Experimental and Computational Mechanistic Investigation of Chlorocarbene Additions to Bridgehead Carbene-Anti-Bredt Systems: Noradamantylcarbene-Adamantene and Adamantylcarbene-Homoadamantene

Article

pubs.acs.org/joc

Experimental and Computational Mechanistic Investigation of

Chlorocarbene Additions to Bridgehead Carbene−Anti-Bredt

Systems: Noradamantylcarbene−Adamantene and

Adamantylcarbene−Homoadamantene

Stephanie R. Hare,^†Marina Orman,^‡Faizunnahar Dewan,^‡Elizabeth Dalchand,^‡Camilla Buzard,^‡

Sadia Ahmed,^‡Julia C. Tolentino,^‡Ulweena Sethi,^‡Kelly Terlizzi,^‡Camille Houferak,^‡Aliza M. Stein,^‡

Alexandra Stedronsky,^‡Dasan M. Thamattoor,^§Dean J. Tantillo,^†and Dina C. Merrer*^,‡

^†Department of Chemistry, University of CaliforniaDavis, 1 Shields Avenue, Davis, California 95616, United States

^‡Department of Chemistry, Barnard College, 3009 Broadway, New York, New York 10027, United States

^§Department of Chemistry, Colby College, 5750 Mayﬂower Hill, Waterville, Maine 04901, United States

S

* Supporting Information

ABSTRACT: Cophotolysis of noradamantyldiazirine with the

phenanthride precursor of dichlorocarbene or phenylchloro-

diazirine in pentane at room temperature produces norada-

mantylethylenes in 11% yield with slight diastereoselectivity.

Cophotolysis of adamantyldiazirine with phenylchlorodiazirine

in pentane at room temperature generates adamantylethylenes

1

in 6% yield with no diastereoselectivity. H NMR showed the

reaction of noradamantyldiazirine + phenylchlorodiazirine to

be independent of solvent, and the rate of noradamantyldiazirine consumption correlated with the rate of ethylene formation.

Laser ﬂash photolysis showed that reaction of phenylchlorocarbene + adamantene was independent of adamantene

concentration. The reaction of phenylchlorocarbene + homoadamantene produces the ethylene products with k = 9.6 × 10⁵M⁻¹

s⁻¹. Calculations at the UB3LYP/6-31+G(d,p) and UM062X/6-31+G(d,p)//UB3LYP/6-31+G(d,p) levels show the formation

of exocyclic ethylenes to proceed (a) on the singlet surface via stepwise addition of phenylchlorocarbene (PhCCl) to bridgehead

alkenes adamantene and homoadamantene, respectively, producing an intermediate singlet diradical in each case, or (b) via

addition of PhCCl to the diazo analogues of noradamantyl- and adamantyldiazirine. Preliminary direct dynamics calculations on

adamantene + PhCCl show a high degree of recrossing (68%), indicative of a ﬂat transition state surface. Overall, 9% of the total

trajectories formed noradamantylethylene product, each proceeding via the computed singlet diradical.

quite complex. In 2001, Platz and co-workers reported that the

photolysis of noradamantyldiazirine (1a) leads to adamantene

(3a) through the excited state of the diazirine, bypassing

noradamantylcarbene (2a).^18,19They computed the singlet 2a

⇌ 3a equilibrium to greatly favor 3a by 32.4 kcal/mol

(B3LYP/6-31G*) and a nominal 0.35 kcal/mol barrier for the

conversion of singlet adamantylcarbene to adamantene.¹⁸

The minimal barrier for conversion of 2a → 3a helped

explain Platz and colleagues’s matrix isolation and laser ﬂash

photolysis (LFP) studies of the photolysis of 1a. They did not

observe 2a upon photolysis of 1a at 350 nm in an Ar matrix at

14 K, but they did see UV and IR features attributed to 3a:

UV−vis λ_max= 320 nm, IR υ = 1478 cm⁻¹.¹⁹In benzene¹⁹or

cyclohexane¹⁸solution, LFP of 1a produced an absorption

assigned to 3a (λ_max= 325 nm) that decayed over “many

microseconds” via second-order processes. These processes

were attributed to the formation of [2 + 2] dimers of 3a and

INTRODUCTION

■

Molecules with strained, distorted geometries fascinate

chemists, whether from the sheer challenge of synthesizing

these seemingly unfathomable (by the laws of chemistry)

structures or simply the beauty of the “abnormal”.¹In

particular, the geometries, stabilities, and reactivities of

bridgehead alkenes have been a source of intrigue since Bredt

proposed his rule almost a century ago.²⁻⁴Increasing numbers

of natural products containing bridgehead alkenes have been

isolated and characterized, and their total syntheses achieved.⁵

Bridgehead alkenes show diverse reactivity: carbocation

rearrangements⁶to Diels−Alder chemistry⁷to radical trapping.⁸

The Jones^7,9−14and Michl^8,15,16groups were the among ﬁrst

to study and use bridgehead carbenes as a route to bridgehead

alkenes.¹⁷Among the compounds they studied were

adamantene (3a)^7−9,15,16and homoadamantene (3b).^11,14−16

The Platz group generated 3a and 3b photochemically from

noradamantyldiazirine (1a) and adamantyldiazirine (1b),

respectively (Scheme 1).^18,19The photochemistry of both

noradamantyldiazirine (1a) and adamantyldiazirine (1b) is

Received: February 27, 2015

Published: April 22, 2015

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Scheme 1. Irradiation of Diazirines 1 and Their Reactions with PhCCl and CCl₂

protoadamantene (5). Additionally, bimolecular rate constants

of the reactions of 3a with quenchers were determined: 8.4 ×

10⁴M⁻¹s⁻¹(methanol), 1.8 × 10⁵M⁻¹s⁻¹(1,3-cyclo-

hexadiene), and 1.4 × 10⁷M⁻¹s⁻¹(acetic acid).¹⁹Notably,

they were not able to visualize 2a via the pyridine ylide

method,^20,21lending further support to their claim that

noradamantylcarbene was either not formed or did not live

long enough to be trapped.

product.^22,23Brinker’s studies stimulated our interest in

halocarbene additions to these and similarly strained systems.

We since have determined that dihalocarbenes add to

cyclopropene and benzocyclopropene in a concerted manner

through one transition state that undergoes branching to

several products.^24,25When multiple products are formed from

the same transition state, transition state theory is inadequate to

describe the reaction mechanism. Rather, nonstatistical

dynamic eﬀects may inﬂuence or control the course of the

reaction. Our dynamics trajectory calculations have strongly

supported this phenomenon for dichlorocarbene addition to

cyclopropene.²⁶We have thus proposed that dynamic eﬀects

intervene in carbene additions to π-substrates containing a

threshold amount of strain energy. Additionally, Rablen et al.

have proposed that reaction dynamics contributes to the

regioselectivity of singlet carbene additions to the strained C−

C σ-systems of substituted bicyclo[1.1.0]butanes.²⁷

In an attempt to determine the threshold strain energy

required for dynamics to exert control of carbene addition

reactions to strained C−C π-substrates, we have investigated

the photochemical reactions of R′CCl (R′ = Ph, Cl) with

bridgehead alkenes adamantene (3a; E_strain= 37−40 kcal/mol)

and homoadamantene (3b; E_strain≈ 20 kcal/mol).^11,28We ﬁrst

desired to determine if these reactions of two transient species

(PhCCl + 3a and PhCCl + 3b) would yield product at all, given

the highly reactive nature of all involved species. Once PhCCl

adducts of each system were indeed produced, we used

additional experimental (NMR, LFP) and computational tools

to make sense of their formation. We thus report the ﬁrst

trapping of transient bridgehead alkenes with carbenes and that

these reactions proceed in a stepwise manner via a diradical on

the singlet reactive surface of each system or via an S_N2 reaction

with the diazo analogues of noradamantyldiazirine and

adamantyldiazirine, 6a and 6b, respectively.

The Platz group also reported the photochemistry of

adamantyldiazirine (1b).¹⁸They determined that the minimal

structural change of adding one methylene unit in going from

1a to 1b resulted in a signiﬁcant reactivity diﬀerence between

the two systems. Similar to the noradamantylcarbene−

adamantene equilibrium, the computed adamantylcarbene−

homoadamantene equilibrium strongly favored homoadaman-

tene: 3b was 45.9 kcal/mol more stable than singlet 2b

(B3LYP/6-31G*).¹⁸In contrast to the singlet 2a → 3a barrier

of 0.35 kcal/mol, the singlet 2b → 3b barrier was 6.1 kcal/

mol.¹⁸This increase in the activation barrier indicated that

adamantylcarbene may possess a lifetime long enough to be

trapped bimolecularly.

Photolysis of 1b at 350 nm in an Ar matrix at 14 K by Platz

and co-workers did not provide UV evidence of 2b. Rather, 1b

isomerized to adamantyldiazomethane (6b; see the structure

above). Subsequent photolysis of the 6b-containing matrix at

254 nm led to the formation of 3b. LFP of 1b at 351 nm in

pentane or cyclohexane produces no UV-active transient. When

pyridine was added, the pyridine ylide of 2b was produced. The

major (stable) products from these photolyses are adducts of

2b with cyclohexane solvent (11%) and [2 + 2] dimers of

homoadamantene, 3b (28%).¹⁸From these experiments, they

deduced the room-temperature lifetime of 2b to be 1.5 ns in

cyclohexane and 2.5 ns in cyclohexane-d₁₂. They also were able

to trap 2b with piperidine: photolyses in cyclohexane

containing increasing concentrations of piperidine resulted in

increased 2b−piperidine adduct and reduced amounts of

homoadamantene (3b) dimers and 2b−cyclohexane adducts.¹⁸

Thus, Platz et al. concluded that the reactive species in the

solution-phase chemistry of noradamantyldiazirine was adam-

antene (3a), whereas the reactive species in the solution-phase

chemistry of adamantyldiazirine was adamantylcarbene (2b).

