2-dimethylbut-3-enylphenone-N-

tosylhydrazone-K⁺salt (K⁺-10a). Right: Electrochemical characterization of the reaction. The CVs were carried at three diﬀerent times during the

reaction: (1) t = 0 h (black); (2) t = 4 h (red); (3) t = 20 h of irradiation (blue).

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Scheme 5. General Reaction Mechanism

changing the structural features of the starting γ,δ-unsaturated

tosylhydrazones. All reactive pathways exploit a common N-

centered radical which can undergo, in one case, a totally

diastereoselective double cyclization aﬀording 1,4-cyclohex-

adiene-fused tetrahydropyridazinylthiazines as a result of a

dearomatization process. On the other cases, depending on the

presence of an internal double bond or a mesitylsulfonylhy-

drazone, tetrahydropyridazines are obtained by a hydrogen

atom transfer from the solvent CH₃CN after the ﬁrst exo-

cyclization or a photocatalyzed Smiles rearrangement. The

hypothesis on the involved mechanisms is strengthened by the

Stern−Volmer plot obtained from ﬂuorescence measurements

and by the electrochemical analysis. Experimental data are

supported by a computational study of the mechanism, which

is coherent with the experimental ﬁndings, and some

explanation of the outcomes is put forward.

Figure 4. Key transition structures (TS^B, left, and TS^C, right) for the

formation of products 13i and 15e.

aryl or alkyl group linked to CN is also irrelevant: the choice

between pathways ii and iii is uniquely due to the nature of the

Ar, as the comparison between Tables 2 and 3 conﬁrms. For

the tolyl derivatives, when the γ,δ-unsaturated hydrazone

contains an internal double bond instead of a terminal one as

in 10k, the main product is 15. The calculations are in

qualitative agreement with the experiments: the Smiles

rearrangement (pathway iii) is favored over the second

cyclization (pathway ii yielding 13) by almost 2 kcal mol⁻¹

(ΔG^‡= 15.8 kcal mol⁻¹for TS^Cand ΔG^‡= 17.5 kcal mol⁻¹for

TS^B). Therefore, the competition is between pathways i (the

HAT yielding 14) and iii. As discussed above, we are not

conﬁdent in comparing rate constants calculated for mono-

and bimolecular processes, but we can do it for homogeneous

process as HAT for diﬀerent radicals. The calculated rate

constants for the HAT reaction for the primary radicals B

generated from the terminally double bonded 10i and 12e are

in the order of 10²s⁻¹, while that for the more stable secondary

radical B, generated from the internally double bonded 10k, is

10⁻¹s⁻¹. This can explain why in the latter case, pathway iii is

preferred over all the others.

EXPERIMENTAL SECTION

■

Flasks and all equipment used for the generation and reaction of

moisture-sensitive compounds were dried by electric heat gun under

N₂. All commercially available reagents and solvents were used as

received. Anhydrous solvents were purchased by Sigma-Aldrich, or

distilled as indicated by Armarego.⁶⁷Products were puriﬁed by

preparative column chromatography on Sigma-Aldrich silica-gel for

ﬂash chromatography, 0.04−0.063 mm/230−400 mesh. Reactions

were monitored by TLC using silica-gel on TLC-PET foils Sigma-

Aldrich, 2−25 μm, layer thickness 0.2 mm, medium pore diameter 60

Å.

¹H and ¹⁹F NMR spectra were recorded at NMR Jeol ECZR 600

MHz, ¹³C NMR spectra at 150 MHz, in CDCl₃or DMSO-d₆.⁶⁸Data

were reported as follows: chemical shifts in ppm from Me₄Si as an

internal standard, integration, multiplicity, coupling constants (Hz),

and assignment. ¹³C NMR spectra were measured with complete

proton decoupling. DEPT experiments were carried out with a DEPT

135 sequence. Chemical shifts were reported in ppm from the residual

pick solvent as an internal standard. GC-MS spectra were obtained on

a mass selective detector Agilent 5970 B operating at an ionizing

voltage of 70 eV connected to a HP 5890 GC equipped with a HP-1

MS capillary column (25 m length, 0.25 mm I.D., 0.33 μm ﬁlm

thickness. The MS ﬂow-injection analyses were run on a high

resolving power hybrid mass spectrometer (HRMS) Orbitrap Fusion

CONCLUSIONS

In summary, we have reported the synthesis of diverse

tetrahydropyridazines following three diﬀerent patterns simply

■

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(Thermo Scientiﬁc, Rodano, Italy) and a Bruker Daltonics microTOF

Mass Spectrometer equipped with an h-ESI ion source. The samples

were analyzed in methanol or acetonitrile solution using a syringe

pump at a ﬂow rate of 10 μL/min. The tuning parameters adopted for

the ESI source were as follows: source voltage 3.5 kV, RF lens 60%

(positive ion mode MH⁺, MNa⁺); source voltage 2.5 kV, RF lens 60%.

The ion transfer tube was maintained at 270 °C. The mass accuracy of

the recorded ions (vs the calculated ones) was <5 ppm. Analyses were

run using full MS (50−500 m/z range) acquisition, at 240 000

resolution (200 m/z). IR spectra were recorded on a BrukerVertex 70

FT-IR. Fluorescence emission spectra were collected with a Cary

Eclipse Fluorescence Spectrophotometer, with excitation at 452 nm.

Excitation and emission slits set both at 5 nm. Spectra were taken in a

ﬂuorescence fused silica cuvette with 1 cm optical path length. Crystal

of compounds 13a and 16 were obtained by slow precipitation from

CHCl₃at room temperature. Data of single crystals of compound

have been collected on a Gemini R Ultra diﬀractometer (Agilent

Technologies U.K. Ltd., Oxford, U.K.). All the data were collected

using graphite monochromated Mo Kα radiation (k = 0.71073 Å)

with the x-scan method. Cell parameters were retrieved using

CrysAlisPro (Agilent Technologies CrysAlisProSoftare system,

version 1.171.35.11 Agilent Technologies U.K. Ltd., Oxford, U.K.

(2012)) software, and the same program has been used for

performing data reduction, with corrections for Lorenz and polarizing

eﬀects. Scaling and absorption corrections were applied by the

CrysAlisPro (Agilent Technologies CrysAlisProSoftare system,

version 1.171.35.11 Agilent Technologies U.K. Ltd., Oxford, U.K.

(2012)) multiscan technique. All the structures were solved by direct

methods using SHELXS-14⁶⁹and reﬁned with full-matrix least-

squares method on F²inserted in SHELXL-14⁷⁰using the program

Olex².⁷¹All non-hydrogen atoms were anisotropically reﬁned.

Hydrogen atoms were located in the ﬁnal Fourier-diﬀerence maps

and reﬁned with coordinates and U^isocalculated and riding on the

corresponding atom. Structural illustrations have been drawn with

Mercury.⁷²

Photochemical reactions were carried out in a cylinder-shaped

photochemical reactor (40 mm as ID and 25 mm height for general

procedures and reactions, 40 mm as ID and 25 mm height for gram-

scale reaction). A Kessil Blue Lamp was used as irradiation source,

which emits a band centered at 450 nm and of about 55 nm width to

half height. The irradiation source is located at 4 cm from the reaction

solution surface.

Computational Method. The structures of reactants, intermedi-

ate adducts, and transition states were optimized using the density

functional method (DFT),⁷³with the functional M06-2X^74,75and the

basis sets 6-311+G(d,p) for H, C, N, and O atoms and 6-311+G(2df)

for S atoms.⁷⁶The nature of the critical points was characterized by

using vibrational analysis^77,78which also furnished the zero point

energies (ZPE) and entropies for the calculations of the free energies.

These have been converted from the gas phase to the 1 M standard

state at 1 atm and 298 and 338 K⁷⁹and used to calculate the rate

constant with the Eyring equation.⁸⁰Solvent eﬀects were introduced

in all calculations using the universal solvation model density method

(SMD).^81,82Calculations were performed by the quantum package

Gaussian 16-A.03.⁸³Figures were obtained using the graphical

program Molden.⁸⁴

× 15 mL) then the organic phase reunited, washed with brine (30

mL), dried over Na₂SO₄, and ﬁltered. The obtained crude was then

puriﬁed by ﬂash chromatography on silica gel (PE/EE 65/35) and

subsequently crystallized from methanol to obtain 1.42 g of 1-phenyl-

4-penten-1-one N-tosylhydrazone 1 as cubic-shaped colorless crystals

(yield 86%). A mixture of isomers was found. Spectral data are

coherent with those previously reported in literature.^85,86¹H NMR

(600 MHz, CDCl₃, Me₄Si) δ mixture of isomers (51:49) 7.96 (s, 1H,

N−H, isomer A), 7.95 (s, 1H, N−H, isomer B), 7.89 (d, J = 8.0 Hz,

2H, Ar−H, isomer A), 7.78 (d, J = 8.0 Hz, 2H, Ar−H, isomer B), 7.44

(m, 4H, Ar−H both isomers), 7.32 (m, 8H, Ar−H, both isomers),

7.06 (m, 2H, Ar−H, both isomers), 5.67 (J = 16.9, 10.2, 6.5 Hz, 1H,

CHCH₂, both isomers), 4.96 (dd, J = 17.4, 1.1 Hz, 1H, CHCH₂,

H trans, both isomers); 4.92 (dd, J = 10.7, 1.1 Hz, 1H, CHCH₂, H

cis, both isomers), 2.66 (t, J = 7.6 Hz, 2H, NC(Ph)−CH₂isomer

A), 2.57 (t, J = 7.6 Hz, 2H, NC(Ph)−CH₂isomer B), 2.42 (s, 3H,

Ar−CH₃isomer A), 2.41 (s, 3H, Ar−CH₃isomer B), 2.21 (m, 4H,

NC(Ph)−CH₂−CH₂both isomers).

General Procedure for the Synthesis of 6-Methyl-3-phenyl-

1-tosyl-1,4,5,6-tetrahydropyridazine (2). In a sealed photo-

chemical reactor, 6.8 mg of [Ru(bpy)₃]Cl₂·6H₂O (0.009 mmol)

were dissolved in 5 mL of anhydrous CHCl₃and the solution was

degassed with N₂for 15 min. Then phenylprop-3-enyl-N-tosylhy-

drazone (1) (98.5 mg, 0.300 mmol) and KOH (20.0 mg, 0.360

mmol) were added in one portion and the solution degassed for

additional 10 min. The mixture was then stirred at 4 cm from the

irradiation source at room temperature until reaction completion. The

solution was then ﬁltered on a short pad of silica gel using CH₂Cl₂as

eluent and Et₂O to wash the column. The crude product was puriﬁed

by ﬂash chromatography on silica gel (PE/EE 65/35) to obtain 24.1

mg of a greenish solid 2 (24%). ¹H NMR (600 MHz, CDCl₃, Me₄Si)

δ 7.88 (d, J = 8.3 Hz, 2H, Ar−H), 7.71 (dd, J = 8.1, 1.7 Hz, 2H, Ar−

H), 7.38−7.31 (m, 3H, Ar−H), 7.27 (d, J = 8.1 Hz, 2H, Ar−H), 4.59

(m, 1H, N−CH−CH₃), 2.61 (dt, J = 18.2, 3.4 Hz, 1H, NC(Ph)

C(H)H), 2.42 (dt, J = 18.3, 10.2 Hz, 1H, NC(Ph)C(H)H), 2.38

(s, 3H, Ar−CH₃), 1.88 (dt, J = 9.3, 2.9 Hz, 2H, CH₂−CH₂-CH), 1.14

(d, J = 6.8 Hz, 3H, N−CH−CH₃). ¹³C{¹H} NMR (151 MHz, CDCl₃,

Me₄Si) δ 147.3 (Cq), 143.6 (Cq), 137.1 (Cq), 135.4 (Cq), 129.5 (2

× CH), 129.2 (CH), 128.4 (2 × CH), 128.2 (2 × CH), 125.3 (2 ×

CH), 47.4 (CH), 24.4 (CH₂), 21.7 (CH₃), 18.3 (CH₂), 17.5 (CH₃).

mp 142−145 °C. ν_max(neat)/cm⁻¹3060, 2926, 2866, 1603, 1444,

1238, 907, 839, 762, 690. HRMS (ESI) m/z [M + H]⁺Calcd for

C₁₈H₂₁N₂O₂S 329.1318, found 329.1310.

General Procedure for the Synthesis of α,β-Unsaturated

Ketones (6). A dried three-necked round-bottom ﬂask connected

with a drip funnel and a reﬂux condenser was dried under nitrogen

atmosphere. Magnesium (290 mg, 12.0 mmol) and a small crystal of

double sublimed Iodine was added to the ﬂask, covered with

anhydrous THF and vigorously stirred. A small aliquot of the solution

of the appropriate aryl bromide 4 (10.0 mmol, 1 M in THF) was

added, and the resulting orange mixture was stirred until a turning to

gray or colorless was observed. At this point, the rest of the aryl

bromide solution was added dropwise through funnel and heated to

reﬂux for 6 h. The solution was then cooled to rt and 3-methylbut-2-

enal 3 (930 mg, 11.0 mmol, 1 M in THF) was added dropwise.

Stirring was maintained until complete consumption of the aldehyde

3 (about 2 h) then the reaction was cooled to 0 °C and quenched

diluting with NH₄Cl saturated solution (30 mL) and Et₂O (30 mL).

The aqueous layer was extracted with Et₂O (2 × 30 mL) and the

collected organic phases were washed with brine (30 mL) and ﬁnally

dried over Na₂SO₄. Filtration of the solids and removal of the volatiles

under reduced pressure aﬀorded an oil corresponding to α,β-

unsaturated alcohol 5 that was then poured in a 250 mL round-

bottom ﬂask and dissolved in 150 mL of CH₂Cl₂. MnO₂(7.00 g, 80.0

mmol) was added to the mixture in small portions every hour until

complete oxidation of the alcohol 5. The resulting mixture was ﬁltered

over a thin pad of Celite that was then washed with CH₂Cl₂and

AcOEt. The solvents were removed under reduced pressure to give an

orange oil, whose puriﬁcation by ﬂash chromatography (PE/AcOEt

General Procedure for the Synthesis of 1-Phenyl-4-penten-

1-one N-Tosylhydrazone (1). Under a nitrogen atmosphere in a

dried Schlenk bottle, acetophenone N-tosylhydrazone (1.44 g, 5.0

mmol) was dissolved in 10 mL of THF. The resulting mixture was

vigorously stirred for 5 min, cooled to −78 °C, then n-BuLi (2.5 M

solution, 4.4 mL, 11.0 mmol) was added dropwise over 30 min.

Turning of the solution from yellow to orange (after addition of 1

equiv) then from orange to red (after addition of 2 equiv of n-BuLi)

was observed. The reaction was stirred at −78 °C for 45 min.

Subsequently allyl bromide was added (0.73 g, 6.0 mmol),

temperature allowed to raise and stirring maintained until complete

consumption of the reactant (monitored by TLC). The reaction was

then quenched with a NH₄Cl saturated solution (20 mL) and diluted

with Et₂O (30 mL). The aqueous phase was extracted with CH₂Cl₂(3

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97.5/2.5, 1% Et₃N) aﬀorded the desired α,β-unsaturated ketone 6 as a

yellowish oil.

2-Methylprop-1-enyl-2-pyridylketone (6g). According to the

described procedure, 1.57 g (10.0 mmol) of 2-bromopyridine were

reacted with magnesium. Diﬀerently from the general procedure,

turning from yellow to black was observed. After complete formation

of the Grignard reagent, 3-methylbut-2-enal 3 was added and the

obtained crude was subsequently reacted with MnO₂to aﬀord 0.61 g

of 2-methylprop-1-enyl-2-pyridylketone(6g) as a brown oil (38%). ¹H

NMR (600 MHz, CDCl₃, Me₄Si) δ 8.66 (ddd, J = 4.8, 1.8, 1.0 Hz,

1H. Ar−H); 8.08 (dt, J = 7.9, 1.1 Hz, 1H, Ar−H); 7.83 (tt, J = 7.7, 1.4

Hz, 1H, Ar−H); 7.45 (sept, J = 1.3 Hz, 1H, CO−CH); 7.42 (ddt, J =

7.4, 4.8, 1.2 Hz, 1H, Ar−H); 2.30 (d, J = 1.3 Hz, 3H, CH

C(CH₃)₂); 2.06 (d, J = 1.3 Hz, 3H, CHC(CH₃)₂). ¹³C{¹H}-

NMR (151 MHz; CDCl₃, Me₄Si) δ 190.22 (Cq); 159.71 (Cq);

155.35 (Cq); 148.63 (CH); 137.13 (CH); 126.46 (CH); 122.65

(CH); 119.74 (CH); 28.57 (CH₃); 21.51 (CH₃). HRMS (ESI) m/z

[M + H]⁺Calcd for C₁₀H₁₂NO 162.0913, found 162.0909. IR ν_max

(neat)/cm⁻¹3082, 2960, 1688, 1639, 1583, 1353, 994.

2-Methylprop-1-enylphenone (6a). Following the described

procedure, 1.59 g (10.0 mmol) of bromobenzene were reacted with

magnesium and 3-methylbut-2-enal, then subsequently with MnO₂to

aﬀord 1.04 g (6.5 mmol) of 2-methylprop-1-enylphenone (6a) as a

yellowish oil (yield 65%). Spectral data are coherent with those

reported in literature.⁸⁷¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.96−

7.90 (m, 2H, ArH); 7.41−7.56 (m, 3H, ArH); 6.75 (sept, J = 1.3 Hz,

1H, CO−CH); 2.21 (d, J = 1.3 Hz, 3H, CHC(CH₃)₂); 2.03 (d, J

= 1.3 Hz, 3H, CHC(CH₃)₂).

2-Methylprop-1-enylnaphtone (6b). Following the described

procedure, 2.05 g (10.0 mmol) of 2-bromonaphtalene were reacted

with magnesium and 3-methylbut-2-enal 3, then subsequently with

MnO₂to aﬀord 1.22 g (5.8 mmol) of 3-methyl-1-(naphthalen-2-

yl)but-2-en-1-one 6b (58%). Spectral data are coherent with those

reported in literature.⁸⁸¹H NMR (600 MHz, CDCl₃, Me₄Si δ 8.43−

8.40 (m, 1H, Ar−H); 8.03 (dd, J = 8.7, 1.8 Hz, 1H, Ar−H); 7.95 (d, J

= 8.3 Hz, 1H, Ar−H); 7.87 (ddt, J = 7.5, 5.4, 0.7 Hz, 2H, Ar−H);

7.57 (t, J = 7.5 Hz, 1H, Ar−H); 7.53 (t, J = 7.5 Hz, 1H, Ar−H); 6.90

(bs, 1H, CO−CH); 2.26 (d, J = 1.3 Hz, 3H, CHC(CH₃)₂); 2.05

(d, J = 1.3 Hz, 3H, CHC(CH₃)₂).

General Procedure for the Synthesis of 2-Phenylprop-1-

enylphenone (6h). Following a modiﬁed procedure to that reported

by Luo,⁹²acetophenone (2.4 g, 20 mmol) and ethyl orthotitanate (2.4

g, 10 mmol) in 100 mL of heptane were heated to reﬂux in a

bottomed ﬂask equipped with a Dean−Stark trap which was ﬁlled

with 5 mL of sulfuric acid (96% solution) to absorb the liberating

alcohol. When the reaction was complete, the mixture was cooled to

room temperature, then 30 mL of acetonitrile were added, and the

resulting mixture stirred for 1 h. The mixture was then transferred to a

separatory funnel and the bottom layer was separated and moved to a

50 mL round bottomed ﬂask where it was further treated with 4 mL

of hydrochloric acid 37% solution. This mixture was stirred for 10 min

then heated to reﬂux and cooled to rt. A precipitate formed which was

separated from the ﬁltrated solution. The accumulated precipitate was

washed with cold acetonitrile and the resulting organic phase was

united with the ﬁltrated solution and the solvent evaporated. The

obtained residue was puriﬁed on silica gel column chromatography to

aﬀord the desired product 6h as a yellow solid (63% yield, PE/AcOEt

2-Methylprop-1-enyl-m-tolylketone (6c). Following the described

procedure, 1.70 g (10.0 mmol) of m-tolyl bromide were reacted with

magnesium and 3-methylbut-2-enal 3, then subsequently with MnO₂

to aﬀord 0.71 g of 2-methylprop-1-enyl-m-tolylketone 6c as yellowish

oil (41%). ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.73 (s, 1H, ArH);

7.70 (m, 1H, ArH) 7.34 (d, J = 1.1 Hz, 1H, ArH); 7.32 (m, 1H, ArH);

6.72 (quint, J = 1.3 Hz, 1H, CO−CH); 2.40 (s, 3H, Ar−CH₃); 2.19

(d, J = 1.3 Hz, 3H, CHC(CH₃)₂); 2.01 (d, J = 1.3 Hz, 3H,

CHC(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) δ

191.9 (Cq); 156.4(Cq); 139.4 (Cq); 138.3 (Cq); 133.1 (CH); 128.9

(CH); 128.4 (CH); 125.5 (CH); 121.5 (CH); 28.0 (CH₃); 21.58

(CH₃); 21.2 (CH₃). HRMS (ESI) m/z [M + H]⁺Calcd for C₁₂H₁₅O

175.1117, found 175.1111. IR ν_max(neat)/cm⁻¹3019, 2942, 1659,

1610, 1495, 899 cm⁻¹.

1

99/1). H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.98 (dm, J = 6.0 Hz,

2H. Ar−H), 7.54−7.58 (m, 3H, Ar−H), 7.47 (tm, J = 7.8 Hz, 2H,

Ar−H), 7.39−7.42 (ddt, J = 7.4, 4.8, 1.2 Hz, 3H, Ar−H), 2.16 (s, 3H,

CHCCH₃).

2-Methylprop-1-enyl-p-tolylketone (6d). Following the described

procedure, 1.70 g (10.0 mmol) of p-tolyl bromide were reacted with

magnesium and 3-methylbut-2-enal 3, then subsequently with MnO₂

to aﬀord 1.01 g of 2-methylprop-1-enyl-m-tolylketone 6d as yellowish

oil (59%).^89,90¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.26 (d, J = 7.8,

2H, ArH); 7.15 (d, J = 7.8, 2H, ArH); 5.41 (m, CO−CH); 2.32 (s,

3H, Ar−CH₃); 1.78 (s, 3H, CHC(CH₃)₂); 1.73 (s, 3H, CH

C(CH₃)₂).

General Procedure for the Synthesis of γ,δ-Unsaturated

Ketones (8). According to the procedure reported by Von

Fraunberg⁹³with slight modiﬁcations, under a nitrogen atmosphere

in a dried Schlenk bottle, copper iodide (190 mg, 0.5 mmol) was

added at −40 °C to vinylmagnesium bromide 7a (11.0 mL,

commercial 1.0 M solution in THF) or propenylmagnesium bromide

7b (22.0 mL, commercial 0.5 M solution in THF). The resulting

mixture was vigorously stirred for 15 min, then a cooled 0.5 M

solution of the appropriate α,β-unsaturated ketone 6 (10.0 mmol) in

THF was added dropwise over 30 min keeping temperature of the

bath below −40 °C. Once the addition was completed, temperature

was allowed to raise up to rt and stirring was maintained until

complete consumption of the reactant. The reaction was then

quenched with a NH₄Cl/NH₄OH 9/1 solution (30 mL) and diluted

with Et₂O (30 mL). The organic phase was washed with NH₄Cl (10

mL aliquots) until the aqueous phase stopped turning blue. It was

then washed with brine (30 mL), dried over Na₂SO₄, and ﬁltered. The

volatiles were removed under reduced pressure to give a colorless oil,

that was used without any further puriﬁcation.

