Formal α-Allylation of Primary Amines by a Dearomative, Palladium-Catalyzed Umpolung Allylation of N-(Aryloxy)imines

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Formal α‑Allylation of Primary Amines by a Dearomative, Palladium-

Catalyzed Umpolung Allylation of N‑(Aryloxy)imines

Luis M. Mori-Quiroz, Shrikant S. Londhe, and Michael D. Clift*

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ABSTRACT: N-(Aryloxy)imines, readily accessible by condensa-

tion/tautomerization of (pseudo)benzylic primary amines and 2,6-

di-tert-butyl-1,4-benzoquinone, undergo eﬃcient allylation to aﬀord

a wide range of homoallylic primary amines following hydrolytic

workup. Deprotonation of N-(aryloxy)imines generates a delocal-

ized 2-azaallyl anion-type nucleophile that engages in dearomative

C−C bond-forming reactions with allylpalladium(II) electrophiles

generated from allylic tert-butyl carbonates. This reactivity

umpolung enables the formal α-allylation of (pseudo)benzylic

primary amines. Mechanistic studies reveal that the apparent

regioselectivity of the desired bond-forming event is a convergent

process that is initiated by unselective allylation of N-(aryloxy)-

imines to give several regioisomeric species, which subsequently

rearrange via stepwise [1,3]- or concerted [3,3]-sigmatropic shifts,

ultimately converging to provide the desired regioisomer of the amine products.

eq 1). Common to these formal quinone-catalyzed C−H or

C−C bond functionalizations is the formation of an N-

(aryloxy)imine (3, Scheme 1), which functions as an

electrophile that undergoes transimination with anisidine to

provide N-para-methoxyphenyl imine 4, an intermediate that is

engaged in a subsequent nucleophilic addition to provide the

α-functionalized secondary amine products (5). In an eﬀort to

develop methods for direct amine α-functionalization, we have

explored the possibility of engaging catalytically generated N-

(aryloxy)imine 3 in direct reactions with various nucleophilic

reaction partners (not shown); however, these eﬀorts have not

yet been successful. We hypothesized that this lack of success

might be in part related to the relatively electron-rich nature of

imine 3, which is likely to exist as its conjugate base under the

typical reaction conditions that are employed for amine

oxidation. This led us to consider the possibility of utilizing N-

(aryloxy)imine 3 as a nucleophilic coupling partner that might

productively engage in dearomative C−C bond-forming

reactions with a variety of electrophiles (Scheme 1, eq 2).

The proposed reactivity umpolung would involve the

generation of an amino α-carbanion synthon, which typically

INTRODUCTION

■

Amines are key constituents of naturally occurring molecules

of varying complexity and are commonly present in

pharmaceuticals, agrochemicals, and materials. Owing to

their ubiquitous nature and proven utility, synthetic tools for

their eﬃcient and rapid preparation and/or modiﬁcation are in

high demand. Classical approaches to amine synthesis rely

heavily on C−N bond construction and include N-alkylation,¹

reductive amination,²and the addition of carbon nucleophiles

to preformed imines.³Many modern methods for amine

synthesis, including cross-coupling,⁴hydroamination,⁵and C−

H amination,⁶also employ C−N bond construction.

Alternatively, amine α-C−H bond functionalization is an

attractive transform that not only enables the conversion of

simple, readily available amines into more complex structures,

but also has the potential to facilitate the late-stage

functionalization of amine-containing substrates. Emerging

methods to enable this type of reactivity have been driven by

advances in photoredox catalysis,⁷dehydrogenative cross-

coupling,⁸and amine oxidation chemistry.⁹These new

methods for amine α-functionalization commonly rely on the

generation of an electron-deﬁcient species (e.g., imine, or

iminium) whose native reactivity facilitates coupling with

various nucleophilic coupling partners or α-amino radicals that

react with radical acceptors.

Received: April 25, 2020

Our group has recently reported protocols for the stepwise

α-C−H functionalization of amines (2)^9cas well as α-C−C

functionalization of α-amino acids^9dand 1,2-amino alcohols^9e

(Scheme 1, C−H functionalization chemistry is highlighted in

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Scheme 1. Previous Quinone-Catalyzed Amine Functionalization Chemistry and Possible Reactivity Umpolung of N-

(Aryloxy)imine 3

Scheme 2. Classical Azaallyl Anion Chemistry and Proposed Quinone-Mediated α-Functionalization of Amines

Scheme 3. Two Methods for the Synthesis of N-(Aryloxy)imines (3)

appears in the form of cyanide, nitronate, or 2-azaallyl anions.

This nucleophilic synthon provides complementary reactivity

when compared to the classical pattern of reactivity associated

with amines. The need for subsequent reduction of the nitrile

or nitro function has, to some extent limited, the utility of

methods that employ cyanide and nitronates. On the other

hand, 2-azaallyl anions have received signiﬁcant attention in

recent years, as conversion of the imine products generated in

these reactions to the corresponding primary amines is readily

accomplished via imine hydrolysis (Scheme 2, eq 1). 2-Azaallyl

anions are typically generated by deprotonation of preformed

aldimines or ketimines,¹⁰but they can also be accessed by

decarboxylative,¹¹reductive,¹²and hydrometallation pro-

cesses.¹³Additionally, the ability of 2-azaallyl anions to engage

in a wide range of reactions with electrophilic coupling

partners has led to the successful development of many new

reactions of broad utility.¹⁴

With this framework in mind, we envisioned that

deprotonation of N-(aryloxy)imine 3, readily accessible from

an amine substrate 2 and quinone 1 by way of condensation,

followed by proton transfer (Scheme 2, eq 2), would deliver an

azaallyl anion-like nucleophile that could potentially be

intercepted by a diverse range of electrophiles (E+) to provide

iminoquinone 6. Hydrolysis of 6 would then release the

B

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a

Table 1. Optimization of Reaction Conditions for Dearomative, Pd-Catalyzed Allylation of N-(Aryloxy)imine 3a

entry

solvent (s)

MeCN

THF

dioxane

dioxane/MeCN

dioxane

base

temp. (°C)

Pd catalyst

yield 6a (%)

yield isomers (%)

1

2

3

4

5

6

7

8

9

NaOMe

K₂CO₃

K₃PO₄

50

80

50

80

[allylPdCl]₂(5 mol %)

Pd₂(dba)₃(5 mol %)

Pd₂(dba)₃(2 mol %)

Pd₂(dba)₃(1 mol %)

17

76

70

71

69

46

33

82

73

76

89

0

21

17

13

19

17

3

16

6

11

9

b

10

11

12

b

10

0

bc

,

13

dioxane

a

b

1

Yields were determined by H nuclear magnetic resonance (NMR) using 1,3,5-trimethoxybenzene as an internal standard. 10 equiv of MeCN

c

was used. 0% conversion.

functionalized amine product (7) and quinone (1). While

previous work in quinone-catalyzed amine functionalization

chemistry has provided ample support for the initial steps of

the overall transformation,^9a,c,d,15we could ﬁnd no literature

precedent to support the proposed bond-forming event, which

would require a regioselective, dearomative functionalization of

the key N-(aryloxy)imine intermediate. Therefore, in an initial

eﬀort to establish the feasibility of the proposed chemistry, we

chose to study the reaction of preformed N-(aryloxy)imines 3

with various electrophilic coupling partners. Herein, we report

the discovery of N-(aryloxy)imines as useful precursors to 2-

azaallyl anion-like species that participate in eﬃcient,

dearomative C−C bond-forming reactions. Speciﬁcally, we

have demonstrated that palladium catalysis unites N-(aryloxy)-

imines with allyl carbonates to deliver a wide range of

homoallylic primary amines.

This side reaction became increasingly problematic with

electron-deﬁcient benzylic amines, presumably owing to the

increased electrophilicity of the corresponding N-(aryloxy)-

imines. To circumvent this issue, we used a modiﬁed

protocol¹⁶(method B) involving condensation of the

corresponding benzaldehyde derivative (13) with readily

available 4-amino-2,6-di-tert-butyl phenol hydrochloride (12).

Using these methods, we were able to prepare a wide variety of

N-(aryloxy)imines (3) for use in the present study.

We then examined the ability of N-(aryloxy)imine 3a to

undergo palladium-catalyzed allylation using allyl tert-butyl

carbonate (Table 1). We ﬁrst observed productive allylation

when using allyl Pd chloride dimer as a catalyst and sodium

methoxide as a base at 50 °C in MeCN (entry 1). This result

established that productive bond formation was possible and

mitigated our concerns regarding the potential for undesired

oxidation of Pd(0) by the iminoquinone product of the

reaction (e.g., 6a)a process that would likely prevent

successful catalysis. We then evaluated a series of bases

under these initial reaction conditions. As we had speculated,

several regioisomeric products (C3-iso-6a, C5-iso-6a, and O-

iso-6a) were also observed. Among the bases evaluated (entries

1−3), potassium phosphate provided the best yield of the

desired product (6a, 82%) while minimizing the formation of

the regioisomeric products (combined yield of regioisomers =

12%). The lower yield provided by sodium methoxide is

probably because of unproductive consumption of the allylic

carbonate or competitive reaction with the allylpalladium

electrophile. Using Pd₂(dba)₃as a catalyst led to a comparable

yield of 6a (71%, entry 4) together with only 13% of the

RESULTS AND DISCUSSION

■

To facilitate the proposed studies, two methods have been

developed to enable the synthesis and isolation of the requisite

preformed N-(aryloxy)imines (3, Scheme 3). In the ﬁrst

method (method A), benzylic amines (2) and 2,6-di-tert-butyl-

1,4-benzoquinone (1) were combined and heated to promote

condensation and tautomerization, which delivered the

corresponding N-(aryloxy)imines 3. These surprisingly stable

intermediates were readily puriﬁed by recrystallization. In some

cases, competitive transimination between the desired product

3 and unreacted amine was observed, thereby leading to the

formation of an undesired N-benzylic imine as a major side

product (not shown) and limiting the eﬃciency of this process.