We are interested in the mechanisms of halocarbene

additions to strained C−C π-bonds. Pioneering work by

Brinker and co-workers on halocarbene additions to 1,2-

diarylcyclopropenes showed evidence of a polar transition state

that resulted in the unexpected formation of a butadiene

RESULTS AND DISCUSSION

■

Product Studies. We synthesized diazirines 1^18,19,29and

cophotolyzed each with phenylchlorodiazirine (8)³⁰at 350 nm

at room temperature in pentane; 1a was also cophotolyzed with

the phenanthride precursor of CCl₂(7),³¹⁻³³at 300 nm.

Products corresponding to the addition of 2a or 3a plus each of

chlorocarbenes R′CCl and products corresponding to the

addition of 2b or 3b plus PhCCl were isolated and puriﬁed.

NMR (¹H, ¹³C, DEPT-135, HSQC, HMBC, NOESY) and

HRMS characterization reveal these products to have structures

corresponding to 4a-Ph and 4a-Cl, and 4b-Ph, respectively. As

determined by GC, the photosylate of 1a + 8 contains 11% of

4a-Ph, 1a + 7 gives 5% of 4a-Cl, and 1b + 8 yields 6% of 4b-

Ph. Additionally, the formation of 4a-Ph showed slight

diastereoselectivity favoring the E-isomer: the E:Z ratio was

58.2

0.7:41.8

0.7. There was no preference for either

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Scheme 2. Proposed Mechanisms of the Formation of Alkene 4a from Cophotolysis of 1a with 7 or 8

diastereomer of 4b-Ph: the E:Z ratio was 48.4 2.1:51.6 2.1.

The majority of the remainder of the photosylates are

comprised of reactions of PhCCl with pentane, PhCCl

dimerization, adamantene dimerization (which had also been

reported by Platz),^18,19homoadamantene dimerization (which

also had been reported by Platz),¹⁸and adducts of each of

noradamantylcarbene/adamantene + pentane and adamantyl-

carbene/homoadamantene + pentane. A table containing the

product distributions is included in the Supporting Information.

Although the yields were low, the formations of 4a and 4b were

the most important and the most unanticipated. We not only

were surprised by their formation at all, as a result of the

reaction of two transients, we were surprised by their structures.

We discuss possible mechanisms and our experimental and

computational investigations of these possibilities below.

Possible Mechanisms of Formation of Exocyclic

Alkenes 4. Noradamantyldiazirine/Adamantene System.

Scheme 2 depicts several proposed mechanisms for the

formation of noradamantylethylene 4a. The ﬁrst four pathways

center on PhCCl reacting with adamantene 3a. Path A involves

PhCCl cycloaddition to 3a followed by ring contraction via

cyclopropane intermediate 9a. In paths B and C, R′CCl adds to

3a in a stepwise manner via a diradical (path B) or zwitterion

(path C) followed by concurrent ring contraction and

rearrangement to 4a. These proposed stepwise paths are

rooted in evidence provided by Brinker’s group of a polar

transition state, if not a full zwitterionic intermediate, and the

stepwise character of dihalocarbene additions to 1,2-diary-

lcyclopropenes,^22,23as well as the involvement of a

zwitterionand thus a nonconcerted pathwayin singlet

carbene addition to bicyclo[1.1.0]butanes proposed by Rablen

et al.²⁷Path D depicts the possibility of the concerted addition

and ring contraction of R′CCl + 3a → 4a. Path D has a lot of

concurrent motion and may seem unconventional, but it is not

unfounded, as it parallels the route by which CCl₂adds to

cyclopropene to produce a 1,1-dichloro-1,3-butadiene (Scheme

4). We previously showed the formation of butadiene to result

from dynamic eﬀects.^25,26

Paths E and F stem from the possible isomerization of 1a to

diazo compound 6a. Platz and co-workers observed the

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Scheme 3. Proposed Mechanisms of the Formation of Alkene 4b-Ph from Cophotolysis of 1b with 8

tylcarbene 2b was found to be the important reactive

intermediate.¹⁸

Scheme 4. Mechanism of Formation of Butadiene from CCl₂

Addition to 1,2-Disubstituted Cyclopropenes

Experimental Investigations of Mechanistic Path-

ways. Because of the ease in obtaining and handling

phenylchlorodiazirine (8), we focused our experimental and

computational mechanistic investigations on the reactions of

PhCCl additions to each of the two anti-Bredt systems. These

studies are described below.

isomerization of 1a to 6a in an Ar matrix.¹⁹Path E outlines

stepwise carbene addition to 6a followed by rearrangement and

loss of N₂, whereas path F is the concerted analogue. Lastly,

path G forms 4a via a carbene “dimerization” of R′CCl with

noradamantylcarbene (2a).

Noradamantyldiazirine/Adamantene System. To inves-

tigate path A experimentally, we monitored the 350-nm

photolysis of 1a + 8 in cyclohexane-d₁₂(C₆D₁₂) and in

1

benzene-d₆(C₆D₆) at room temperature by UV−vis and H

NMR spectroscopy, taking spectra at t = 0, 5, 10, 15, 20, 30, 40,

and 60 min (three to six trials). The disappearance of 1a was

monitored by following the decay of the diazirine n → π*

absorption at 340−360 nm (λ_max= 358 nm). The starting

Adamantyldiazirine/Adamantylcarbene System. Given the

Platz group’s observations of diﬀering photochemistry between

noradamantyldiazirine versus adamantyldiazirine, we were

surprised by the formation of exocyclic alkenes 4b-Ph from

the cophotolysis of adamantyldiazirine 1b and phenylchlor-

odiazirine 8 that paralleled the alkenes obtained from the

noradamantyl system (i.e., 4a). In Scheme 3, we propose

mechanisms A′−G′ for the formation of 4b-Ph analogous to

those proposed for the formation of 4a-Ph. We note that paths

E′ and F′ stem from Platz and co-worker’s observation of the

isomerization of 1b to diazo compound 6b in an Ar matrix.¹⁸

Furthermore, the carbene “dimerization” shown in path G′ is

the route most consistent with the Platz group’s solution-phase

photochemical studies of adamantyldiazirine, where adaman-

photolytic solutions in C₆D₁₂and C₆D₆contained 1a (ε_1a

=

330 M⁻¹cm⁻¹) with A₃₃₈= 1.3−1.4 and 8 (ε₈= 100 M⁻¹cm⁻¹)

with A₃₇₁= 0.8−0.9. Using ¹H NMR, we followed the

disappearance of the diazirine proton of 1a (at δ 0.96 ppm in

C₆D₁₂and at δ 0.51 ppm in C₆D₆) and the appearance of the

vinyl protons of E- and Z-4a-Ph (at δ 6.43 and 6.52 ppm,

respectively, in C₆D₁₂, and at δ 6.29 and 6.33 ppm, respectively,

in C₆D₆). The integrations of these protons were calibrated

against an internal standard of 0.31 mmol of CH₂Cl₂in each

NMR sample and converted to millimoles of 1a and to

millimoles of E- and Z-4a-Ph.

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Given the Platz group’s report of a tens-of-microseconds

lifetime of adamantene at room temperature,¹⁸we did not

expect to see 3a by NMR, but we did investigate the possibility

of the formation (and subsequent disappearance) of cyclo-

propyl adduct 9a-Ph. Careful exploration of the far upﬁeld

range (δ −0.1 to +0.5 ppm, i.e., where we would expect to

observe a cyclopropyl proton resonance) showed no

appearance of the putative cyclopropyl proton of 9a-Ph.

Despite our inability to observe 9a-Ph by NMR, it is entirely

possible that 9a-Ph may form and react faster than can be

measured on the NMR time scale.

Nevertheless, to obtain rate data for the photolysis of 1a + 8

at room temperature, we wished to either follow the decay of

PhCCl or 3a (or 3a-d) directly; however, these two transients

absorb at nearly the same wavelength (λ_max= 320 nm for

PhCCl and 325 nm for 3a).^18,19In need of a clear spectral

window, we thus measured the rate of formation of the pyridine

ylide^20,21of PhCCl at 460 nm at varying concentrations of 3a.

To vary the concentration of 3a, we measured k_obsat diﬀerent

concentrations of 1a. To connect the concentration of 3a with

that of 1a, separately we measured the A₃₂₅of 3a at each

concentration of 1a. The concentration of 1a ranged from

0.525 to 3.6 mM. Using the reported molar absorptivities of

anti-Bredt oleﬁns 13³⁴as an estimate of ε for 3a, we used Beer’s

law to obtain the concentration of 3a. We found k_obsfor the

formation of the pyridine ylide of PhCCl in the presence of 3a

Although our NMR studies proved inconclusive on the

formation of 9a-Ph in the cophotolysis of 1a + 8, we were able

to obtain other information about the rates of consumption of

diazirine 1a and production of E- and Z-4a-Ph. Via UV−vis and

NMR, we determined that 1a was consumed by t = 60 min in

C₆D₁₂and 40 min C₆D₆. A plot of the millimoles of diazirine 1a

(via integration of the 1a diazirine proton at δ 0.96 ppm in

C₆D₁₂and at δ 0.51 ppm in C₆D₆) versus time showed

exponential decay, with k_avg= (1.0 0.7) × 10⁻³mmol⁻¹s⁻¹in

(from 1a) to be independent of the concentrations of 3a: k_obs

=

(4−5) × 10⁷M⁻¹s⁻¹. Because the proposed product of 3a +

PhCCl, i.e., 4a-Ph, is produced in 11% yield (by GC), we

conclude that this reaction is not competitive with other

processes present in the reaction mixture (e.g., adamantene

dimerization, PhCCl insertion into pentane solvent, adaman-

tene or noradamantylcarbene reaction with pentane solvent) to

C₆D₁₂and 1.24

0.04 × 10⁻³mmol⁻¹s⁻¹in C₆D₆(see

Supporting Information for graphs). Within 5 min of

photolysis, the formation of both E- and Z-4a-Ph was observed

by ¹H NMR. Although our product studies (see above)

exhibited slight diastereoselectivity, we did not measure any

signiﬁcant stereoisomeric preference via these NMR measure-

ments: both diastereomers were produced in equal or nearly

equal quantities for the entire 60 min photoreaction. The rate

of formation of the two alkenes was determined by summing

the integrations of the vinyl protons. By t = 15−20 min in both

solvents, generation of 4a-Ph had maximized and plateaued. A

plot of the millimoles of ethylenes 4a-Ph (via integration of the

E- and Z-4a-Ph vinyl protons at δ 6.43 and 6.52 ppm in C₆D₁₂

and at δ 6.29 and 6.33 ppm in C₆D₆) versus time showed

exponential growth, with k_avg= (2.5 0.5) × 10⁻³mmol⁻¹s⁻¹

(C₆D₁₂) and (3.4 0.8) × 10⁻³mmol⁻¹s⁻¹(C₆D₆) (see the

Supporting Information for graphs). Thus, the rates of

disappearance of 1a and the rates of appearance of 4a-Ph

were each independent of solvent. Additionally, the rate of

disappearance of 1a and the rate of appearance of 4a-Ph were

approximately equal.