2-Methylprop-1-enyl-o-tolylketone (6e). Following the described

procedure, 1.70 g (10.0 mmol) of o-tolyl bromide were reacted with

magnesium and 3-methylbut-2-enal 3, then subsequently with MnO₂

to aﬀord 0.96 g of 2-methylprop-1-enyl-o-tolylketone 6e as yellowish

oil (55%).⁹¹¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.49 (dm, J = 9

Hz, 1H, ArH); 7.31 (td, J = 7.2, 1.2 Hz, 1H, ArH) 7.22 (t, J = 7.0 Hz,

2H, ArH); 7.32 (m, 1H, ArH); 6.42 (m, 1H, CO−CH); 2.45 (s, 3H,

Ar−CH₃); 2.16 (s, 3H, CHC(CH₃)₂); 1.96 (s, 3H, CH

C(CH₃)₂).

2-Methylprop-1-enyl-m-methoxyphenone (6f). Following the

described procedure, 1.86 g (10.0 mmol) of m-bromoanisole were

reacted with magnesium and 3-methylbut-2-enal 3, then subsequently

with of MnO₂to aﬀord 1.05 g of 2-methylprop-1-enyl-m-

1

methoxyphenylketone 6f as a yellowish oil (55%). H NMR (600

2,2-Dimethylbut-3-enylphenone (8a). Following the described

procedure, 1.60 g (10.0 mmol) of 2-methylprop-1-enylphenone (6a)

were reacted with CuI and vinylmagnesium bromide 7a to aﬀord 1.64

g (8.7 mmol) of 2,2-dimethylbut-3-enylphenone 8a (87%) as a

MHz, CDCl₃, Me₄Si) δ 7.49 (ddd, J = 7.7, 1.5, 0.9 Hz, 1H, Ar−H);

7.46 (dd, J = 2.7, 1.5 Hz, 1H, Ar−H); 7.34 (t, J = 7.9 Hz, 1H, Ar−H);

7.06 (ddd, J = 8.2, 2.7, 1.0 Hz, 1H, Ar−H); 6.72 (sept, J = 1.3 Hz, 1H,

CO−CH); 3.85 (s, 3H, O−CH₃); 2.20 (d, J = 1.3 Hz, 3H, CH

C(CH₃)₂); 2.01 (d, J = 1.4 Hz, 3H, CHC(CH₃)₂). ¹³C{¹H}-

NMR (151 MHz; CDCl₃, Me₄Si) δ 191.3 (Cq); 159.9 (Cq); 156.9

(Cq); 140.8 (Cq); 129.5 (CH); 121.3 (CH); 120.9 (CH); 118.9

(CH); 112.6 (CH); 55.5 (CH₃); 28.1 (CH₃); 21.3 (CH₃). HRMS

(ESI) m/z [M + H]⁺Calcd for C₁₂H₁₅O₂191.1067, found 191.1062.

IR ν_max(neat)/cm⁻¹3022, 2899, 1658, 1612, 1495, 1249, 1043, 899

cm⁻¹.

1

colorless oil. H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.93−7.89 (m,

2H, Ar−H); 7.53 (ddt, J = 7.9, 6.9, 1.3 Hz, 1H, Ar−H); 7.46−7.40

(m, 2H, Ar−H); 5.95 (dd, J = 17.4, 10.7 Hz, 1H, CHCH₂); 4.95

(dd, J = 17.5, 1.1 Hz, 1H, CHCH₂); 4.90 (dd, J = 10.7, 1.1 Hz, 1H,

CHCH₂); 2.96 (s, 2H, CO−CH₂); 1.17 (s, 6H, CH₂−(CH₃)₂−

CH). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) 199.6 (Cq); 147.5

(CH); 138.4 (Cq); 132.9 (CH); 128.6 (2 × CH); 128.3 (2 × CH);

110.7 (CH₂); 49.2 (CH₂); 36.8 (Cq); 27.4 (2 × CH₃). HRMS (ESI)

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Article

m/z [M + H]⁺Calcd for C₁₃H₁₇O 189.1274, found 189.1268. IR ν_max

(neat)/cm⁻¹3082, 2960, 1676, 1618, 1240.

4.95 (dd, J = 17.4, 1.2 Hz, 1H, CHCH_2a); 4.89 (d, J = 10.8, 1.2 Hz,

1H, CHCH_2b); 4.08 (s, 3H, Ar-OCH₃); 2.94 (s, 2H, CO−CH₂);

1.16 (s, 6H, CH₂−(CH₃)₂−CH). ¹³C{¹H}NMR (151 MHz; CDCl₃,

Me₄Si) δ199.3 (Cq); 159.8 (Cq); 147.5 (CH); 139.8 (Cq); 129.5

(CH); 121.0 (CH); 119.4 (CH); 112.5 (CH); 110.7 (CH₂); 55.5

(CH₃); 49.4 (CH₂); 36.8 (Cq); 27.4 (CH₃). HRMS (ESI) m/z [M +

H]⁺Calcd for C₁₄H₁₉O₂219.1380, found 219.1379. IR ν_max(neat)/

cm⁻¹3073, 2937, 1614, 1593, 1260.

2,2-Dimethylbut-3-enyl-pyridyl ketone (8g). Following the

described procedure, 1.61 g (10.0 mmol) of 2-methylprop-1-enyl-2-

pyridylketone (6g) were reacted with CuI and vinylmagnesium

bromide 7a to aﬀord 1.66 g of 2,2-dimethylbut-3-enyl-pyridyl ketone

(8g) (88%) as a colorless oil. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ

8.64 (ddq, J = 4.4, 1.7, 0.9 Hz, 1H, Ar−H); 7.97 (dq, J = 7.9, 1.2 Hz,

1H, Ar−H); 7.81−7.75 (m, 1H, Ar−H); 7.41 (ddt, J = 7.5, 4.8, 1.4

Hz, 1H, Ar−H); 5.97 (ddd, J = 17.4, 10.7, 1.2 Hz, 1H, CHCH₂);

4.92 (dt, J = 17.4, 1.3 Hz, 1H, CHCH₂); 4.85 (dt, J = 10.7, 1.3 Hz,

1H, CHCH₂); 3.26 (s, 2H, CO−CH₂); 1.15 (d, J = 1.4 Hz, 6H,

CH₂−(CH₃)₂−CH). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) δ

201.1 (Cq); 154.4 (Cq); 148.7 (CH); 147.6 (CH); 136.9 (CH);

126.9 (CH); 121.8 (CH); 110.4 (CH₂); 47.6 (CH₂); 36.80 (Cq);

27.34 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺Calcd for C₁₂H₁₆NO

190.1226, found 190.1222. IR ν_max(neat)/cm⁻¹3038, 2961, 1689,

1583, 1328, 1013.

2,2-Dimethylbut-3-enylnaphtone (8b). Following the described

procedure, 2.10 g (10.0 mmol) of 2-methylprop-1-enylnaphtone (6b)

were reacted with CuI and vinylmagnesium bromide 7a to aﬀord 1.48

g 2,2-dimethylbut-3-enylnaphtone 8b (62%) as a colorless oil which

crystallize as a white-yellowish solid after cooling. ¹H NMR (600

MHz, CDCl₃, Me₄Si) δ 8.43−8.40 (m, 1H, Ar−H); 8.00 (dd, J = 8.7,

1.8 Hz, 1H, Ar−H); 7.95 (ddq, J = 8.2, 1.4, 0.7 Hz, 1H, Ar−H);

7.89−7.84 (m, 2H, Ar−H); 7.58 (ddd, J = 8.2, 6.9, 1.3 Hz, 1H, Ar−

H); 7.54 (ddd, J = 8.1, 6.9, 1.3 Hz, 1H, Ar−H); 6.00 (dd, J = 17.4,

10.7 Hz, 1H, CHCH₂); 4.98 (dd, J = 17.4, 1.1 Hz, 1H, CH

CH₂); 4.92 (dd, J = 10.7, 1.1 Hz, 1H, CHCH₂); 3.09 (s, 2H, CO−

CH₂); 1.22−1.20 (s, 6H, CH₂−(CH₃)₂−CH). ¹³C{H}NMR (151

MHz; CDCl₃, Me₄Si) δ 199.6 (Cq); 147.6 (CH); 135.8 (Cq); 135.5

(Cq); 132.6 (Cq); 130.1 (CH); 129.7 (CH); 128.5 (CH); 128.4

(CH); 127.8 (CH); 126.8 (CH); 124.2 (CH); 110.7 (CH₂); 49.3

(CH₂); 37.0 (Cq); 27.4 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺

Calcd for C₁₇H₁₉O 239.1430, found 239.1426. IR ν_max(neat)/cm⁻¹

3226, 1639, 1381, 1305, 1164. mp 53−56 °C.

2,2-Dimethylbut-3-enyl-m-tolyl ketone (8c). Following the

described procedure, 1.74 g (10.0 mmol) of 2-methylprop-1-enyl-m-

tolylketone (6c) were reacted with CuI and vinylmagnesium bromide

7a to aﬀord 1.69 g (8.4 mmol) of 2,2-dimethylbut-3-enyl-m-tolyl

1

ketone 8c (84%) as a colorless oil. H NMR (600 MHz, CDCl₃,

2-Phenyl-2-methylbut-3-enylphenone (8h). Following the de-

scribed procedure, 2.08 g (10.0 mmol) of 2-phenylprop-1-

enylphenone 6h were reacted with CuI and vinylmagnesium bromide

7a to aﬀord 2.07 g of 2-phenyl-2-methylbut-3-enylphenone (8h).

Me₄Si) δ 7.7 (dq, J = 1.8, 0.9 Hz, 1H, Ar−H); 7.69 (dt, J = 7.4, 1.7

Hz, 1H, Ar−H); 7.34 (ddq, J = 7.7, 1.8, 0.8 Hz, 1H, Ar−H); 7.33−

7.29 (m, 1H, Ar−H); 5.95 (dd, J = 17.4, 10.7 Hz, 1H, CHCH₂);

4.95 (dd, J = 17.4, 1.1 Hz, 1H, CHCH₂); 4.90 (dd, J = 10.7, 1.1 Hz,

1H, CHCH₂); 2.94 (s, 2H, CO−CH₂); 2.39 (d, J = 0.8 Hz, 3H,

Ar−CH₃); 1.16 (s, 6H, CH₂−(CH₃)₂−CH). ¹³C{¹H}NMR (151

MHz; CDCl₃, Me₄Si) δ 199.8 (Cq); 147.6 (CH); 138.5 (Cq); 138.3

(Cq); 133.6 (CH); 128.8 (CH); 128.4 (CH); 125.6 (CH); 110.6

(CH₂); 49.3 (CH₂); 36.8 (Cq); 27.4 (CH₃); 21.5 (2 × CH₃). HRMS

(ESI) m/z [M + H]⁺Calcd for C₁₄H₁₉O 203.1430, found 203.1427.

IR ν_max(neat)/cm⁻¹3082, 2961, 2871, 1673, 1603, 1249.

2,2-Dimethylbut-3-enyl-p-tolyl ketone (8d). Following the

described procedure, 1.74 g (10.0 mmol) of 2-methylprop-1-enyl-p-

tolylketone (6d) were reacted with CuI and vinylmagnesium bromide

7a to aﬀord 1.71 g (8.4 mmol) of 2,2-dimethylbut-3-enyl-p-tolyl

ketone 8d (85%) as a colorless oil.⁹⁴¹H NMR (600 MHz, CDCl₃,

Me₄Si) δ 7.82 (d, J = 7.8 Hz, 2H, Ar−H); 7.22 (d, J = 7.8 Hz, 2H,

Ar−H); 5.97 (dd, J = 17.4, 10.8 Hz, 1H, CHCH₂); 4.94 (d, J = 17.4

Hz, 1H, CHCH_2a); 4.89 (d, J = 10.8 Hz, 1H, CHCH_2b); 2.94 (s,

2H, CO−CH₂); 2.39 (s, 3H, Ar−CH₃); 1.16 (s, 6H, CH₂−(CH₃)₂−

CH).

1

(83%) as colorless oil. H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.85

(dm, J = 8.4 Hz, 2H, Ar−H); 7.51 (tm, 1H, J = 9.0 Hz, Ar−H); 7.39

(tm, 2H, J = 7.8 Hz, Ar−H); 7.33 (dm, J = 8.4 Hz, 2H, Ar−H); 7.23

(tm, 2H, J = 9.0 Hz, Ar−H); 7.16 (tm, 1H, J = 7.8 Hz, Ar−H); 6.26

(dd, J = 17.4, 10.2 Hz, 1H, CHCH₂); 5.13 (dd, J = 10.2, 1.8 Hz,

1H, CHCH_2a); 5.06 (dd, J = 17.4, 1.8 Hz, 1H, CHCH_2b); 3.48

(s, 2H, CO−CH₂); 1.58 (s, 3H, CH₃). ¹³C{¹H}NMR (151 MHz;

CDCl₃, Me₄Si) δ 198.4 (Cq); 146.0 (CH); 132.8 (CH); 129.2 (Cq);

128.7 (2 × CH) ; 128.5 (2 × CH); 128.4 (Cq); 128.3 (2 × CH);

128.1 (2 × CH); 126.3 (2 × CH); 112.4 (CH₂); 48.4 (CH₂); 43.8

(Cq); 26.0 (CH₃). HRMS (ESI) m/z [M + H]⁺. Calcd for C₁₈H₁₉O

251.1430, found 251.1430. IR ν_max(neat)/cm⁻¹2829, 2667, 2554,

1678, 1452, 1288, 1154, 925.

4,4-Dimethylhex-5-en-2-one (8i). Following the described proce-

dure, 0.98 g (10.0 mmol) of mesityl oxide 6i (4-methylpent-3-en-2-

one) were reacted with CuI and vinylmagnesium bromide 7a to aﬀord

1.12 g of 4,4-dimethylhex-5-en-2-one 8i (89%) as a colorless oil.⁹⁵¹H

NMR (600 MHz, CDCl₃, Me₄Si) δ5.90 (dd, J = 18.0, 10.81H, CH

CH₂); 4.94 (dd, J = 18.0, 1.1 Hz, 1H, CHCH₂(H trans)); 4.93

(dd, J = 10.8, 1.1 Hz, 1H, CHCH₂(H cis)); 2.41 (s, 2H, CO−

CH₂); 2.09 (s, 3H, CH₃-CO); 1.10 (s, 6H, CH₂−(CH₃)₂−CH).

2,2-Dimethylpent-3-enylphenone (8j). Following the described

procedure, 1.60 g (10.0 mmol) of 2-methylprop-1-enylphenone 6a (4-

methylpent-3-en-2-one) were reacted with CuI and propenylmagne-

sium bromide 7b to aﬀord 1.75 g of 2,2-dimethylpent-3-enylphenone

2,2-Dimethylbut-3-enyl-o-tolyl ketone (8e). Following the

described procedure, 1.74 g (10.0 mmol) of 2-methylprop-1-enyl-o-

tolylketone (6e) were reacted with CuI and vinylmagnesium bromide

7a to aﬀord 1.09 g (8.4 mmol) of 2,2-dimethylbut-3-enyl-o-tolyl

1

ketone 8e (54%) as a colorless oil. H NMR (600 MHz, CDCl₃,

Me₄Si) δ 7.52 (d, J = 7.2 Hz, 1H, Ar−H); 7.52 (td, J = 7.2, 1.2 Hz,

1H, Ar−H); 7.22 (t, J = 7.8 Hz, 2H, Ar−H); 5.91 (dd, J = 17.4, 11.4

Hz, 1H, CHCH₂); 4.93 (dd, J = 17.4, 0.6 Hz, 1H, CHCH_2a);

4.89 (d, J = 11.4, 0.6 Hz, 1H, CHCH_2b); 2.89 (s, 2H, CO−CH₂);

2.43 (s, 3H, Ar−CH₃); 1.14 (s, 6H, CH₂−(CH₃)₂−CH). ¹³C{¹H}-

NMR (151 MHz; CDCl₃, Me₄Si) δ204.4 (Cq); 147.4 (CH); 140.0

(Cq); 137.4 (Cq); 131.9 (CH); 130.8 (CH); 128.3 (CH); 125.6

(CH); 110.6 (CH₂); 52.9 (CH₂); 37.2 (Cq); 27.4 (CH₃); 21.0 (2 ×

CH₃). HRMS (ESI) m/z [M + H]⁺. Calcd for C₁₄H₁₉O 203.1430,

found 203.1428. IR ν_max(neat)/cm⁻¹3082, 2962, 1678, 1640, 1456,

1346, 1235.

1

(8j) (87%) as a colorless oil. H NMR (600 MHz, CDCl₃, Me₄Si),

mixture of isomers (75:25) δ 7.91(dm, J = 7.2 Hz, 2H, Ar−H, Z

isomer); 7.88(dm, J = 7.2 Hz, 2H, Ar−H, E isomer); 7.50 (m, 3H,

Ar−H, both isomers); 7.41 (m, 3H, Ar−H, both isomers); 5.52 (dq, J

= 15.6, 1.8 Hz, 1H, CHCHCH₃, E isomer); 5.42 (dq, J = 12.0, 1.8

Hz, 1H, CHCHCH₃, Z isomer); 5.33 (dq, J = 15.6, 6.0 Hz, 1H,

CHCHCH₃, E isomer); 5.31 (dq, J = 12.0, 7.2 Hz, 1H, CH

CHCH₃, Z isomer); 3.08 (s, 2H, CO−CH₂, Z isomer); 2.91 (s, 2H,

CO−CH₂, E isomer); 1.68 (dd, J = 7.2, 1.8 Hz, 1H, CHCHCH₃, Z

isomer); 1.57 (dd, J = 6.0, 1.8 Hz, 1H, CHCHCH₃, E isomer); 1.27

(s, 6H, CH₂−(CH₃)₂−CH, Z isomer), 1.13 (s, 6H, CH₂−(CH₃)₂−

CH, E isomer). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si), mixture of

isomers (75:25) 199.9 (Cq, E isomer); 199.5 (Cq, Z isomer); 140.4

(CH, E isomer); 138.9 (CH, Z isomer); 138.6 (Cq, E isomer); 138.4

(Cq, Z isomer); 132.8 (2 × CH, Z isomer); 132.7 (2 × CH, E

isomer); 128.5 (2 × CH, Z isomer); 128.5 (2 × CH, E isomer); 128.4

(CH, E isomer); 128.2 (CH, Z isomer); 123.0 (CH, Z isomer); 121.0

2,2-Dimethylbut-3-enyl-m-methoxyphenone (8f). Following the

described procedure, 1.90 g (10.0 mmol) of 2-methylprop-1-enyl-m-

methoxyphenone (6f) were reacted with CuI and vinylmagnesium

bromide 7a to aﬀord 1.57 g of 2,2-dimethylbut-3-enyl-m-methox-

1

yphenone 8f (72%) as a colorless oil. H NMR (600 MHz, CDCl₃,

Me₄Si) δ 7.52 (dm, J = 7.8 Hz, 1H, Ar−H); 7.44 (dd, J = 3.0, 1.2 Hz,

1H, Ar−H); 7.34 (t, J = 7.8 Hz, 2H, Ar−H); 7.07 (ddd, J = 7.8, 3.0,

1.2 Hz, 2H, Ar−H); 5.91 (dd, J = 17.4, 10.8 Hz, 1H, CHCH₂);

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J. Org. Chem. 2021, 86, 3300−3323

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Article

(CH, E isomer); 50.2 (CH₂, Z isomer); 50.0 (CH₂, E isomer); 36.1

(Cq, Z isomer); 36.1 (Cq, E isomer); 29.3 (CH₃,Z isomer), 27.9

(CH₃, E isomer), 18.0 (2 × CH₃, E isomer), 14.4 (2 × CH₃, Z

isomer).

Hz, 1H, CHCH₂H trans), 4.88 (dd, J = 10.6, 0.9 Hz, 1H, CH

CH₂H cis), 2.67 (s, 2H, NC(Ar)−CH₂), 2.44 (s, 3H, Ar−CH₃),

0.91 (s, 6H, C(CH₃)₂); (minor isomer) δ 7.78 (d, J = 8.3 Hz, 2H, Ar−

H), 7.54 (s, 1H, N-H), 7.42−7.36 (m, 5H, Ar−H), 7.04−7.00 (m,

2H, Ar−H), 5.54 (dd, J = 17.5, 10.7 Hz, 1H, CHCH₂), 4.67 (dd, J

= 17.4, 1.3 Hz, 1H, CHCH₂H trans), 4.60 (dd, J = 10.7, 1.2 Hz,

1H, CHCH₂H cis), 2.53 (s, 2H, s, 2H, NC(Ar)−CH₂), 2.43 (s,

3H, Ar−CH₃), 0.85 (s, 6H, C(CH₃)₂). ¹³C{¹H}NMR (151 MHz;

CDCl₃, Me₄Si) (major isomer) δ 155.2 (Cq), 146.8 (CH), 144.2

(Cq), 138.6 (Cq), 135.5 (Cq), 129.6 (CH), 129.6 (2 × CH), 128.4

(2 × CH), 128.2 (2 × CH), 127.0 (2 × CH), 113.4 (CH₂), 39.6

(CH₂), 38.0 (Cq), 27.9 (CH₃), 21.8 (2 × CH₃); (minor isomer) 156.8

(Cq), 147.2 (CH), 144.0 (Cq), 139.2 (Cq), 136.7 (Cq), 129.8 (CH),

129.5 (2 × CH), 128.3 (2 × CH), 128.0 (2 × CH), 127.2 (2 × CH),

110.5 (CH₂), 50.4(CH₂), 37.4 (Cq) 27.2 (CH₃), 21.7(2 × CH₃).

HRMS (ESI) m/z [M + H]⁺Calcd for C₂₀H₂₅N₂O₂S 357.1631, found

357.1626.

2,2-Dimethylbut-3-enylnaphtone-N-tosylhydrazone (10b). Fol-

lowing the described procedure 2,2-dimethylbut-3-enylnaphtone 8b

(1.02 g, 4.3 mmol) was reacted with N-tosylhydrazide 9a (0.87g, 4.7

mmol) in methanol (6.0 mL) reﬂuxed at 50 °C overnight. The

reaction was then cooled to rt to obtain 1.01 g (2.5 mmol) of 2,2-

dimethylbut-3-enylnaphtone-N-tosylhydrazone (10b) (only one

isomer found) as a white powder (58%, PE/EE 7/3). ¹H NMR

(600 MHz, CDCl₃, Me₄Si) δ 7.99 (s, 1H, N−H), 7.93 (dt, J = 8.3, 1.7

Hz, 2H, Ar−H), 7.90 (d, J = 1.3 Hz, 1H, Ar−H), 7.83−7.80 (m, 2H,

Ar−H), 7.78 (d, J = 8.7 Hz, 1H, Ar−H), 7.74 (dd, J = 8.6, 1.8 Hz, 1H,

Ar−H), 7.51−7.46 (m, 2H), 7.36 (d, J = 8.0 Hz, 1H, Ar−H), 5.64

(dd, J = 17.5, 10.6 Hz, 1H, CHCH₂), 5.00 (dd, J = 17.5, 0.7 Hz,

1H, CHCH₂H trans), 4.90 (dd, J = 10.7, 0.8 Hz, 1H, CHCH₂H

cis), 2.79 (s, 2H, NC(Ar)−CH₂), 2.45 (s, 3H, Ar−CH₃), 0.95 (s,

6H, C(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) δ 154.7

(Cq), 146.9 (CH), 144.3 (Cq), 136.0 (Cq), 135.5 (Cq), 133.9 (Cq),

132.9 (Cq), 129.6 (2 × CH), 128.7 (CH), 128.3 (2 × CH), 128.2

(CH), 127.7 (CH), 126.9 (CH), 126.9 (CH), 126.7 (CH), 124.4

(CH), 113.4 (CH₂), 39.4 (CH₂), 38.1 (Cq), 28.0 (CH₃), 21.8 (2 ×

CH₃). HRMS (ESI) m/z [M + H]⁺Calcd for C₂₄H₂₇N₂O₂S

407.1788, found 407.1777. IR ν_max(neat)/cm⁻¹3057, 2958, 1599,

1445, 1179.