C

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Table 2. Scope of N-(Aryloxy)imines 3 in the Dearomative, Pd-Catalyzed Allylation with Allyl tert-Butyl Carbonate

a

b

Xantphos (2.5 mol %) was used instead of MeCN. Reaction run at 90 °C.

isomeric products. Interestingly, decreasing the catalyst loading

from 5 to 2 mol % led to virtually the same yield of 6a (69%,

entry 5) but an increased yield of isomeric allylic products.

Evaluation of other solvents typically led to lower yields. For

instance, ethereal solvents such as tetrahydrofuran (THF) and

dioxane (entries 6 and 7) led to low yields of the desired

product 6a; however, dioxane provided the highest regioiso-

meric ratio (>10:1). The use of a 1:1 mixture of dioxane/

MeCN led to a signiﬁcant increase in yield with concomitant

loss of regioselectivity (entry 8). Fortunately, further increasing

the temperature to 80 °C led to an improvement of the

regioselectivity (entry 9) albeit with a slightly lower yield of 6a

(73%). Adjusting the amount of MeCN to only 10 equiv

provided 6a in comparable yield at 50 °C (76%, entry 10) and

increasing the temperature under these conditions led to an

improved yield (89%, entry 11). Further reducing the amount

of catalyst to 1 mol % had a negligible eﬀect on the yield and

regioselectivity (89%, 9:1 regioselectivity, entry 12). Finally, we

demonstrated that the reaction does not proceed by direct

attack of the N-(aryloxy)imine nucleophile on the allylic

carbonate, as no conversion of 3a was observed in the absence

of Pd (entry 13).

products 7. Accordingly, following the Pd-catalyzed allylation

under the optimized conditions, the crude reaction mixture

was treated with 2 M HCl_(aq)in THF. After extraction and

column chromatography, the desired amine product 7a was

isolated in 86% yield (Table 2). With this protocol in hand, we

next evaluated the eﬃciency of this process using other N-

(aryloxy)imines in reactions with allyl tert-butyl carbonate.

Chloro and bromo substitutions were tolerated (7b and 7c, 79

and 62%, respectively), although the latter was obtained in

modest yield, presumably because of competitive oxidative

addition to the C−Br bond. Electron-neutral (7d, 87%) and

electron-deﬁcient substrates (7e, 70%) were also competent

reaction partners. 2,6-Diﬂuoro substitution initially failed to

provide any of the expected product, presumably because of

slow electrophile trapping resulting from the attenuated

nucleophilicity of this electronically deactivated substrate.

However, we found that replacing acetonitrile with Xantphos

allowed the desired allylation to take place eﬃciently (7f,

70%).^17,183-Methyl substitution was tolerated, but led to

modest yield of the desired product (7g, 48%). Electron-rich

substrates also underwent eﬃcient allylation under the

standard reaction conditions (7h, 7i, and 7j; 80, 72, and

83%, respectively). 1-Naphthyl substituted (7k, 64%) and

several heterocyclic homoallylic amines (7l, 7m, 7n; 57, 55,

and 51%, respectively) could also be accessed using this

Having established optimal conditions for the key bond-

forming event, we then developed a hydrolytic workup

protocol that would allow direct access to the desired amine

D

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Table 3. Scope of Allylic Carbonates in the Dearomative, Pd-Catalyzed Allylation of N-(Aryloxy)imine 3d

a

b

c

Reaction run at 90 °C. Xantphos (2.5 mol %) was used instead of MeCN. 2 equiv of prenyl carbonate was used.

protocol. Finally, an ortho arylsulﬁde substituent bearing a

benzylic alcohol was also tolerated; however, the use of

Xantphos as a ligand was required to achieve productive

reaction (80% overall), and competitive O-allylation (7o and

7o′, 45 and 35%, respectively) was observed.

nucleophilic attack of the azaallyl anion on a less-electrophilic

allylpalladium species. Furyl-substituted electrophile required

similar conditions to aﬀord product 7x (67%, E/Z = 20:1).

Methyl-substituted allylic carbonate did not provide the

desired allylation product under the standard reaction

conditions; however, the use of Xantphos allowed access to

7y in modest yield (47%) as a 5.4:1 mixture of linear and

branched isomers, the latter of which was formed with modest

diastereoselectivity (anti/syn = 4:1). Not surprisingly, reaction

of a prenyl carbonate did not provide any of the desired

product 7z under the present conditions, presumably because

of the relatively high barrier for this substrate to engage in

oxidative addition. Notably, a cyclic allylic electrophile was

tolerated and provided homoallylic amine 7aa in 36% yield

with excellent diastereoselectivity (>20:1).

Mechanistically, the desired C−C bond formation could

take place by direct regioselective addition of the deprotonated

N-(aryloxy)imine, a “soft” nucleophile (pK_a∼ 10),¹⁹to the Pd-

π-allyl species (outer-sphere mechanism).²⁰However, the

propensity of this highly delocalized anion to react with a high

level of regioselectivity to deliver the desired product 6 was not

easily explained. In fact, early optimization studies revealed

that undesired regioisomeric products C3-iso-6, C5-iso-6, and

O-iso-6 were formed in high concentrations at lower

temperatures, whereas the desired product 6 was the major

We then explored the scope of allyl carbonates that could

function as electrophiles in the dearomative, Pd-catalyzed

allylation of N-(aryloxy)imine 3d (Table 3). Cinnamyl tert-

butyl carbonate successfully participated in the reaction to give

7p in 72% yield as a >20:1 mixture of E/Z isomers.

Halogenated cinnamyl electrophiles were tolerated aﬀording

7q (69%, E/Z = 6.8:1) and 7r (59%, E/Z = 11.3:1). More

electron-deﬁcient cinnamyl carbonates bearing nitro and

triﬂuoromethyl substituents at the aromatic ring provided

products 7s and 7t in good yields (73 and 76%, respectively)

albeit with modest E/Z selectivities (5.5:1 and 4.5:1,

respectively). Electron-donating groups on the aryl ring of

the cinnamyl electrophile such as methyl (7u, 64%, E/Z =

18:1) and methoxy (7v, 73%, E/Z = 20:1) were tolerated and

aﬀorded the products with high E/Z selectivities. However, the

2,3-dimethoxy cinnamyl carbonate required both the use of

higher temperature and Xantphos as a ligand to obtain a good

yield of product 7w (79%, E/Z = 20:1). This was necessary to

overcome the higher energy barriers associated with oxidative

addition to a more electron-rich allylic carbonate and

E

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Scheme 4. Reaction Progress Followed by NMR Shows High Concentrations of Isomeric Products at Early Reaction Times

regioisomer at higher temperatures. To study this further, the

reaction between 3d and 4-ﬂuorocinnamyl tert-butyl carbonate

under standard conditions (80 °C, dioxane) was monitored as

a function of time. This experiment revealed that isomeric

allylic products (C3-iso-6q, C5-iso-6q, and O-iso-6q) were

present in substantial quantities at early reaction times (0−30

min, Scheme 4). The isomeric allylated product C3-iso-6q, in

particular, reached 39% NMR yield after 30 min under these

conditions. Interestingly, the concentration of this isomeric

product gradually decreased over the next 2.5 h as the yield of

the desired product (6q) increased up to a maximum of 77%

NMR yield. At this point, the overall yield of isomeric allylated

products (i.e., the sum of C3-iso-6q, C5-iso-6q, and O-iso-6q)

was only 4%. Notably absent in this reaction were any

branched allylated products.

These observations led us to consider an alternative

mechanism involving an unselective C−C bond-forming

event between the N-(aryloxy)imine and the Pd-π-allyl species

to form several allylated products, followed by convergent

isomerization of some of these intermediates to the desired

product 6. Such convergent isomerizations to 6 could, in

principle, take place via one of three mechanisms: (1) a Pd-

catalyzed rearrangement via an associative or dissociative

pathway,^21,22(2) a concerted, thermal [3,3]-sigmatropic

rearrangement,^18d,23or (3) a stepwise process involving

homolytic C−C bond cleavage and radical recombination.²⁴

Given that all isomeric allylated products C3-iso-6q, C5-iso-6q,

and O-iso-6q were linear isomers, the possibility of concerted

[3,3]-sigmatropic rearrangements was limited to only one

regioisomer (C5-iso-6q), which would need to undergo two

sequential [3,3]-sigmatropic rearrangements to give the

observed linear allylation product 6q. On the other hand,

isomers C3-iso-6q and O-iso-6q would have to undergo

rearrangement via a dissociative pathway to deliver the

observed linear allylation product 6q.

To shed light on the mechanism of this rearrangement, we

isolated several isomeric products (C3-iso-6q, C3-iso-6y, and

C3-iso-6d) derived from the reaction of N-(aryloxy)imine 3d

with 4-ﬂuorocinnamyl, methallyl, and allyl carbonates. These

isomeric products were the major competitive isomers

observed in these reactions. We independently subjected

them to the standard reaction conditions, in the presence or

absence of Pd, to assess their ability to undergo isomerization

to the corresponding iminoquinones (6, Table 4). These

intermediates were diﬀerentiated by the substitution at the

terminal oleﬁn position, and were chosen to evaluate their

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Table 4. Isomerization of C3-iso-6 in the Presence and Absence of Palladium

entry

X

Pd₂(dba)₃(mol %)

1

conv. (%)

6 (%)

branched-6 (%)

C5-iso-6 (%)

3d (%)

1

2

4-F-C₆H₄

CH₃

79

78

100

75

63

46

39

17

0

25

19

0

4

1

3

0

20

18

22

76

0

b

3

1

b

4

c

CH₃

50

5

H

c

6

a

b

c

For detailed reaction conditions, see the Experimental Section. Xantphos (2.5 mol %) was used instead of MeCN. Trace quantities of the O-allyl

isomer were observed.