Further mechanistic investigation of this system has involved

nanosecond kinetics measurements via laser ﬂash photolysis

(LFP). We thought that rate constant information would

provide additional mechanistic information. In particular, the

temperature independence of the bimolecular rate constants for

the noradamantyldiazirine + phenylchlorodiazirine system (i.e.,

1a + 8) would lend support to dynamic control. Additionally,

we endeavored to probe whether or not there existed an

isotope eﬀect on k_obsfor 1a + 8 by measuring the kinetics of the

reactions with 1a and, separately, 1a-d.

aﬀect k_obs

.

Adamantyldiazirine/Adamantylcarbene System. LFP was

also used to determine the rate constant for the formation of

adamantylethylenes 4b-Ph, which we believe are formed by the

reaction of homoadamantene (3b) with PhCCl. The measure-

ments for this system were more straightforward than those for

adamantene because homoadamantene does not absorb near

PhCCl (λ_maxof PhCCl = 320 nm).¹⁸We measured the k_obsof

the decay of PhCCl at a constant concentration of 1b at room

temperature in pentane: 1.6 × 10⁷M⁻¹s⁻¹. For these

experiments, we make the assumption that a constant

concentration of 1b corresponds to a constant concentration

of 3b. Partitioning k_obsaccording to the product distribution,

where 4b-Ph accounts for 6% of the photolysis products, gives

the bimolecular rate constant of 9.6 × 10⁵M⁻¹s⁻¹. We believe

this value to possibly be the ﬁrst reported rate constant for the

reaction of a carbene with homoadamantene.

Computational Investigations of Mechanistic Path-

ways. Gaussian 09³⁵was used to compute the potential energy

surfaces (PESs) of several of the proposed mechanisms for the

formation of noradamantylethylenes 4a-Ph and adamantyl-

ethylenes 4b-Ph at the UB3LYP/6-31+G(d,p), UM062X/6-

31+G(d,p)//UB3LYP/6-31+G(d,p), and RB3LYP/6-31+G-

(d,p) levels of theory (see Computational Methods for details).

The energies reported are unscaled, and electronic energies do

not include zero-point corrections. All energies are relative to

the starting point of carbene 2a (or 2b) + PhCCl at inﬁnite

separation (E_relor G_rel= 0 kcal/mol). Two viable pathways for

the formation of 4a-Ph and 4b-Ph were found: one that

includes the respective anti-Bredt alkene (3a or 3b) and one

that does not. We will begin by discussing the pathway on the

PESs that includes 3a or 3b.

As is described below, the isotope eﬀect studies never came

to fruition because the consumption of PhCCl was independent

of the concentration of parent 2a or 3a (via variance of the

concentration of 1a). Hence, we were not able to measure a

rate constant for the formation of 4a-Ph via PhCCl + 2a or 3a.

These reactions were computed on the singlet and triplet

electronic surfaces. Although the singlet−triplet gap of PhCCl

has not yet been determined experimentally, a previous

computational study supports a singlet ground state and

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experimental reactivity from the singlet manifold.³³We found

singlet PhCCl to be 5.4 kcal/mol lower in energy (ΔG) than its

triplet state (UB3LYP/6-31+G(d,p) structures in Figure 1),

kcal/mol. These nominal diﬀerences may be an artifact of the

B3LYP functional, which is known to do a poor job of

calculating singlet−triplet gaps.³⁷For a benchmark study of

how this level of theory compares to some experimental

singlet−triplet gaps, see the Supporting Information. In any

case, the two possible electronic ground states of 2a and 2b are

likely very close in energy; a pathway involving either electronic

state is reasonable.

Noradamantyldiazirine/Adamantene System. We found

the lowest energy pathway for the addition of PhCCl to

noradamantylcarbene/adamantene to correspond to proposed

mechanistic path B (Scheme 2). Previously, the mechanisms of

singlet carbene additions to strained C−C π-bonds (cyclo-

propenes)^22,23and σ-bonds (bicyclo[1.1.0]butanes)²⁷have

shown evidence of stepwise character, albeit via polar transition

states or intermediates. Here, path B, which proceeds on the

singlet electronic state surface, was found using UB3LYP/6-

31+G(d,p) and UM062X/6-31+G(d,p)//UB3LYP/6-31+G-

(d,p) and is depicted in Figure 2. In the ﬁrst step, carbene 2a

undergoes a ring expansion with a nominal barrier of 0.60 kcal/

mol to aﬀord adamantene (3a), an exothermic transformation

which releases 29.9 kcal/mol. This result is consistent with the

Platz group’s computational ﬁndings of the singlet 2a ⇌ 3a

equilibrium favoring 3a by 32.4 kcal/mol (B3LYP/6-31G*)

Figure 1. A geometrical comparison of ¹PhCCl and ³PhCCl calculated

at the UB3LYP/6-31+G(d,p) level of theory. The geometries

described here are consistent with previous computations done by

the Platz group, who found at the B3LYP/6-31G(d) level of theory the

singlet Cl−C−C angle to be 111.8° and the triplet angle to be 131.6°.

They also found the C−C bond lengths indicated to be 1.46 and 1.40

Å for the singlet and triplet structures, respectively.³⁶

qualitatively consistent with previous computational studies

that used several diﬀerent levels of theory.³⁶At this same level

of theory and basis set, the triplet state of noradamantylcarbene

(2a) was 1.1 kcal/mol lower in energy than its singlet state, and

triplet adamantylcarbene (2b) was the ground state by 0.74

Figure 2. PES of PhCCl addition to noradamantylcarbene (2a) and adamantene (3a) on the singlet surface at UB3LYP/6-31+G(d,p) (electronic

energies E and free energies G) and UM062X/6-31+G(d,p)//UB3LYP/6-31+G(d,p) (electronic energies E).

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Figure 3. PES of PhCCl addition to noradamantylcarbene (2a) and adamantene (3a) on the triplet surface at UB3LYP/6-31+G(d,p) (electronic

energies E and free energies G) and UM062X/6-31+G(d,p)//UB3LYP/6-31+G(d,p) (electronic energies E). Images of stationary point structures

other than TSSs and triplet 4a-Ph are omitted for clarity (see the Supporting Information).

Figure 4. Comparison of singlet (red) and triplet (blue) free-energy PESs of PhCCl addition to noradamantylcarbene (2a) and adamantene (3a) at

UB3LYP/6-31+G(d,p), with S²values reported for each stationary point.

with a 0.35 kcal/mol barrier for the conversion of singlet 2a to

3a.¹⁸PhCCl then adds to the bridgehead alkene of 3a, creating

diradical 10a-Ph in another extremely exothermic step,

releasing 52.3 kcal/mol. The ﬁnal transition-state structure

(TSS) corresponding to ring contraction and rearrangement of

the adamantyl moiety to 4a-Ph must overcome a barrier of 15.3

kcal/mol via TS 3 before 44.1 kcal/mol is released in this step.

A complicating factor of this pathway is that TS 2, the TSS

corresponding to the addition of PhCCl to adamantene (3a), is

an extremely early transition state. The distance between the

atoms of the forming bond (the carbene carbon of PhCCl and

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the nonbridgehead alkene carbon of 3a) is 3.77 Å in TS 2. The

free energy of activation for this step is 8.8 kcal/mol, where this

value is dominated by the entropy penalty of bringing the two

molecules together. The electronic energy of TS 2 including

zero point energy corrections is a nominal 0.41 kcal/mol lower

than that of 3a + PhCCl at inﬁnite separation, implying that the

addition is electronically barrierless. Unfortunately, an intrinsic

reaction coordinate (IRC) connecting TS 2 to either of its

ﬂanking minima (3a + PhCCl or 10a-Ph) could not be found.

We infer that this diﬃculty stems from the ﬂatness of the PES

around 3a + PhCCl, making the minimum energy path diﬃcult

to elucidate.

While only the pathway corresponding to Z-4a-Ph is

illustrated above, both E- and Z-isomers were observed

experimentally, with slight preference for the E-diastereomer:

E:Z = 1.4. It is postulated that the product’s alkene geometry is

deﬁned in TS 3, because free rotation around the newly formed

single C−C bond of 10a-Ph would allow either isomer to form

(in the absence of nonstatistical dynamic eﬀects). Compared to

the 15.3 kcal/mol barrier that precedes formation of Z-4a-Ph,

the TS 3 structure corresponding to formation of E-4a-Ph

exhibited a free energy barrier of 17.4 kcal/mol. A ΔΔG of 2

kcal/mol would mean almost exclusive experimental formation

of the product with the lower-energy TSS, and nonstatistical

dynamics could be causing the ratio of isomers seen

experimentally (vide infra).