4,4-Dimethylhept-5-en-2-one (8k). Following the described

procedure, 0.98 g (10.0 mmol) of mesityl oxide 6i (4-methylpent-3-

en-2-one) were reacted with CuI and propenylmagnesium bromide

7b to aﬀord 0.97 g of 4,4-dimethylhept-5-en-2-one 8k (69%) as a

colorless oil. ¹H NMR (600 MHz, CDCl₃, Me₄Si), mixture of isomers

(60:40) δ 5.52 (dq, J = 15.6, 1.8 Hz, 1H, CHCHCH₃, E isomer);

5.34−5.38 (m, 3H, CHCHCH₃, Z isomer, CHCHCH₃, E and Z

isomer); 2.53 (s, 2H, CO−CH₂, Z isomer); 2.37 (s, 2H, CO−CH₂, E

isomer); 2.11 (s, 2H, CO−CH₃, Z isomer); 2.07 (s, 2H, CO−CH₃, E

isomer); 1.71 (dd, J = 6.0, 3.0 Hz, 1H, CHCHCH₃, Z isomer); 1.65

(dd, J = 6.6, 1.2 Hz, 1H, CHCHCH₃, E isomer); 1.20 (s, 6H,

CH₂−(CH₃)₂−CH, Z isomer), 1.07 (s, 6H, CH₂−(CH₃)₂−CH, E

isomer). ¹³C{¹H} NMR (151 MHz; CDCl₃, Me₄Si), mixture of

isomers (75:25)208.8 (Cq, E isomer); 208.5 (Cq, Z isomer); 140.0

(CH, E isomer); 138.5 (CH, Z isomer); 123.6 (CH, Z isomer); 121.4

(CH, E isomer); 56.0 (CH₂, Z isomer); 55.8 (CH₂, E isomer); 35.8

(Cq, Z isomer); 35.4 (Cq, E isomer); 32.4 (CH₃, Z isomer), 32.0

(CH₃, E isomer), 29.2 (CH₃, Z isomer), 27.7 (CH₃, E isomer), 18.1

(2 × CH₃, E isomer), 14.4 (2 × CH₃, Z isomer).

(2S,5R)- and (2R,5R)-5-Methyl-2-(2,2-dimethylprop-2-enyl)-

cyclohexanone (8l). Following the described procedure, 1.52 g

(10.0 mmol) of commercially available R-pulegone (4-methylpent-3-

en-2-one) were reacted with CuI and vinylmagnesium bromide 7a to

aﬀord 1.49 g of (2S,5R) and(2R,5R)-5-methyl-2-(2,2-dimethylprop-2-

enyl)cyclohexanone 8l (83%) as a colorless oil. ¹H NMR (600 MHz,

CDCl₃, Me₄Si) (isomer A) δ 5.95 (ddd, J = 16.3, 10.8, 1.1 Hz, 1H,

CHCH₂), 4.98−4.88 (m, 2H, CHCH₂), 2.45 (dd, J = 13.0, 5.5

Hz, 1H, CH-C(H)H-CO), 2.25 (m, 2H, CO−CH, CO−CH−C(H)

H), 2.00 (m, J = 2H, CH-C(H)H-CO with CO−CH−C(H)H),

1.88−1.83 (m, 2H, CH−CH₂−CH₂−CH), 1.56 (m, 1H, CH₃−CH),

0.98 (d, J = 6.2 Hz, 6H, CH-C-(CH₃)₂), 0.92 (d, J = 7.0 Hz, 3H,

CH−CH₃). (isomer B) δ 5.94 (ddd, J = 16.3, 10.8, 1.1 Hz, 1H, CH-

CH₂), 4.98−4.88 (m, 2H, CHCH₂), 2.18 (m, 1H, CH-C(H)H-

CO), 2.10−2.02 (m, 2H, CH-C(H)H-CO), 1.86 (m, 2H, CH−CH₂−

CH₂−CH), 1.80−1.70 (m, 1H, CH₃−CH), 1.40 (qdd, J = 12.9, 3.0,

1.1 Hz, 1H, CH-C(H)H-CH₂), 1.30 (qd, J = 13.2, 12.8, 2.7 Hz, 1H,

CH-C(H)H-CH₂), 1.16−1.04 (m, 9H, CH−CH₃with CH-C-

(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) (mixture of

isomers) δ 212.6 (Cq), 211.6 (Cq), 147.4 (CH), 147.2 (CH), 111.3

(CH₂), 111.0 (CH₂), 58.9 (CH), 58.8 (CH), 52.5 (CH₂), 50.4

(CH₂), 38.4 (CH), 37.9 (Cq), 36.4 (Cq), 34.7 (CH2), 32.7 (CH),

31.3 (CH₂), 29.0 (CH₂), 25.9 (CH), 25.4 (CH), 25.0 (CH2), 24.3

(CH₃), 23.7 (CH₃), 22.4 (CH₃), 19.8 (CH₃).

2,2-Dimethylbut-3-enyl-m-tolyl ketone-N-tosylhydrazone (10c).

Following the described procedure 2,2-dimethylbut-3-enyl-m-tolyl

ketone 8c (0.46 g, 2.3 mmol) was reacted with N-tosylhydrazide 9a

(0.47 g, 2.5 mmol) in methanol (2 mL) to obtain 0.366 g (1.0 mmol)

of 2,2-dimethylbut-3-enyl-m-tolyl ketone-N-tosylhydrazone 10c (only

1

one isomer found) as a white powder (43%, PE/EE 7/3). H NMR

(600 MHz, CDCl₃, Me₄Si) δ 7.90 (dt, J = 8.4, 1.8 Hz, 2H, Ar−H),

7.85 (s, 1H, N−H), 7.34 (d, J = 8.4 Hz, 1H, Ar−H), 7.28 (m, 2H,

Ar−H), 7.19 (t, J = 7.8 Hz, 1H, Ar−H), 7.15 (bd, J = 7.8 Hz, 1H, Ar−

H), 5.58 (dd, J = 17.4, 10.8 Hz, 1H, CHCH₂), 4.99 (dd, J = 17.4,

0.6 Hz, 1H, CHCH₂H trans), 4.90 (dd, J = 10.8, 0.6 Hz, 1H, CH

CH₂H cis), 2.65 (s, 2H, NC(Ar)−CH₂), 2.44 (s, 3H, Ar−CH₃),

2.34 (s, 3H, Ar−CH₃), 0.89 (s, 6H, C(CH₃)₂). ¹³C{¹H}NMR (151

MHz; CDCl₃, Me₄Si) δ 155.3 (Cq), 146.9 (CH), 144.2 (Cq), 138.6

(Cq), 137.9 (Cq), 135.5 (Cq), 130.3 (CH), 129.5 (CH), 128.3 (2 ×

CH), 128.2 (CH), 127.7 (CH), 124.2 (CH), 113.4 (CH₂), 39.7

(CH₂), 37.9 (Cq), 27.9 (CH₃), 21.7 (CH₃), 21.6 (2 × CH₃). mp

120−123 °C. IR ν_max(neat)/cm⁻¹3284, 3186, 2961, 1641, 1597,

1341, 1164, 792. HRMS (ESI) m/z [M + H]⁺Calcd for

C₂₁H₂₇N₂O₂S 371.1793, found 371.1779.

2,2-Dimethylbut-3-enyl-p-tolyl ketone-N-tosylhydrazone (10d).

Following the described procedure 2,2-dimethylbut-3-enyl-p-tolyl

ketone 8d (1.01 g, 5.0 mmol) was reacted with N-tosylhydrazide 9a

(1.04 g, 5.6 mmol) in methanol (2 mL) to obtain 1.48 g (4.0 mmol)

of 2,2-dimethylbut-3-enyl-p-tolyl ketone-N-tosylhydrazone 10d as a

white powder (80%, PE/EE 7/3). ¹H NMR (600 MHz, CDCl₃,

Me₄Si) (mixture of isomers, 59:41) δ7.87 (d, J = 7.8 Hz, 2H, Ar−H,

major isomer), 7.78 (d, J = 8.4 Hz, 2H, Ar−H, minor isomer), 7.52

(bs, 1H, N−H), 7.40 (d, J = 8.4 Hz, 2H, Ar−H, major isomer), 7.33

(d, J = 8.4 Hz, 2H, Ar−H, minor isomer), 7.31 (d, J = 7.8 Hz, 2H,

Ar−H, minor isomer), 7.22 (d, J = 7.8 Hz, 2H, Ar−H, minor isomer),

General Procedures for the Synthesis of γ,δ-Unsaturated N-

Arylsulfonylhydrazones (10, 11, 12). To a vigorously stirred

suspension of arylsulfonylhydrazide 9 (5.6 mmol, 1.12 equiv) in

MeOH (3.0 mL); the appropriate ketone or aldehyde 8 (5.0 mmol,

1.0 equiv) was added dropwise. The mixture was reacted to

completion (about 18 h); then cooled to 0 °C. When the product

precipitated it was removed by ﬁltration and used without any further

puriﬁcation, otherwise the solvent was removed under reduced

pressure and the crude puriﬁed by ﬂash chromatography on

deactivated silica gel (PE/AcOEt 90/10) to aﬀord in both cases the

N-arylsulfonylhydrazone (10 when tosylhydrazone, 11 when phenyl-

sulfonylhydrazone, 12 when mesitylsulfonylhydrazone) as a mixture

of isomers (precipitation usually aﬀorded one single stereoisomer or a

mixture clearly enriched in only one of the possible stereoisomer).

2,2-Dimethylbut-3-enylphenone-N-tosylhydrazone (10a). Fol-

lowing the described procedure 2,2-dimethylbut-3-enylphenone 8a,

(0.95 g, 5.0 mmol) was reacted with N-tosylhydrazide 9a (1.00. g, 5.4

mmol) in methanol (3.0 mL) to obtain 1.03 g (2.9 mmol) of 2,2-

dimethylbut-3-enylphenone-N-tosylhydrazone (10a) (mixture of

1

isomers) as a white powder (58%). H NMR (600 MHz, CDCl₃,

Me₄Si) (major isomer) δ 7.89 (d, J = 8.3 Hz, 2H, Ar−H), 7.87 (s, 1H,

N−H), 7.49 (dm, J = 6.3, 1H, Ar−H), 7.35−7.29 (m, 5H, Ar−H),

5.58 (dd, J = 17.5, 10.6 Hz, 1H, CHCH₂), 4.97 (dd, J = 17.5, 0.9

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7.19 (d, J = 7.8 Hz, 2H, Ar−H, major isomer), 7.11 (d, J = 7.8 Hz,

2H, Ar−H, major isomer), 6.91 (d, J = 8.4 Hz, 2H, Ar−H, major

isomer), 5.58 (dd, J = 14.4, 10.8 Hz, 1H, CHCH₂, major isomer),

5.56 (dd, J = 15.0, 10.8 Hz, 1H, CHCH₂, minor isomer), 4.97 (d, J

= 16.8 Hz, 1H, CHCH₂, H trans, major isomer), 4.88 (dd, J = 10.8,

1.2 Hz, 1H, CHCH₂, H cis, major isomer), 4.68 (dd, J = 17.4, 1.2

Hz, 1H, CHCH₂, H trans, minor isomer), 4.61 (dd, J = 10.8, 1.2

Hz, 1H, CHCH₂, H cis, minor isomer), 2.92 (s, 2H, NCCH₂,

minor isomer), 2.64 (s, 2H, NCCH₂, major isomer), 2.44 (s, 3H

Ar−CH₃, major isomer), 2.43 (s, 3H Ar−CH₃, minor isomer), 2.36

(s, 3H Ar−CH₃, minor isomer), 2.33 (s, 3H Ar−CH₃, major isomer),

0.91 (s, 6H, C(CH₃)₂, major isomer), 0.84 (s, 6H, C(CH₃)₂, minor

isomer). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) (mixture of

isomers 59:41) δ 156.4 (Cq), 156.1 (Cq), 147.3 (CH), 146.9 (CH),

144.2 (Cq), 143.9 (Cq), 139.9 (Cq), 139.7 (Cq), 135.8 (Cq), 135.5

(Cq), 130.6 (2 × CH), 130.2 (2 × CH), 129.6 (2 × CH), 129.6 (2 ×

CH), 129.2 (2 × CH), 129.1 (2 × CH), 128.5 (2 × CH), 128.2 (2 ×

CH), 128.0 (2 × CH), 127.1 (Cq), 126.9 (Cq), 113.4 (CH₂), 110.4

(CH₂), 50.3 (CH₂), 39.5 (CH₂), 37.9 (Cq), 37.3 (Cq), 28.0 (CH₃),

27.4 (CH₃), 27.2 (CH₃), 21.8 (2 × CH₃), 21.7 (2 × CH₃). HRMS

(ESI) m/z [M + H]⁺Calcd for C₂₁H₂₇N₂O₂S 371.1793, found

371.1781.

2,2-Dimethylbut-3-enyl-o-tolyl ketone-N-tosylhydrazone (10e).

Following the described procedure 2,2-dimethylbut-3-enyl-o-tolyl

ketone 8e (1.01 g, 5.0 mmol) was reacted with N-tosylhydrazide 9a

(1.04 g, 5.6 mmol) in methanol (2 mL) to obtain 1.48 g (4.0 mmol)

of 2,2-dimethylbut-3-enyl-o-tolyl ketone-N-tosylhydrazone 10e as a

white powder (56%, PE/EE 7/3). ¹H NMR (600 MHz, CDCl₃,

Me₄Si) δ 7.89 (bs, 1H, N−H), 7.83 (d, J = 8.3 Hz, 2H, Ar−H), 7.31

(d, J = 7.8 Hz, 2H, Ar−H), 7.17 (dt, J = 7.8, 1.6 Hz, 2H, Ar−H), 7.10

(m, 3H, Ar−H), 5.68 (dd, J = 17.4, 10.8 Hz, 1H, CHCH₂), 5.01

(dd, J = 17.4, 0.6 Hz, 1H, CHCH₂H trans), 4.92 (dd, J = 10.8, 0.6

Hz, 1H, CHCH₂H cis), 2.64 (s, 2H, NC(Ar)−CH₂), 2.44 (s, 3H,

Ar−CH₃), 2.03 (s, 3H, Ar−CH₃), 0.88 (s, 6H, C(CH₃)₂). ¹³C{¹H}-

NMR (151 MHz; CDCl₃, Me₄Si) 156.7 (Cq), 146.7 (CH), 144.2

(Cq), 139.1 (Cq), 136.0 (Cq), 135.8 (Cq), 131.3 (CH), 129.6 (2 ×

CH), 128.5 (CH), 128.4 (2 × CH), 125.5 (CH), 113.2 (CH₂), 43.3

(CH₂), 38.5 (Cq), 27.7 (CH₃), 21.7 (2 × CH₃), 20.5 (CH₃). mp 98−

102 °C. IR ν_max(neat)/cm⁻¹3280, 3179, 2960, 1645, 1598, 1340,

1167, 768. HRMS (ESI) m/z [M + H]⁺Calcd for C₂₁H₂₇N₂O₂S

371.1793, found 371.1779.

(CH₂), 39.6 (CH₂), 38.1 (Cq), 38.0 (Cq), 27.9 (CH₃), 27.2 (CH₃),

21.7 (2 × CH₃), 21.7 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺Calcd

for C₂₁H₂₇N₂O₃S 387.1737, found 387.1728.

2,2-Dimethylbut-3-enyl-pyridyl ketone-N-tosylhydrazone (10g).

Following the described procedure 2,2-dimethylbut-3-enyl-pyridyl

ketone 8g (0.57 g, 3.0 mmol) were reacted with N-tosylhydrazide 9a

(0.61 g, 3.3 mmol) in methanol (5.0 mL) reﬂuxed at 50 °C for 16h.

The reaction was cooled to rt to obtain 0.450 g (1.26 mmol) of 2,2-

dimethylbut-3-enyl-pyridyl ketone-N-tosylhydrazone 10g as a white

powder (42%, PE/AcOEt 98/2). ¹H NMR (600 MHz, CDCl₃,

Me₄Si) (isomer A) δ 8.60 (dm, J = 4.9 Hz, 1H, Ar−H), 8.19−8.09

(bs, 1H, N−H), 7.87 (dd, J = 8.4, 1.9 Hz, 1H, Ar−H), 7.88−7.85 (m,

2H, Ar−H), 7.43 (d, J = 8.1 Hz, 1.1 Hz, 1H, Ar−H), 7.43 (dt, J = 8.1,

1.1 Hz, 1H, Ar−H), 7.31−7.26 (m, 2H, Ar−H), 5.52 (dd, J = 17.5,

10.7 Hz, 1H, CHCH₂), 4.62 (dd, J = 17.5, 1.2 Hz, 1H, CHCH₂,

H trans), 4.52 (dd, J = 10.7, 1.2 Hz, 1H, CHCH₂, H cis), 2.65 (s,

2H, NCCH₂), 2.42 (s, 3H Ar−CH₃), 0.77 (s, 6H, C(CH₃)₂).

(isomer B) δ 8.49 (dd, J = 4.9, 1.8, 0.9 Hz, 1H, Ar−H), 8.19−8.09

(bs, 1H, N−H), 7.90 (dd, J = 8.4, 1.9 Hz, 1H, Ar−H), 7.64 (td, J =

7.7, 1.8 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H, Ar−H), 7.31−7.26 (m, 2H,

Ar−H), 7.21 (ddd, J = 7.5, 4.8, 1.2 Hz, 1H, Ar−H), 5.66 (dd, J = 17.5,

10.6 Hz, 1H, CHCH₂), 4.93 (dt, J = 17.4, 1.1 Hz, 1H, CHCH₂,

H trans), 4.87 (dt, J = 10.7, 1.4 Hz, 1H, CHCH₂, H cis), 2.98 (2H,

NCCH₂), 2.40 (s, 3H, Ar−CH₃), 0.92 (s, 6H, C(CH₃)₂).

¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) (mixture of isomers) δ

155.6 (Cq), 155.0 (Cq), 153.6 (Cq), 148.2 (CH), 147.8 (CH), 147.6

(CH), 147.5 (CH), 144.9 (Cq), 144.3 (Cq), 143.5 (Cq), 137.4

(CH), 136.6 (Cq), 136.5 (Cq), 135.5 (Cq), 129.7 (2 × CH), 129.5

(2 × CH), 128.1 (2 × CH), 128.1 (2 × CH), 124.0 (CH), 124.0

(CH), 123.9 (CH), 121.3 (CH), 112.9 (CH₂), 110.4 (CH₂), 46.6

(CH₂), 38.15 (Cq), 37.6 (Cq), 37.3 (CH₂), 27.6 (CH₃), 26.9 (CH₃),

21.7 (2 × CH₃), 21.6 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺Calcd

for C₁₉H₂₅N₃O₂S 358.1584, found 358.1582.

2-Phenyl-2-methylbut-3-enylphenone N-tosylhydrazone (10h).

Following the described procedure 2-phenyl-2-methylbut-3-enylphe-

none, 8h (1.27 g, 5.1 mmol) was reacted with N-tosylhydrazide 9a

(1.05 g, 5.6 mmol) in methanol (3.0 mL) to obtain 1.07 g (3.3 mmol)

2-phenyl-2-methylbut-3-enylphenone N-tosylhydrazone 10h (mixture

1

of isomers) as a white powder (64%). H NMR (600 MHz, CDCl₃,

Me₄Si) (mixture of isomers) δ 7.75 (d, J = 7.8 Hz, 1H, Ar−H), 7.69

(d, J = 8.4 Hz, 1H, Ar−H), 7.47 (m, 1H, Ar−H), 7.33 (m, 4H, Ar−

H), 7.18−7.26 (m, 4H, Ar−H), 7.08 (m, 3H, Ar−H), 6.73 (bs, 1H,

N−H, isomer 1), 6.47 (bs, 1H, N−H, isomer 2), 6.00 (dd, J = 17.4,

10.8, 1H, CHCH₂, isomer 1), 5.97 (dd, J = 17.4, 10.2, 1H, CH

CH₂, isomer 2), 5.15 (d, J = 17.4, 1H, CHCH₂, isomer 1), 5.13 (d,

J = 10.8, 1H, CHCH₂, isomer 1), 4.90 (d, J = 17.4, 1H, CHCH₂,

isomer 2), 4.88 (d, J = 10.2, 1H, CHCH₂, isomer 2), 3.18 (d, J =

13.2, 1H, NC(Me)CH_2a, isomer 1), 3.12 (d, J = 13.2, 1H, N

C(Me)CH_2b, isomer 1), 3.07 (d, J = 13.8, 1H, NC(Me)CH_2a,

isomer 2), 2.98 (d, J = 13.8, 1H, NC(Me)CH_2b, isomer 2), 2.46

(m, 3H, Ar−CH₃, both isomers), 1.27 (s, 3H, CH₃, isomer 1), 1.16 (s,

3H, CH₃, isomer 2). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si)

(mixture of isomers) δ 156.2 (Cq), 155.5 (Cq), 146.1 (CH), 146.1

(Cq), 146.0 (Cq), 145.5 (Cq), 144.0 (Cq), 144.0 (Cq), 139.0 (Cq),

135.7 (Cq), 135.0 (Cq), 133.5 (Cq), 129.7 (2 × CH), 129.6 (2 ×

CH), 129.4 (2 × CH), 129.1 (2 × CH), 128.6 (2 × CH), 128.4 (2 ×

CH), 128.1 (2 × CH), 128.0 (2 × CH), 128.0 (2 × CH), 127.7

(CH), 127.5 (CH), 127.1 (CH), 126.9 (CH), 126.6 (CH), 126.3

(CH), 126.0 (CH), 126.0 (CH), 113.0 (CH₂), 112.3(CH₂), 49.1

(CH₂), 44.7 (Cq), 44.3 (Cq), 39.4 (CH₂), 25.9 (CH₃), 25.3 (CH₃),

21.8 (CH₃), 21.8 (CH₃). HRMS (ESI) m/z [M + H]⁺Calcd for

C₂₅H₂₈N₂O₂S 419.1788, found 419.1789.