Scheme 5. TEMPO-Trapping Experiments

ability to undergo isomerization in the absence of substitution

(C3-iso-6d), or in the presence of aryl (C3-iso-6q) or methyl

(C3-iso-6y) substituents. The latter two substrates (C3-iso-6q

and C3-iso-6y) were expected to be particularly informative

because they could distinguish between a stepwise (dis-

sociative) or concerted (associative) mechanism for the

observed rearrangement.

Thus, in the presence of Pd, isomeric product C3-iso-6q

underwent rearrangement to give 6q in 46% yield, together

with trace amounts of the linear C5 product (C5-iso-6q) and

18% yield of N-(aryloxy)imine 3d, the latter formed as a

consequence of deallylation (Table 4, entry 1). Importantly, in

the absence of Pd, these isomerizations took place at virtually

the same rate and led to the same distribution of products

(entry 2), proving that Pd is not involved in the sigmatropic

rearrangements that lead to the desired product. In addition,

the exclusive formation of the linear product 6q indicated that

the isomerization involved a stepwise (dissociative) mecha-

nism, which likely occurs via C−C bond homolysis and radical

recombination. Indeed, heating C3-iso-6q in the presence of

2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) at 80 °C in

dioxane led to the formation of the cinnamyl TEMPO adduct

14q in 37% yield (Scheme 5), indicating that a radical

mechanism for the observed rearrangement is operative. On

the other hand, crotyl-derived compound C3-iso-6y underwent

rearrangement in the presence of Pd and Xantphos to give a

mixture of both linear and branched products (21% yield,

4.25:1.0 ratio), accompanied by a signiﬁcant amount of

deallylated product 3d (76% yield). Surprisingly, in the

absence of Pd, C3-iso-6y underwent exclusive [3,3]-sigma-

tropic rearrangement to give the branched product branched-

6y in 50% yield without formation of deallylated product 3d.

These experiments suggest that Pd can mediate the isomer-

ization of certain C3 isomers to the desired products albeit

with signiﬁcant deallylation taking place. However, crotyl-

derived C3 isomers exclusively undergo concerted [3,3]-

sigmatropic rearrangements in the absence of Pd. As

supporting evidence, heating C3-iso-6y in the presence of

TEMPO (80 °C, dioxane) led again to clean isomerization to

the branched product (branched-6y, 65%) without formation

of any crotylated TEMPO adduct as determined by both NMR

and high-resolution mass spectrometry (HRMS) analyses

(Scheme 5). This suggests that the mechanism by which C3-

iso-6q and C3-iso-6y undergo thermal isomerization diﬀers,

presumably owing to the diﬀerence in stability of the

corresponding allylic radicals that would have to form when

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Table 5. Allylation of 3a with Cinnamyl Bromide and Subsequent [1,3]-Sigmatropic Rearrangement via a Dissociative

Mechanism

entry

temperature

time

C5-iso-6bb (%)

C3-iso-6bb (%)

6bb (%)

1

2

3

0 °C

0 °C to rt

rt to 65 °C

20 min

2 h

79

78

2

8

4

13

14

92

the homolytic mechanism is operative. We also evaluated the

isomerization of the unsubstituted allyl-derived compound C3-

iso-6d. Here, we observed the formation of the desired product

6d together with signiﬁcant amounts of C5 allylated product

C5-iso-6d in virtually the same yields with the same conversion

in the presence or absence of Pd (entries 5 and 6). Therefore,

the isomerization of unsubstituted C3-iso-6d-type intermedi-

ates does not require Pd. In addition, these rearrangements are

likely concerted, as no deallylation product was observed. As

supporting evidence, the trapping experiment with TEMPO

led to rearrangement without formation of the TEMPO allyl

adduct. These results suggest that initial Pd-mediated allylation

provides a number of regioisomeric products with modest

kinetic selectivity; however, the various regioisomers are

capable of undergoing rearrangement to the desired,

presumably thermodynamic, product through one of three

mechanisms where the operative mechanism is dependent on

both the substrate and the reaction conditions employed.

Further evidence demonstrating that the observed isomer-

ization is not limited to the C3 isomer and that Pd is not

required for this process was obtained as outlined in Table 5.

When the anion generated from 3a was treated with cinnamyl

bromide at 0 °C, a mixture of allylated products was observed

product, which is the presumed thermodynamic product of this

process.

CONCLUSIONS

■

In conclusion, we have developed a stepwise protocol for the

allylation of (pseudo)benzylic amines that proceeds by

dearomative, Pd-catalyzed allylation of N-(aryloxy)imines to

aﬀord homoallylic amines in good yields. Our protocol is

compatible with diverse N-(aryloxy)imines and allylic tert-butyl

carbonates, thereby enabling access to a wide range of

homoallylic amines. Our studies suggest that the kinetic

products of C−C bond formation between the N-(aryloxy)-

imines and the Pd-π-allyl electrophiles consist of a mixture of

the desired product and other regioisomeric products.

Mechanistic experiments demonstrate that these regioisomeric

products undergo thermal rearrangement by one of two

mechanisms: (1) homolytic C−C bond cleavage followed by

recombination, or (2) concerted [3,3]-sigmatropic rearrange-

ment; the operative mechanism appears to be substrate

dependent. Reactions involving Xantphos²⁵as a ligand allow

Pd to catalyze the isomerization of C3 allyl intermediates,

albeit with competitive, unproductive deallylation. This work

has established for the ﬁrst time that N-(aryloxy)imines can

function as 2-azaallyl anion-like nucleophiles and are

compatible with Pd(0)/Pd(II) catalysis. We expect to report

related reactions of N-(aryloxy)imines with other electrophiles

in due course.

1

by H NMR in which the C5 product (C5-iso-6bb) was the

major component (entry 1). Upon warming the reaction

mixture to room temperature (rt), little change was observed

(entry 2), but heating to 65 °C led to almost complete

isomerization to the desired isomer 6bb (entry 3, 92%).

Presumably, this rearrangement occurs via a stepwise

(dissociative) [1,3]-sigmatropic rearrangement (as shown in

Table 4); however, we cannot rule out the possibility that this

reaction might proceed via consecutive, concerted [3,3]-

sigmatropic rearrangements. This result also indicates that it

might be possible to develop a palladium-free variant of the

chemistry reported herein.

Taken together, our experiments suggest that our allylation

methodology proceeds by a mechanism involving the initial

attack of N-(aryloxy)imine on the Pd-π-allyl electrophile to

form several regioisomeric products. The kinetic regioselectiv-

ity of this step typically favors the desired product and C3-iso-

6-type intermediates over C5-iso-6-type or O-iso-6-type

intermediates. Following a relatively unselective kinetic

allylation, rearrangement of the undesired regioisomers occurs

to funnel material toward the desired regioisomer of the

EXPERIMENTAL SECTION

■

General Information. Reactions were run in oven-dried or ﬂame-

dried glassware under an argon atmosphere and stirred magnetically.

Acetonitrile, THF, diethyl ether, and dichloromethane were puriﬁed

by passing the solvent through activated alumina using a solvent

puriﬁcation system. Unless otherwise noted, puriﬁcation of the

products was carried out by ﬂash chromatography using silica gel

(230−400 mesh, Grade 60). Reactions were monitored by thin layer

chromatography (TLC) (silica gel 60 F₂₅₄) and visualized using UV

or KMnO₄, phosphomolybdic acid, and ceric ammonium molybdate

1

stain solutions. H NMR and ¹³C NMR were recorded at rt in a

Bruker 400, Bruker 500, or Bruker 600 instrument. Chemical shifts

are reported in ppm and referenced with respect to residual protic

solvents: chloroform at 7.26 ppm (¹H NMR); and the carbon

resonances of the solvent: chloroform at 77.16 ppm (¹³C NMR). The

following abbreviations were used to refer to multiplicities: s = singlet,

d = doublet, dd = doublet of doublets, t = triplet, q = quartet, and m =

multiplet. Infrared spectra were recorded using a Shimadzu FTIR-

H

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8400S spectrometer. Mass spectra were obtained on a Micromass

LCT Premier quadrupole and time-of-ﬂight tandem mass analyzer.

Preparation of N-(Aryloxy)iminesGeneral Procedure A.

To a 100 mL round bottom ﬂask were added a magnetic stir bar, 2,6-

di-tert-butyl-1,4-benzoquinone (1 equiv), and EtOH (reaction

concentration = 0.8−1.0 M). The ﬂask was sealed with a septum,

ﬂushed with Ar, and the corresponding benzylic amine (1 equiv) was

added using a syringe. The reaction was heated in an oil bath to 80 °C

and the reaction followed by ¹H NMR until the ratio of iminophenol/

N-benzylimine was maximized. The reaction was cooled to rt and left

undisturbed until the product precipitated. The solid was ﬁltered and

recrystallized from warm hexanes or EtOAc/hexanes. The ﬁltrate was

concentrated and recrystallization from hexanes or EtOAc/hexanes

was attempted. If no precipitation took place, the crude reaction

mixture was partially concentrated and left to crystallize at rt. In a few

cases, the desired product did not precipitate; in these cases, the

products were partially puriﬁed by column chromatography (typically,

5% EtOAc in hexanes, buﬀered with 1% Et₃N) followed by

recrystallization from hexanes or EtOAc/hexanes.

Preparation of 2,6-Di-tert-butyl-4-(benzylideneamino)-

phenol (3d). Following General Procedure A, benzylamine (2.48

mL, 9.078 mmol, 1 equiv), 2,6-di-tert-butyl-1,4-benzoquinone (5 g,

9.078 mmol, 1 equiv), and EtOH (23 mL) at 80 °C for 16 h aﬀorded,

after recrystallization from hexanes, 2.24 g (60%) of 3d as light yellow

1

crystals. mp 149−151 °C. H NMR (500 MHz, CDCl₃): δ 8.49 (s,

1H), 7.89 (dd, J = 6.8, 2.9 Hz, 2H), 7.46 (dd, J = 4.9, 1.9 Hz, 3H),

7.13 (s, 2H), 5.19 (s, 1H), 1.48 (s, 18H). ¹³C{¹H} NMR (126 MHz,

CDCl₃): δ 158.0, 152.7, 143.8, 136.81, 136.79, 131.0, 128.9, 128.7,

118.0, 34.7, 30.4. FTIR: 3146, 2954, 1636, 1437 cm⁻¹. HRMS (ESI)

m/z: calcd for [C₂₁H₂₈NO]⁺, 310.2171; found, 310.2175.