Figure 5. Spin density map of the transformation from separate

species 3a and PhCCl to alkene product, 4a-Ph [isovalue = 0.005;

UB3LYP/6-31+G(d,p)].

subsystems. In the preceding TSS, TS 2, the unpaired spin

density is localized on the attacking carbene fragment,

consistent with how early this TSS is, and the alkene fragment

does not display diradical character, despite its distorted

geometry. In the subsequent TSS, TS 3, the spin density shifts

away from the aromatic ring and onto carbon atoms involved in

the alkyl shift.

The other mechanistic possibilities in Scheme 2 were

investigated with limited success. A TSS corresponding to a

concerted addition of PhCCl to 3a to aﬀord cyclopropane 9a-

Ph, as illustrated in path A of Scheme 2, could not be found,

perhaps due to the twist of the CC π-bond in 3a (see below).

Additionally, attempts at ﬁnding a TSS for the rearrangement of

9a-Ph to the alkene product 4a-Ph only aﬀorded a TSS

corresponding to cyclopentene product 16a-Ph, a product

observed in the preliminary dynamics studies discussed below

and illustrated in Figure 7 but not observed experimentally.

Path C was the ﬁrst complete pathway that was identiﬁed when

calculations were run using RB3LYP/6-31+G(d,p). However,

when the pathway was calculated using the same level of theory,

but using an unrestricted wave function to allow the possibility

of unpaired electrons, diradical 10a-Ph was found to be lower

in free energy than zwitterion 11a-Ph by 16.6 kcal/mol. No

TSS corresponding to path D, in which 3a ring-opening and

PhCCl addition occurs in a single concerted step, could be

located.

The analogous triplet pathway for the same mechanism of

noradamantylcarbene/adamantene + PhCCl is shown in Figure

3, and a comparison of the singlet and triplet PESs for this

reaction is depicted in Figure 4. Although triplet 2a (³2a) was

found to be lower in energy than singlet 2a (¹2a), the barrier

1

for rearrangement of 2a to 3a (via TS 1 in Figure 1) is

approximately 10 kcal/mol lower in energy than the ﬁrst TSS

3

for the rearrangement of 2a to 3a (i.e., TS 1a in Figure 3).

Because the barrier on the singlet surface is so small, the

collapse of ¹2a to ¹3a is expected to be rapid at room

1

temperature. The ease of 2a → 3a was invoked by Platz and

co-workers as the reason why adamantene served as the reactive

species in their studies and why they were unable to detect the

formation of noradamantylcarbene.¹⁸The singlet pathway is

calculated to be the lower-energy path until intermediate 10a-

Ph, where the triplet structure of this species is 0.77 kcal/mol

lower in energy than the singlet. The activation barrier to

descend to the next minimum is also slightly lower for the

triplet path (via TS 3a in Figure 3) than the singlet path (via TS

3 in Figure 2) by approximately 1.7 kcal/mol. Because

intermediate 10a-Ph is a distal diradical, the radical electrons

likely do not interact signiﬁcantly. This is evidenced by the fact

that ³10a-Ph and ¹10a-Ph are very similar in energy and

geometry. While it is possible for crossing to occur between the

singlet and triplet surfaces in this system, singlet 4a-Ph is

undoubtedly the expected product, being 40 kcal/mol lower in

energy than its triplet counterpart.

Paths E and F were investigated by attempting to locate a

TSS with a tetrahedral carbon center, corresponding to PhCCl

addition to 6a. A relaxed PES scan of the distance between the

diazo carbon of 6a and the carbene carbon of PhCCl from 3.70

to 1.60 Å in steps of 0.15 Å exhibited a distinct maximum at a

distance of about 2.20 Å. The structure with this C−C distance

was optimized to a TSS, revealing another possible pathway for

4a-Ph formation (see below). The stepwise version of this

pathway, path E, was discounted as 12a-Ph was not found to be

a minimum on the PES at this level of theory.

The triplet version of species 2a was calculated to be lower in

energy than its singlet counterpart by 1.12 kcal/mol. While this

energy diﬀerence is small and might be an artifact of the level of

theory employed, it is also possible that this reaction proceeds

through an excited state of 2a. A map of the spin densities for

each stationary point along the transformation from PhCCl

adding to 3a to the ﬁnal alkene product is shown in Figure 5.

These surfaces show how unpaired spin density evolves along

the reaction coordinate. Of particular note is the spin density

for 10a-Ph, which shows separate alkyl and benzyl radical

Path G was investigated using a similar method, with a scan

along the distance between carbene carbons of 2a and PhCCl.

The addition appeared to be electronically barrierless and no

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TSS could be located, but a free energy barrier is expected due

to the entropy penalty associated with bringing two carbenes

together. It is additionally inferred that the small barrier and

high exothermicity in the rearrangement of carbene 2a to anti-

Bredt alkene 3a mean that the lifetime of 2a is too short for it

to be the reactive species in this bimolecular addition, in accord

with the Platz group’s ﬁndings.¹⁸

Despite releasing approximately 30 kcal/mol of energy in its

formation, the geometry of singlet 3a has signiﬁcant strain.

Figure 6d illustrates the degree of “twisting” that this alkene

is forced to have only one angle near ideal (119.2°) and the

others markedly smaller, closer to an ideal sp³-hybridized

carbon bond angle (Figure 6b,c). Another indication of strain in

this molecule is its longer-than-average alkene bond length of

1.37 Å, whereas the average unstrained alkene bond length is

closer to 1.33 Å (Figure 6a). See the Supporting Information

for a detailed distortion-interaction analysis^38,39of TS 2.

Previous studies have shown that carbene additions to

strained C−C π-bonds may result in product formation that is

controlled by nonstatistical dynamics.^{22,23,25,26,40−44}The high

exothermicity of each intermediate step in the singlet diradical-

mediated mechanism of PhCCl addition to adamantene (i.e.,

path B) and the relative shallowness of each intermediate well

were grounds to begin a preliminary dynamics study.

Additionally, because an IRC connecting TS 2 with 10a-Ph

could not be calculated, dynamics calculations would help

substantiate a connection between TS 2 and the product.

We thus computed direct dynamics trajectories with a time

step of 1 fs initiated at singlet TS 2 for path B using Gaussian 09

at UB3LYP/6-31+G(d,p) (see Computational Methods for

details), the results of which are shown in the table embedded

in Figure 7. A total of 47 (68%) of 69 trajectories resulted in

recrossing, where the separated reactants 3a and PhCCl

(characterized as separated by a distance of 5 Å) formed on

either side of the TSS. We know TS 2 to be a quite early TSS,

and these results lend support to the ﬂatness of the PES around

TS 2, making it more diﬃcult for TS 2 to evolve toward the

descent to 10a-Ph. This high degree of crossing may also be

due to use of the transition state associated with electronic

energy rather than a variational transition state. The other 32%

of the trajectories proceeded to possible products, with six

trajectories (9%) leading to the observed products 4a-Ph.

Though no conclusions about computational (dynamics)

versus experimental product ratios from a sample size this

Figure 6. Four views of the geometry of adamantene (3a) at

UB3LYP/6-31+G(d,p). (a) A side view, with the alkene bond length

labeled (in angstroms). (b) A centralized view of the nonbridgehead

carbon of the alkene. This carbon is highly pyramidalized, with the

sum of the angles labeled being 328.3°. (c) A view of the bridgehead

carbon of the alkene. This sp²-hybridized carbon is also pyramidalized,

with the sum of the angles labeled being 343.3°. (d) One of the C−

C−C−C dihedral angles of the alkene portion of 3a is highlighted in

green. While this angle in a planar alkene would be closer to 180°, the

tricyclic nature of 3a forces the dihedral into a strained 85.1°

conﬁguration. The signiﬁcant “twist” exhibited by the C−C π-bond

prompts its unique reactivity.

exhibits compared to an unstrained oleﬁn, where the C−C−C−

C dihedral angle of the alkene is 85.1°, signiﬁcantly smaller than

an unstrained 180° geometry. While the ideal bond angles

around an sp²-hybridized carbon would be 120°, this structure

Figure 7. Results of direct dynamics calculations of 3a + PhCCl. Trajectories were initiated at TS 2 [UB3LYP/6-31+G(d,p)].

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Figure 8. PES of PhCCl addition to adamantylcarbene (2b) and homoadamantene (3b) on the singlet surface at UB3LYP/6-31+G(d,p) (electronic

energies E and free energies G) and UM062X/6-31+G(d,p)//UB3LYP/6-31+G(d,p) (electronic energies E).

small can be drawn, it is of note that both diastereomers of 4a-

Ph were observed in the six dynamics trajectories that led to

this product (ﬁve E and one Z). The fact that both isomers

formed may be indicative of nonstatistical dynamics playing a

role in the ratio of E- vs Z-isomers obtained experimentally.

Another nine trajectories (13%) resulted in the formation of

cyclopropane 9a-Ph. An additional six trajectories (9%)

resulted in the formation of a cyclopentene 16a-Ph that was

not observed experimentally, and one trajectory (1%) resulted

in chloride dissociation (to 17a-Ph). Notably, every trajectory

that did not result in recrossing, including those forming 9a-Ph,

16a-Ph, and 17a-Ph, proceeded through diradical 10a-Ph,

supporting the proposed mechanism (path B).

The TSSs corresponding to possible ring closing of 10a-Ph

to cyclopropane 9a-Ph and cyclopentene 16a-Ph were

investigated. Surprisingly, the barrier for 10a-Ph undergoing

ring closure to 9a-Ph was 12.5 kcal/mol and the barrier for

10a-Ph → 16a-Ph was found to be 13.9 kcal/mol, which are

both lower than the 15.3 kcal/mol barrier for 10a-Ph → 4a-Ph,

though neither 9a-Ph nor 16a-Ph was observed experimentally.