2,2-Dimethylbut-3-enyl-m-methoxyphenone-N-tosylhydrazone

(10f). Following the described procedure, 2,2-dimethylbut-3-enyl-m-

methoxyphenone 8f (0.48 g, 2.2 mmol) was reacted with N-

tosylhydrazide 9a in methanol (0.45 g, 2.4 mmol) to obtain (0.64

g, 1.5 mmol) of 2,2-dimethylbut-3-enyl-m-methoxyphenone-N-

1

tosylhydrazone 10f as a white powder (70%,). H NMR (600 MHz,

CDCl₃, Me₄Si) (mixture of isomers 66:33) δ 7.95 (bs, 1H, N−H,

major isomer), 7.89 (d, J = 8.4, Hz, 2H, Ar−H, major isomer), 7.78

(d, J = 8.4 Hz, 2H, Ar−H, minor isomer), 7.61 (bs, 1H, N−H, minor

isomer), 7.29 (m, 2H, Ar−H, both isomers), 7.20 (t, J = 7.8 Hz, 1H,

Ar−H, major isomer), 7.07 (dm, J = 7.8 Hz, 1H, Ar−H, major

isomer), 7.03 (m, 1H, Ar−H, major isomer), 6.57 (dt, J = 7.2, 0.6 Hz,

1H, Ar−H, minor isomer), 6.52 (m, 1H, Ar−H, minor isomer), 5.58

(dd, J = 17.4, 10.8 Hz, 1H, CHCH₂, major isomer), 5.52 (dd, J =

17.4, 10.2 Hz, 1H, CHCH₂, major isomer), 4.98 (d, J = 17.4 Hz,

1H, CHCH₂, H trans, major isomer), 4.86 (d, J = 10.2 Hz, 1H,

CHCH₂, H cis, major isomer), 4.67 (dd, J = 17.4, 1.8 Hz, 1H,

CHCH₂, H trans, minor isomer), 4.61 (dd, J = 10.8, 1.2 Hz, 1H,

CHCH₂, H cis, minor isomer), 3.78 (s, 3H, OCH₃, minor isomer),

3.77 (s, 3H, OCH₃, minor isomer), 2.64 (s, 2H, NCCH₂, major

isomer), 2.51 (s, 2H, NCCH₂, minor isomer), 2.42 (s, 3H Ar−

CH₃, both isomers), 0.90 (s, 6H, C(CH₃)₂, major isomer), 0.85 (s,

6H, C(CH₃)₂, minor isomer). ¹³C{¹H}NMR (151 MHz; CDCl₃,

Me₄Si) (mixture of isomers) δ 160.3 (Cq), 159.4 (Cq), 156.0 (Cq),

154.9 (Cq), 147.2 (CH), 146.8 (CH), 144.2 (Cq), 144.0 (Cq), 140.0

(Cq), 135.7 (Cq), 135.5 (Cq), 134.9 (Cq), 130.8 (CH), 129.6 (2 ×

CH), 129.5 (2 × CH), 128.2 (2 × CH), 128.0 (2 × CH), 119.6

(CH), 119.1 (CH), 115.2 (CH), 115.0 (CH), 113.3 (CH₂), 112.9

(CH), 112.5 (CH), 110.5 (CH₂), 55.4 (CH₃), 55.3 (CH₃), 50.3

4,4-Dimethylhex-5-en-2-one-N-tosylhydrazone (10i). Following

the described procedure 4,4-dimethylhex-5-en-2-one, 8i (0.640 g, 5.1

mmol) was reacted with N-tosylhydrazide 9a (1.05 g, 5.6 mmol) in

methanol (3.0 mL) to obtain 0.720 g (2.45 mmol) of 4,4-

dimethylhex-5-en-2-one-N-tosylhydrazone 10i (mixture of isomers)

as a white powder (48%). ¹H NMR (600 MHz, CDCl₃, Me₄Si)

(major isomer) δ 7.82 (d, J = 8.3 Hz, 2H, Ar−H), 7.79 (bs, 1H, N−

H), 7.29 (d, J = 7.9 Hz, 2H, Ar−H), 5.69 (dd, J = 17.3, 10.8 Hz, 1H,

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CHCH₂),), 4.76 (dd, J = 10.8, 1.6 Hz, 1H, CHCH₂(H cis)),

4.73 (dd, J = 17.3, 1.2 Hz, 1H, CHCH₂(H trans)), 2.42 (s, 3H,

Ar−CH₃), 2.21 (s, 2H, CH₂), 1.71 (s, 3H, NCCH₃), 0.84 (s, 6H,

C(CH₃)₂); (minor isomer) δ 7.79 (d, J = 8.3 Hz, 2H, Ar−H), 7.5 (s,

1H, N−H), 7.34 (d, J = 7.9 Hz, 2H, Ar−H), 5.90 (dd, J = 17.3, 10.8

Hz, 1H, CHCH₂), 4.98 (bd, J = 10.8 Hz, 1H, CHCH₂(H cis)),

4.94 (bd, J = 17.4 Hz, 1H, CHCH₂(H trans)), 2.41 (s, 3H, Ar−

CH₃), 2.19 (s, 2H, CH₂), 1.91 (s, 3H, NCCH₃), 1.04 (s, 6H,

C(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) (mixture of

isomers) δ 147.5 (CH), 144.0 (Cq), 135.5 (Cq), 130.1 (2 × CH),

129.5 (2 × CH), 128.4 (2 × CH), 128.2 (2 × CH), 128.1 (Cq), 110.9

(CH₂), 51.4 (CH₂), 37.2 (Cq), 27.8 (CH₃), 27.1 (CH₃), 26.9 (CH₃),

21.7 (CH₃), 18.0 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺Calcd for

C₁₅H₂₃N₂O₂S 295.1475, found 295.1477.

(5R)-5-Methyl-2-(1,1-dimethylprop-2-enyl)cyclohexanone N-to-

sylhydrazone (10l). Following the described procedure pulegone

derivative 8l, (1.2 g, 6.7 mmol) was reacted with N-tosylhydrazide 9a

(1.4 g, 7.5 mmol) in methanol (5.0 mL) to obtain 1.3 g (3.8 mmol)

upon precipitation with water of pulegone tosylhydrazone 10l as a

white powder (57%). Only 2 isomers observed. ¹H NMR (600 MHz,

CDCl₃, Me₄Si) (mixture of 2 isomers 85/15), (major isomer) δ 7.84

(d, J = 8.2 Hz, 2H, Ar−H), 7.46 (s, 1H, N−H), 7.29 (d, J = 8.2 Hz,

2H, Ar−H), 5.83 (dd, J = 17.6, 10.8 Hz, 1H, CHCH₂), 4.79 (dd, J

= 17.6, 1.5 Hz, 1H, CH−CH₂H trans), 4.76 (dd, J = 10.8, 1.5 Hz, 1H,

CH−CH₂H cis), 2.56 (dd, 1H, J = 13.5, 4.0 Hz, NCC(H)H

C(Me)H), 2.41 (s, 3H, Ar−CH₃), 1.91−1.85 (m, 2H, CH−CH₂−

CH₂−C(Me)H), 1.76−1.71 (m, 1H, CH−CH₂−CH₂−C(Me)H),

1.59−1.53 (m, 1H, CH₂−C(Me)H−CH₂), 1.41 (dd, 1H, J = 13.5,

11.5 Hz, NCC(H)HC(Me)H), 1.22 (ddd, J = 14.5, 12.8, 4.0

Hz, 1H, CH−CH₂−C(H)H−C(Me)H), 1.03 (ddm, J = 13.5, 11.5,

1H, CH−CH₂−C(H)H−C(Me)H), 0.98 (s, 3H, C(CH₃) CH₃), 0.97

(s, 3H, C(CH₃) CH₃), 0.91 (d, J = 6.5 Hz, 3H, CH₂−CH−CH₃);

(minor isomer) δ 7.79 (d, J = 8.2 Hz, 2H, Ar−H), 7.35 (d, J = 8.0 Hz,

2H, Ar−H), 5.75 (dd, J = 17.3, 11.0 Hz, 1H, CHCH₂), 5.60 (s, 1H,

N−H), 4.76 (dd, 1H, J = 17.5, 1.5 Hz, CH−CH₂H trans), 4.75 (dd,

1H, J = 10.8, 1.5 Hz, CH−CH₂H cis), 2.44 (s, 3H, Ar−CH₃), 2.35−

2.29 (m, 1H, NCC(H)HC(Me)H), 2.15 (t, 1H, J = 5.8 Hz,

NCC(H)HC(Me)H), 1.95−1.83 (m, 2H, CH−CH₂−CH₂−

C(Me)H), 1.78−1.67 (m, 2H, CH₂−C(Me)H−CH₂with CH−

CH₂−CH₂−C(Me)H), 1.36−1.27 (m, 1H, CH−CH₂−C(H)H−

C(Me)H), 1.10 (d, 1H, J = 12.2 Hz, CH−CH₂−C(H)H−C(Me)H),

0.90 (s, 3H, C(CH₃)−CH₃), 0.89 (s, 3H, C(CH₃)−CH₃), 0.87 (d, J =

6.2 Hz, 3H, CH₂−CH−CH₃). ¹³C{¹H}NMR (151 MHz; CDCl₃,

Me₄Si) (mixture of isomers), δ 162.1 (Cq), 148.0 (CH), 144.0 (Cq),

135.6 (Cq), 130.0 (CH), 129.5 (2 × CH), 128.5 (2 × CH), 128.4 (2

× CH), 110.9 (CH₂), 110.5 (CH₂), 53.9 (CH), 51.8 (CH), 39.7

(Cq), 38.8 (Cq), 36.2 (CH₂), 34.4 (CH₂), 34.0 (CH), 32.1 (Cq),

31.2 (Cq), 28.9 (CH₂), 27.0 (CH₂), 25.8 (CH₃), 25.4 (CH₃), 23.9

(CH₃), 22.2 (CH₃), 21.4 (CH₃), 21.7 (CH₃). HRMS (ESI) m/z [M

+ H]⁺Calcd for C₁₉H₂₉N₂O₂S 349.1944, found 349.1952.

2,2-Dimethylpent-3-enylphenone-N-tosylhydrazone (10j). Fol-

lowing the described procedure 2,2-dimethylpent-3-enylphenone 8j

(1.01 g, 5.0 mmol) was reacted with N-tosylhydrazide 9a (1.00. g, 5.4

mmol) in methanol (3.0 mL) to obtain 1.07 g (2.9 mmol) of 2,2-

dimethylbut-3-enylphenone-N-tosylhydrazone (10j) (mixture of

1

isomers) as a white powder (58%). H NMR (600 MHz, DMSO-

d₆, Me₄Si) (mixture of isomers) δ 10.58 (s, 1H, NH, isomer 1), 10.56

(s, 1H, NH, isomer 2), 9.90 (s, 1H, NH, isomer 3), 9.89 (s, 1H, NH,

isomer 4), 7.70−7.72m, 4H, Ar−H), 7.47 (m, 2H, Ar−H), 7.45 (m,

1H, Ar−H), 7.32−7.39 (m, 4H, Ar−H), 7.23−7.28 (m, 6H, Ar−H),

5.23 (dq, J = 15.6, 1.8 Hz, 1H, CHCHCH₃, isomer 1), 5.23 (dq,

J = 12.0, 1.8 Hz, 1H, CHCHCH₃, isomer 2), 4.93−5.03 (bm,

2H, CHCHCH₃all isomers, CHCHCH₃, isomer 3 and 4),

2.85 (s, 2H, NC(Ar)−CH₂, isomers 1 and 2), 2.75 (s, 2H, N

C(Ar)−CH₂),isomers 3 and 4), 2.30 (s, 3H, Ar−CH₃, isomer 1 and

2), 2.29 (s, 3H, Ar−CH₃, isomer 3 and 4), 1.49 (dd, J = 6.6, 1.2 Hz,

1H, CHCHCH₃, isomer 3), 1.47 (dd, J = 7.2, 1.8 Hz, 1H, CH

CHCH₃, isomer 1), 1.28 (m, 1H, CHCHCH₃, isomer 2 and 4),

0.91 (s, 6H, C(CH₃)₂, isomer 1), 0.89 (s, 6H, C(CH₃)₂, isomer 4),

0.80 (s, 6H, C(CH₃)₂, isomer 2), 0.77 (s, 6H, C(CH₃)₂, isomer 3).

¹³C{¹H}NMR (151 MHz; DMSO-d₆, Me₄Si) (mixture of isomers) δ

154.9 (Cq), 154.5 (Cq), 143.5 (CH), 143.4 (Cq), 143.2 (Cq), 140.9

(CH), 139.7 (Cq), 139.6 (CH), 138.8 (CH), 138.6 (CH), 136.8

(Cq), 136.6 (Cq), 136.5 (Cq), 129.7 (CH), 129.5 (2 × CH), 129.2

(2 × CH), 129.0 (2 × CH), 128.8 (2 × CH), 128.6 (2 × CH), 128.5

(2 × CH), 128.3 (2 × CH), 128.2 (2 × CH), 128.0 (2 × CH), 127.6

(2 × CH), 127.6 (2 × CH), 127.2 (2 × CH), 127.1 (2 × CH), 122.8

(2 × CH), 120.1 (CH), 120.0 (CH), 50.7 (CH₂), 46.0 (CH₂), 38.3

(CH₂), 38.3 (CH₂), 38.0 (Cq), 37.6 (Cq), 29.2 (CH₃), 29.2 (CH₃),

27.7 (CH₃), 21.3 (CH₃), 17.9 (2 × CH₃), 17.8 (2 × CH₃), 14.3 (2 ×

CH₃), 14.2 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺Calcd for

C₂₁H₂₇N₂O₂S 371.1788, found 371.1792.

2,2-Dimethylbut-3-enylphenone-N-phenylsulfonylhydrazone

(11a). Following the described procedure 2,2-dimethylbut-3-enylphe-

none 8a (0.38 g, 2.0 mmol) was reacted with phenylsulfonylhydrazide

9b (0.38 g, 2.2 mmol) in methanol (2 mL) to obtain 1.13 g (3.5

mmol) of 2,2-dimethylbut-3-enylphenone-N-phenylsulfonylhydrazone

1

11a (only one isomer found) as a white powder (50%). H NMR

(600 MHz, CDCl₃, Me₄Si) δ 8.04−7.99 (m, 2H, Ar−H), 7.88 (s, 1H,

N−H), 7.63 (tt, J = 7.4, 1.8 Hz, 1H, Ar−H), 7.57 (ddt, J = 8.2, 6.7,

1.1 Hz, 2H, Ar−H), 7.48 (dt, J = 6.6, 1.7, 1.3 Hz, 2H, Ar−H), 7.37−

7.28 (m, 3H, Ar−H), 5.57 (dd, J = 17.5, 10.6 Hz, 1H, CHCH₂),

4.96 (dd, J = 17.5, 0.9 Hz, 1H, CHCH₂H trans), 4.87 (dd, J = 10.6,

0.9 Hz, 1H, CHCH₂,H cis), 2.70−2.64 (m, 2H, NC(Ph)−CH₂),

0.91−0.88 (bs, 6H, C-(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃,

Me₄Si) δ 155.4 (Cq), 146.8 (CH), 138.6 (Cq), 138.4 (Cq), 133.4

(CH), 129.7 (CH), 129.0 (2 × CH), 128.4 (2 × CH), 128.2 (2 ×

CH), 128.0 (2 × CH), 113.5 (CH₂), 39.7 (CH₂), 37.9 (Cq), 27.9 (2

× CH₃). HRMS (ESI) m/z [M + H]⁺. Calcd for C₁₉H₂₃N₂O₂S

343.1475, found 343.1485. IR ν_max(neat)/cm⁻¹3059, 2956, 1641,

1445, 1349, 1160. mp 104−107 °C.

4,4-Dimethylhept-5-enone-N-tosylhydrazone (10k). Following

the described procedure 4,4-dimethylhept-5-en-2-one, 8k (0.71 g,

5.1 mmol) was reacted with N-tosylhydrazide 9a (1.05 g, 5.6 mmol)

in methanol (3.0 mL) to obtain 1.01 g (3.3 mmol) of 4,4-

dimethylhex-5-en-2-one-N-tosylhydrazone 10k (mixture of isomers)

1

as a white powder (64%). H NMR (600 MHz, DMSO-d₆, Me₄Si)

(mixture of isomers) δ 9.90 (bs, 1H, N−H, isomer 1), 9.88 (bs, 1H,

N−H, isomer 2), 7.62 (d, J = 8.4 Hz, 2H, Ar−H, both isomers), 7.33

(d, J = 8.4 Hz, 2H, Ar−H, isomer 1), 7.31 (d, J = 8.4 Hz, 2H, Ar−H,

isomer 1), 5.29 (dq, J = 13.8, 1.8 Hz, 1H, CHCHCH₃, isomer 1),

5.10 (m, 3H, CHCHCH₃, isomer 2 and CHCHCH₃, both

isomers), 2.46 (m, 3H, Ar−CH₃, isomer 2), 2.33 (m, 3H, Ar−CH₃,

isomer 1), 2.12 (s, 2H, NC(Me)CH₂, isomer 1), 2.02 (s, 2H,

NC(Me)CH₂, isomer 2), 1.73 (s, 3H, NCCH₃, isomer 1),

1.69 (s, 3H, NCCH₃, isomer 2), 1.50 (m, 1H, CHCHCH₃,

isomer 1), 1.45 (m, 3H, CHCHCH₃, isomer 2), 0.88 (s, 6H,

C(CH₃)₂, isomer 1), 0.72 (s, 6H, C(CH₃)₂, isomer 2). ¹³C{¹H}NMR

(151 MHz; DMSO-d₆, Me₄Si) (mixture of isomers) δ 157.8 (Cq),

157.6 (Cq), 143.4 (Cq), 141.1 (CH), 139.0 (CH), 136.9 (Cq), 129.7

(2 × CH), 129.7 (2 × CH), 128.1 (2 × CH), 128.1 (2 × CH), 123.3

(CH), 120.5 (CH), 51.4 (CH₂), 51.3 (CH₂), 39.6 (Cq), 36.7 (Cq),

29.1 (CH₃), 27.7 (CH₃), 21.5 (CH₃), 19.5 (CH₃), 19.2 (CH₃), 18.2

(2 × CH₃), 14.5 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺Calcd for

C₁₆H₂₅N₂O₂S 309.1631, found 309.1638.

4,4-Dimethylhex-5-en-2-one-N-phenylsulfonylhydrazone (11b).

Following the described procedure 4,4-dimethylhex-5-en-2-one, 8i

(0.50 g, 4.0 mmol) was reacted with N-phenylsulfonylhydrazide 9b

(0.770 g, 4.5 mmol) in methanol (2.5 mL) to obtain 0.762 g (2.72

mmol) of 4,4-dimethylhex-5-en-2-one-N-phenylsulfonylhydrazone

1

11b (mixture of isomers) as a white powder (68%). H NMR (600

MHz, CDCl₃, Me₄Si) (major isomer) δ 7.96 (d, J = 1.2 Hz, 2H, Ar−

H), 7.95 (t, J = 1.7 Hz, 1H, Ar−H), 7.74 (bs, 1H, N−H), 7.57 (tt, J =

7.4, 1.2 Hz, 2H, Ar−H), 5.66 (dd, J = 17.4, 10.8 Hz, 1H, CHCH₂),

4.73 (dd, J = 10.8 1.2 Hz, 1H, CHCH₂, H cis), 4.71 (dd, J = 17.4,

1.3 Hz, 1H, CHCH₂, H trans), 2.19 (s, 2H, NC(Me)CH₂),

1.72 (s, 3H, NCCH₃), 0.81 (s, 6H, C(CH₃)₂); (minor isomer) δ

7.96 (d, J = 1.2 Hz, 2H, Ar−H), 7.92 (t, J = 1.7 Hz, 1H, Ar−H), 7.74

(s, 1H, N−H), 7.59 (tt, J = 7.4, 1.2 Hz, 2H, Ar−H), 5.67 (dd, J =

17.4, 10.8 Hz, 1H, CHCH₂), 4.96−4.81 (m, 2H, CHCH₂), 2.19

3313

https://dx.doi.org/10.1021/acs.joc.0c02605

J. Org. Chem. 2021, 86, 3300−3323

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

(s, 2H, NC(Me)CH₂), 1.91 (s, 3H, NCCH₃), 1.02 (s, 6H,

C(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) (mixture of

isomers) δ 156.9 (Cq), 156.8 (Cq), 147.4 (CH), (147.1 (CH), 138.5

(Cq), 133.1 (CH), 129.4 (2 × CH), 129.0 (2 × CH), 128.3 (CH),

128.2 (2 × CH), 128.0 (2 × CH), 112.9 (CH₂), 110.9 (CH₂),

51.4(CH₂), 43.8 (CH₂), 37.7 (Cq), 37.2 (Cq), 27.7 CH₃), 26.8

(CH₃), 26.3 (2 × CH₃), 18.2 (2 × CH₃). HRMS (ESI) m/z [M +

H]⁺. Calcd for C₁₄H₂₁N₂O₂S 281.1318, found 281.1324.

minor isomer), 0.76 (s, 6H, C(CH₃)₂major isomer). ¹³C{¹H}NMR

(151 MHz; CDCl₃, Me₄Si) (mixture of isomers) δ154.7 (Cq), 154.3

(Cq), 147.0 (CH), 142.9 (CH), 140.6 (Cq), 140.5 (Cq), 139.4

(CH), 136.1 (CH), 132.6 (CH), 131.9 (2 × CH), 130.2 (2 × CH),

129.0 (2 × CH), 126.9 (2 × CH), 126.8 (2 × CH), 113.0 (CH₂),

110.4 (CH₂), 39.0 (CH₂), 38.1 (Cq), 37.7 (Cq), 36.2 (CH₂); 35.9

(CH); 28.0 (CH₃), 27.4 (CH₃), 23.6 (CH₃), 23.5 (CH₃), 21.3 (2 ×

CH₃) 21.1 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺Calcd for

C₂₃H₃₁N₂O₂S 399.2101, found 399.2104.

2,2-Dimethylbut-3-enyl-o-tolyl ketone-N-mesitylsulfonylhydra-

zone (12d). Following the described procedure 2,2-dimethylbut-3-

enyl-o-tolyl ketone 8e, (0.40 g, 2.0 mmol) was reacted with N-

mesitylsulfonylhydrazide 9c (0.45 g, 2.2 mmol) in methanol (2 mL)

to obtain 139 mg (0.35) of 2,2-dimethylbut-3-enyl-o-tolyl ketone-N-

mesitylsulfonylhydrazone 12d as a white powder that was

immediately subjected to irradiation (15%, PE/AcOEt 98/2).⁹⁶¹H

NMR (600 MHz, CDCl₃-d) δ 7.30 (m, 1H, Ar−H), 7.27 (m, 2H,

Ar−H), 7.20 (m, 1H, Ar−H), 6.96 (s, 2H, Ar−H), 5.62 (dd, J = 17.5,

10.7 Hz, 1H, CHCH₂), 4.70 (dd, J = 17.5, 1.3 H, 1H, CHCH₂H

trans), 4.64 (dd, J = 10.7, 1.3 Hz, 1H, CHCH₂H cis), 2.57 (s, 2H,

NC(Ar)−CH₂), 2.56 (s, 6H, 2 × Ar−CH₃), 2.31 (s, 3H, o-tolyl

CH₃), 2.30 (s, 3H, Ar−CH₃), 0.90 (s, 6H, C(CH₃)₂).