P r e p a r a t i o n o f 2 , 6 - D i - t e r t - b u t y l - 4 - ( ( 4 -

triﬂuoromethylbenzylidene)amino)phenol (3e). Following Gen-

eral Procedure B, 4-(triﬂuoromethyl)benzaldehyde (683 μL, 5 mmol,

1 equiv), 4-amino-2,6-di-tert-butylphenol hydrochloride (1.29 g, 5

mmol, 1 equiv), benzene (25 mL), and K₂CO₃(15 mmol, 3 equiv,

2.07 g) aﬀorded, after recrystallization from hexanes, 793.2 mg (42%)

1

of 3e as light orange crystals. mp 114−117 °C. H NMR (400 MHz,

CDCl₃): δ 8.54 (s, 1H), 8.01 (d, J = 7.9 Hz, 2H), 7.71 (d, J = 8.1 Hz,

2H), 7.16 (s, 2H), 5.26 (s, 1H), 1.49 (s, 18H). ¹³C{¹H} NMR (126

MHz, CDCl₃): δ 155.6, 153.2, 142.9, 139.8, 136.8, 132.2 (q, J = 32.3,

31.2 Hz), 128.6, 125.7 (q, J = 3.5 Hz), 124.0 (q, J = 272.2 Hz), 118.0,

34.6, 30.3. ¹⁹F NMR (376 MHz, CDCl₃): δ −62.70. FTIR: 3636,

2957, 1621, 1579, 1434, 1323, 836 cm⁻¹. HRMS (ESI) m/z: calcd for

[C₂₂H₂₇F₃NO]⁺, 378.2045; found, 378.2048.

Preparation of N-(Aryloxy)iminesGeneral Procedure B.

To a 100 mL round bottom ﬂask were added a magnetic stir bar and

4-amino-2,6-di-tert-butylphenol hydrochloride²⁶(5 mmol, 1 equiv)

(obtained by reduction of 2,6-di-tert-butyl-4-(hydroxyimino)-

cyclohexa-2,5-dien-1-one²⁷). Benzene (25 mL) was added to the

ﬂask and the ﬂask was ﬂushed with Ar. The corresponding

benzaldehyde derivative (5 mmol, 1 equiv) and anhydrous K₂CO₃

(15 mmol, 3 equiv) were quickly added. The ﬂask was equipped with

a Dean−Stark trap and ﬂushed with Ar. The reaction was subjected to

P r e p a r a t i o n o f 2 , 6 - D i - t e r t - b u t y l - 4 - ( ( 2 , 6 -

diﬂuorobenzylidene)amino)phenol (3f). Following General

Procedure A, 2,6-diﬂuorobenzylamine (2 g, 13.98 mmol, 1 equiv),

2,6-di-tert-butyl-1,4-benzoquinone (3.08 g, 13.98 mmol, 1 equiv), and

EtOH (18 mL) at 80 °C for 2 h aﬀorded, after recrystallization from

1

reﬂux and followed by H NMR. The reaction was cooled to rt and

ﬁltered to remove solids. Iminophenol product was obtained as

crystals after concentrating the ﬁltrate, followed by trituration with

hexanes. The product was puriﬁed by recrystallization from hot

hexanes.

1

hexanes, 2.13 g (44%) of 3f as orange crystals. mp 164−166 °C. H

NMR (500 MHz, CDCl₃): δ 8.67 (s, 1H), 7.36 (tt, J = 8.4, 6.1 Hz,

1H), 7.13 (s, 2H), 7.02−6.94 (m, 2H), 5.24 (s, 1H), 1.48 (s, 18H).

¹³C{¹H} NMR (126 MHz, CDCl₃): δ 162.1 (dd, J = 6.4, 257.6 Hz),

Preparation of 2,6-Di-tert-butyl-4-((4-ﬂuorobenzylidene)-

amino)phenol (3a). Following General Procedure A, 4-ﬂuoroben-

zylamine (3 g, 23.97 mmol, 1 equiv), 2,6-di-tert-butyl-1,4-

benzoquinone (5.27 g, 23.97 mmol, 1 equiv), and EtOH (25 mL)

at 80 °C for 16 h aﬀorded, after recrystallization from hexanes, 3.77 g

(48%) of 3a as light orange crystals. mp 135−137 °C. ¹H NMR (500

MHz, CDCl₃): δ 8.45 (s, 1H), 7.93−7.85 (m, 2H), 7.15 (t, J = 8.7 Hz,

2H), 7.11 (s, 2H), 5.19 (s, 1H), 1.48 (s, 18H). ¹³C{¹H} NMR (126

MHz, CDCl₃): δ 164.6 (d, J = 250.8 Hz), 156.4, 152.8, 143.6, 136.9,

133.2 (d, J = 3.5 Hz), 130.5 (d, J = 9.0 Hz), 117.9, 116.0 (d, J = 21.9

Hz), 34.7, 30.4. ¹⁹F NMR (376 MHz, CDCl₃): δ −109.1. FTIR: 3625,

2957, 1621, 1589, 1432, 823 cm⁻¹. HRMS (ESI) m/z: calcd for

[C₂₁H₂₇FNO]⁺, 328.2071; found, 328.2065.

Preparation of 2,6-Di-tert-butyl-4-((4-chlorobenzylidene)-

amino)phenol (3b). Following General Procedure A, 4-chloroben-

zylamine (1.93 g, 13.62 mmol, 1 equiv), 2,6-di-tert-butyl-1,4-

benzoquinone (3 g, 13.62 mmol, 1 equiv), and EtOH (25 mL) at

80 °C for 16 h aﬀorded, after recrystallization from hexanes, 1.84 g

(39%) of 3b as light yellow crystals. mp 135−137 °C. ¹H NMR (400

MHz, CDCl₃): δ 8.45 (s, 1H), 7.85−7.80 (m, 2H), 7.45−7.41 (m,

2H), 7.12 (s, 2H), 5.21 (s, 1H), 1.48 (s, 18H). ¹³C{¹H} NMR (101

MHz, CDCl₃): δ 156.1, 152.8, 143.3, 136.7, 135.2, 129.7, 129.0,

117.9, 34.6, 30.3. FTIR: 3630, 2955, 1623, 1589, 1432, 823 cm⁻¹.

HRMS (ESI) m/z: calcd for [C₂₁H₂₇ClNO]⁺, 344.1781; found,

344.1770.

Preparation of 2,6-Di-tert-butyl-4-((4-bromobenzylidene)-

amino)phenol (3c). Following General Procedure A, 4-bromoben-

zylamine (2.53 g, 13.62 mmol, 1 equiv), 2,6-di-tert-butyl-1,4-

benzoquinone (3 g, 13.62 mmol, 1 equiv), and EtOH (25 mL) at

80 °C for 16 h aﬀorded, after recrystallization from hexanes, 1.61 g

(30%) of 3c as light yellow crystals. mp 153−154 °C. ¹H NMR (400

MHz, CDCl₃): δ 8.44 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.59 (d, J =

8.4 Hz, 2H), 7.12 (s, 2H), 5.22 (s, 1H), 1.48 (s, 18H). ¹³C{¹H} NMR

(101 MHz, CDCl₃): δ 156.2, 152.9, 143.2, 136.7, 135.6, 132.0, 130.0,

125.2, 117.9, 34.6, 30.3. FTIR: 3632, 2955, 1622, 1585, 1433, 819

cm⁻¹. HRMS m/z: calcd for [C₂₁H₂₇BrNO]⁺, 388.1276; found,

388.1286.

153.3, 148.6, 144.2, 136.8, 131.8 (t, J = 10.9 Hz), 118.1, 114.6 (t, J =

12.7 Hz), 112.2 (dd, J = 4.6, 20.3 Hz), 34.7, 30.4. ¹⁹F NMR (376

MHz, CDCl₃): δ −112.9. FTIR: 3610, 2954, 1622, 1462, 1017.

HRMS (ESI) m/z: calcd for [C₂₁H₂₆F₂NO]⁺, 346.1982; found,

346.1995.

Preparation of 2,6-Di-tert-butyl-4-((3-methylbenzylidene)-

amino)phenol (3g). Following General Procedure A, m-tolylme-

thanamine (1.7 mL, 13.62 mmol, 1 equiv), 2,6-di-tert-butyl-1,4-

benzoquinone (3 g, 13.62 mmol, 1 equiv), and EtOH (18 mL) at 80

°C for 16 h aﬀorded, after recrystallization from hexanes, 1.9 g (43%)

1

of 3g as bright red crystals. mp 97−100 °C. H NMR (400 MHz,

CDCl₃): δ 8.46 (s, 1H), 7.75 (d, J = 1.9 Hz, 1H), 7.68−7.62 (m, 1H),

7.35 (t, J = 7.6 Hz, 1H), 7.30−7.26 (m, 1H), 7.12 (s, 2H), 5.18 (s,

1H), 2.44−2.40 (m, 3H), 1.48 (s, 18H). ¹³C{¹H} NMR (101 MHz,

CDCl₃): δ 158.1, 152.5, 143.8, 138.5, 136.65, 136.60, 131.7, 128.7,

128.6, 126.1, 117.8, 34.6, 30.3, 21.3. FTIR: 3634, 2955, 2912, 1624,

1583, 1433, 888 cm⁻¹. HRMS (ESI) m/z: calcd for [C₂₂H₃₀NO]⁺,

324.2327; found, 324.2337.