The sample size in this preliminary investigation of the role of

dynamics in this reaction is small. A more in-depth dynamics

study beyond the scope of the current investigation would need

to be undertaken to draw deﬁnitive conclusions from the

results, but the formation of 9a-Ph and 16a-Ph in the dynamics

calculations yet not in the experiments, along with the fact that

their computed TSSs are low in energy, hints that nonstatistical

dynamic eﬀects may play a role in this reaction in a way that is

not able to be captured by this small sample of trajectories.

Adamantyldiazirine/Adamantylcarbene System. As shown

in Figure 8, the lowest energy route for the addition of PhCCl

to adamantylcarbene (2b)/homoadamantene (3b) is analogous

to that for the previous system, i.e., path B′ (Scheme 3) on the

singlet surface. The PES shown in Figure 8 was computed at

the UB3LYP/6-31+G(d,p) and UM062X/6-31+G(d,p)//

UB3LYP/6-31+G(d,p) levels of theory (see Computational

Methods for details). Although the overall mechanism parallels

that found for noradamantylcarbene/adamantene, there are

several key diﬀerences. Whereas the barrier to rearrangement of

noradamantylcarbene 2a to adamantene 3a was <1 kcal/mol,

the barrier for rearrangement of adamantylcarbene 2b to

homoadamantene 3b is a more substantial 9.6 kcal/mol,

consistent with the Platz group’s previous ﬁndings.¹⁸This

barrier height suggests a longer lifetime of carbene 2b, which is

once again supported experimentally by Platz et al.’s LFP

studies, which found the reactive species of adamantyldiazirine

in solution to be carbene 2b.¹⁸The additional barrier for this

system can be justiﬁed physically by comparing the optimized

geometries of singlet 2a and 2b (Figure 9). The miniscule

rearrangement barrier of 2a to 3a is likely a result of σ_C−C

donation into the empty p-orbital of the carbene. The C−C−C

angle between the carbons of the donating C−C bond and the

carbene carbon is an acute 82.8°, indicating signiﬁcant orbital

overlap. This donation lengthens, and weakens, the C−C bond

to be inserted into, lowering the rearrangement barrier. The

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kcal/mol higher than addition to 3a, which could be an

indication of less strain in oleﬁn 3b.

As for the noradamantylcarbene/adamantene system, we

computed the triplet PES for path B′ (Figure 11). Similar to

noradamantylcarbene, although the structure of ³2b was

1

calculated to be 0.74 kcal/mol lower in energy than 2b, the

1

barrier for rearrangement of 2b → 3b was 16.1 kcal/mol

lower in energy than the ﬁrst step in the triplet pathway for

3

rearrangement of 2b (to 14b).

A comparison of the singlet and triplet pathways for the

reaction of adamantylcarbene with PhCCl is shown in Figure

12. Once again, the singlet pathway is signiﬁcantly lower in

energy until intermediate 10b-Ph and TS 3, where the singlet

and triplet energies are quite close, with the triplet path being

slightly lower in energy.

Figure 9. A comparison of the optimized structure geometries of

singlet and triplet 2a and 2b at UB3LYP/6-31+G(d,p). The

rearrangement barrier indicated is that for carbene insertion into a

C−C bond to aﬀord 3a or 3b in the case of the singlet surfaces or the

barrier for the ﬁrst step of this rearrangement on the triplet suraces.

1

The minimal barrier for rearrangement of 2a to 3a is attributed to

σ_C−Cdonation into the empty p-orbital of the carbene.

A concerning aspect of the adamantyl triplet pathway is the

3

lack of a barrier when 3b + PhCCl proceeds to TS 2. The

structure of ³3b was optimized separately from PhCCl in order

extra methylene unit of 2b makes this geometry less favorable,

so the bridgehead carbon preferentially adopts tetrahedral bond

angles (∼109°).

to calculate an approximate energy for that intermediate state.

3

It is possible that 3b + PhCCl may form a loose complex as

they are brought together. This putative complex may be lower

in energy than TS 2, leading to a barrier when surmounting TS

2. Calculating the energy of this type of complex was not

pursued because we believe the reaction to proceed via the

singlet surface, particularly on this part of the PES.

The rearrangement of 2b to homoadamantene 3b releases

40.5 kcal/mol. Singlet PhCCl adds to 3b in a stepwise manner

over a 10.4 kcal/mol barrier (TS 2) to give singlet diradical

10b-Ph. The intermediate well of 10b-Ph is deeper than that of

10a-Ph, but the 22.5 kcal/mol barrier to surpass TS 3 is still

possible at room temperature, especially when the formation of

10b-Ph is calculated to be so exothermic (33.0 kcal/mol

released). The ﬁnal step to form alkene product 4b-Ph from

10b-Ph releases 52.6 kcal/mol.

Similar investigations were undertaken for the adamantyl-

carbene/homoadamantene system as for the noradamantylcar-

bene/adamantene system to explore other mechanistic

possibilities. No TSS for either the concerted addition of

PhCCl to 3b to aﬀord 9a-Ph or the concerted cyclopropane

opening/ring contraction step of path A′ was located. Path C′

was calculated completely, but diradical 10b-Ph was found to

be 24.9 kcal/mol lower in free energy than zwitterion 11b-Ph

(see the Supporting Information). The entirely concerted

mechanism in path D′ was discounted when attempts at ﬁnding

a relevant TSS aﬀorded only the TSS for PhCCl addition to

produce 10b-Ph (Figure 8). A TSS containing a tetrahedral

carbon center at the diazo carbon of 6b was also located for this

system, in accordance with path F′ (more below). However, the

stepwise analog of this path, path E′, was discounted as

intermediate 12b-Ph, like 12a-Ph, was not found as a minimum

on the PES. A relaxed PES scan along the carbene−carbene

distance of PhCCl and 2b investigated the possibility of path

G′. Once again, though the addition appeared electronically

barrierless, no TSS was identiﬁed for a carbene−carbene mixed

dimerization.

Similar to the noradamantyl system, both diastereomers of

4b-Ph were seen experimentally and in approximately equal

amounts (E:Z = 0.94). The pathway shown above is that

corresponding to formation of Z-4b-Ph. The TS 3 structure

shown above has a barrier of 22.5 kcal/mol, while that for E-4b-

Ph had a barrier of 25.6 kcal/mol. Again, while this ΔΔG^⧧of

3.1 kcal/mol would imply that only the Z-isomer would be seen

experimentally, nonstatistical dynamic eﬀects could be causing

both isomers of 10b-Ph to be formed.

Much like its relative adamantene 3a, the ground-state singlet

structure of homoadamantene 3b exhibits a twisted geometry

(Figure 10). However, the additional methylene in 3b allows

the bridgehead alkene carbon freedom to adopt a more planar

geometry than the bridgehead alkene carbon of 3a. This

additional freedom manifests itself in the higher exothermicity

of the carbene 1,2-alkyl shift for 2b → 3b than for 2a → 3a.

Additionally, the barrier to PhCCl addition to 3b is about 1

Figure 10. Four views of the geometry of homoadamantene (3b) at UB3LYP/6-31+G(d,p). (a) A side view illustrating the alkene bond length (in

angstroms). (b) A top view of the nonbridgehead alkene carbon. The sum of the angles labeled is 351.2°. Though not planar, this carbon is

signiﬁcantly less pyramidalized than its analogous carbon in structure 3a (Figure 6). (c) A top view of the C−C bond angles around the bridgehead

carbon. The extra methylene unit of 3b compared to 3a allows the bridgehead carbon to be almost planar, demonstrated by the sum of the labeled

angles being 351.4°. (d) The −115.9° C−C−C−C dihedral angle highlighted shows there is still noticeable strain in the π-bond, as this value

deviates signiﬁcantly from an ideal −180° dihedral for a planar system.

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Figure 11. PES of triplet PhCCl addition to adamantylcarbene (2b) and homoadamantene (3b) on the triplet surface at UB3LYP/6-31+G(d,p)

(electronic energies E and free energies G) and UM062X/6-31+G(d,p)//UB3LYP/6-31+G(d,p) (electronic energies E). Images of stationary point

structures other than TSSs and triplet 4a-Ph are omitted for clarity (see the Supporting Information).

Figure 12. Comparison of singlet (red) and triplet (blue) free-energy PESs of PhCCl addition to adamantylcarbene (2b) and homoadamantene

(3b) at UB3LYP/6-31+G(d,p).

Paths F and F′. The other viable pathway discovered for

both systems was path F or F′, in which PhCCl adds to the

diazo carbon of 6a or 6b in a concerted manner, with N₂loss

occurring without an intermediate. The PESs for paths F and F′

are shown in Figures 13 and 14, respectively.

for PhCCl adding to 6b. In the noradamantyl system, the rate-

determining step of path B (TS 3) has a barrier of 17.4 kcal/

mol for formation of E-4a-Ph, which, in the absence of other

factors, would imply that paths B and F are competitive in

formation of the same product. However, this system is

complicated by the fact that the two viable pathways found

involve two diﬀerent reactive species: 2a or 6a. Rapid

Path F/F′ is a one-step, S_N2-like mechanism with a barrier of

17.2 kcal/mol in the case of 6a and a barrier of 17.0 kcal/mol

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Figure 14. A reaction coordinate diagram of the proposed path F′ for

the adamantyl system optimized at UB3LYP/6-31+G(d,p) with single

point energy calculations at UM062X/6-31+G(d,p)//UB3LYP/6-

31+G(d,p).