2,2-Dimethylbut-3-enylphenone-N-mesitylsulfonylhydrazone

(12a). Following the described procedure 2,2-dimethylbut-3-enylphe-

none 8a (0.75 g, 4.0 mmol) was reacted with N-mesitylsulfonylhy-

drazide 9c (0.96 g, 4.5 mmol) in methanol (2.5 mL) to obtain 0.81 g

(2.1 mmol) of 2,2-dimethylbut-3-enylphenone-N-2,4,6-mesitylsulfo-

nylhydrazone 12a (only one isomer found) as a white powder (53%,

1

PE/EE 9/1). H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.93−7.96 (bs,

1H, N−H), 7.47 (dd, J = 8.0, 1.6 Hz, 2H, Ar−H), 7.34−7.25 (m, 3H,

Ar−H), 6.97 (s, 2H, Ar−H), 5.78 (dd, J = 17.5, 10.6 Hz, 1H, CH

CH₂), 5.01 (d, J = 17.4 Hz, 1H, CHCH₂H trans), 4.95 (dd, J =

10.8, 0.7 Hz, 1H, CHCH₂H cis), 2.71 (s, 6H, ortho Ar-CH₃), 2.68

(s, 2H, NCCH₂), 2.30 (s, 3H, para Ar-CH₃), 0.97 (s, 6H,

C(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) δ 154.2 (Cq),

146.8 (CH), 143.0 (Cq), 140.6 (2 × Cq), 138.8 (Cq), 132.5 (Cq),

131.9 (2 × CH), 129.3 (CH), 128.3 (2 × CH), 127.0 (2 × CH),

113.0 (CH₂), 39.0 (CH₂), 38.1(Cq), 28.0 (CH₃), 23.6 (2 × CH₃),

21.1 (2 × CH₃). mp 76−82 °C. HRMS (ESI) m/z [M + H]⁺Calcd

for C₂₂H₂₉N₂O₂S 385.1944, found 385.1951. IR ν_max(neat)/cm⁻¹

3201, 2962, 1602, 1444, 1377, 1159.

4,4-Dimethylhex-5-en-2-one-N-mesitylsulfonylhydrazone (12e).

Following the described procedure 4,4-dimethylhex-5-en-2-one, 8i

(0.630 g, 5.0 mmol) was reacted with N-mesitylsulfonylhydrazide 9c

(1.070 g, 5.00 mmol) in methanol (3.1 mL) to obtain 1.13 g (3.5

mmol) 4,4-dimethylhex-5-en-2-one-N-mesitylhydrazone 12e (mixture

1

of isomers) as a white powder (70%, PE/EE 95/5). H NMR (600

2,2-Dimethylbut-3-enylnaphtone-N-mesitylsulfonylhydrazone

(12b). Following the described procedure 2,2-dimethylbut-3-enyl-

naphtone 8b, (0.480 g, 2.0 mmol) was reacted with N-

mesitylsulfonylhydrazide 9c (0.47 g, 2.2 mmol) in methanol (2

mL) at rt to obtain 0.312 g of 2,2-dimethylbut-3-enylnaphtone-N-

2,4,6-mesitylsulfonylhydrazone (12b) (0.72 mmol) as a white powder

(36%, PE/AcOEt 99/1). ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 8.02

(s, 1H, N−H), 7.89 (m, 1H, Ar−H), 7.87 (m, 1H, Ar−H), 7.80 (m,

2H, Ar−H), 7.75 (dd, J = 8.7, 3.3 Hz, 1H, Ar−H), 7.66 (m, 1H, Ar−

H) 7.47 (m, 1H, Ar−H), 6.99 (s, 2H, Ar−H), 5.83 (dd, J = 17.4, 10.6

Hz, 1H, CHCH₂), 5.07 (d, J = 17.4 Hz, 1H, CHCH₂H trans),

4.99 (dd, J = 10.8, 0.7 Hz, 1H, CHCH₂H cis), 2.80 (s, 2H, N

CCH₂), 2.75 (s, 6H, ortho Ar-CH₃), 2.31 (s, 3H, para Ar-CH₃),

1.01 (s, 6H, C(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si)

153.9 (Cq), 146.9 (CH), 143.1 (Cq), 140.6 (2 × Cq), 136.2 (Cq),

133.8 (Cq), 132.9 (Cq), 132.5 (Cq), 132.0 (2 × CH), 128.6 (CH),

128.0 (CH), 127.7 (CH), 126.8 (CH), 126.7 (Cq), 126.4 (CH),

124.5 (CH), 113.2 (CH₂), 39.0 (CH₂), 38.2 (Cq), 28.1 (CH₃), 23.5

(CH₃), 21.2 (2 × CH₃). mp 59−65 °C. HRMS (ESI) m/z [M + H]⁺

Calcd for C₂₆H₃₁N₂O₂S 435.2101, found 435.2107. IR ν_max(neat)/

cm⁻¹3228, 2960, 1602, 1467, 1376, 1331, 1187, 1161, 1052.

2,2-Dimethylbut-3-enyl-p-tolyl ketone-N-mesitylsulfonylhydra-

zone (12c). Following the described procedure 2,2-dimethylbut-3-

enyl-p-tolyl ketone 8d, (0.85 g, 4.0 mmol) was reacted with N-

mesitylsulfonylhydrazide 9c (0.95 g, 4.5 mmol) in methanol (2 mL)

to obtain 0.98 g (2.5 mmol) of 2,2-dimethylbut-3-enyl-p-tolyl ketone-

N-mesitylsulfonylhydrazone 12c as a white powder (62%, PE/AcOEt

98/2). ¹H NMR (600 MHz, CDCl₃, Me₄Si) (mixture of isomers

MHz, CDCl₃, Me₄Si) (major isomer) δ 7.37 (bs, 1H, N−H), 6.94 (s,

2H, Ar−H), 5.64 (dd, J = 17.4, 10.7 Hz, 1H, CHCH₂), 4.74 (bd, J

= 10.7, 1H, CHCH₂, H cis), 4.70 (dd, J = 17.5, 1.2 Hz, 1H, CH

CH₂H trans), 2.64 (s, 6H, ortho Ar−CH₃), 2.28 (s, 3H, para Ar−

CH₃), 2.13 (s, 2H, NC(Me)CH₂), 1.71 (s, 3H, NCCH₃),

0.79 (s, 6H, C(CH₃)₂); (minor isomer) δ 7.37 (bs, 1H, N−H), 6.97 (s,

2H, Ar−H), 5.82 (dd, J = 17.5, 10.7 Hz, 1H, CHCH₂), 5.04 (d, J =

10.7, 1H, CHCH₂, H cis), 5.02 (d, J = 17.5, 1H, CHCH₂H

trans), 2.66 (s, 6H, ortho Ar−CH₃), 2.29 (s, 3H, para Ar−CH₃), 1.89

(s, 2H, NC(Me)CH₂), 1.78 (s, 3H, NCCH₃), 1.09 (s, 6H,

C(CH₃)₂). ¹³C{¹H}NMR (151 MHz; CDCl₃, Me₄Si) (mixture of

isomers) δ 154.6 (Cq), 147.5 (CH), 142.8 (Cq), 140.4 (2 × Cq),

140.2 (2 × Cq), 132.6 (Cq), 131.8 (2 × CH), 131.8 (2 × CH), 110.8

(CH₂), 51.3 (CH₂), 37.2 (Cq), 27.9 (Cq), 27.0 (2 × CH₃), 26.7 (2 ×

CH₃), 23.2 (CH₃), 21.0 (CH₃), 17.8 (2 × CH₃). HRMS (ESI) m/z

[M + H]⁺Calcd for C₁₇H₂₇N₂O₂S 323.1788, found 323.1780.

2,2-Dimethylpent-3-enylphenone-N-mesitylsulfonylhydrazone

(12f). Following the described procedure 2,2-dimethylpent-3-

enylphenone 8j, (1.01 g, 5.0 mmol) was reacted with N-

mesitylsulfonylhydrazide 9c (1.00. g, 5.4 mmol) in methanol (3.0

mL) to obtain 1.43 g (2.9 mmol) of 2,2-dimethylbut-3-enylphenone-

N-tosylhydrazone(12f) (mixture of 4 isomers) as a white powder

1

(72%). H NMR (600 MHz, CDCl₃, Me₄Si) (mixture of isomers) δ

7.93 (s, 1H, NH, isomer 1), 7.93 (s, 1H, NH, isomer 2), 7.92 (s, 1H,

NH, isomer 3), 7.91 (s, 1H, NH, isomer 4), 7.50 (m, 4H, Ar−H),

7.41−7.43 (m, 3H, Ar−H), 7.29 (m, 3H, Ar−H), 7.13 (dm, J = 7.2

Hz, 2H, Ar−H, isomer 1), 7.06 (dm, J = 6.6 Hz, 2H, Ar−H, isomer 1

and 2), 7.03 (dm, J = 6.6 Hz, 2H, Ar−H, isomer 1 and 2), 6.93−6.96

(m, 2H, Mes−H, all isomers), 4.97−5.00 (bm, 1H, CHCHCH₃,

all isomers), 4.93−5.03 (bm, 2H, CHCHCH₃,all isomers), 2.71 (s,

2H, NC(Ar)−CH₂, isomers 1 and 2), 2.60 (s, 2H, NC(Ar)−

CH₂), isomers 3 and 4), 2.30 (s, 3H, Ar−CH₃, isomer 1 and 2), 2.29

(s, 3H, Ar−CH₃, isomer 3 and 4), 1.70 (dd, J = 6.6, 1.2 Hz, 1H,

CHCHCH₃, isomer 3), 1.68 (dd, J = 7.2, 1.8 Hz, 1H, CH

CHCH₃, isomer 1), 1.66 (bd, J = 7.2 Hz, 1H, CHCHCH₃, isomer

12), 1.58 (dd, J = 6.0, 1.8 Hz, 1H, CHCHCH₃, isomer 4), 1.07 (s,

6H, C(CH₃)₂, isomer 1), 0.98 (s, 6H, C(CH₃)₂, isomer 4), 0.93 (s,

6H, C(CH₃)₂, isomer 2), 0.66 (s, 6H, C(CH₃)₂, isomer 3). ¹³C{¹H}-

NMR (151 MHz; CDCl₃, Me₄Si) (mixture of isomers) δ 155.6 (Cq),

155.0 (Cq), 154.0 (Cq), 142.9 (CH), 142.9 (Cq), 142.7 (Cq), 140.7

(Cq), 140.5 (Cq), 140.3 (CH), 140.1 (Cq), 140.0 (CH), 139.2 (Cq),

139.0 (CH), 138.2 (CH), 134.0 (Cq), 132.7 (Cq), 131.9 (CH), 131.8

1

83:17). H NMR (600 MHz, Chloroform-d) δ 7.93 (s, 1H, N−H,

major isomer), 7.63 (bs, 1H, N−H minor isomer), 7.37 (d, J = 8.3 Hz,

2H, Ar−H, minor isomer), 7.34 (d, J = 8.1 Hz, 2H, Ar−H major

isomer), 7.22 (d, J = 7.8 Hz, 2H, Ar−H, both isomers), 7.09 (m, 4H,

Ar−H, both isomers), 6.96 (d, J = 4.0 Hz, 2H, Mes−H, both

isomers), 5.79 (dd, J = 17.4, 10.2 Hz, 1H, CHCH₂major isomer),

5.54 (dd, J = 17.4, 10.2 Hz, 1H, CHCH₂minor isomer), 5.02 (dd, J

= 17.4, 0.6 Hz, 1H, CHCH₂, H trans major isomer), 4.96 (dd, J =

10.2, 1.2 Hz, 1H, CHCH₂, H cis major isomer) 4.66 (dd, J = 17.4,

1.2 Hz, 1H, CHCH₂, H trans, minor isomer), 4.59 (dd, J = 10.8, 1.2

Hz, 1H, CHCH₂, H cis, minor isomer), 2.70 (m, 12H Ar−CH₃,

both isomers), 2.59 (s, 2H, NCCH₂, major isomer), 2.45 (s, 2H,

NCCH₂, major isomer), 2.31 (s, 3H, p-tolyl CH₃major isomer),

2.30 (s, 3H, p-tolyl CH₃, minor isomer), 2.29 (s, 3H Ar−CH₃major

isomer), 2.29 (s, 3H Ar−CH₃,minor isomer), 0.97 (s, 6H, C(CH₃)₂,

3314

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(2 × CH), 129.6 (2 × CH), 129.6 (2 × CH), 129.5 (2 × CH), 129.5

(2 × CH), 129.4 (2 × CH), 129.3 (2 × CH), 128.3 (2 × CH), 128.2

(2 × CH), 127.2 (2 × CH), 127.0 (2 × CH), 124.0 (CH), 123.4 (2 ×

CH), 120.8 (2 × CH), 51.0 (CH₂), 50.7 (CH₂), 44.7 (CH₂), 39.7

(CH₂), 39.4 (CH₂), 37.8 (Cq), 37.3 (Cq), 36.7 (Cq), 36.6 (Cq), 30.6

(CH₃), 29.3 (CH₃), 28.6 (CH₃), 27.7 (CH₃), 23.6 (CH₃), 23.2

(CH₃), 21.1 (2 × CH₃), 18.0 (2 × CH₃), 17.8 (2 × CH₃), 17.1 (2 ×

CH₃), 14.7 (2 × CH₃), 14.3 (2 × CH₃). HRMS (ESI) m/z [M + H]⁺

Calcd for C₂₃H₃₁N₂O₂S 399.2101, found 399.2096.

(600 MHz, Methanol-d₄) δ 7.75 (d, J = 8.2 Hz, 2H, Ar−H), 7.39−

7.35 (m, 2H, Ar−H), 7.21 (d, J = 7.9 Hz, 3H, Ar−H), 7.18 (t, J = 7.4

Hz, 2H, Ar−H), 7.14 (d, J = 7.0 Hz, 1H, Ar−H), 5.73 (dd, J = 17.4,

10.7 Hz, 1H, CHCH₂), 4.63 (dd, J = 17.5, 1.7 Hz, 1H, CHCH₂H

trans), 4.49 (dd, J = 10.7, 1.6 Hz, 1H, CHCH₂H cis), 2.88 (s, 2H,

NC(Ph)−CH₂), 2.34 (s, 3H, Ar−CH₃), 0.80 (s, 6H, C(CH₃)₂).

¹³C{¹H} NMR (151 MHz, Methanol-d₄) δ 150.3 (Cq), 149.0 (CH),

142.1 (Cq), 141.9 (Cq), 140.3 (Cq), 128.3 (2 × CH), 127.4 (2 ×

CH), 126.9 (2 × CH), 126.8 (2 × CH), 126.6 (CH), 108.1 (CH₂),

37.9 (Cq), 37.2 (CH₂), 29.9 (CH₃), 26.71 (2 × CH₃). HRMS (ESI)

m/z [M−]⁻Calcd for C₂₀H₂₃N₂O₂S 355.1486, found 355.1483. IR

ν_max(neat)/cm⁻¹2957, 2923, 2053, 1636, 1441, 1279, 1078.

(5R)-5-Methyl-2-(1,1-dimethylprop-2-enyl)cyclohexanone N-me-

sitylsulfonylhydrazone (12g). Following the described procedure,

pulegone derivative 8l (0.61 g, 3.4 mmol) was reacted with N-

mesitylsulfonylhydrazide 9c (0.79 g, 3.7 mmol) in methanol (2.5 mL)

to obtain 0.68 g (1.8 mmol) of (5R)-5-methyl-2-(1,1-dimethylprop-2-

enyl)cyclohexanone N-mesitylsulfonylhydrazone 12g after column

chromatography, aﬀording a white solid product as a mixture of the 4

isomer (54%, PE/EE 9/1). ¹H NMR (600 MHz, CDCl₃, Me₄Si)

(mixture of 4 isomers) 6.97 (s, 2H, Ar−H, isomers 1), 6.93 (s, 2H,

Ar−H isomer 2 and 3), 6.83 (s, 2H, Ar−H isomer 4), 5.95 (dd, J =

17.4, 10.9 Hz, 1H, CHCH₂isomer 1), 5.81 (dd, J = 17.5, 10.6 Hz,

1H, CHCH₂isomer 2 and 3), 5.70 (dd, J = 17.6, 10.7 Hz, H, CH

CH₂isomer 4), 4.94 (bm, 2H, CHCH₂isomer 1 and 4), 4.70 (bm,

2H, CHCH₂isomer 2 and 3), 2.64 (s, 6H, ortho Ar−CH₃all

isomers), 2.56 (dd, J = 13.4, 4.3, 1.7 Hz, 1H, NCC(H)H

C(Me)H, isomer 2), 2.53 (m, 1 H, isomer 3), 2.33 (m, 1H,) 1.41 (dd,

1H, J = 13.4, 11.5 Hz, NCC(H)HC(Me)H, isomer 2), 2.27

(s, 6H, para Ar−CH₃all isomers), 2.56 ((dd, 1H, J = 13.5, 4.0 Hz,

isomer 2), 2.35−2.31 (m, 1H, NCC(H)HC(Me)H isomer 3),

2.29 (d, J = 14.8 Hz, 2H NCC(H)HC(Me)H, isomer 2), 2.17

(ddd, J = 13.0, 4.9, 1.3 Hz, 2H, CH−CH₂−CH₂−C(Me)H isomer 2),

2.07 (t, 1H, J = 5.8 Hz, NCC(H)HC(Me)H isomer 3), 1.99

(dd, J = 12.5, 1.3 Hz, CH−CH₂−CH₂−C(Me)H isomer 2), 1.95−

1.83 (m, 2H, CH−CH₂−CH₂−C(Me)H isomer 3), 1.80−1.72 (m,

6H, CH₂−C(Me)H−CH₂with CH−CH₂−CH₂−C(Me)H with

CH−CH₂−CH₂−C(Me)H all isomers), 1.59 (ddt, J = 10.9, 8.7, 3.2

Hz, 1H, isomer 2), 1.55−1.49 (m, 0H), 1.43 (dm, J = 11.5, 1H, CH−

CH₂−C(H)H−C(Me)H isomer 2), 1.41 (d, J = 11.4 Hz, 1H, CH−

CH₂−C(H)H−C(Me)H, isomer 1) 1.34−1.29 (m, 1H, CH−CH₂−

C(H)H−C(Me)H), isomer 3), 1.24−1.15 (m, 2H, CH−CH₂−C(H)

H−C(Me)H, all isomers), 1.19 (ddd, J = 14.5, 12.8, 4.0 Hz, 1H, CH−

CH₂−C(H)H−C(Me)H isomer 2), 1.10 (d, 1H, J = 12.2 Hz, CH−

CH₂−C(H)H−C(Me)H isomer 3), 1.05 (dt, J = 8.0, 2.0 Hz, 2H,

CH−CH₂−C(H)H−C(Me)H, isomer 2), 0.98 (d, J = 6.5 Hz, 3H,

CH₂−CH−CH₃, isomer 1), 0.94 (d, J = 6.5 Hz, 3H, CH₂−CH−CH₃,

isomer 2 and 3), 0.91 ((d, J = 6.5 Hz, 3H, CH₂−CH−CH₃), 0.87 (s,

3H, C(CH₃) CH₃isomer 1), 0.86 (s, 3H, C(CH₃) CH₃isomer 2 and

3), 0.84 (s, 3H, C(CH₃) CH₃isomer 4), 0.73 (s, 3H, C(CH₃) CH₃

isomer 1), 0.71 (s, 3H, C(CH₃) CH₃isomer 2), 0.70 (s, 3H, C(CH₃)

CH₃isomer 3), 0.69 (s, 3H, C(CH₃) CH₃isomer 4). ¹³C{¹H}NMR

(151 MHz; CDCl₃, Me₄Si) (mixture of 4 isomers) δ 159.8 (Cq),

159.8 (Cq), 147.9 (CH), 147.7 (CH), 147.4 (CH), 147.2 (CH),

142.7 (Cq), 142.7 (Cq), 140.1 (2 × Cq), 140.0 (2 × Cq), 137.5

(Cq), 132.7 (CH), 132.2 (CH), 131.9 (2 × CH), 131.8 (2 × CH),

130.7 (CH₂), 112.8(CH₂), 111.0(CH₂), 110.9(CH₂), 110.0(CH₂),

58.8 (CH), 53.8 (CH), 52.1 (CH), 51.8 (CH), 39.6 (Cq), 38.7 (Cq),

36.4 (CH), 35.7 (CH₂), 35.6 (CH₂), 34.7 (CH₂), 34.4 (CH₂), 34.3

(CH) 34.1 (CH) 33.6 (CH₂), 31.8 (CH), 31.2 (CH₂), 29.0 (CH₂),

28.9 (CH₂), 26.8 (CH₃), 25.6(CH₂), 25.5(CH₃), 25.4(CH₃), 25.0

(CH₃), 23.7 (CH₃), 23.5, (CH₃), 23.2 (CH₃), 23.1 (CH₃), 23.0

(CH₃), 22.4 (CH₃), 22.3 (CH₃), 21.4 (CH₃), 21.2 (2 × CH₃), 21.1

(2 × CH₃), 21.0 (2 × CH₃), 19.1 (2 × CH₃). HRMS (ESI) m/z [M +

H]⁺Calcd for C₂₁H₃₃N₂O₂S 377.2257, found 377.2248.

General Procedure for the Photocatalytic Synthesis of

Dearomatization Products (13). In a sealed photochemical

reactor, 6.75 mg of [Ru(bpy)₃]Cl₂·6H₂O (0.009 mmol) were

dissolved in 5 mL of anhydrous CH₃CN, the solution was degassed

with N₂for 15 min then the suitable tosylhydrazone 10 or

phenylsulfonylhydrazone 11 (0.30 mmol) and 62.2 mg of K₂CO₃

(0.45 mmol) were added. The solution was then stirred at 4 cm from

the irradiation source (see above) at room temperature until the

reaction was completed as monitored by TLC analysis. The solution

was then ﬁltered on a short pad of silica gel using CH₂Cl₂as eluent.

The crude product was puriﬁed by ﬂash chromatography on silica gel

(hexane/acetone 92/8) to obtain the dearomatized product 13.

4,4,7-Trimethyl-2-phenyl-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide (13a). Following the

general procedure A, 107 mg (0.30 mmol) of 2,2-dimethylbut-3-

enylphenone-N-tosylhydrazone (10a) were reacted with K₂CO₃and

[Ru(bpy)₃]Cl₂·6H₂O for 16 h under blue light irradiation to obtain

75 mg (0.210 mmol) of 4,4,7-trimethyl-2-phenyl-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13a

(70%) as a white solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.80−

7.75 (m, 2H, Ar−H), 7.38−7.32 (m, 3H, Ar−H), 6.74 (tm, J = 3.5,

Hz, 1H, CH₂CHC), 5.25 (dq, J = 3.1, 1.6 Hz, 1H, CH₃CH

CH), 4.01 (dd, J = 12.6, 2.4 Hz, 1H, N−CH), 3.48 (bs,CH₂CH

CH), 2.75 (m, 2H, CH−CH₂−C(CH₃)₂), 2.38 (d, J = 18.4 Hz,

1H, CH-C(H)H-C(CH₃)), 2.28 (d, J = 18.3 Hz, 1H, CH-C(H)H-

C(CH₃)), 1.78 (ddd, J = 13.5, 4.0, 1.8 Hz, 1H, CH-C(H)H-CH),

1.64 (t, J = 1.5 Hz, 3H, CH₃CHCH), 1.23 (q, J = 12.7 Hz, 1H,

CH-C(H)H-CH), 1.11 (s, 6H, CH₂−C(CH₃)₂). ¹³C{¹H}NMR (151

MHz, CDCl₃, Me₄Si) δ 149.1 (Cq), 137.0 (Cq), 135.5 (Cq), 131.9

(CH), 130.5 (Cq), 129.5 (CH), 128.4 (2 × CH), 125.6 (2 × CH),

121.2 (CH), 62.5 (CH), 35.4 (CH), 34.6 (CH₂), 31.5 (CH₂), 31.4

(CH₂), 31.0 (Cq), 28.3 (CH₃), 27.0 (CH₃), 22.7 (CH₃). mp 169.2−

170.5 °C, degradation. ν_max(neat)/cm⁻¹2966, 2921, 2908, 1448,

1345, 1159, 1060, 1021. HRMS (ESI) m/z [M + Na]⁺Calcd for

C₂₀H₂₄N₂O₂SNa 379.1451, found 379.1451.