P r e p a r a t i o n o f 2 , 6 - D i - t e r t - b u t y l - 4 - ( ( 3 -

methoxybenzylidene)amino)phenol (3h). Following General

Procedure A, 3-methoxybenzylamine (2 g, 14.58 mmol, 1 equiv),

2,6-di-tert-butyl-1,4-benzoquinone (3.2 g, 14.58 mmol, 1 equiv), and

EtOH (18 mL) at 80 °C for 7 h aﬀorded, after recrystallization from

hexanes, 2.01 g (41%) of 3h as an orange solid. mp 117−119 °C. ¹H

NMR (500 MHz, CDCl₃): δ 8.46 (s, 1H), 7.52 (dd, J = 2.7, 1.4 Hz,

1H), 7.43−7.33 (m, 2H), 7.13 (s, 2H), 7.05−6.99 (m, 1H), 5.19 (s,

1H), 3.89 (s, 3H), 1.48 (s, 18H). ¹³C{¹H} NMR (126 MHz, CDCl₃):

δ 160.1, 157.8, 152.8, 143.7, 138.3, 136.8, 129.8, 122.1, 117.98,

117.96, 111.7, 55.6, 34.7, 30.4. FTIR: 3628, 2953, 1597, 1431 cm⁻¹.

HRMS (ESI) m/z: calcd for [C₂₂H₃₀NO₂]⁺, 340.2277; found,

340.2288.

P r e p a r a t i o n o f 2 , 6 - D i - t e r t - b u t y l - 4 - ( ( 2 , 4 -

dimethoxybenzylidene)amino)phenol (3i). Following General

Procedure A, 2,4-dimethoxybenzylamine (2 g, 11.96 mmol, 1 equiv),

2,6-di-tert-butyl-1,4-benzoquinone (2.6 g, 11.96 mmol, 1 equiv), and

EtOH (13 mL) at 80 °C for 12 h aﬀorded, after recrystallization from

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hexanes, 2.24 g (51%) of 3i as light orange crystals. mp 124−125 °C.

¹H NMR (500 MHz, CDCl₃): δ 8.79 (s, 1H), 8.06 (d, J = 8.6 Hz,

136.6, 131.2, 129.4, 127.7, 117.9, 34.6, 30.3. FTIR: 3626, 3195, 2951,

1606, 1579, 1428 cm⁻¹. HRMS (ESI) m/z: calcd for [C₁₉H₂₆NOS]⁺,

316.1735; found, 316.1739.

1H), 7.07 (s, 2H), 6.57 (dd, J = 8.6, 2.3 Hz, 1H), 6.47 (d, J = 2.3 Hz,

1H), 5.11 (s, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 1.47 (s, 18H). ¹³C{¹H}

NMR (126 MHz, CDCl₃): δ 163.4, 160.8, 154.0, 152.1, 145.0, 136.7,

128.8, 118.9, 118.0, 105.7, 98.2, 55.7, 55.6, 34.7, 30.5. FTIR: 3627,

2955, 1605, 1431, 1033 cm⁻¹. HRMS (ESI) m/z: calcd for

[C₂₃H₃₂NO₃]⁺, 370.2382; found, 370.2383.

Preparation of 2,6-Di-tert-butyl-4-((2-((2-(hydroxymethyl)-

phenyl)thio)benzylidene)amino)phenol (3o). Following General

Procedure A, (2-((2-(aminomethyl)phenyl)thio)phenyl)methanol

(1.5 g, 6.12 mmol, 1 equiv), 2,6-di-tert-butyl-1,4-benzoquinone

(1.35 g, 6.12 mmol, 1 equiv), and EtOH (7 mL) at 80 °C for 12 h

aﬀorded, after recrystallization from EtOAc/hexanes, 874 mg (32%)

P r e p a r a t i o n o f 2 , 6 - D i - t e r t - b u t y l - 4 - ( ( 3 , 4 , 5 -

trimethoxybenzylidene)amino)phenol (3j). Following General

Procedure A, 3,4,5-trimethoxybenzylamine (1.8 g, 9.08 mmol, 1

equiv), 2,6-di-tert-butyl-1,4-benzoquinone (2 g, 9.08 mmol, 1 equiv),

and EtOH (20 mL) at 80 °C for 16 h aﬀorded, after recrystallization

from hexanes, 1.14 g (31%) of 3j as light brown crystals. mp 146−147

1

of 3o as an orange solid. mp 116−118 °C. H NMR (500 MHz,

CDCl₃): δ 8.95 (s, 1H), 8.15 (dd, J = 7.6, 1.8 Hz, 1H), 7.51 (d, J = 7.6

Hz, 1H), 7.39−7.29 (m, 3H), 7.25−7.20 (m, 2H), 7.15 (dd, J = 7.8,

1.5 Hz, 1H), 7.07 (s, 2H), 5.20 (s, 1H), 4.82 (s, 2H), 1.45 (s, 18H).

¹³C{¹H} NMR (126 MHz, CDCl₃): δ 155.7, 153.0, 143.6, 141.4,

1

°C. H NMR (400 MHz, CDCl₃): δ 8.39 (s, 1H), 7.15 (s, 2H), 7.11

136.8, 136.5, 136.4, 133.5, 132.7, 132.1, 131.3, 128.9, 128.8, 128.2,

127.8, 118.2, 63.7, 34.6, 30.4. FTIR: 3629, 3059, 2954, 1615, 1431,

1031 cm⁻¹. HRMS (ESI) m/z: calcd for [C₂₈H₃₄NO₂S]⁺, 448.2310;

found, 448.2331.

Preparation of Allylic Carbonates and Precursors. Prepara-

tion of Methyl CinnamatesGeneral Procedure C. To a 100 mL

round bottom ﬂask were added a magnetic stir bar, the corresponding

cinnamic acid (11 mmol), methanol (30 mL), and sulfuric acid (0.5

mL). A reﬂux condenser was attached and the reaction was heated to

reﬂux overnight (12−16 h). The reaction was cooled to rt, diluted

with ethyl acetate (100 mL), and washed with water (2 × 10 mL),

NaHCO_3(sat), and brine. The organic layer was dried over MgSO₄,

ﬁltered, and concentrated. The crude product was used in the next

step without further puriﬁcation.

(s, 2H), 5.19 (s, 1H), 3.95 (s, 6H), 3.91 (s, 3H), 1.48 (s, 18H).

¹³C{¹H} NMR (126 MHz, CDCl₃): δ 157.1, 153.5, 152.5, 143.5,

140.5, 136.7, 132.2, 117.8, 105.5, 61.0, 56.3, 34.5, 30.3. FTIR: 3630,

2998, 2954, 1620, 1578, 1432, 1329, 805 cm⁻¹. HRMS (ESI) m/z:

calcd for [C₂₄H₃₄NO₄]⁺, 400.2488; found, 400.2501.

Preparation of 2,6-Di-tert-butyl-4-((naphthalen-1-

ylmethylene)amino)phenol (3k). Following General Procedure

A, naphthalen-1-ylmethanamine (2 mL, 13.62 mmol, 1 equiv), 2,6-di-

tert-butyl-1,4-benzoquinone (3 g, 13.62 mmol, 1 equiv), and EtOH

(30 mL) at 80 °C for 16 h aﬀorded, after recrystallization from

hexanes, 1.76 g (36%) of 3k as shiny, yellow, ﬂaky crystals. mp 128−

1

130 °C. H NMR (400 MHz, CDCl₃): δ 9.15 (s, 1H), 8.98 (dq, J =

8.6, 1.0 Hz, 1H), 8.09 (dd, J = 7.1, 1.3 Hz, 1H), 7.94 (ddt, J = 14.0,

8.2, 0.9 Hz, 2H), 7.62 (ddd, J = 8.5, 6.8, 1.5 Hz, 1H), 7.60−7.53 (m,

2H), 7.20 (s, 2H), 5.22 (s, 1H), 1.51 (s, 18H). ¹³C{¹H} NMR (101

MHz, CDCl₃): δ 157.5, 152.6, 144.5, 136.8, 133.9, 132.0, 131.5,

131.3, 129.0, 128.8, 127.3, 126.2, 125.4, 124.2, 117.9, 77.4, 77.0, 76.7,

34.6, 30.3. FTIR: 3627, 3055, 2955, 1626, 1587, 1431 cm⁻¹. HRMS

(ESI) m/z: calcd for [C₂₅H₃₀NO]⁺, 360.2327; found, 360.2336.

Preparation of 2,6-Di-tert-butyl-4-(((2,3-dihydrobenzofur-

an-5-yl)methylene)amino)phenol (3l). Following General Proce-

dure A, 2,3-dehydro-5-benzofuranmethanamine (1.2 g, 8.04 mmol, 1

equiv), 2,6-di-tert-butyl-1,4-benzoquinone (1.77 g, 8.04 mmol, 1

equiv), and EtOH (10 mL) at 80 °C for 7 h aﬀorded, after column

chromatography (gradient 5−40% EtOAc in hexanes) and recrystal-

lization from dichloromethane/hexanes, 623 mg (22%) of 3l as a

white solid. mp 136−137 °C. ¹H NMR (600 MHz, CDCl₃): δ 8.39 (s,

1H), 7.85 (s, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.08 (s, 2H), 6.84 (d, J =

8.2 Hz, 1H), 5.15 (s, 1H), 4.65 (t, J = 8.7 Hz, 2H), 3.26 (t, J = 8.7 Hz,

2H), 1.47 (s, 18H). ¹³C{¹H} NMR (151 MHz, CDCl₃): δ 162.8,

157.8, 152.3, 144.2, 136.7, 130.7, 130.0, 128.2, 124.5, 117.8, 109.5,

72.1, 30.4, 29.5, 29.3. FTIR: 3622, 2954, 1608, 1429 cm⁻¹. HRMS

(ESI) m/z: calcd for [C₂₃H₃₀NO₂]⁺, 352.2277; found, 352.2277.