Figure 13. A reaction coordinate diagram of the proposed path F for

the noradamantyl system optimized at UB3LYP/6-31+G(d,p) with

single point energy calculations at UM062X/6-31+G(d,p)//UB3LYP/

6-31+G(d,p).

adamantyldiazirine with phenylchlorodiazirine proceeds

through path B/B′ (singlet diradical) or path F/F′ (diazo

addition). While the inﬂuence of dynamic control of this

reaction is presently unclear, it is possible that the formation of

4-Ph is controlled by nonstatistical reaction dynamics. A more

in-depth dynamics study is necessary to draw deﬁnitive

conclusions about the role of nonstatistical reaction dynamics

in these particular carbene-mediated reactions.

interconversion between these two species would need to be

assumed in order to say deﬁnitively that both of these

mechanisms are producing E-4a-Ph. In the adamantyl system,

the rate-determining steps of each path have signiﬁcantly

diﬀerent barriers. TS 3 of path B′ has a barrier of 25.6 kcal/mol,

8.6 kcal/mol greater than the barrier for PhCCl addition to 6b

to aﬀord E-4b-Ph, which would indicate exclusive formation of

product via path F′ if these mechanisms were directly

competing.

We are thus left with two mechanistic possibilities: path B/B′

via stepwise addition of PhCCl to bridgehead alkene 3a or 3b

to yield singlet diradical 10a-Ph or 10b-Ph and/or path F/F′

via PhCCl addition to diazo compound 6a or 6b. The question

remains whether photolysis of 1a or 1b at λ = 350 nm at room

temperature aﬀords the respective diazo isomer 6a or 6b. While

the Platz group found the photolysis of noradamantyldiazarine

1a at λ = 350 nm to produce 3a via an excited state of 1a, as

well as diazo isomer 6a, 350 nm irradiation of adamantyldia-

zirine (1b) formed only adamantyldiazomethane 6b.^18,19

Because both E- and Z-4a-Ph and 4b-Ph were observed

experimentally, TSSs corresponding to formation of both

diastereomers were investigated for paths F and F′.

Unfortunately, no TSS for the formation of the Z-isomer for

either system could be located, leaving us without a clear

prediction to compare with the experimental data. It is unclear

whether this result is due to physical restrictions on this

potential TSS (i.e., it may not be a stationary point on the

PES).

CONCLUSIONS

■

The cophotolysis of noradamantyldiazirine (1a) with the

phenanthride precursor of dichlorocarbene (7) or phenyl-

chlorodiazirine (8) produces noradamantylethylenes 4a in 11%

yield. The analogous cophotolysis of adamantyldiazirine 1b

with 8 generates adamantylethylenes 4b-Ph in 6% yield.

Experimentally, the rate of consumption of 1a was equal to

the rate of formation of 4a-Ph, as determined by ¹H NMR. LFP

measurements showed PhCCl + adamantene (3a) to be

independent of the concentration of 3a, and PhCCl +

homoadamantene (3b) produces 4b-Ph with k = 9.6 × 10⁵

M⁻¹s⁻¹, which we believe to be the ﬁrst reported rate constant

for the reaction of a carbene with 3b. Theoretical calculations

support the formation of the exocyclic alkene products 4a-Ph

and 4b-Ph via two possible pathways: (1) stepwise addition of

phenylchlorocarbene to adamantene (3a) and to homoada-

mantene (3b) proceeding on the singlet surface via a key

diradical intermediate (10a-Ph or 10b-Ph) or (2) concerted

PhCCl addition−N₂extrusion of the diazomethane isomer of

1a or 1b (6a or 6b). The reactions in both cage systems are

extremely exothermic, with energy releases of 86−96 kcal/mol

In conclusion, it is suspected that the formation of alkene

products from the reaction of each of noradamantyl- and

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equiv), 19a-d (1.59 g, 10 mmol, 1.0 equiv), or 19b (1.67 g, 10 mmol,

1.0 equiv), which was dissolved in 60 mL of anhydrous CH₂Cl₂. Dess−

Martin periodinane (DMP) (6.53 g, 15 mmol, 1.5 equiv) was added to

the solution and the mixture stirred. To a 250-mL, pear-shaped ﬂask

containing 100 mL of CH₂Cl₂was added 400 μL of distilled H₂O via

syringe. The wet CH₂Cl₂mixture was mixed thoroughly and

transferred by syringe to the reaction ﬂask dropwise via addition

funnel (∼1 drop/s). The cloudy white reaction mixture was stirred for

30 min and then diluted to 500 mL with ether. The mixture was

concentrated by rotary evaporation to approximately 60 mL and

diluted again with ether (to 100 mL). Excess unreacted DMP was

removed by vacuum ﬁltration. The reaction mixture was transferred to

a 500 mL separatory funnel and washed with a 1:1 mixture of 10%

Na₂S₂O₃and saturated aqueous NaHCO₃(80 mL, 40 mL of each

solution), followed by H₂O (60 mL) and brine (60 mL). The aqueous

layer was extracted with ether (80 mL), which was then washed with

H₂O (40 mL) and brine (40 mL). The organic layers were combined,

dried over MgSO₄, vacuum ﬁltered, concentrated, and dried under

vacuum, yielding an oily, pale yellow slush (20a) or granular, oﬀ-white

crystals (20a-d and 20b) that was used without further puriﬁcation.

from the bridgehead alkenes + PhCCl. Preliminary direct

dynamics trajectory calculations indicate the possible inter-

vention of dynamic control of the adamantene−PhCCl system.

Additional computational studies are thus underway on both

systems.

EXPERIMENTAL SECTION

■

General. All reactions were performed under N₂in oven-dried

glassware unless otherwise noted. Anhydrous solvents were used as

received. All other reagents were also used as received. NMR spectra

were recorded in CDCl₃, cyclohexane-d₁₂, or benzene-d₆at 300 MHz

1

for H spectra and 75 MHz for ¹³C spectra. H chemical shifts are

reported in parts per million (δ) relative to tetramethylsilane (TMS, δ

0.00) using TMS as a reference. ¹³C NMR chemical shifts are reported

in parts per million; the center peak of the solvent signal is used as a

reference. IR spectra were taken using an FT-IR spectrometer. IR

absorptions are reported in cm⁻¹. Steady-state photolyses were

conducted with a photochemical reactor at 300 or 350 nm. Laser

ﬂash photolysis experiments were conducted with an Nd:YAG laser at

355 nm. Details of the LFP system are provided in the Supporting

Information. All quantitative product analyses were conducted with a

gas chromatograph with a ﬂame ionization detector using mesitylene

as an internal standard. High-resolution mass spectra (HRMS) were

recorded on a sector-type double-focusing instrument with electron

ionization or fast-atom bombardment ionization.

1

20a: 0.91 g, 61%; H NMR (300 MHz, CDCl₃) δ 9.74 (s, 1 H); ¹³C

NMR (75 MHz, CDCl₃) δ 205.5, 46.9, 43.8, 42.2, 37.6, 35.4, 34.8.

20a-d: 0.79 g, 52%; EI-MS (m/z) 151 (M+), 133, 121, 118, 109, 93,

79, 73, 67, 53, 39, 27, 15. 20b: 1.56 g, 95%; EI-MS (m/z) 164 (M+),

145, 135, 119, 107, 93, 79, 67, 55, 41, 29, 25, 12.

Preparation of Diazirines 1a, 1a-d, or 1b.^18,29,45Crude aldehyde

20a (0.91 g, 6.1 mmol, 1.0 equiv), 20a-d (0.79 g, 5.2 mmol, 1.0 equiv),

or 20b (1.56 g, 9.5 mmol, 1.0 equiv) was dissolved in anhydrous THF

(9−13 mL) in a pear-shaped ﬂask. The solution was transferred via

syringe to an oven-dried, three-necked, 250-mL, round-bottom ﬂask,

equipped with a low-temperature thermometer, two 25-mL addition

funnels, and magnetic stir bar, all under N₂. The cloudy, orange-brown

mixture was cooled to −5 °C using an acetone−dry ice bath. A 1.0 M

solution of lithium bis(trimethylsilyl)amide in THF (17−20 mL, 17−

20 mmol, 2.5 equiv) was added dropwise via addition funnel at 0 °C to

form a transparent dark orange-brown mixture. The solution was

stirred at 0 °C for 30 min and then cooled to −35 °C. Hydroxylamine-

O-sulfonic acid (1.66−2.25 g, 17−20 mmol, 1.1 equiv) was dissolved

in anhydrous diethylene glycol dimethyl ether (13−15 mL) in an

oven-dried, 25-mL, pear-shaped ﬂask under N₂and added dropwise to

the reaction vessel via addition funnel. The cloudy, yellow-orange

mixture was warmed to 0 °C and stirred for 1 h over an ice−salt bath.

The lights were dimmed and freshly prepared tert-butyl hypochlorite⁴⁵

(1.2 mL) in tert-butanol (1.4−1.7 mL) was added, behind a blast

shield, dropwise via syringe after replacing one of the addition funnels

with a rubber septum. The mixture was stirred for 30 min at 0 °C and

distilled water (40 mL) was added. The reaction mixture was

transferred to a 250 mL separatory funnel, extracted with pentane (2 ×

20 mL), and then washed with distilled water (2 × 20 mL). The

organic layer was transferred to an amber bottle, dried over

magnesium sulfate, and stored at −80 °C. The diazirines were puriﬁed

Syntheses. Syntheses of noradamantyldiazirine (1a), noradaman-

tyldiazirine-d (1a-d), and adamantyldiazirine (1b) were conducted

according to previously reported procedures by Platz and co-

workers^18,19,29and others.⁴⁵⁻⁴⁸Phenylchlorodiazirine was synthesized

according to Graham’s method.³⁰Authentic samples of E- and Z-4b-

Ph were synthesized according to a previous report.⁴⁹

Preparation of Noradamantyl Alcohol 19a or 19a-d.^18,48To an

oven-dried, three-necked, 500-mL, round-bottom ﬂask equipped with

a reﬂux condenser, 125-mL addition funnel, magnetic stir bar, and

glass stopper ﬂushed with N₂was cautiously and rapidly added

LiAlH(D)₄(1.85 g of LiAlH₄(2.06 g of LiAlD₄), 49 mmol, 1.2 equiv).