4,4,7-Trimethyl-2-(naphthalen-2-yl)-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide

(13b). Following the general procedure A, 122 mg (0.30 mmol) of

2,2-dimethylbut-3-enylnaphtone-N-tosylhydrazone (10b) were re-

acted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O under blue light

irradiation for 16 h to obtain 52.5 mg (0.13 mmol) of 2,4,4-

trimethyl-3,4,4a,5,5a,8-hexahydrobenzo[e]pyridazino[1,6-b][1,2]-

1

thiazine 10,10-dioxide 13b (43%) as a white solid. H NMR (600

MHz, CDCl₃, Me₄Si) δ 8.11 (dd, J = 8.7, 1.8 Hz, 1H, Ar−H), 8.01 (s,

1H, Ar−H), 7.82 (ddd, J = 9.0, 5.6, 3.4 Hz, 2H Ar−H), 7.79 (d, J =

9.0 Hz, 1H, Ar−H), 7.47 (tt, J = 5.8, 4.7 Hz, 2H, Ar−H), 6.78 (m,

1H, CH₂CHC), 5.26 (m, 1H, CH₃CHCH), 4.06 (dd, J =

12.7, 2.4 Hz, 1H, N−CH), 3.51 (bs, 1H, CH₂−CH−CH), 2.75 (m,

2H, CH−CH₂−C(CH₃)₂), 2.54 ((d, J = 18.0 Hz, 1H, CH-C(H)H-

C(CH₃)), 2.42 (d, J = 18.2 Hz, 1H, CH-C(H)H-C(CH₃)), 1.81

(ddd, J = 13.3, 4.2, 2.4 Hz, 1H, CH-C(H)H-CH), 1.64 (s, 3H,

CH₃CHCH) 1.29 (q, J = 12.7 Hz, 1H, CH-C(H)H-CH), 1.16 (s,

6H, CH₂−C(CH₃)₂). ¹³C{¹H}NMR (151 MHz, CDCl₃, Me₄Si) δ

148.9 (Cq), 135.5 (Cq), 134.5 (Cq), 133.9 (Cq), 133.0 (Cq), 132.0

(CH), 130.5 (Cq), 128.5 (CH), 128.0 (CH), 127.8 (CH), 126.8

(CH), 126.4 (CH), 125.0 (CH), 123.4 (CH), 121.2 (CH), 62.7

(CH), 35.4 (CH), 34.5 (CH₂), 31.6 (CH₂), 31.4 (CH₂), 31.1 (Cq),

28.4 (CH₃), 27.0 (CH₃), 22.7 (CH₃). mp 63.4−67.2 °C. ν_max(neat)/

Synthesis of 2,2-Dimethylbut-3-enylphenone-N-tosylhydrazone-

K⁺salt (K⁺-10a). According to our previously reported procedure,⁵¹

2,2-dimethylbut-3-enylphenone-N-tosylhydrazone 10a (1 mmol,

0.360 g) was dissolved in the minimal amount of anhydrous MeOH

at 0 °C and under nitrogen atmosphere, then sublimed tert-BuO-K⁺

(1 mmol, 0.112 g) was added, and the solution was stirred in the dark

for 30 min. Solvent evaporation aﬀorded 0.39 g of 2,2-dimethylbut-3-

1

enylphenone-N-tosylhydrazone-K⁺salt (K⁺-10a) (>99%). H NMR

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cm⁻¹3057, 2958, 2923, 1599, 1445, 1349, 1349, 1179, 1158, 1018.

HRMS (ESI) m/z [M + H]⁺Calcd for C₂₄H₂₇N₂O₂S 407.1788, found

407.1773.

121.3 (CH), 62.0 (CH), 38.3 (CH₂), 35.4 (CH), 31.6 (CH₂), 31.4

(CH₂), 31.2 (Cq), 28.3 (CH₃), 26.7 (CH₃), 22.8 (CH₃), 20.8 (CH₃).

mp degradation 165.0−169.2 °C. ν_max(neat)/cm⁻¹2961, 2942, 2871,

2114, 1734, 1346, 1156, 1176. HRMS (ESI) m/z [M + H]⁺Calcd for

C₂₁H₂₇N₂O₂S 371.1788, found 371.1776.

4,4,7-Trimethyl-2-(m-tolyl)-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide (13c). Following the

general procedure A, 111 mg (0.30 mmol) of 2,2-dimethylbut-3-enyl-

m-tolyl ketone-N-tosylhydrazone (10c) were reacted with K₂CO₃and

[Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for 16 h to obtain

66.6 mg (0.18 mmol) of 4,4,7-trimethyl-2-(m-tolyl)-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13c

(60%) as a white solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.58 (s,

1H, Ar−H), 7.55 (d, J = 8.4 Hz, 1H, Ar−H), 7.25 (dd, J = 7.8, 7.2 Hz,

1H, Ar−H), 7.18 (d, J = 7.2 Hz, 1H, Ar−H), 6.76 (bs, 1H, CH₂

CHC), 5.26 (m, 1H, CH₃CHCH), 4.02 (dd, J = 12.5, 2.4 Hz,

1H, N−CH), 3.49 (m, 1H, CH₂−CH−CH), 2.76 (m, 1H, CH−

CH₂−C(CH₃)₂), 2.37 (s, 3H, Ar−CH₃), 2.36 (s, 1H, CH-C(H)H-

C(CH₃)), 2.29 (d, J = 18.2 Hz, 1H, CH-C(H)H-C(CH₃)), 1.78

(ddd, J = 13.3, 4.2, 2.5 Hz, 1H, CH-C(H)H-CH), 1.65 (s, 3H,

CH₃CHCH), 1.24 (q, J = 12.7 Hz, 1H, CH-C(H)H-CH), 1.12 (s,

6H, CH₂−C(CH₃)₂). ¹³C{¹H}NMR (151 MHz, CDCl₃, Me₄Si) δ

149.2 (Cq), 138.1 (Cq), 137.0 (Cq), 135.4 (Cq), 131.9 (CH), 130.5

(Cq), 130.3 (CH), 128.3 (CH), 126.2 (CH), 122.8 (CH), 121.2

(CH), 62.5 (CH), 35.4 (CH), 34.7 (CH₂), 31.5 (CH₂), 31.4 (CH₂),

31.0 (Cq), 28.3 (CH₃), 27.0 (CH₃), 22.7 (CH₃), 21.6 (CH₃). mp

73.0−75.2 °C. ν_max(neat)/cm⁻¹2957, 2921, 2854, 1604, 1446, 1349,

1159, 1157, 1021. HRMS (ESI) m/z [M + H]⁺Calcd for

C₂₁H₂₇N₂O₂S 371.1788, found 371.1783.

2-(3-Methoxyphenyl)-4,4,7-trimethyl-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide

(13f). Following the general procedure A, 116 mg (0.30 mmol) of

2,2-dimethylbut-3-enyl-m-methoxyphenone-N-tosylhydrazone (10f)

were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O under blue

light irradiation for 16 h to obtain 58 mg (0.15 mmol) of 2-(3-

methoxyphenyl)-4,4,7-trimethyl-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13f (50%) as a white

solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.34 (d, 1H, J = 1.8 Hz,

Ar−H), 7.32 (dm, 1H, J = 6.6 Hz, Ar−H), 7.28 (d, 1H, J = 8.4 Hz,

Ar−H), 7.24 (t, 1H, J = 7.8 Hz, Ar−H), 6.90 (dd, J = 7.8, 2.0, 1H,

Ar−H), 6.74 (td, J = 3.6, 1.5 Hz, 1H, CH₂CHC), 5.25 (q, J = 1.8

Hz, 1H, CH₃CHCH), 4.01 (dd, J = 13.0, 2.4 Hz, 1H, N−CH), 3.82

(s, 3H, O−CH₃), 3.48 (m, 1H, CH₂CHCH), 2.75 (m, 2H,

CH₂-C(CH₃)₂), 2.35 (d, J = 18.3 Hz, 1H, CH-C(H)H-C(CH₃)), 2.26

(d, J = 18.5 Hz, 1H, CH-C(H)H-C(CH₃)), 1.77 (ddd, J = 13.4, 4.3,

2.5 Hz, 1H, CH-C(H)H-CH), 1.64 (s, 3H, CH₃CHCH), 1.22 (m,

1H, CH-C(H)H-CH), 1.11 (d, J = 3.0 Hz, 6H, CH₂−C(CH₃)₂).

¹³C{¹H} NMR (151 MHz, CDCl₃, Me₄Si) δ 159.7 (Cq), 148.9 (Cq),

138.5 (Cq), 135.5 (Cq), 131.9 (CH), 130.5 (Cq), 129.4 (CH), 121.2

(CH), 118.1 (CH), 115.1 (CH), 111.1 (CH), 62.5 (CH), 55.5

(CH₃), 35.4 (CH), 34.7 (CH₂), 31.5 (CH₂), 31.4 (CH₂), 31.0 (Cq),

28.3 (CH₃), 26.9 (CH₃), 22.7 (CH₃). mp 85.0−89.5 °C ν_max(neat)/

cm⁻¹3030, 2961, 1598, 1449, 1349, 1287. HRMS (ESI) m/z [M +

H]⁺Calcd for C₂₁H₂₇N₂O₃S 387.1737, found 387.1726.

4,4,7-Trimethyl-2-(p-tolyl)-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide (13d). Following the

general procedure A, 111 mg (0.30 mmol) of 2,2-dimethylbut-3-enyl-

p-tolyl ketone-N-tosylhydrazone (10d) were reacted with K₂CO₃and

[Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for 16 h to obtain

68.8 mg (0.18 mmol) of 4,4,7-trimethyl-2-(p-tolyl)-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13d

4,4,7-Trimethyl-2-(pyridin-2-yl)-3,4,4a,5,5a,8-hexahydrobenzo-

[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide (13g). Following the

general procedure A, 107 mg (0.30 mmol) of 2,2-dimethylbut-3-enyl-

pyridyl ketone-N-tosylhydrazone (10g) were reacted with K₂CO₃and

[Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for 16 h to obtain

40 mg (0.11 mmol) of 4,4,7-trimethyl-2-(pyridin-2-yl)-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13g

1

(62%) as a white solid. H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.66

(dd, J = 8.4, 1.8 Hz, 2H, Ar−H), 7.26 (bd, J = 8.4 Hz, 2H, Ar−H),

6.74 (td, J = 3.6, 1.8 Hz, 1H, CH₂CHC), 5.26 (dd, J = 12.6, 1.8

Hz, 1H, CH₃CHCH), 3.47 (m, 1H, CH₂−CH−CH), 2.76 (m, 1H,

CH₂-C(CH₃)₂), 2.37 (dd, J = 18.0, 0.6 Hz, 1H, CH-C(H)H-C(CH₃),

2.34 (s, 3H, Ar−CH₃), 2.25 (bd, J = 18.0, 1H, CH-C(H)H-C(CH₃),

1.76 (ddd, J = 13.2, 4.2, 2.4 Hz, 1H, CH-C(H)H-CH), 1.63 (s, 3H,

CH₃CHCH), 1.24 (d, J = 12.0 Hz, 1H, CH-C(H)H-CH), 1.20 (d,

J = 12.0 Hz, 1H, CH-C(H)H-CH), 1.11 (s, 3H, CH₂−C(CH₃)₂),

1.10 (s, 3H, CH₂−C(CH₃)₂). ¹³C{¹H} NMR (151 MHz, CDCl₃,

Me₄Si) δ 149.1 (Cq), 139.6 (Cq), 135.4 (Cq), 134.2 (Cq), 131.8

(CH), 130.5 (Cq), 129.1 (2 × CH), 125.5 (2 × CH), 121.2 (CH),

62.5 (CH), 35.4 (CH), 34.6 (CH₂), 31.4 (2 × CH₂), 31.0 (Cq), 28.3

(CH₃), 27.0 (CH₃), 22.7 (CH₃), 21.3 (CH₃). mp degradation 172.5−

180 °C. ν_max(neat)/cm⁻¹2971, 2916, 2862, 1449, 1344, 1177, 1159.

HRMS (ESI) m/z [M + H]⁺Calcd for C₂₁H₂₇N₂O₂S 371.1788, found

371.1777.

4,4,7-Trimethyl-2-(o-tolyl)-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide (13e). Following the

general procedure A, 111 mg (0.30 mmol) of 2,2-dimethylbut-3-enyl-

o-tolyl ketone-N-tosylhydrazone (10e) were reacted with K₂CO₃and

[Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for 16 h to obtain

57.7 mg (0.16 mmol) of 4,4,7-trimethyl-2-(o-tolyl)-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13e

(52%) as a white solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.17−

7.21 (m, 4H, Ar−H), 6.74 (td, J = 3.6, 1.8 Hz, 1H, CH₂CHC),

5.26 (m, 1H, CH₃CHCH), 3.99 (dd, J = 12.6, 1.8 Hz, 1H, C

CHCH), 3.51 (m, 1H, CH₂-C(CH₃)₂), 2.77 (dm, J = 6.6 Hz, 2H,

CH₂CHC), 2.34 (s, 3H, Ar−CH₃), 2.22 (dd, J = 19.0 1.2 Hz,

1H, CH-C(H)H-C(CH₃), 2.15 (d, J = 18.7 Hz, 1H, CH-C(H)H-

C(CH₃), 2.15 (ddd, J = 13.2, 4.8, 3.0 Hz, 1H, CH-C(H)H-CH), 1.69

(s, 3H, CH₃CHCH), 1.37 (d, J = 12.6 Hz, 1H, CH-C(H)H-CH),

1.33 (d, J = 12.6 Hz, 1H, CH-C(H)H-CH), 1.17 (s, 3H, CH₂−

C(CH₃)₂), 1.06 (s, 3H, CH₂−C(CH₃)₂). ¹³C{¹H} NMR (151 MHz,

CDCl₃, Me₄Si) δ 153.2 (Cq), 137.8 (Cq), 136.1 (Cq), 135.5 (Cq),

132.1 (CH), 131.1 (CH), 128.6 (CH), 127.8 (CH), 125.8 (CH),

1

(37%) as a white solid. H NMR (600 MHz, CDCl₃, Me₄Si) δ 8.52

(ddd, J = 4.8, 1.8, 0.9 Hz, 1H, Ar−H), 8.11 (dt, J = 8.1, 1.1 Hz, 1H,

Ar−H), 7.66 (ddd, J = 8.1, 7.4, 1.8 Hz, 1H, Ar−H), 7.24 (ddd, J = 7.4,

4.8, 1.2 Hz, 1H, Ar−H), 6.74 (td, J = 3.5, 1.5 Hz, 1H, CH₂CH

C), 5.26 (dq, J = 3.2, 1.6 Hz, 1H, CH₃CHCH), 4.02 (ddd, J = 12.7,

2.5, 1.2 Hz, 1H, N−CH), 3.52−3.45 (m, 1H, CH₂−CH−CH), 2.73

(dd, J = 19.3, 1.3 Hz, 1H, CH−CH₂−C(CH₃)₂), 2.38 (dd, J = 19.3,

1.0 Hz, 1H, CH-C(H)H-C(CH₃)), 1.81 (ddd, J = 13.4, 4.2, 2.5 Hz,

1H, CH-C(H)H-CH), 1.64 (dd, J = 1.9, 1.0 Hz, 3H, CH₃CHCH),

1.26 (dt, J = 13.4, 12.5 Hz, 1H, CH-C(H)H-CH), 1.11 (s, 3H, CH₂−

CH₃(CH₃)), 1.09 (s, 3H, CH₂−CH₃(CH₃)). ¹³C{¹H} NMR (151

MHz, CDCl₃, Me₄Si) δ 154.8 (Cq), 150.6 (Cq), 148.4 (CH), 136.3

(CH), 135.7 (Cq), 131.8 (CH), 130.4 (Cq), 124.0 (CH), 121.2

(CH), 120.6 (CH), 63.0 (CH), 35.4 (CH), 33.6 (CH₂), 31.7 (CH₂),

31.4 (CH₂), 30.7 (Cq), 28.3 (CH₃), 26.8 (CH₃), 22.7 (CH₃). mp

55.0−58.7 °C. ν_max(neat)/cm⁻¹3053, 2964, 1581, 1434, 1349, 1179.

HRMS (ESI) m/z [M + H]⁺Calcd for C₁₉H₂₄N₃O₂S 358.1584, found

358.1573.

4,7-Dimethyl-2,4-diphenyl-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide (13h). Following the

general procedure A, 125 mg (0.30 mmol) of 2-phenyl-2-methylbut-3-

enylphenone N-tosylhydrazone(10h)were reacted with K₂CO₃and

[Ru(bpy)₃]Cl₂·6H₂O for 16 h under blue light irradiation to obtain

43 mg (0.10 mmol) of 4,4,7-trimethyl-2-phenyl-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13h

1

(34%) as a white solid. H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.85

(m, 2H, Ar−H), 7.40 (m, 3H, Ar−H), 7.30 (m, 2H, Ar−H), 7.25 (m,

3H, Ar−H), 6.76 (tm, J = 3.0, Hz, 1H, CH₂CHC), 5.23 (q, J =

1.2 Hz, 1H, CH₃CHCH), 4.47 (dd, J = 12.6, 1.8 Hz, 1H, N−CH),

3.51 (bs, 1 H, CH₂CHCH), 3.21 (d, J = 18.4 Hz, 1H,

CPhMe−CH_2a), 2.78 (m, 2H, CH−CH₂−C(CH₃Ph), 2.54 (d, J =

18.4 Hz, 1H, CPhMe−CH_2b), 1.88 (ddd, J = 13.8, 4.2, 3.0 Hz, 1H,

CH-C(H)H-CH), 1.67 (s, 3H, CH₃CHCH), 1.43 (q, J = 13.0 Hz,

3316

https://dx.doi.org/10.1021/acs.joc.0c02605

J. Org. Chem. 2021, 86, 3300−3323

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

1H, CH-C(H)H-CH). ¹³C{¹H} NMR (151 MHz, CDCl₃, Me₄Si) δ

149.3 (Cq), 145.2 (Cq), 135.6 (Cq), 135.5 (Cq), 132.0 (CH), 130.7

(Cq), 129.7 (CH), 128.8 (2 × CH), 128.5 (2 × CH), 127.1 (CH),

125.7 (2 × CH), 125.4 (2 × CH), 121.1 (CH), 62.6 (CH), 35.3

(CH), 34.0 (CH₂), 32.2 (CH₂), 31.4 (CH₂), 29.8 (Cq), 26.5 (CH₃),

22.7 (CH₃). mp 113.0−117.0 °C. ν_max(neat)/cm⁻¹2964, 2929, 2256,

1498, 1412, 1338, 1180, 1157. HRMS (ESI) m/z [M + Na]⁺Calcd

for C₂₅H₂₆N₂O₂SNa 441.1607, found 441.1614.

(151 MHz, CDCl₃, Me₄Si) δ152.7 (Cq), 135.2 (Cq), 131.7 (CH),

126.7 (CH), 123.0 (CH), 62.0 (CH), 38.5 (CH₂), 34.3 (CH), 30.9

(Cq), 30.6 (CH₂), 28.2 (Cq), 26.8 (CH₂), 26.6 (CH₃), 24.2 (CH₃).

mp degradation 185.0−190.2 °C. ν_max(neat)/cm⁻¹2975, 712, 1639,

1341, 1171. HRMS (ESI) m/z [M + H]⁺Calcd for C₁₄H₂₁N₂O₂S

281.1318, found 281.1312.

2,9,12,12-Tetramethyl-3,8,9,10,11,11a,12,12a,13,13a-

decahydrobenzo[5,6][1,2]thiazino[2,3-b]cinnoline 5,5-dioxide

(13l). Following the general procedure A, 101 mg (0.300 mmol) of

pulegone tosylhydrazone (10l) were reacted with K₂CO₃and

[Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for 16 h to obtain

36, 5 mg (0.105 mmol) of 2, 9,12, 12-tetramethyl-

3,8,9,10,11,11a,12,12a,13,13a-decahydrobenzo[5,6][1,2]thiazino[2,3-

2,4,4,7-Tetramethyl-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide (13i). Following the

general procedure A, 88 mg (0.30 mmol) of 4,4-dimethylhex-5-en-2-

one-N-tosylhydrazone (10i) were reacted with K₂CO₃and [Ru-

(bpy)₃]Cl₂·6H₂O for 16 h under blue light irradiation to obtain 65 mg

(0.22 mmol) of 2,4,4,7-tetramethyl-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13i (73%) as a white

1

b]cinnoline 5,5-dioxide 13l (35%) as a white solid. H NMR (600

MHz, CDCl₃, Me₄Si) δ 6.72 (bs, 1H, CH₂CHC), 5.25 (bs, 1H,

CH₃CHCH), 3.90 (dd, J = 12.7, 2.3 Hz, 1H, N−CH), 3.40 (m, 1H,

CH₂−CH−C(CH₃)₂), 2.81 (dm, J = 22.2 Hz, 1H, CH_2a-CH-C(CH₃)

₂), 2.74 (dd, J = 22.2 Hz, 7.4 Hz, 1H, CH_2b-CH−C(CH₃) ₂), 2.58 (dt,

1

solid. H NMR (600 MHz, CDCl₃, Me₄Si) δ6.74 (t, J = 3.8 Hz, 1H,

CH₂CHC); 5.26 (q, J = 2.1 Hz 1H, CH₃CHCH); 3.87 (dd, J

= 12.8, 2.3 Hz, 1H, N−CH); 3.43 (bs, 1H, CH₂−CH−CH); 2.83

(ddd, J = 23.3, 7.8, 3.5 Hz, 1H, CH-C(H)H-C(CH₃)); 2.75 (dd, J =

22.7, 8.6, 1H, CH-C(H)H-C(CH₃)), 1.95 (s, 3H, CH₃CN);

1.88 (d, J = 18.9 Hz, 1H, CH-C(H)H-C(CH₃)₂); 1.84 (d, J = 19.0

Hz, 1H, CH-C(H)H-C(CH₃)₂), 1.72 (ddd, J = 13.5, 4.5, 2.3 Hz, 1H,

CH-C(H)H-CH), 1.69 (s, 3H, CH₃CHCH); 1.59 (d, J = 3.6, 1H,

CH(CH₃)CH), 1.17 (q, J = 12.9 Hz, 1H, CH-C(H)H-CH); 1.05

(s, 3H, CH₂−C(CH₃)CH₃); 1.00 (s, 3H, CH₂−C(CH₃) (CH₃)).

¹³C{¹H} NMR (151 MHz, CDCl₃, Me₄Si) δ 152.7 (Cq); 135.1 (Cq);

131.8 (CH); 130.6 (Cq); 121.4 (CH); 62.0 (CH); 38.6 (CH₂); 35.41

(CH); 31.5(CH₂); 31.01 (Cq); 30.9 (CH₂); 28.3(CH₃); 26.7(CH₃);

24.3(CH₃); 22.9(CH₃). mp degradation 192.0−195 °C. ν_max(neat)/

cm⁻¹2962, 1637, 1343, 1177, 1155. HRMS (ESI) m/z [M + Na]⁺

Calcd for C₁₅H₂₂N₂O₂SNa 317.1294, found 317.1294.