Preparation of 4-((Benzo[d][1,3]dioxo-5-ylmethylene)-

amino)-2,6-di-tert-butylphenol (3m). Following General Proce-

dure A, 3,4-(methylenedioxy)benzylamine (2 g, 13.23 mmol, 1 equiv),

2,6-di-tert-butyl-1,4-benzoquinone (2.91 g, 13.23 mmol, 1 equiv), and

EtOH (14 mL) at 80 °C for 12 h aﬀorded, after recrystallization from

hexanes, 1.89 g (40%) of 3m as light orange crystals. mp 170−171 °C.

¹H NMR (500 MHz, CDCl₃): δ 8.37 (s, 1H), 7.52 (d, J = 1.7 Hz,

Preparation of Cinnamyl AlcoholsGeneral Procedure D. To a

dry 250 mL round bottom ﬂask were added a magnetic stir bar, the

corresponding methyl cinnamate (11 mmol, 1 equiv), and dichloro-

methane (90 mL, 0.12 M). The ﬂask was ﬂushed with Ar and cooled

using an ice bath. diisobutylaluminum hydride (DIBAL) (3.9 mL, 22

mmol, 2 equiv) was added dropwise using a syringe. The ice bath was

removed, and the reaction was monitored by TLC. After ∼2 h, the

reaction was cooled to 0 °C and quenched with water (0.88 mL),

followed by addition of 15% NaOH_(aq)(0.88 mL). Water (2.2 mL)

was added and the mixture was warmed to rt with stirring. After 15

min, ∼2 scoops of MgSO₄were added and the mixture was stirred at

rt for 30 min. The mixture was ﬁltered through Celite, concentrated,

and the product was puriﬁed by column chromatography.

Preparation of Allylic and Cinnamyl CarbonatesGeneral

Procedure E³. Following a reported procedure,²⁸to a solution of

the corresponding cinnamyl alcohol (1 equiv) in dichloromethane

(reaction concentration ∼ 2.2 M) were added Boc anhydride (1.4

equiv) and Bu₄NHSO₄(0.03 equiv). The solution was cooled to 0 °C

and 30% NaOH_(aq)(0.25 mL/mmol alcohol) was added dropwise

with vigorous stirring. The reaction was followed by TLC. After ∼2 h,

the reaction was diluted with dichloromethane (50 mL) and washed

with water and brine. The organic layer was dried over Na₂SO₄,

ﬁltered, and concentrated. Column chromatography (5−10% EtOAc

in hexanes) aﬀorded the cinnamyl carbonates.

Preparation of (E)-tert-Butyl Cinnamyl Carbonate. Following

General Procedure E, (E)-3-(phenyl)prop-2-en-1-ol (3.4 g, 25.34

mmol, 1 equiv), dichloromethane (15 mL), Boc anhydride (6.34 g,

29.1 mmol, 1.4 equiv), Bu₄NHSO₄(228 mg, 0.67 mmol, 0.03 equiv),

and 30% NaOH (6 mL) at 0 °C for 2.5 h aﬀorded, after extraction

and column chromatography (10% EtOAc in hexanes), 4.78 g (80%)

of (E)-tert-butyl cinnamyl carbonate as a colorless oil. ¹H NMR (400

MHz, CDCl₃): δ 7.42−7.36 (m, 3H), 7.32 (ddd, J = 8.0, 6.9, 1.0 Hz,

3H), 7.28−7.23 (m, 2H), 6.67 (d, J = 15.9 Hz, 1H), 6.30 (dt, J = 15.9,

6.5 Hz, 1H), 4.72 (dd, J = 6.5, 1.3 Hz, 3H), 1.51 (s, 9H). ¹³C{¹H}

NMR (101 MHz, CDCl₃): δ 153.5, 136.3, 134.6, 128.7, 128.2, 126.8,

123.0, 82.4, 67.6, 27.9. Spectral data are in accordance with published

values.²⁸

1H), 7.26 (m, 1H), 7.09 (s, 2H), 6.88 (d, J = 7.9 Hz, 1H), 6.03 (s,

2H), 5.16 (s, 2H), 1.48 (s, 18H). ¹³C{¹H} NMR (126 MHz, CDCl₃):

δ 157.1, 152.5, 150.21, 148.5, 143.8, 136.8, 131.8, 125.3, 117.9, 108.3,

106.9, 101.7, 34.7, 30.42. FTIR: 3628, 2954, 1624, 1446, 1039 cm⁻¹.

HRMS (ESI) m/z: calcd for [C₂₂H₂₈NO₃]⁺, 354.2069; found,

354.2084.

Preparation of 2,6-Di-tert-butyl-4-((2-thiophen-2-

ylmethylene)amino)phenol (3n). Following General Procedure

A, thiophen-2-ylmethanamine (1.4 mL, 13.62 mmol, 1 equiv), 2,6-di-

tert-butyl-1,4-benzoquinone (3 g, 13.62 mmol, 1 equiv), and EtOH

(30 mL) at 80 °C for 16 h aﬀorded, after recrystallization from

Preparation of (E)-tert-Butyl-(3-(4-methylphenyl)allyl) Car-

bonate. Following General Procedure E, (E)-3-(4-methylphenyl)-

prop-2-en-1-ol (1.44 g, 9.72 mmol, 1 equiv), dichloromethane (5

mL), Boc anhydride (2.97 g, 13.6 mmol, 1.4 equiv), Bu₄NHSO₄(99

mg, 0.291 mmol, 0.03 equiv), and 30% NaOH (2.4 mL) at 0 °C for

1

hexanes, 2.34 g (54%) of 3n as yellow crystals. mp 161−162 °C. H

NMR (400 MHz, CDCl₃): δ 8.58 (d, J = 0.9 Hz, 1H), 7.45 (ddd, J =

5.2, 4.1, 1.1 Hz, 2H), 7.14−7.09 (m, 3H), 5.18 (s, 1H), 1.47 (s, 18H).

¹³C{¹H} NMR (101 MHz, CDCl₃): δ 152.6, 150.5, 143.4, 143.1,

J

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2.5 h aﬀorded, after extraction and column chromatography (10%

EtOAc in hexanes), 2.05 g (85%) of (E)-tert-butyl-(3-(4-

methylphenyl)allyl) carbonate as a white solid. ¹H NMR (500

MHz, CDCl₃): δ 7.31 (d, J = 8.0 Hz, 2H), 7.15 (d, J = 7.8 Hz, 2H),

6.66 (d, J = 15.8 Hz, 1H), 6.27 (dt, J = 15.8, 6.5 Hz, 1H), 4.73 (dd, J

= 6.6, 1.3 Hz, 2H), 2.36 (s, 3H), 1.53 (s, 9H). ¹³C{¹H} NMR (126

MHz, CDCl₃): δ 153.5, 138.2, 134.7, 133.6, 129.4, 126.7, 122.0, 82.3,

67.8, 27.9, 21.4. Spectral data are in accordance with published

values.²⁹

Preparation of (E)-tert-Butyl-(3-(4-ﬂuorophenyl)allyl) Car-

bonate. Following General Procedure E, (E)-3-(ﬂuorophenyl)prop-

2-en-1-ol (1.64 g, 10.78 mmol, 1 equiv), dichloromethane (5 mL),

Boc anhydride (3.3 g, 15.1 mmol, 1.4 equiv), Bu₄NHSO₄(110 mg,

0.327 mmol, 0.03 equiv), and 30% NaOH (2.7 mL) at 0 °C for 2.5 h

aﬀorded, after extraction and column chromatography (10% EtOAc in

hexanes), 1.99 g (73%) of (E)-tert-butyl-(3-(4-ﬂuorophenyl)allyl)

carbonate as a white solid. ¹H NMR (500 MHz, CDCl₃): δ 7.35 (dd, J

= 8.6, 5.5 Hz, 2H), 7.00 (t, J = 8.7 Hz, 2H), 6.63 (dd, J = 15.8, 1.6 Hz,

1H), 6.21 (dt, J = 15.9, 6.4 Hz, 1H), 4.70 (dd, J = 6.4, 1.4 Hz, 2H),

1.50 (s, 9H). ¹³C{¹H} NMR (126 MHz, CDCl₃): δ 163.71, 153.47,

146.88, 133.38, 132.52, 132.50, 128.38, 128.32, 122.82, 122.80,

115.76, 115.58, 82.40, 77.41, 77.36, 77.16, 76.91, 67.46, 27.53.

Spectral data are in accordance with published values.²⁹

Preparation of (E)-tert-Butyl-(3-(4-chlorophenyl)allyl) Car-

bonate. Following General Procedure E, (E)-3-(chlorophenyl)prop-

2-en-1-ol (1.79 g, 10.62 mmol, 1 equiv), dichloromethane (3 mL),

Boc anhydride (3.24 g, 14.86 mmol, 1.4 equiv), Bu₄NHSO₄(108 mg,

0.319 mmol, 0.03 equiv), and 30% NaOH (2.6 mL) at 0 °C for 2.5 h

aﬀorded, after extraction and column chromatography (10% EtOAc in

hexanes), 2.21 g (77%) of (E)-tert-butyl-(3-(4-chlorophenyl)allyl)

carbonate as a white solid. ¹H NMR (500 MHz, CDCl₃): δ 7.34−7.27

(m, 1H), 6.62 (dd, J = 15.9, 1.5 Hz, 0H), 6.27 (dt, J = 15.8, 6.4 Hz,

0H), 4.71 (dd, J = 6.4, 1.4 Hz, 0H), 1.50 (s, 2H). ¹³C{¹H} NMR (126

MHz, CDCl₃): δ 153.5, 134.9, 133.9, 133.2, 128.9, 128.0, 123.8, 82.5,

67.4, 27.9. Spectral data are in accordance with published values.³⁰

Preparation of (E)-tert-Butyl-(3-(3-methoxyphenyl)allyl)

Carbonate. Following General Procedure E, (E)-3-

(methoxyphenyl)prop-2-en-1-ol (1.44 g, 8.77 mmol, 1 equiv),

dichloromethane (3 mL), Boc anhydride (2.68 g, 12.28 mmol, 1.4

equiv), Bu₄NHSO₄(89 mg, 0.263 mmol, 0.03 equiv), and 30%

NaOH (4.4 mL) at 0 °C for 2.5 h aﬀorded, after extraction and

column chromatography (10% EtOAc in hexanes), 2.15 g (93%) of

(E)-tert-butyl-(3-(4-methoxyphenyl)allyl) carbonate as a white solid.