Anhydrous diethyl ether (85 mL) was added to dissolve the

LiAlH(D)₄via glass syringe. To an oven-dried, 100-mL, pear-shaped

ﬂask ﬂushed with N₂was added 3-noradamantylcarboxylic acid (18a)

(6.77 g, 41 mmol, 1.0 equiv), which was dissolved in 82 mL of

anhydrous tetrahydrofuran. The solution was then transferred to the

addition funnel and added dropwise (∼1−2 drop/s) at room

temperature to the stirring LiAlH(D)₄solution. The reaction mixture

was then reﬂuxed for 2 h, cooled to room temperature, and further

cooled in an ice bath. Ice-cold distilled water (2 mL) was added to the

solution dropwise, followed by cold 15% aqueous NaOH solution (2

mL) and more distilled water (3 mL). The light gray precipitate was

removed via vacuum ﬁltration, rinsing with warm ether. The ﬁltrate

was dried over MgSO₄, ﬁltered, concentrated by rotary evaporation,

and dried under vacuum overnight. Crude noradamantyl alcohol

[19a(-d)] was collected as an oﬀ-white solid and used without further

puriﬁcation. 19a: 2.43 g, 39%; EI-MS (m/z) 152 (M+), 134, 121, 119,

105, 92, 79, 77, 67, 55, 41, 27; ¹H NMR (300 MHz, CDCl₃) δ 3.64 (s,

2 H), 2.19 (s, 2 H), 2.09 (m, 1 H), 1.65 (m, 11 H); ¹³C NMR (75

MHz, CDCl₃) δ 69.3, 51.2, 46.1, 40.8, 44.2, 37.6, 35.7. 19a-d: 3.90 g,

63%; EI-MS (m/z) 154 (M+), 136, 125, 121, 107, 94, 79, 77, 67, 53,

39, 33, 25, 12; ¹H NMR (300 MHz, CDCl₃) δ 2.24 (s, 2 H), 2.13 (m,

1 H), 1.69 (m, 11 H); ¹³C NMR (75 MHz, CDCl₃) δ 68.5, 51.0, 46.0,

44.2, 40.7, 37.6, 35.7; IR [ATR] (cm⁻¹) 3313, 2921, 2863, 2190, 2078.

Preparation of Aldehydes 20a, 20a-d, or 20b.^18,19,47,48To an

oven-dried, 500-mL, three-neck, round-bottom ﬂask equipped with a

125-mL addition funnel, two glass stoppers, and magnetic stir bar, all

under an atmosphere of nitrogen, was added 19a (1.56 g, 10 mmol, 1.0

via column chromatography on silica gel (pentane eluent). 1a: λ_max

=

1

337, 344, 355 nm; H NMR (300 MHz, C₆D₆) δ 2.09 (t, J = 6.4 Hz,

1H), 1.92 (br s, 2H), 1.48−1.19 (m, 10H), 0.51 (s, 1H); ¹³C NMR

(75 MHz, C₆D₆) δ 48.4, 46.5, 44.3, 41.9, 37.6, 35.3, 27.0, 2.4. 1a-d:

λ_max= 337, 344, 354 nm; ¹H NMR (300 MHz, CDCl₃) δ 2.26 (t, J =

6.6 Hz, 1H), 2.20 (br s, 2H), 1.58−1.43 (m, 10H); ¹³C NMR (75

MHz, CDCl₃) δ 48.0, 46.3, 44.1, 41.6, 37.3, 35.2. 1b: λ_max= 337, 344,

1

355 nm; H NMR (300 MHz, CDCl₃) δ 1.89 (br s, 2 H), 1.64−1.51

(m, 6H), 1.32 (d, J = 2.7 Hz, 6H); ¹³C NMR (75 MHz, CDCl₃) δ

39.5, 36.8, 31.8, 29.7, 28.2.

Phenylchlorodiazirine (8).³⁰To a mixture of lithium chloride (3.57

g, 84 mmol, 12 equiv) and benzamidine hydrochloride (1.09 g, 7.0

mmol, 1.0 equiv) were added 50 mL of dimethyl sulfoxide and 50 mL

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of pentane in a three-neck, 1-L, round-bottom ﬂask ﬁtted with a 125-

mL addition funnel, large stir bar, and thermometer. Aqueous NaOCl

solution (100 mL, 8.25% hypochlorite) saturated with sodium chloride

was added slowly, the temperature being maintained between 35 and

40 °C with an ice bath. After 5 min, 88 mL of DMSO, 25 mL of

pentane, and 150 mL of aqueous NaOCl were added, and the mixture

was allowed to stir for 1 h at room temperature. The reaction solution

was poured into a separatory funnel containing 300 mL of ice water,

and the pentane layer was separated, washed with brine (4 × 250 mL),

and dried over CaCl₂. The crude diazirine 8 was chromatographed on

a silica gel column with pentane eluent, aﬀording pure 8: λ_max= 390,

puriﬁcation of these products, especially for the separation of E- and Z-

4a-Ph.

1,1-Dichloro-2-noradamantylethene (4a-Cl). ¹H NMR (300

MHz, CDCl₃) δ 6.14 (s, 1H), 2.50 (t, J = 6.7 Hz, 1H), 2.24 (s,

2H), 1.88−1.84 (m, 6H), 2.55−1.62 (m, 4H); ¹³C NMR (75 MHz,

CDCl₃) δ 138.0, 49.6, 49.2, 45.1, 43.9, 37.6, 35.0; GC/MS (EI) (t_R=

9.9 min) m/z (rel intensity) 216/218/220 [13.0/9.3/3.7, M⁺/(M⁺+

2)/(M⁺+ 4)], 181/183 [12.0/3.8, (M⁺− 35)/((M⁺+ 2) − 35)], 173

(11.1, M⁺− 43), 145 (7.4, M⁺− 71), 139 (8.1, M⁺− 77), 125 (7.7,

M⁺− 91), 103 (11.1, M⁺− 113), 91 (29.6, M⁺− 125), 80 (100, M⁺−

81), 51 (16.7, M⁺− 165); HRMS (EI+) calcd for C₁₁H₁₄Cl₂216.0473,

found 216.0466.

1

385, 379, 369, 351; H NMR (300 MHz, CDCl₃) δ 7.39 (m, 3 H),

7.11 (m, 2 H); ¹³C NMR (75 MHz, CDCl₃) δ 135.9, 129.5, 128.7,

126.2.

E-1-Chloro-2-noradamantyl-1-phenylethene (E-4a-Ph). ¹H NMR

(300 MHz, CDCl₃) δ 7.40−7.30 (m, 5H), 6.28 (s, 1H), 2.21 (t, J = 6.7

Hz, 1H), 2.08 (s, 2H), 1.70−1.35 (m, 14H); ¹³C NMR (75 MHz,

CDCl₃) δ 139.3, 138.6, 129.8, 129.5, 128.6, 128.2, 50.3, 46.9, 43.8,

37.8, 34.8, 34.3; GC/MS (EI) (t_R= 12.3 min) m/z (rel intensity) 258

(3.7, M⁺), 223 (100, M⁺− 35), 179/181 [32.4/14.8, (M⁺− 79)/((M⁺

+ 2) − 79)], 152 (23.1, M⁺− 106), 143 (70.4, M⁺− 115), 115 (40.7,

M⁺− 143), 103 (15.0, M⁺− 155), 91 (41.7, M⁺− 167), 79 (59.3, M⁺

− 179), 65 (18.5, M⁺− 193); HRMS (EI+) calcd for C₁₇H₁₉Cl

258.1175, found 258.1169.

E- and Z-2-Adamantyl-1-chloro-1-phenylethene (4b-Ph).⁴⁹To an

oven-dried, 25-mL, round-bottom ﬂask under an atmosphere of N₂

and equipped with a magnetic stir bar were added 1-chloroadamantane

(720 mg, 4.2 mmol), 1-phenyl-2-trimethylsilylacetylene (700 mg, 4

mmol), and zinc chloride (1.8 g, 14 mmol) in anyhydrous CH₂Cl₂(8

mL). This mixture was kept under nitrogen and stirred for 48 h at

room temperature. Color changes were observed over the 48-h stirring

period: the mixture turned from white to oﬀ-white to yellow to light

green to dark green. The crude, thick, dark green reaction mixture

containing 4b-Ph (0.71 g, 72%) was collected, concentrated by rotary

evaporation, and dried under vacuum. The E- and Z-isomers of 4b-Ph

were separated and puriﬁed by column chromatography (pentane

eluent). The identity of these compounds in the photolysis mixture of

adamantyldiazirine (1b) and phenylchlorodiazirine (8) was conﬁrmed

by a GC spiking experiment: the photolysis mixture was spiked with

authentic E- and Z-4b-Ph. Characterization data follow below.

E-2-Adamantyl-1-chloro-1-phenylethene (E-4b-Ph). mp 75−77

Z-1-Chloro-2-noradamantyl-1-phenylethene (Z-4a-Ph). ¹H NMR

(300 MHz, CDCl₃) δ 7.59 (m, 2H), 7.34 (m, 3H), 6.39 (s, 1H), 2.65

(t, J = 6.7 Hz, 1H), 2.28 (s, 2H), 2.07−1.92 (m, 6H), 1.69−1.54 (m,

5H); ¹³C NMR (75 MHz, CDCl₃) δ 139.6, 136.2, 131.6, 128.4, 128.3,

126.5, 49.8, 49.6, 45.2, 44.0, 37.8, 35.3; GC/MS (EI) (t_R= 12.3 min)

m/z (rel intensity) 258/260 [(11.0/3.7, M⁺/(M⁺+ 2)), 223 (100, M⁺

− 35), 179/181 [28.0/9.8, (M⁺− 79)/((M⁺+ 2) − 79)], 165, (29.3,

M⁺− 93), 152 (15.9, M⁺− 106), 143 (65.9, M⁺− 115), 115 (34.1,

M⁺− 143), 91 (37.8, M⁺− 167), 79 (54.9, M⁺− 179), 65 (14.6, M⁺

− 193); HRMS (EI+) calcd for C₁₇H₁₉Cl 258.1175, found 258.1172.