4,4-Dimethyl-2-phenyl-3,4,4a,5,5a,8-hexahydrobenzo[e]-

pyridazino[1,6-b][1,2]thiazine 10,10-dioxide (13j). Following the

general procedure A, 103 mg (0.30 mmol) of 2,2-dimethylbut-3-

enylphenone-N-phenylsulfonylhydrazone (11a) were reacted with

K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O for 16 h under blue light irradiation

to obtain 41 mg (0.120 mmol) of 4,4-dimethyl-2-phenyl-3,4,4a,5,5a,8-

hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine 10,10-dioxide 13j

(40%) as a white solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.80−

7.74 (m, 2H, Ar−H), 7.38−7.33 (m, 3H, Ar−H), 6.76 (bm, 1H,

CH₂CHC), 5.63 (dm, J = 10.1, 1H, CHCHCHCH₂,

1H), 5.54 (dm, J = 10.2, 3.3, 2.0 Hz, 1H, CH₃CHCH), 4.03 (dd, J

= 12.7, 2.5 Hz, 1H, N−CH), 3.52 (m, 1H, CH₂−CH−CH), 2.87 (tm,

J = 8.6 Hz, 2H), 2.39 (dd, J = 18.3, 1.1 Hz, 1H, CH-C(H)H-C(CH₃

2.29 (dd, J = 18.4, 0.9 Hz, 1H, CH-C(H)H-C(CH₃), 1.79 (ddd, J =

13.3, 4.2, 2.5 Hz, 1H, CH-C(H)H-CH), 1.29 (q, J = 12.8 Hz, 1H,

CH-C(H)H-CH), 1.12 (d, J = 1.8 Hz, 6H, CH₂−C(CH₃)₂). ¹³C{¹H}

NMR (151 MHz, CDCl₃, Me₄Si) δ 149.1 (Cq), 136.9 (Cq), 135.5

(Cq), 131.8 (CH), 129.5 (CH), 128.4 (2 × CH), 126.6 (CH), 125.6

(2 × CH), 123.0 (CH), 62.5 (CH), 34.6 (CH₂), 34.4 (CH), 31.2

(CH₂), 31.0 (Cq), 28.3 (CH₃), 27.0 (CH₃), 26.8 (CH₂). mp 141.9−

144.5 °C. ν_max(neat)/cm⁻¹3059, 2956, 2922, 2868, 1445, 1349,

1169, 1019, 955. HRMS (ESI) m/z [M + Na]⁺Calcd for

C₁₉H₂₂N₂O₂SNa 365.1294, found 365.1285.

J = 14.5, 2.4 Hz, 1H, CH-CH_2a-C(CH₃)), 1.84 (m, 2H, CH(CH₃)−

CH₂−CN), 1.72 (d, J = 13.7 Hz, 1H, CH−CH_2a−CH₂), 1.68 (m,

1H, CH(CH₃)-CH₂-C(H)H-CH); 1.67 (s, 3H, CH₃CHCH); 1.59

(bm, 1H, CH₂−CH(CH₃)−CH₂), 1.55 (s, 2H, CH₃CHCH),

1.32−1.19 (m, 2H, CH(CH₃)-CH₂-C(H)H-CH with CH₂−C-

(CH)N), 1.06 (qd, J = 12.5, 11.4, Hz, 1H, CH(CH₃)−C(H)H−

CH₂−CH), 1.00 (s, 3H, (CH₃)_2a), 0.99 (s, 3H, (CH₃)_2b), 0.93 (d, J =

6.5 Hz, 3H, CH−CH₃). ¹³C{¹H} NMR (151 MHz, CDCl₃, Me₄Si) δ

158.3 (Cq), 135.1 (Cq), 132.0 (CH), 130.5 (CH), 121.3 (CH), 64.7

(CH), 43.3 (Cq), 42.5 (Cq), 35.5 (CH), 34.1 (CH₂), 33.8 (Cq), 33.2

(CH), 31.4 (CH₂), 30.0 (CH₂), 25.6 (CH₂), 25.1 (CH₃), 24.9

(CH₃), 22.8 (CH₃), 22.1 (CH₃). mp degradation 118.0−124.0 °C.

ν_max(neat)/cm⁻¹2949, 1737, 1630, 1453, 1352, 1150. HRMS (ESI)

m/z [M + H]⁺Calcd for C₁₉H₂₉N₂O₂S 349.1944, found 349.1936.

General Procedure for the Photoirradiation of β-Hindered-

γ,δ-Unsaturated N-Mesitylsulfonylhydrazones (12) and Inter-

nal β-Hindered-γ,δ-Unsaturated N-Arylsulfonylhydrazones

(10j,k). In a sealed photochemical reactor, 6.75 mg of [Ru(bpy)₃]-

Cl₂·6H₂O (0.009 mmol) were dissolved in 5 mL of anhydrous

CH₃CN, the solution was degassed with N₂for 15 min then the

suitable arylsulfonylhydrazone (12a−g, 10j,k) (0.30 mmol) and 62.2

mg of K₂CO₃(0.45 mmol) were added. The solution was then stirred

at 4 cm from the irradiation source (see above) at room temperature

until the reaction was completed as monitored by TLC analysis.

Then, it was ﬁltered on a short pad of silica gel using CH₂Cl₂as eluent

and Et₂O to wash the column. The crude product was puriﬁed by

ﬂash chromatography on silica gel (hexane/Et₂O 9/1).

1-(Mesitylsulfonyl)-4,5,5-trimethyl-3-phenyl-1,4,5,6-tetrahydro-

pyridazine (14a). According to general procedure 115 mg (0.30

mmol) of 2,2-dimethylbut-3-enylphenone-N-2,4,6-mesitylsulfonylhy-

drazone 12a were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O

under blue light irradiation for 16 h to obtain 57.5 mg (0.15 mmol) of

1-(mesitylsulfonyl)-4,5,5-trimethyl-3-phenyl-1,4,5,6-tetrahydropyrida-

zine 14a (50%) as a white solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si)

δ 7.56 (d, J = 6.8 Hz, 2H, Ar−H), 7.30 (m, 3H, Ar−H), 6.97 (s, 2H,

Ar−H), 4.14 (q, J = 6.6 Hz, 1H, N−CH), 2.74 (s, 6H, ortho Ar-

(CH₃)), 2.40 (d, J = 18.0 Hz, 1H, (CH₃)₂-CH-C(H)H)), 2.30 (s, 3H,

para Ar-(CH₃)), 2.26 (d, J = 18.0, 1H, (CH₃)₂-CH-C(H)H), 1.30 (d,

J = 6.6 Hz, 3H,N−CH−CH₃), 1.11 (s, 3H, CH(CH₃)−C(CH₃)₂),

0.94 (s, 3H, CH(CH₃)−C(CH₃)₂). ¹³C{¹H} NMR (151 MHz,

CDCl₃, Me₄Si) δ 145.3 (Cq), 142.7 (Cq), 141.0 (2 × Cq), 137.3

(Cq), 133.1 (Cq), 131.8 (2 × CH), 129.0 (CH), 128.3 (2 × CH),

125.3 (2 × CH), 56.5 (CH), 33.4 (CH₂), 30.9 (Cq), 28.5 (CH₃),

27.0 (CH₃), 23.5 (2 × CH₃), 21.1 (CH₃), 15.1 (CH₃). mp 136.5−

139.4 °C. ν_max(neat)/cm⁻¹2964, 2930, 2873, 1598, 1461, 1443,

1327, 1162. HRMS (ESI) m/z [M + H]⁺Calcd for C₂₂H₂₉N₂O₂S

385.1944, found 385.1942.

2,4,4-Trimethyl-3,4,4a,5,5a,8-hexahydrobenzo[e]pyridazino[1,6-

b][1,2]thiazine 10,10-dioxide (13k). Following the general procedure

A, 84 mg (0.30 mmol) of 4,4-dimethylhex-5-en-2-one-N-phenyl-

sulfonylhydrazone (11b) were reacted with K₂CO₃and [Ru(bpy)₃]-

Cl₂·6H₂O under blue light irradiation for 16 h to obtain 46 mg (0.165

mmol) of 2,4,4-trimethyl-3,4,4a,5,5a,8-hexahydrobenzo[e]pyridazino-

1

[1,6-b][1,2]thiazine 10,10-dioxide 13k (55%) as a white solid. H

NMR (600 MHz, CDCl₃, Me₄Si) δ 6.74 (bs, 1H, CH₂CHC),

5.67 (dm, J = 10.2 Hz, 1H, CHCHCHCH₂), 5.54 (dm, J =

10.1 Hz, 1H, CH−CHCH-CH₂), 3.87 (dd, J = 12.8, 2.3 Hz, 1H,

N−CH), 3.45 (m, 1H, CH₂−CH−CH), 2.94 (dm, J = 23.9 Hz, 1H,

CH-C(H)H-C(CH₃)), 2.85 (ddq, J = 23.9, 8.7, 3.3 Hz, 1H, CH-

C(H)H-C(CH₃)), 1.95 (s, 3H, CH₃CN), 1.87 (d, J = 6.5 Hz,

2H, CH−CH₂−C(CH₃)₂), 1.72 (ddd, J = 13.3, 4.2, 2.4 Hz, 1H, CH-

C(H)H-CH), 1.22 (q, J = 12.8 Hz, 1H, CH-C(H)H-CH), 1.05 (s,

3H, CH₂−C(CH₃)₂), 0.99 (s, 3H, CH₂−C(CH₃)₂). ¹³C{¹H} NMR

1-(Mesitylsulfonyl)-5,5,6-trimethyl-3-(naphthalen-2-yl)-1,4,5,6-

tetrahydropyridazine (14b). According to the general procedure, 130

mg(0.30 mmol) of 2,2-dimethylbut-3-enylnaphtone-N-2,4,6-mesityl-

sulfonylhydrazone (12b) were reacted with K₂CO₃and [Ru(bpy)₃]-

Cl₂·6H₂O under blue light irradiation for 16 h to obtain 54 mg (0.12

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mmol) of 1-(mesitylsulfonyl)-5,5,6-trimethyl-3-(naphthalen-2-yl)-

1,4,5,6-tetrahydropyridazine 14b (42%) as a white solid. H NMR

C(CH₃)₂). ¹³C{¹H}NMR (151 MHz, CDCl₃, Me₄Si) δ 148.3 (Cq),

142.3 (Cq), 141.0 (2 × Cq), 133.6 (Cq), 131.6 (2 × CH), 55.9

(CH), 37.2 (CH₂), 31.0 (Cq), 28.4 (CH₃), 26.8 (CH₃), 24.1 (CH₃),

23.4 (2 × CH₃), 21.1 (CH₃), 14.5(CH₃). mp degradation 150−170

°C. ν_max(neat)/cm⁻¹2967, 1712, 1602, 1314, 1080. HRMS (ESI) m/

z [M + H]⁺Calcd for C₁₇H₂₇N₂O₂S 323.1788, found 323.1776.

(7R)-2-(Mesitylsulfonyl)-3,4,4,7-tetramethyl-2,3,4,4a,5,6,7,8-oc-

tahydrocinnoline (14f). According to the general procedure, 105 mg

(0.30 mmol) of pulegone derivative N-mesitylsulfonylhydrazone

(12g) were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O under

blue light irradiation for 16 h to obtain 37 mg (0.124 mmol) of (7R)-

2-(mesitylsulfonyl)-3,4,4,7-tetramethyl-2,3,4,4a,5,6,7,8-octahydrocin-

noline 14f (35%) as a white solid. ¹H NMR (600 MHz, CDCl₃,

Me₄Si) δ 6.92 (s, 2H, Ar−H), 3.97 (q, J = 6.6 Hz, 1H, N−C(CH₃)

H), 2.68 (s, 6H, ortho Ar−CH₃), 2.35 (ddd, J = 14.7, 4.1, 2.3 Hz, 1H,

CH−CH₂-C(CH₃)H), 2.28 (s, 3H, para Ar-(CH₃)), 1.86 (dd, J =

12.0, 4.4 Hz, 1H, C(H)HCN); 1.81−1.77 (m, 2H, CH−C(H)

H−CH₂−CH), 1.72 (t, J = 12.6, 1H, CH-C(H)H-C(CH₃)H), 1.49−

1.42 (m, 1H, CH−CH₂−C(H)H−CH), 1.18 (d, J = 6.6 Hz, 3H, N−

CH−CH₃), 1.17−0.98 (m, 2H, CH−C(H)H−CH₂−CH with CH−

CH₂−C(H)H−CH), 0.96 (s, 3H, −C(CH₃)−CH₃), 0.90 (d, J = 6.5

Hz, 3H, CH₂−CH(CH₃)−CH₂), 0.84 (s, 3H, −C(CH₃)−CH₃).

¹³C{¹H} NMR (151 MHz, CDCl₃, Me₄Si) δ 153.9 (Cq), 142.3 (Cq),

1

(600 MHz, CDCl₃, Me₄Si) δ 7.90 (s, 1H, Ar−H), 7.79 (m, 3H, Ar−

H), 7.74 (d, J = 8.7 Hz, 1H, Ar−H), 7.45 (m, 2H, Ar−H), 6.99 (s,

2H, Ar−H), 4.17 (q, J = 6.6 Hz, 1H, N−CH), 2.78 (s, 6H, ortho Ar-

(CH₃)), 2.52 (d, J = 17.7 Hz, 1H, (CH₃)₂-CH-C(H)H))), 2.42 (d, J

= 17.7 Hz, 1H, (CH₃)₂-CH-C(H)H)), 2.31 (s, 3H, para Ar-(CH₃)),

1.34 (d, J = 6.6 Hz, 3H, N−CH−CH₃)), 1.16 (s, 3H, CH(CH₃)−

C(CH₃)₂), 0.98 (s, 3H, CH(CH₃)−C(CH₃)₂). ¹³C{¹H} NMR (151

MHz, CDCl₃, Me₄Si) δ 145.2 (Cq), 142.8 (Cq), 141.0 (2 × Cq),

134.9 (Cq), 133.6 (Cq), 133.1 (Cq), 133.0 (Cq), 131.8 (2 × CH),

128.4 (CH), 127.9 (CH), 127.7 (CH), 126.6 (CH), 126.4 (CH),

124.7 (CH), 123.1 (CH), 56.6 (CH), 33.3 (CH₂), 30.9 (Cq), 28.6

(CH₃), 27.1 (CH₃), 23.5 (2 × CH₃), 21.1 (CH₃), 15.1 (CH₃). mp

136.2−139.8 °C. ν_max(neat)/cm⁻¹3052, 2958, 1602, 1503, 1321,

1160. HRMS (ESI) m/z [M + H]⁺Calcd for C₂₆H₃₁N₂O₂S 435.2101,

found 435.2090.

1-(Mesitylsulfonyl)-5,5,6-trimethyl-3-(p-tolyl)-1,4,5,6-tetrahydro-

pyridazine (14c). According to the general procedure, 119 mg (0.30

mmol) of 2,2-dimethylbut-3-enyl-p-tolyl ketone-N-mesitylsulfonylhy-

drazone (12c) were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O

under blue light irradiation for 16 h to obtain 74 mg (0.19 mmol) of

1-(mesitylsulfonyl)-5,5,6-trimethyl-3-(p-tolyl)-1,4,5,6-tetrahydropyri-

1

dazine 14c (62%) as a white solid. H NMR (600 MHz, CDCl₃,

141.1 (2 × Cq), 133.6 (Cq), 131.6 (2 × CH), 58.4 (CH), 42.9

(CH₂), 41.03 (CH), 34.0 (CH₂), 32.8 (CH), 25.3 (CH₃), 25.1

(CH₂), 24.9 (CH₃), 23.4 (2 × CH₃), 22.2 (CH₃), 21.1 (CH₃), 13.2

(CH₃). mp degradation 106−115 °C. ν_max(neat)/cm⁻¹3001, 2937,

1627, 1602, 1379, 1159. HRMS (ESI) m/z [M + H]⁺Calcd for

C₂₁H₃₃N₂O₂S 377.2257, found 377.2244.

Me₄Si) δ 7.46 (d, J = 7.8 Hz, 1H, Ar−H), 7.10 (d, J = 7.8 Hz, 1H,

Ar−H), 6.95 (s, 2H, Ar−H), 4.12 (q, J = 6.6 Hz, 1H, N−CH), 2.76

(s, 6H, ortho Ar-(CH₃)₂), 2.38 (d, J = 18.0 Hz, 1H, (CH₃)₂-CH-C(H)

H), 2.32 (s, 3H, para Ar−CH₃), 2.29 (s, 3H, Ar−CH₃, tolyl), 2.23 (d,

J = 18.0 Hz, 1H, (CH₃)₂-CH-C(H)H), 1.29 (d, J = 6.6 Hz, 3H, N−

CH−CH₃), 1.10 (s, 3H, CH(CH₃)−C(CH₃)₂), 0.92 (s, 3H,

CH(CH₃)−C(CH₃)₂). ¹³C{¹H}NMR (151 MHz, CDCl₃, Me₄Si) δ

145.4 (Cq), 142.6 (Cq), 141.0 (2 × Cq), 138.9 (Cq), 134.6 (Cq),

133.2 (Cq), 131.7 (2 × CH), 129.0 (2 × CH), 125.2 (2 × CH), 54.4

(CH), 33.4 (CH₂), 30.9 (Cq), 28.5 (CH₃), 27.0 (CH₃), 23.5 (2 ×

CH₃), 21.3 (CH₃), 21.1 (CH₃), 15.0 (CH₃). mp 142.0−147.0 °C.

ν_max(neat)/cm⁻¹3020, 2958, 1682, 1611, 1511, 1324, 1109. HRMS

(ESI) m/z [M + Na]⁺Calcd for C₂₃H₃₀N₂O₂SNa 421.1920, found

421.1919.

5,5-Dimethyl-3-phenyl-6-(2,4,6-trimethylbenzyl)-1,4,5,6-tetrahy-

dropyridazine (15a). According to general procedure 115 mg (0.30

mmol) of 2,2-dimethylbut-3-enylphenone-N-2,4,6-mesitylsulfonylhy-

drazone 12a were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O

under blue light irradiation for 16 h to obtain 43 mg (0.13 mmol) of

5,5-dimethyl-3-phenyl-6-(2,4,6-trimethylbenzyl)-1,4,5,6-tetrahydro-

pyridazine 15a (45%) as a greenish oil. ¹H NMR (600 MHz, CDCl₃,

Me₄Si) δ 7.62 (d, J = 7.2 Hz, 2H, Ar−H), 7.31 (tm, J = 7.5, 2H, Ar−

H), 7.24 (m, 1H, Ar−H), 6.85 (s, 2H, Ar−H), 5.39 (bs, 1H, N−H),

3.06 (dm, J = 11.5 Hz, 1H, NH−CH−C(H)H−CH), 2.89 (dd, J =

13.8, 3.5 Hz, 1H, NH−CH−C(H)H−CH), 2.77 (tm, J = 12.5, 1H,

NH−CH), 2.43 (d, J = 17.6 Hz, 1H, NC(Ph)C(H)H), 2.38 (d, J

= 17.7 Hz, 1H, NC(Ph)C(H)H), 2.33 (s, 6H, ortho Ar-(CH₃)),

2.25 (s, 3H, para Ar-(CH₃)), 1.18 (s, 3H C(CH₃)−CH₃), 1.11 (s,

3H, C(CH₃)−CH₃). ¹³C{¹H} NMR (151 MHz, CDCl₃, Me₄Si) δ

141.6 (Cq), 138.8 (Cq), 137.3 (2 × Cq), 136.0 (Cq), 131.5 (Cq),

129.5 (2 × CH), 128.3 (2 × CH), 127.6 (CH), 124.2 (2 × CH), 59.0

(CH), 39.1 (CH₂), 30.6 (Cq), 27.4 (2 × CH₃), 26.8 (CH₂), 22.4

(CH₃), 20.9 (CH₃), 20.6 (CH₃). ν_max(neat)/cm⁻¹3064, 2978, 1598,

1428, 1379, 1065. HRMS (ESI) m/z [M + H]⁺Calcd for C₂₂H₂₉N₂

321.2325, found 321.2330.

5,5-Dimethyl-3-(naphthalen-2-yl)-6-(2,4,6-trimethylbenzyl)-

1,4,5,6-tetrahydropyridazine (15b). According to general Procedure

B, 130 mg (0.30 mmol) of 2,2-dimethylbut-3-enylnaphtone-N-2,4,6-

mesitylsulfonylhydrazone (12b) were reacted with K₂CO₃and

[Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for 16 h to obtain

35 mg (0.093 mmol) of 5,5-dimethyl-3-(naphthalen-2-yl)-6-(2,4,6-

trimethylbenzyl)-1,4,5,6-tetrahydropyridazine15b (30%) as a greenish

solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.94 (dd, J = 8.8, 1.8 Hz,

1H, Ar−H), 7.86 (s, 1H, Ar−H), 7.76 (m, J = 15.9, 7.7 Hz, 3H, Ar−

H), 7.43 (q, J = 6.6 Hz, 2H, Ar−H), 6.86 (s, 2H, Ar−H), 5.48 (s, 1H,

N−H), 3.09 (dd, J = 11.6, 2.7 Hz, 1H, NH−CH−C(H)H−CH), 2.89

(dd, J = 13.7, 3.1 Hz, 1H, NH−CH), 2.80 (dd, J = 13.7, 11.6 Hz, 1H,

NH−CH−C(H)H−CH), 2.51 (d, J = 2.8 Hz, 2H, NC(Ar)−CH₂),

2.32 (s, 6H, ortho Ar-(CH₃)), 2.23 (s, 3H, para Ar-(CH₃), 1.20 (s,

3H, C(CH₃)−CH₃), 1.13 (s, 3H, C(CH₃)−CH₃). ¹³C{¹H} NMR

(151 MHz, CDCl₃, Me₄Si) δ 141.3 (Cq), 137.3 (2 × Cq), 136.3

(Cq), 136.0 (Cq), 133.5 (Cq), 133.0 (Cq), 131.4 (Cq), 129.5 (2 ×

CH), 128.2 (CH), 127.7 (CH), 127.7 (CH), 126.1 (CH), 125.8

(CH), 122.9 (CH), 122.7 (CH), 59.1 (CH), 39.0 (CH₂), 30.6 (Cq),

27.5 (2 × CH₃), 26.9 (CH₂), 22.4 (CH₃), 20.9 (CH₃), 20.6 (CH₃).

1-(Mesitylsulfonyl)-5,5,6-trimethyl-3-(o-tolyl)-1,4,5,6-tetrahydro-

pyridazine (14d). According to the general procedure, 119 mg (0.30

mmol) of 2,2-dimethylbut-3-enyl-o-tolyl ketone-N-mesitylsulfonylhy-

drazone (12d) were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O

under blue light irradiation for 16 h to obtain 49 mg (0.13 mmol) of

1-(mesitylsulfonyl)-5,5,6-trimethyl-3-(o-tolyl)-1,4,5,6-tetrahydropyri-

1

dazine 14d (42.5%) as a white solid. H NMR (600 MHz, CDCl₃,

Me₄Si) δ 7.13 (m, 4H), 6.89 (s, 2H, Ar−H), 4.10 (q, J = 6.6 Hz, 1H),

2.76 (s, 6H, ortho Ar-(CH₃)₂), 2.43 (d, J = 18.0 Hz, 1H, (CH₃)₂-CH-

C(H)H), 2.27 (s, 3H, para Ar−CH₃), 2.01 (s, 3H, ortho tolyl), 1.99

(d, J = 18.0 Hz, 1H, (CH₃)₂-CH-C(H)H),), 1.35 (d, J = 6.6 Hz, 3H,

N−CH−CH₃), 1.06 (s, 3H, CH(CH₃)−C(CH₃)₂), 0.99 (s, 3H,

CH(CH₃)−C(CH₃)₂). ¹³C{¹H}NMR (151 MHz, CDCl₃, Me₄Si) δ

148.1 (Cq) 141.0 (2 × Cq), 138.3 (Cq), 136.0 (Cq), 133.3 (Cq)

131.7 (2 × CH), 131.0 (CH), 128.1 (CH), 127.7 (CH), 125.5 (CH),

56.1 (CH), 37.0 (CH₂), 31.0 (Cq), 29.8 (CH₃), 28.4 (CH₃), 26.8

(CH₃), 23.3 (CH₃), 21.0 (CH₃), 20.1 (CH₃), 15.2 (CH₃). mp 112.0−

116.7 °C. ν_max(neat)/cm⁻¹2992, 2958, 1602, 1456, 1317, 1161,

1032, 776. HRMS (ESI) m/z [M + H]⁺Calcd for C₂₃H₃₁N₂O₂S

399.2101, found 399.2087.