¹H NMR (500 MHz, CDCl₃): δ 7.24 (t, J = 7.9 Hz, 1H), 6.98 (dt, J =

CDCl₃): δ 8.00 (d, J = 16.2 Hz, 1H), 7.15 (dd, J = 7.9, 1.4 Hz, 1H),

7.06 (t, J = 8.0 Hz, 1H), 6.94 (dd, J = 8.2, 1.4 Hz, 1H), 6.49 (d, J =

16.2 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 3.81 (s, 3H). ¹³C{¹H} NMR

(126 MHz, CDCl₃): δ 167.7, 153.3, 148.6, 139.7, 128.7, 124.3, 119.4,

119.3, 114.1, 61.5, 56.0, 51.8.

Following General Procedure D, (E)-methyl-2,3-dimethoxycinna-

mate (2.98 g, 10.3 mmol, 1 equiv) and DIBAL (3.74 mL, 20.9 mmol,

2 equiv) in dichloromethane (90 mL) aﬀorded, after workup and

column chromatography (10% EtOAc in hexanes), 1.85 g (91%) of

1

(E)-2,3-dimethoxycinnamyl alcohol as a colorless oil. H NMR (500

MHz, CDCl₃): δ 7.09 (dd, J = 7.9, 1.6 Hz, 1H), 7.01 (t, J = 8.0 Hz,

1H), 6.92 (dd, J = 16.0, 1.8 Hz, 1H), 6.82 (dd, J = 8.1, 1.5 Hz, 1H),

6.39 (ddd, J = 16.1, 6.7, 5.0 Hz, 1H), 4.53−4.21 (m, 2H), 3.86 (s,

3H), 3.81 (s, 3H), 1.58 (s, 1H). ¹³C{¹H} NMR (126 MHz, CDCl₃):

δ 153.1, 146.9, 130.95, 130.1, 130.1, 125.6, 125.5, 124.2, 118.4, 111.6,

64.2, 64.2, 61.0, 55.9. Spectral data are in accordance with published

values.³¹

Following General Procedure E, (E)-2,3-dimethoxycinnamyl

alcohol (1.83 g, 9.42 mmol, 1 equiv), dichloromethane (3 mL),

Boc anhydride (2.88 g, 13.19 mmol, 1.4 equiv), Bu₄NHSO₄(96 mg,

0.28 mmol, 0.03 equiv), and 30% NaOH (2.4 mL) at 0 °C for 2.5 h

aﬀorded, after extraction and column chromatography (10% EtOAc in

hexanes), 2.73 g (99%) of (E)-tert-butyl-(3-(2,3-dimethoxyphenyl)-

1

allyl) carbonate as a colorless oil. H NMR (500 MHz, CDCl₃): δ

7.10 (dd, J = 7.9, 1.5 Hz, 1H), 7.07−6.98 (m, 2H), 6.86 (dd, J = 8.1,

1.5 Hz, 1H), 6.34 (dt, J = 16.0, 6.5 Hz, 1H), 4.76 (dd, J = 6.4, 1.4 Hz,

2H), 3.88 (s, 3H), 3.83 (s, 2H), 1.53 (s, 9H). ¹³C{¹H} NMR (126

MHz, CDCl₃): δ 153.5, 153.1, 147.1, 130.5, 129.0, 124.4, 124.2,

118.5, 112.0, 82.3, 68.0, 61.1, 55.9, 27.9. FTIR: 3061, 2983, 1742,

1585, 1483, 1240 cm⁻¹. HRMS (ESI) m/z: calcd for [C₁₆H₂₂O₅Na]⁺,

317.1365; found, 317.1380.

Preparation of (E)-tert-Butyl-(3-(3-(triﬂuoromethyl)phenyl)-

allyl) Carbonate. Following General Procedure C, (E)-3-(3-

(triﬂuoromethyl)phenyl)acrylic acid (2.38 g, 11 mmol) in MeOH

(30 mL) with sulfuric acid (0.5 mL) at reﬂux aﬀorded, after workup,

2.58 g (100%) of methyl (E)-3-(3-(triﬂuoromethyl)phenyl)acrylate as

1

an oﬀ-white solid. H NMR (500 MHz, CDCl₃): δ 7.76 (d, J = 2.1

Hz, 1H), 7.75−7.60 (m, 3H), 7.52 (t, J = 7.8 Hz, 1H), 6.51 (d, J =

16.0 Hz, 1H), 3.83 (s, 3H). ¹³C{¹H} NMR (126 MHz, CDCl₃): δ

167.0, 143.2, 135.3, 132.6 (q, J = 32.7 Hz), 131.2, 129.6, 126.8 (q, J =

3.7 Hz), 124.8 (q, J = 3.7 Hz), 123.9 (q, J = 273.1 Hz), 119.9, 52.1.

Following General Procedure D, (E)-3-(3-(triﬂuoromethyl)-

phenyl)acrylate (2.58 g, 11 mmol, 1 equiv) and DIBAL (3.9 mL,

22 mmol, 2 equiv) in dichloromethane (90 mL) aﬀorded, after

workup and column chromatography (10% EtOAc in hexanes), 1.96 g

(88%) of (E)-3-(3-(triﬂuoromethyl)phenyl)prop-2-en-1-ol as a color-

7.8, 1.2 Hz, 1H), 6.95−6.88 (m, 1H), 6.82 (ddd, J = 8.2, 2.6, 0.9 Hz,

1H), 6.64 (dt, J = 15.8, 1.4 Hz, 1H), 6.29 (dt, J = 15.8, 6.4 Hz, 1H),

4.72 (dd, J = 6.4, 1.4 Hz, 2H), 3.81 (s, 3H), 1.50 (s, 9H). ¹³C{¹H}

NMR (126 MHz, CDCl₃): δ 159.9, 137.8, 134.4, 129.7, 123.4, 119.5,

113.9, 112.01, 82.4, 67.5, 55.4, 27.9. Spectral data are in accordance

with published values.²⁸

1

less oil. H NMR (500 MHz, CDCl₃): δ 7.63 (d, J = 2.0 Hz, 1H),

7.59−7.54 (m, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.43 (t, J = 7.7 Hz, 1H),

6.66 (dt, J = 15.9, 1.7 Hz, 1H), 6.44 (dt, J = 15.9, 5.4 Hz, 1H), 4.36

(dd, J = 5.4, 1.7 Hz, 2H), 1.57 (s, 1H). ¹³C{¹H} NMR (126 MHz,

CDCl₃): δ 137.7, 131.2 (q, J = 32.0 Hz), 130.7, 129.7, 129.5, 129.2,

124.3 (q, J = 3.7 Hz), 123.2 (q, J = 273.0 Hz), 123.24 (q, J = 3.9 Hz),

63.5. Spectral data are in accordance with published values.³²

Preparation of (E)-tert-Butyl-(3-(4-nitrophenyl)allyl) Carbo-

nate. Following General Procedure E, (E)-3-(4-nitrophenyl)prop-2-

en-1-ol (1.79 g, 10 mmol, 1 equiv), dichloromethane (10 mL), Boc

anhydride (3.2 mL, 14 mmol, 1.4 equiv), Bu₄NHSO₄(101.9 mg, 0.3

mmol, 0.03 equiv), and 30% NaOH (2.5 mL) at 0 °C for 2.5 h

aﬀorded, after extraction and column chromatography (5−15%

EtOAc in hexanes), 1.29 g (46%) of (E)-tert-butyl-(3-(4-

nitrophenyl)allyl) carbonate as a white solid. mp 78−79 °C. ¹H

NMR (400 MHz, CDCl₃): δ 8.22−8.15 (m, 2H), 7.55−7.48 (m, 2H),

6.73 (dt, J = 16.0, 1.6 Hz, 1H), 6.46 (dt, J = 16.0, 5.9 Hz, 1H), 4.76

(dd, J = 6.0, 1.5 Hz, 2H). ¹³C{¹H} NMR (151 MHz, CDCl₃): δ

153.2, 147.2, 142.6, 131.4, 128.0, 127.2, 124.1, 82.7, 66.6, 27.8. FTIR:

Following General Procedure E, (E)-3-(3-(triﬂuoromethyl)-

phenyl)prop-2-en-1-ol (1.96 g, 9.69 mmol, 1 equiv), dichloromethane

(2.5 mL), Boc anhydride (2.96 g, 13.19 mmol, 1.4 equiv), Bu₄NHSO₄

(99 mg, 0.28 mmol, 0.03 equiv), and 30% NaOH (4.9 mL) at 0 °C for

4 h aﬀorded, after extraction and column chromatography (10%

EtOAc in hexanes), 2.61 g (89%) of (E)-tert-butyl-(3-(3-

1

(triﬂuoromethyl)phenyl)allyl) carbonate as a colorless oil. H NMR

(500 MHz, CDCl₃): δ 7.62 (d, J = 2.1 Hz, 1H), 7.59−7.53 (m, 1H),

7.53−7.48 (m, 1H), 7.44 (t, J = 7.7 Hz, 1H), 6.70 (dd, J = 16.0, 1.5

Hz, 1H), 6.36 (dt, J = 15.9, 6.2 Hz, 1H), 4.74 (dd, J = 6.2, 1.5 Hz,

2H), 1.51 (s, 9H). ¹³C{¹H} NMR (126 MHz, CDCl₃): δ 153.4,

137.2, 132.7, 131.2 (q, J = 31.8 Hz), 129.9, 129.2, 125.2, 124.73 (q, J

= 3.6 Hz), 124.2 (q, J = 273 Hz), 123.5 (q, J = 3.6 Hz), 82.6, 67.01,

27.9. ¹⁹F NMR (376 MHz, CDCl₃): δ −62.8. FTIR: 3468, 2982,

1743, 1278, 1128 cm⁻¹. HRMS (ESI) m/z: calcd for [C₁₅H₁₈F₃O₃]⁺,

303.1203; found, 303.1219.