Laser Flash Photolysis (LFP) Studies. Stock solutions in pentane

of the diazirines 1a, 1a-d, and 1b were prepared to a concentration of

A₃₅₅= 2.6 ([1a] = [1a-d] = 7.9 mM; [1b] = 6.0 mM). A stock solution

in pentane of phenylchlorodiazirine (8) was prepared to a

concentration of A₃₈₉≈ 3 ([8] = 30 mM). For the measurements

of 1a + 8, a stock solution of anhydrous pyridine in pentane was also

prepared at a concentration of 2 mM. For the noradamantylcarbene/

adamantene studies, into duplicate quartz LFP cuvettes were placed

100, 200, 300, 400, or 500 μL of the 1a (or 1a-d) stock solution; 250

μL of the 8 stock solution; 10 μL of the pyridine stock solution; and

the remainder (740−1140 μL) of pentane for a total volume of 1500

μL. Thus, the ﬁnal (LFP) concentrations were [1a] = [1a-d] = 0.525−

2.6 mM, [8] = 5 mM, [pyridine] = 0.013 mM. For the

adamantylcarbene/homoadamantene system, into duplicate quartz

LFP cuvettes were placed 450 μL of 1b, 200 μL of 8, and 850 μL of

pentane for a total volume of 1500 μL. Thus, the ﬁnal (LFP)

concentrations were [1b] = 1.8 mM and [8] = 4 mM. Each LFP

cuvette was capped with a rubber septum and purged with argon for

45−60 s. For the LFP measurements, each cuvette was subjected to

three sets of ﬁve laser pulses at 355 nm (Nd:YAG), where the signal

outputs for each set of pulses were averaged. For 1a (or 1a-d) + 8 +

pyridine, we monitored the growth of the PhCCl−pyridine ylide at

480 nm. For 1b + 8, we monitored the decay of PhCCl at 320 nm.

Rate constant data from LFP measurements appear in the Supporting

Information.

°C (lit.⁴⁹mp 74−75 °C); H NMR (300 MHz, CDCl₃) δ 7.25 (s,

1

5H), 5.72 (s, 1H), 1.76 (m, 3H), 1.48 (m, 12H); ¹³C NMR (75 MHz,

CDCl₃) δ 140.6, 139.6, 129.7, 129.3, 128.5, 42.9, 36.8, 36.6, 28.5; GC/

MS (EI) (t_R= 11.7 min) m/z (rel intensity) 272/274 [83.3/26.7, M⁺/

(M⁺+ 2)], 237 (100, M⁺− 35), 179 (71.1, M⁺− 93), 141 (51.1, M⁺−

131), 115 (22.2, M⁺− 157), 91 (17.8, M⁺− 181), 79 (15.6, M⁺−

193); HRMS (FAB+) calcd for C₁₈H₂₁Cl 272.1332, found 272.1326.

Z-2-Adamantyl-1-chloro-1-phenylethene (Z-4b-Ph). ¹H NMR

(300 MHz, CDCl₃) δ 7.45 (dd, J = 1.7, 8.1 Hz, 2H), 7.24 (m, 3H),

5.79 (s, 1H), 1.94 (br s, 9H), 1.67 (br s, 6H); ¹³C NMR (75 MHz,

CDCl₃) δ 140.3, 137.4, 130.3, 128.12, 128.06, 126.6, 41.1, 36.8, 35.7,

28.6; GC/MS (EI) (t_R= 12.3 min) m/z (rel intensity) 272/274 [100/

33.8, M⁺/(M⁺+ 2)], 237 (100, M⁺− 35), 179 (81.2, M⁺− 93), 141

(57.5, M⁺− 131), 128 (18.8, M⁺− 144), 115 (25.0, M⁺− 157), 91

(25.0, M⁺− 181), 79 (20.0, M⁺− 193); HRMS (FAB+) calcd for

C₁₈H₂₁Cl 272.1332, found 272.1339.

Steady State PhotolysesQuantitative Product Studies.

Stock solutions in pentane of each of the diazirines 1a, 1a-d, and 1b

were prepared to concentrations of A₃₅₅= 2.6 {[1a] = [1a-d] = 7.9

mM (ε = 330 M⁻¹cm⁻¹); [1b] = 6.0 mM (ε = 430 M⁻¹cm⁻¹)}. A

stock solution in pentane of phenylchlorodiazirine (8) was prepared to

a concentration of A₃₈₉≈ 3 {[8] = 30 mM (ε = 100 M⁻¹cm⁻¹)}. A

stock solution of diazirine 1a in pentane or 1b in pentane was

combined with a stock solution of 8 in pentane in a quartz cuvette to a

total volume of 1.5 mL. The resulting prephotolysis diazirine

absorptions were as follows: 1a and 1a-d, A₃₅₅= 0.9−1.0; 1b, A₃₅₀

=

0.7−0.9; 8, A₃₉₀= 0.7−1.2. Three cuvettes each of 1a + 8, 1a-d + 8,

and 1b + 8 were prepared. Then, each of the six cuvettes was purged

with N₂for approximately 1 min and subsequently irradiated at 350

nm for 1−2 h at room temperature, monitoring the photolysis by

UV−vis. After all of the diazirines were consumed, 1.5 μmol of

mesitylene [10 μL of 0.15 M mesitylene (in pentane solvent)] was

added as an internal standard to each cuvette. Each sample was

analyzed by GC/FID in triplicate. Results are reported in the

Supporting Information.

Isolation of Ethylenes 4a-Cl and E- and Z-4a-Ph. Ethylenes 4a-

Cl and E- and Z-4a-Ph were isolated from steady-state photolysis

mixtures via column chromatography on silica gel (pentane eluent).

Several successive columns were required for complete separation and

COMPUTATIONAL METHODS

■

All calculations were performed with Gaussian 09³⁵in the gas phase.

Molecular geometries were optimized using UB3LYP/6-31+G-

(d,p)^50,51and single-point energies were calculated at UM062X/6-

31+G(d,p).^52,53Stationary points were veriﬁed by the existence of no

imaginary frequencies for energy minima and exactly one imaginary

frequency for transition-state structures. All energies reported are

electronic energies without zero-point corrections or Gibbs free

energies, unless otherwise noted. Three-dimensional molecular images

were generated with CylView.⁵⁴Direct dynamics trajectories were

initiated at 3a + PhCCl TS 2 using Progdyn,⁵⁵which utilizes Gaussian

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09 to calculate force constants. Trajectories were run at the UB3LYP/

6-31+G(d,p) level of theory with a time step of 1 fs. Stopping

parameters for the trajectories were deﬁned as follows: a trajectory was

considered to produce separated reactants when the C2−C11 distance

was greater than 5 Å (atom numbers shown below). A trajectory

formed cyclopentene 14a-Ph when the C1−C12 distance was less

than 1.62 Å, which is within 4% of the C1−C12 distance in its ground-

state, optimized structure (1.56 Å). Cyclopropane 9a-Ph was formed

when the C1−C11 distance was less than 1.58 Å, also within 4% of the

same distance in its optimized structure (1.53 Å). A more rigid

stopping criterion for 4a-Ph was imposed, in which the C1−C3

distance had to be less than 1.59 Å to say with conﬁdence that the

noradamantyl moiety had been formed (where the C1−C3 distance in

the optimized structure of 4a-Ph was 1.61 Å).

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ASSOCIATED CONTENT

* Supporting Information

■

S

(20) Jackson, J. E.; Soundararajan, N.; Platz, M. S.; Liu, M. T. H. J.

Am. Chem. Soc. 1988, 110, 5595−5596.

NMR spectra of 4a-Cl, E- and Z-4a-Ph, and E- and Z-4b-Ph;

product study results; data from the NMR kinetic studies;

details of the LFP system; and computational details including

IRC data, Cartesian coordinates, and imaginary frequencies of

all stationary points. The Supporting Information is available

free of charge on the ACS Publications website at DOI:

10.1021/acs.joc.5b00456.

(21) Jackson, J. E.; Platz, M. S. In Advances in Carbene Chemistry;

Brinker, U. H., Ed.; JAI Press: Stamford, CT, 1994; Vol. 1, p 89−160.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: dmerrer@barnard.edu

■

(27) Rablen, P. R.; Paiz, A. A.; Thuronyi, B. W.; Jones, M. J. Org.

Notes

Chem. 2009, 74, 4252−4261.

(28) Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic

Chemistry; University Science: Sausalito, CA, 2006.

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

(29) Likhotvorik, I. R.; Tae, E. L.; Ventre, C.; Platz, M. S. Tetrahedron

We are grateful to the Thamattoor group for providing us with

phenanthride 7 and for being helpful hosts during our trips to

Colby College for the LFP studies. We also thank Profs. Wes

Borden, Kathleen Morgan, Paul Rablen, and Christian Rojas for

helpful discussions. We thank Drs. John Decatur and Yasuhiro

Itagaki of Columbia University for NMR and HRMS assistance,

respectively. D.J.T. and S.R.H. thank the National Science

Foundation’s XSEDE program (CHE-030089) and the U.S.

Department of Education’s GAANN Fellowship for support.

D.C.M. acknowledges the NSF (CHE-0844034), ACS-PRF

(52099-UR4), Con Edison (F.D.), the Howard Hughes

Medical Institute (E.D., J.C.T.), the Jewish Foundation for

Education of Women (M.O.), and Barnard College for ﬁnancial

support.

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