EVALUACIÓN DEL EFECTO DE LOS PARÁMETROS DE LA ELECTROCOAGULACIÓN

An intramolecular variant of the [3+2] methylenecyclopropane annulation led Singleton^^ to report a quick and efficient synthesis of diquinanes (scheme 1.34).

An intriguing aspect of this reaction is that under conditions successful in previous intermolecular reactions, no cyclised products were obtained. However, irradiation of a benzene solution of the substituted methylenecyclopropane in the presence of 20% hexamethylditin led to the desired diquinanes.

X (SnMe3>2/PhH/hv/2dys (22)X=Bu 52% (23) X=TMS 77% C O f t scheme 1.34

2.1 RING OPENING OF BICYCLO[n.l.O]ALK-2-YL SYSTEMS. exocychc endocyclic SLOW (26) scheme 2.1

The regiochemical outcome in systems where the cyclopropane is fused to a second ring is also o f interest. In principle, the bicyclo[n.l.O] radical (24) can ring open to give the thermodynamically more stable cycloalkyl-3-enyl radical (26), via endocyclic bond cleavage. Thus, ring opening in this mode would be favourable under conditions of thermodynamic control, for example, in the presence of strategically positioned radical stabilising substituents, or if the transition state is product like. Conversely, exocyclic cleavage may occur to give the higher energy primary cycloalkyl-2-enylmethyl radical (25) (scheme 2.1). However, it is the latter which is favoured on stereoelectronic grounds since the o* orbitals of the external bond overlap more efficiently with the adjacent p-orbitals o f the radical SOMO (figure 2.1).

good / overlap

poor / overlap

exocyclic mode endocyclic mode

As expected, the rate of ring opening of these systems when compared to their monocyclic counterparts is inherently faster due to the greater release of strain on cleavage.

This overlap “rule” is particularly well demonstrated in the steroidal work of Beckwith and Phillipou^'^ (scheme 2.2).

PhgSnH/hv

(27) Cl

(28)

PhgSnH/hv

scheme 2.2

Examination of models containing the B ring in a chair conformation reveals that the plane of the p-orbital in (27) is aligned with that of the internal bond, while in the analogous (28), favourable overlap occurs with the external bond. It has previously been shown^^ that (28) undergoes regiospecific rupture of the 3-5 bond. Similarly, Beckwith concluded that stereoelectronic effects are the overriding feature in determining the direction of bond fission in (27).

In order to examine this phenomenon in greater detail, Freidrich and Holmstead^^ investigated the radical rearrangements of bicyclo[3.1.0] and [4.1.0]heptyl systems.

2.1.1 The [3.1.0] Hexyl System.

In the absence of solvent, reduction of the appropriate bicyclo[3.1.0] halide (29) gave predominantly the product derived from cleavage of the external bond, i.e. formed under stereoelectronic control (scheme 2.3).

h

-ESI- o ex

scheme 2.3

In order to determine whether any bicyclo[3.1.0]hexane is formed via ring closure to the cyclopropylcarbinyl radical, tributylstannane reductions were conducted on 4- chlorocyclohexene (30) (scheme 2.4). Cyclohexene was the sole product in this reaction, eliminating the possibility of rapid interconversion via the corresponding cyclopropylcarbinyl radical. A sim ilar study was conducted with the 3- cyclopentylmethyl radical derived from (31). No products involving ring closure of the homoallylic radical were observed under neat tributylstannane conditions. However, under more dilute conditions at elevated temperatures, cyclohexene was detected. Therefore, ring closure to the cyclopropylcarbinyl radical, although relatively slow, does occur (scheme 2.4).

Cl nBugSnH/neat hv/3*C/10hr OR hv/65 CPhr iQO% Br nBusSnH/hv 0.2M in n-decane (31) 65‘C/6hr 87% 13% scheme 2.4 2.1.2 [4.1.0]HeptyI System.

Reduction of 2-chlorobicyclo[4.1.0]heptane (32), in accord with stereoelectronic preference, gave the expected 3-methylcyclohexene (scheme 2.5).

(32)

hv/3*C/4hr 1% 2% 97%

55’C/48hr/10kbars 86% 4% 10%

scheme 2.5

However, Pereyre^^ found that under a high pressure environment in the presence of an equimolar amount of tributylstannane, the composition of the mixture was surprisingly different with ring opening essentially halted.

In contrast to the lack of rearrangement of the 4-cyclohexenyl radical, parallel studies with the 4-cycloheptenyl radical at elevated temperatures led to relatively slow isomerization, however, ring closure of the 3-cyclohexenylmethyl radical did not occur (scheme 2.6). nBugSnH 0,5M in n-decane hv/65’C/3hr

a o

a

As an extension of the work by Friedrich, W a l t o n c a r r i e d out ESR studies of his own via hydrogen abstraction of f-butyloxy radicals from bicyclo[n. 1.0]alkanes. He found the main site of attack to be C(2), giving bicyclo[n.l.0]alkyl-2-yl radicals (24, n=3-6) which then under went rearrangement. As expected, for n=3-6, preferential rupture of the outer bond resulted in the formation of the cycloalkenylmethyl radical (25). Models for n=4-6, indicate that the SOMO can overlap with the internal bond when the ring adopts a boat conformation. However, such conformations are unlikely

to be important. Hence, stereoelectronic factors lead to the formation of the product derived from the less stable primary radical.

Estimated values for the relief of ring strain involved in the two modes o f ring cleavage have been made based on the corresponding hydrocarbons (table 2.1).

n Endocyclic Cleavge (klmol^) Exocyclic Cleavge (kJmoI^)

3 131 112

4 98 115

5 99 101

6 89 105

RELIEF OF RING STRAIN ON RING OPENING FOR BICYCLIC[n.l.O] SYSTEMS

table 2.1

As can be seen, fission of either the endocyclic or exocyclic bond leads to a large relief o f strain. For n=4-6, both stereoelectronic effects and ring strain (thermodynamic) favour rapture of the outer bond. Surprisingly, for the n=3 system, at first glance, the endocyclic mode is the preferred pathway (by approximately 20 kJmol‘ l). However, this does not outweigh the favourable stereoelectronics.

2.2 WORK IN THESE LABORATORIES.