3106, 3078, 2984, 2936, 1738, 1516, 1458, 1374, 1343, 821 cm⁻¹

.

HRMS (ESI) m/z: calcd for [C₁₄H₁₈NO₅]⁺, 280.1185; found,

280.1199.

Preparation of (E)-tert-Butyl-(3-(2,3-dimethoxyphenyl)allyl)

Carbonate. Following General Procedure C, 2,3-dimethoxycinnamic

acid (2.27 g, 11 mmol) in MeOH (30 mL) with sulfuric acid (0.5

mL) at reﬂux aﬀorded, after workup, 2.33 g of methyl-2,3-

1

dimethoxycinnamate (95%) as a colorless oil. H NMR (500 MHz,

K

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Preparation of (E)-tert-Butyl-(3-(furan-2-yl)allyl) Carbonate.

Following General Procedure E, (E)-3-(furan-2-yl)prop-2-en-1-ol³³

(1.47 g, 11.84 mmol, 1 equiv), dichloromethane (3.1 mL), Boc

anhydride (3.8 mL, 16.58 mmol, 1.4 equiv), Bu₄NHSO₄(122.2 mg,

0.36 mmol, 0.03 equiv), and 30% NaOH (5.9 mL) at 0 °C for 2.5 h

aﬀorded, after extraction and column chromatography (5−15%

EtOAc in hexanes), 2.29 g (86%) of (E)-tert-butyl-(3-(furan-2-

dried 10 mL Schlenk ﬂask with a magnetic stir bar was charged with

N-(aryloxy)imine (1 mmol, 1 equiv), Pd₂(dba)₃(0.01 mmol, 0.01

equiv), and K₃PO₄(1.1 mmol, 1.1 equiv). If the allylic carbonate was

a solid, it was added at this point. The ﬂask was sealed with a septum

and evacuated/backﬁlled with Ar (3 cycles). Then, dioxane (3.3 mL),

MeCN (10 mmol, 10 equiv), and the cinnamyl tert-butyl carbonate

(1.5 mmol, 1.5 equiv) were added sequentially using a syringe. The

reaction was heated in an oil bath to 80 °C with vigorous stirring.

After 3 h, the reaction was cooled to rt, diluted with EtOAc (∼40

mL), transferred to a separatory funnel, and washed with NH₄Cl_(sat)

(5 mL). The aqueous phase was extracted with EtOAc (2 × 10 mL).

The combined organic extracts were washed with brine (5 mL) and

dried over Na₂SO₄. 1,3,5-Trimethoxybenzene (168.2 mg, 1 equiv)

1

yl)allyl) carbonate as a yellow oil. H NMR (400 MHz, CDCl₃): δ

7.35 (d, J = 1.8 Hz, 1H), 6.47 (dt, J = 15.9, 1.4 Hz, 1H), 6.37 (dd, J =

3.4, 1.8 Hz, 1H), 6.28 (d, J = 3.3 Hz, 1H), 6.21 (dt, J = 15.8, 6.4 Hz,

1H), 4.68 (dd, J = 6.4, 1.4 Hz, 2H), 1.49 (s, 10H). ¹³C{¹H} NMR

(126 MHz, CDCl₃): δ 153.3, 151.9, 142.4, 122.3, 121.4, 111.3, 108.9,

82.2, 67.0, 27.8. Spectral data are in accordance with published

values.³⁴

1

was added and the solution was concentrated and analyzed by H

Preparation of (E)-tert-Butyl(methallyl) Carbonate. Following

General Procedure E, (E)-crotyl alcohol (0.77 mL, 9 mmol, 1 equiv),

dichloromethane (2.3 mL), Boc anhydride (2.75 g, 12.6 mmol, 1.4

equiv), Bu₄NHSO₄(92 mg, 0.27 mmol, 0.03 equiv), and 30% NaOH

(4.5 mL) at 0 °C for 2.5 h aﬀorded, after extraction and column

chromatography (10% EtOAc in hexanes), 976 mg (63%) of (E)-tert-

NMR to obtain an NMR yield of the allylation step.

The crude reaction mixture was then dissolved in THF (∼4 mL)

and 2 M HCl_(aq)(4 mL) was added. The reaction mixture was stirred

at rt and hydrolysis of the iminoquinone product was monitored by

TLC. After ∼2−3 h, the reaction was diluted with THF (15 mL) and

transferred to a separatory funnel using diethyl ether (20 mL) and

water (∼5 mL) to rinse the ﬂask. The organic phase was washed with

1 M HCl_(aq)(4 × 5 mL). The combined aqueous phases were basiﬁed

with 3 M NaOH_(aq)(pH > 10) and extracted with dichloromethane

(4 × 30 mL). The combined organic phase was dried over Na₂SO₄

and concentrated. Column chromatography (1−10% MeOH in

dichloromethane) aﬀorded the cinnamyl-derived homoallylic amine.

Palladium-Catalyzed Allylation of N-(Aryloxy)imines with Less-

Reactive Allylic CarbonatesGeneral Procedure H. A ﬂame-dried

10 mL Schlenk ﬂask with a magnetic stir bar was charged with N-

(aryloxy)imine (1 mmol, 1 equiv), Pd₂(dba)₃(0.01 mmol, 0.01

equiv), Xantphos (0.025 mmol, 0.025 equiv), and K₃PO₄(1.1 mmol,

1.1 equiv). If the allylic carbonate was a solid, it was added at this

point. The ﬂask was sealed with a septum and evacuated/backﬁlled

with Ar (3 cycles). Then, dioxane (3.3 mL) and the allylic carbonate

(1.5 mmol, 1.5 equiv) were added sequentially using a syringe. The

reaction was heated in an oil bath to 80 °C with vigorous stirring.

After 3 h, the reaction was cooled to rt, diluted with EtOAc (∼40

mL), transferred to a separatory funnel, and washed with NH₄Cl_(sat)

(5 mL). The aqueous phase was extracted with EtOAc (2 × 10 mL).

The combined organic extracts were washed with brine (5 mL) and

dried over Na₂SO₄. 1,3,5-Trimethoxybenzene (168.2 mg, 1 equiv)

1

butyl-(methallyl) carbonate as a colorless oil. H NMR (400 MHz,

CDCl₃): δ 5.81 (dddd, J = 15.3, 7.6, 6.5, 5.4 Hz, 0H), 5.61 (dddd, J =

15.2, 8.3, 5.0, 1.6 Hz, 1H), 4.48 (dt, J = 6.6, 1.1 Hz, 1H), 1.80−1.65

(m, 1H), 1.48 (s, 5H). ¹³C{¹H} NMR (101 MHz, CDCl₃): δ 153.6,

132.1, 125.0, 82.1, 27.9, 17.9. Spectral data are in accordance with

published values.²⁹

Preparation of tert-Butyl Cyclohex-2-en-1-yl Carbonate.

Following General Procedure E, (E)-crotyl alcohol (1.0 mL, 10.2

mmol, 1 equiv), dichloromethane (6 mL), Boc anhydride (3.1 g, 14.3

mmol, 1.4 equiv), Bu₄NHSO₄(100 mg, 0.305 mmol, 0.03 equiv), and

30% NaOH (2.5 mL) at 0 °C for 6 h aﬀorded, after extraction and

column chromatography (10% EtOAc in hexanes), 414 mg (21%) of

1

tert-butyl cyclohex-2-en-1-yl carbonate as a colorless oil. H NMR

(400 MHz, CDCl₃): δ 5.97 (dtd, J = 10.1, 3.8, 1.3 Hz, 1H), 5.79 (ddt,

J = 10.1, 4.1, 2.2 Hz, 1H), 5.09 (dp, J = 5.2, 1.8 Hz, 1H), 2.15−1.93

(m, 2H), 1.93−1.73 (m, 3H), 1.70−1.60 (m, 1H), 1.51 (s, 9H).

¹³C{¹H} NMR (101 MHz, CDCl₃): δ 153.5, 133.1, 125.5, 81.9, 70.9,

28.4, 28.0, 25.0, 18.9. Spectral data are in accordance with published

values.³⁵

Synthesis of Homoallylic Amines. Palladium-Catalyzed

Allylation of N-(Aryloxy)imines with Allyl tert-Butyl Carbonate

General Procedure F. A ﬂame-dried 10 mL Schlenk ﬂask with a

magnetic stir bar was charged with N-(aryloxy)imine (1 mmol, 1

equiv), Pd₂(dba)₃(0.01 mmol, 0.01 equiv), and K₃PO₄(1.1 mmol,

1.1 equiv). The ﬂask was sealed with a septum and evacuated/

backﬁlled with Ar (3 cycles). Then, dioxane (5 mL), MeCN (10

mmol, 10 equiv), and allyl tert-butyl carbonate (237 mg, 1.5 mmol,

1.5 equiv) were added sequentially using a syringe. The reaction was

heated in an oil bath to 80 °C with vigorous stirring. After 1 h, the

reaction was cooled to rt, diluted with EtOAc (∼40 mL), transferred

to a separatory funnel, and washed with NH₄Cl_(sat)(5 mL). The

aqueous phase was extracted with EtOAc (2 × 10 mL). The

combined organic extracts were washed with brine (5 mL) and dried

over Na₂SO₄. 1,3,5-Trimethoxybenzene (168.2 mg, 1 equiv) was