1-(Mesitylsulfonyl)-3,5,5,6-tetramethyl-1,4,5,6-tetrahydropyrida-

zine (14e). According to the general procedure, 97 mg (0.30 mmol)

of 4,4-dimethylhex-5-en-2-one-N-mesitylhydrazone 12e were reacted

with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for

16 h to obtain 53 mg (0.165 mmol) of 1-(mesitylsulfonyl)-3,5,5,6-

tetramethyl-1,4,5,6-tetrahydropyridazine 14e (55%) as a white solid.

¹H NMR (600 MHz, CDCl₃, Me₄Si) δ 6.92 (s, 2H, Ar−H), 3.97 (qd,

J = 6.6, 1.5 Hz, 1H, N−CH), 2.68 (s, 6H, ortho Ar-(CH₃)), 2.28 (s,

3H, para Ar-(CH₃)), 2.00 (d, J = 18.5 Hz, 1H, (CH₃)₂-CH-C(H)H)),

1.82 (s, 3H, NCCH₃), 1.67 (dd, J = 18.5, 1.5 Hz, 1H, (CH₃)₂-

CH-C(H)H)), 1.21 (d, J = 6.6 Hz, 3H, N−CH−CH₃)), 0.98 (s, 3H,

CH(CH₃)−C(CH₃)₂), 0.88 (d, J = 0.9 Hz, 3H, CH(CH₃)−

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mp 124.5−128.7 °C. ν_max(neat)/cm⁻¹3052, 2961, 1606, 1479, 1365,

1260. HRMS (ESI) m/z [M + H]⁺Calcd for C₂₆H₃₁N₂371.2482,

found 371.2490.

16 h to obtain 66 mg (0.22 mmol) 5,5-dimethyl-3-phenyl-6-(2,4,6-

trimethylbenzyl)-1,4,5,6-tetrahydropyridazine 15f (72%) as a yellow

solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ7.55 (dd, J = 8.4 Hz, 2H,

PhH), 7.55 (tm, J = 7.2 Hz, 2H, PhH), 7.22 (tt, J = 7.2 Hz, 1.2, 1H,

PhH), 7.15 (dm, J = 6.6 Hz, 2H, Ar−H), 7.11 (dm, J = 6.6 Hz, 2H,

Ar−H), 5.40 (s, 1H, N−H), 2.99 (d, J = 7.8 Hz, 1H, CH-ring), 2.92

(quint, J = 7.2 Hz, 1H, tol−CH−CH₃), 2.40 (d, J = 18.0 Hz, 1H,

C(H)H-ring), 2.32 (s, 3H, Ar−CH₃), 2.20 (d, J = 18.0 Hz, 1H, C(H)

H-ring), 1.41 (d, J = 7.2 Hz, 3H, J = 7.2 Hz, 1H, Tol-CH−CH₃), 1.20

(s, 3H, CH₃ring), 0.90 (s, 3H, CH₃ring). ¹³C{¹H}NMR (151 MHz,

CDCl₃, Me₄Si) δ 141.2 (Cq), 140.9 (Cq), 138.8 (Cq), 136.4 (Cq),

129.5 (2 × CH), 128.2 (2 × CH), 128.0 (2 × CH), 127.4 (CH),

124.2 (2 × CH), 65.4 (CH), 40.3 (CH₂), 40.2 (CH), 31.0 (Cq), 29.4

(CH₃), 22.7 (CH₃), 22.5 (CH₃), 21.1 (CH₃). mp 89.0−95.8 °C. ν_max

(neat)/cm⁻¹3381, 3010, 2990, 1591, 1514, 1467, 1338, 1324, 1071.

HRMS (ESI) m/z [M + H]⁺Calcd for C₂₁H₂₇N₂307.2169, found

307.2175.

5,5-Dimethyl-3-(p-tolyl)-6-(2,4,6-trimethylbenzyl)-1,4,5,6-tetra-

hydropyridazine (15c). According to the general procedure, 119 mg

(0.30 mmol) of 2,2-dimethylbut-3-enyl-p-tolyl ketone-N-mesitylsulfo-

nylhydrazone (12c) were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·

6H₂O under blue light irradiation for 16 h to obtain 25 mg (0.075

mmol) of 5,5-dimethyl-3-(p-tolyl)-6-(2,4,6-trimethylbenzyl)-1,4,5,6-

tetrahydropyridazine 15c (25%) as a greenish oil. ¹H NMR (600

MHz, CDCl₃, Me₄Si) δ 7.52 (dm, J = 8.4, 2H, Ar−H), 7.13 (d, J = 8.4

Hz, 2H, Ar−H), 6.86 (s, 2H, Ar−H), 5.34 (bs, 1H, N−H), 3.05 (dd, J

= 11.4, 3.0 Hz, 1H, NH−CH−C(H)H−CH), 2.89 (dd, J = 13.8, 3.6

Hz, 1H, NH−CH), 2.80 (dd, J = 13.8, 11.4 Hz, 1H, NH−CH−C(H)

H−CH), 2.43 (d, J = 17.4 Hz, 1H, NC(Ar)−CH_2a), 2.36 (d, J =

17.4 Hz, 1H, NC(Ar)−CH_2b), 2.34 (s, 6H, ortho Ar−CH₃), 2.33

(s, 3H, para Ar-(CH₃), 2.25 (s, 3H, para Ar-(CH₃), 1.18 (s, 3H,

C(CH₃)−CH₃), 1.12 (s, 3H, C(CH₃)−CH₃). ¹³C{¹H}NMR (151

MHz, CDCl₃, Me₄Si) δ 142.1 (Cq), 137.2 (2 × Cq), 136.0 (2 × Cq),

131.7 (Cq), 131.5 (2 × Cq), 129.5 (2 × CH), 129.2 (Cq), 129.0 (2 ×

CH), 124.3 (2 × CH), 59.0 (CH), 39.2 (CH₂), 30.6 (Cq), 27.4 (2 ×

CH₃), 26.8 (CH₂), 22.3 (CH₃), 21.2 (CH₃), 20.9 (CH₃), 20.5 (CH₃).

ν_max(neat)/cm⁻¹3372, 2958, 2916, 2885, 1511, 1460, 1366, 1324.

HRMS (ESI) m/z [M + H]⁺Calcd for C₂₃H₃₁N₂335.2482, found

335.2481.

3,5,5-Trimethyl-6-(1-tolylethyl)-1,4,5,6-tetrahydropyridazine

(15g). According to the general procedure, 92 mg (0.30 mmol) of 4,4-

dimethylhept-5-enone-N-tosylhydrazone 10k were reacted with

K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for 16

h to obtain 51.2 mg (0.21 mmol) 5,5-dimethyl-3-phenyl-6-(2,4,6-

trimethylbenzyl)-1,4,5,6-tetrahydropyridazine 15g (70%) as a yellow-

1

ish oil. H NMR (600 MHz, CDCl₃, Me₄Si) δ 7.11 (m, J = 6.6 Hz,

2H, Ar−H), 7.06 (dm, J = 6.6 Hz, 2H, Ar−H), 5.40 (s, 1H, N−H),

2.92 (q, J = 7.2 Hz, 1H, Tol−CH−CH₃), 2.74 (d, J = 7.2 Hz, 1H,

CH-ring), 2.31 (s, 3H, Ar−CH₃), 1.98 (d, J = 16.8 Hz, 1H, C(H)H-

ring), 1.73 (s, 3H, NCCH₃), 1.67 (d, J = 16.8 Hz, 1H, C(H)H-

ring), 1.34 (d, J = 7.2 Hz, 3H, J = 7.2 Hz, 1H, Tol-CH−CH₃), 1.08 (s,

3H, CH₃ring), 0.88 (s, 3H, CH₃ring). ¹³C{¹H NMR (151 MHz,

CDCl₃, Me₄Si) δ 144.8 (Cq), 141.5 (Cq), 136.2 (Cq), 129.3 (2 ×

CH), 128.0 (2 × CH), 65.3 (CH), 44.4 (CH₂), 40.0 (CH), 31.6

(Cq), 29.2 (CH), 23.2 (CH₃), 22.7 (CH₃), 22.4 (CH₃), 21.1 (CH₃).

ν_max(neat)/cm⁻¹3060, 2964, 1498, 1338, 1260, 1157. HRMS (ESI)

m/z [M + H]⁺Calcd for C₁₆H₂₅N₂245.2012, found 245.2006.

5,5-Dimethyl-3-phenyl-6-(1-mesityllethyl)-1,4,5,6-tetrahydropyr-

idazine (15h). According to the general procedure, 119 mg (0.30

mmol) of 2,2-dimethylpent-3-en-2-one-N-mesitylsulfonylhydrazone

12f were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O under blue

light irradiation for 16 h to obtain 66 mg (0.22 mmol) 5,5-dimethyl-3-

phenyl-6-(2,4,6-trimethylbenzyl)-1,4,5,6-tetrahydropyridazine 15h

(72%) as a yellow solid. ¹H NMR (600 MHz, CDCl₃, Me₄Si) δ

7.58 (dd, J = 7.2, 1.8 Hz, 2H, PhH), 7.31 (tm, J = 7.2 Hz, 2H, PhH),

7.24 (tm, J = 7.2 Hz, 1H, PhH, isomer A), 7.22 (tm, J = 7.2 Hz, 1H,

PhH, isomer B), 6.83 (s, 2H, Mes−H, isomer A), 6.82 (s, 2H, Mes−

H, isomer B), 5.31 (s, 1H, N−H), 3.51 (quint, J = 7.2 Hz, 1H, Tol−

CH−CH₃), 3.32 (d, J = 9.0 Hz, 1H, CH-ring), 2.52 (d, J = 17.4 Hz,

1H, C(H)H-ring), 2.39 (s, 3H, Ar−CH₃), 2.34 (s, 3H, Ar−CH₃), 2.28

(d, J = 17.4 Hz, 1H, C(H)H-ring), 2.24 (s, 3H, Ar−CH₃), 1.45 (d, J =

7.2 Hz, 3H, J = 7.2 Hz, 1H, tol-CH−CH₃), 1.25 (s, 3H, CH₃ring),

1.10 (s, 3H, CH₃ring). ¹³C{¹H}NMR (151 MHz, CDCl₃, Me₄Si)

(mixture of isomers) δ 140.3 (Cq), 138.8 (Cq), 137.4 (Cq), 136.1

(Cq), 135.9 (Cq), 131.4 (CH), 129.8 (2 × CH), 128.3 (2 × CH),

127.4 (CH), 124.1 (2 × CH), 63.5 (CH), 40.7 (CH₂), 40.2 (Cq),

34.2 (CH), 31.5 (Cq), 29.5 (CH₃), 22.6 (CH₃), 21.9 (CH₃), 21.4

(CH₃), 20.7 (CH₃), 20.2 (CH₃). ν_max(neat)/cm⁻¹3394, 3010, 2992,

1608, 1572, 1445, 1307, 1131. mp 85.4−89.7 °C. HRMS (ESI) m/z

[M + H]⁺Calcd for C₂₃H₃₁N₂335.2482, found 335.2482.

5,5-Dimethyl-3-(o-tolyl)-6-(2,4,6-trimethylbenzyl)-1,4,5,6-tetra-

hydropyridazine (15d). According to the general procedure, 119 mg

(0.30 mmol) of 2,2-dimethylbut-3-enyl-o-tolyl ketone-N-mesitylsulfo-

nylhydrazone (12d) were reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·

6H₂O under blue light irradiation for 16 h to obtain 16 mg (0.06

mmol) of 5,5-dimethyl-3-(o-tolyl)-6-(2,4,6-trimethylbenzyl)-1,4,5,6-

tetrahydropyridazine 15d (19%) as a greenish oil. ¹H NMR (600

MHz, CDCl₃, Me₄Si) δ 7.15 (m, 4H, Ar−H), 6.85 (s, 2H, Ar−H),

5.04 (bs, 1H, N−H), 3.07 (dd, J = 11.4, 3.0 Hz, 1H, NH−CH−C(H)

H−CH), 2.89 (dd, J = 13.8, 3.6 Hz, 1H, NH−CH), 2.78 (dd, J = 13.8,

11.4 Hz, 1H, NH−CH−C(H)H−CH), 2.36 (d, J = 17.4 Hz, 1H, N

C(Ar)−CH_2a), 2.34 (s, 6H, ortho Ar−CH₃), 2.33 (s, 3H, ortho tolyl),

2.24 (s, 3H, para Ar-(CH₃)), 2.23 (d, J = 17.4 Hz, 1H, NC(Ar)−

CH_2b), 1.24 (s, 3H, C(CH₃)−CH₃), 1.16 (s, 3H, C(CH₃)−CH₃).

¹³C{¹H} NMR (151 MHz, CDCl₃, Me₄Si) δ 141.8 (Cq), 137.3 (Cq),

137.3 (Cq), 137.2 (2 × Cq), 136.0 (2 × Cq), 135.6 (Cq), 130.8

(CH), 129.5 (2 × CH), 127.8 (CH), 125.7 (CH), 59.1 (CH), 42.7

(CH₂), 30.7 (Cq), 27.2 (CH₃), 27.0 (CH₂), 24.2 (CH₃), 22.4(CH₃),

20.9(CH₃), 20.6 (CH₃), 20.4 (CH₃). ν_max(neat)/cm⁻¹3371, 2975,

2920, 1611, 1484, 1453, 1384, 1319, 1259, 1014. HRMS (ESI) m/z

[M + H]⁺Calcd for C₂₃H₃₁N₂335.2482, found 335.2476.

3,5,5-Trimethyl-6-(2,4,6-trimethylbenzyl)-1,4,5,6-tetrahydropyri-

dazine (15e). According to the general procedure, 97 mg (0.30

mmol) of 4,4-dimethylhex-5-en-2-one-N-mesitylhydrazone 12e were

reacted with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O under blue light

irradiation for 16 h to obtain 53 mg (0.165 mmol) of 31 mg (0.120

mmol) of 3,5,5-trimethyl-6-(2,4,6-trimethylbenzyl)-1,4,5,6-tetrahy-

dropyridazine 15e (40%) as a greenish oil. ¹H NMR (600 MHz,

CDCl₃, Me₄Si) δ 6.81 (s, 2H, Ar−H), 4.80 (s, 1H, N−H), 2.84 (dd, J

= 11.5, 3.3 Hz, 2H, NH−CH−C(H)H−CH), 2.80 (dd, J = 13.8, 3.3

Hz, 2H, NH−CH−C(H)H−CH), 2.66 (dd, J = 13.7, 11.5 Hz, 1H,

NH−CH−C(H)H−CH), 2.30 (s, 6H, ortho Ar-(CH₃)), 2.22 (s, 3H

para Ar-(CH₃)), 1.99 (d, J = 18.2 Hz, 1H, NC(Me)-C(H)H), 1.83

(d, J = 18.3 Hz, 1H, NC(Me)-C(H)H), 1.77 (s, 3H, NC

C(CH₂)H₃), 1.06 (s, 3H, C(CH₃)−CH₃), 1.03 (s, 3H, C(CH₃)−

CH₃). ¹³C{¹H}NMR (151 MHz, CDCl₃, Me₄Si) δ 145.0 (Cq), 137.2

(2 × Cq), 136.0 (Cq), 131.8 (Cq), 129.4 (2 × CH), 59.0 (CH), 43.2

(CH₂), 30.9 (Cq), 27.2 (2 × CH₃), 26.6 (CH₂), 23.6 (CH₃), 22.0

(CH₃), 20.8 (CH₃), 20.5 (CH₃). ν_max(neat)/cm⁻¹3377, 2950 2916,

1593, 1480, 1447, 1264, 1127, 1067. HRMS (ESI) m/z [M + H]⁺.

Calcd for C₁₇H₂₇N₂259.2169, found 259.2170.

TEMPO-Trapping Experiment: Isolation of TEMPO Adduct

16. In a sealed photochemical reactor 6.8 mg (0.009 mmol) of

[Ru(bpy)₃]Cl₂·6H₂O were dissolved in 5 mL of anhydrous CH₃CN,

and the solution was degassed with N₂for 15 min. Then 2,2-

dimethylbut-3-enylphenonetosylhydrazone 10a (107.0 mg, 0.300

mmol), TEMPO radical (2,2,6,6-tetramethylpiperidin-1-yl)oxyl)

(94.0 mg, 0.600 mmol) and K₂CO₃(62.5 mg, 0.45 mmol) were

added in one portion and the solution degassed for additional 10 min.

The mixture was then stirred at 4 cm from the irradiation source (see

above) at room temperature for 16 h. The solution was then ﬁltered

on a pad of silica gel and Celite using CH₂Cl₂as eluent and Et₂O to

wash the column. The crude product was puriﬁed by ﬂash

5,5-Dimethyl-3-phenyl-6-(1-tolylethyl)-1,4,5,6-tetrahydropyrida-

zine (15f). According to the general procedure, 119 mg (0.30 mmol)

of 2,2-dimethylpent-3-en-2-one-N-tosylhydrazone 10j were reacted

with K₂CO₃and [Ru(bpy)₃]Cl₂·6H₂O under blue light irradiation for

3319

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J. Org. Chem. 2021, 86, 3300−3323

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

chromatography on silica gel (hexane/acetone 92/8) to obtain 46.4

mg (0.009 mmol) of the TEMPO-adduct (5,5-dimethyl-3-phenyl-6-

(((2,2,6,6-tetramethylpiperidin-1-yl)oxy)methyl)-1-tosyl-1,4,5,6-tetra-

Francesco Pellegrino − Department of Chemistry, University

of Torino, 7-10125 Torino, Italy; orcid.org/0000-0001-

6126-0904

Emanuele Priola − Department of Chemistry, University of

Torino, 7-10125 Torino, Italy; orcid.org/0000-0002-

0270-738X

Polyssena Renzi − Department of Chemistry, University of

Torino, 7-10125 Torino, Italy; orcid.org/0000-0002-

1326-8183

1

hydropyridazine) 16 as light pink crystals (yield = 30%). H NMR

(600 MHz, Methanol-d₄) δ 7.75 (d, J = 8.2 Hz, 2H, Ar−H), 7.39−

7.35 (m, 2H, Ar−H), 7.21 (d, J = 7.9 Hz, 3H, Ar−H), 7.18 (t, J = 7.4

Hz, 2H, Ar−H), 7.14 (d, J = 7.0 Hz, 1H, Ar−H), 5.73 (dd, J = 17.4,

10.7 Hz, 1H, CHCH₂), 4.63 (dd, J = 17.5, 1.7 Hz, 1H, CHCH₂H

trans), 4.49 (dd, J = 10.7, 1.6 Hz, 1H, CHCH₂H cis), 2.88 (s, 2H,

NC(Ph)−CH₂), 2.34 (s, 3H, Ar−CH₃), 0.80 (s, 6H, C(CH₃)₂).

¹³C{¹H}NMR (151 MHz, Methanol-d₄) δ 150.3 (Cq), 149.0 (CH),

142.1 (Cq), 141.9 (Cq), 140.3 (Cq), 128.3 (2 × CH), 127.4 (2 ×

CH), 126.9 (2 × CH), 126.8 (2 × CH), 126.6 (CH), 108.1 (CH₂),

37.9 (Cq), 37.2 (CH₂), 29.9 (CH₃), 26.71 (2 × CH₃). HRMS (ESI)

m/z [M + H]⁺Calcd for C₂₉H₄₂N₃O₃S 512.2941, found 512.2938. IR

ν_max(neat)/cm⁻¹3002, 2951, 1733, 1598, 1493, 1344, 1167, 1092. X-

ray: see SI.

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.0c02605

Notes

The authors declare no competing ﬁnancial interest.

Scaled-up Procedure for the Synthesis of 2,4,4,7-Tetramethyl-

3,4,4a,5,5a,8-hexahydrobenzo[e]pyridazino[1,6-b][1,2]thiazine

10,10-dioxide (13i). In a large-sized sealed photochemical reactor (40

mm as ID and 25 mm height), 40 mg of [Ru(bpy)₃]Cl₂·6H₂O (0.06

mmol) were dissolved in 25 mL of anhydrous CH₃CN, and the

solution was degassed with N₂for 15 min. Then 4,4-dimethylhex-5-

en-2-one-N-tosylhydrazone 10i (0.590 g, 2.00 mmol) andK₂CO₃

(0.415 g, 3.00 mmol) were added in one portion and the solution

degassed for additional 10 min. The mixture was then stirred at 4 cm

from the irradiation source (see above) at room temperature until

reaction completion, which occurred in 72 h. The solution was then

ﬁltered on a pad of silica gel and Celite using CH₂Cl₂as eluent and

Et₂O to wash the column. The crude product was puriﬁed by ﬂash

chromatography on silica gel (hexane/acetone 92/8) to obtain 0.300

g of 2,4,4,7-tetramethyl-3,4,4a,5,5a,8-hexahydrobenzo[e]pyridazino-

[1,6-b][1,2]thiazine 10,10-dioxide 13ias a white solid (yield = 51%).

ACKNOWLEDGMENTS

■

We thank prof. Valter Maurino for the useful discussions on

the mechanism. This work was supported by MIUR (Ministero

̀

Italiano dell’Universita e dellaRicerca)

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ASSOCIATED CONTENT

* Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.0c02605.

■

sı

Computational (PDF)

Spectra (PDF)

Accession Codes

CCDC 2029165−2029166 contain the supplementary crys-

tallographic data for this paper. These data can be obtained

free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by

emailing data_request@ccdc.cam.ac.uk, or by contacting The

Cambridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

AUTHOR INFORMATION

Corresponding Author

■

Annamaria Deagostino − Department of Chemistry,

University of Torino, 7-10125 Torino, Italy; orcid.org/

0000-0003-2622-2798; Email: annamaria.deagostino@

unito.it

Authors

Emanuele Azzi − Department of Chemistry, University of

Torino, 7-10125 Torino, Italy; orcid.org/0000-0002-

2284-2925

Giovanni Ghigo − Department of Chemistry, University of

Torino, 7-10125 Torino, Italy; orcid.org/0000-0002-

2480-5415

Stefano Parisotto − Department of Chemistry, University of

Torino, 7-10125 Torino, Italy; Department of Organic

Chemistry, Arrhenius Laboratory, Stockholm University, 106

91 Stockholm, Sweden; orcid.org/0000-0002-3074-4284

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Visible Light Mediated Photocatalytic N-Radical Cascade Reactivity of O,δ-Unsaturated N-Arylsulfonylhydrazones: A General Approach to Structurally Diverse Tetrahydropyridazines

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