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Background: Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the VV-ECMO with an additional arterial backflow cannula (termed VVA-ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality. Methods: Retrospective analysis of outcome in VV ECMO patients with ARDS that received VVA upgrade due to acute cardio-circulatory deterioration from 2008-2021 at three ECMO referral centers.Results: We identified 73 VVA ECMO patients that either required an upgrade from VV to VVA (n=53) or were directly triple cannulated (n=20), most commonly for concomitant right-sided heart failure. Median (Interquartile Range) age was 49 (28-57) years and SOFA score was 14 (12-17) at VVA ECMO upgrade. ECMO support was required over 12 (6-22) days and ICU length of stay was 32 (16-46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). A SOFA score > 14 at the day of VVA upgrade and higher lactate level were independent predictors of mortality in the multivariate regression analysis.Conclusions: In this analysis, the use of VVA ECMO in patients with initial ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score >14 and elevated lactate levels at the day of VVA upgrade predict unfavorable outcome.

A mechanistic model is presented for the base-catalyzed intramolecular cyclization of polycyclic unsaturated alcohols of type A to ethers D (Scheme 1). The alkoxide anion B is formed first in a fast acid-base equilibrium. For the subsequent reaction to D, a carbanion-like transition state C is proposed. This mechanism is in full agreement with our results regarding the influence of substituents on the regioselectivity and the rate of cyclization. We studied the effect of alkyl substituents in allylic position (alkylated endocylic olefinic alcohols 1–3) and, especially, at the exocyclic double bond (12–15). The fastest cyclization (krel=1) is 1216, which proceeds via a primary carbanion-like transition state (E: R1=R2=H). The corresponding processes 1317 and 1417 are characterized by a less-stable secondary carbanion-like transtition state (E: R1=Me, R2=H, or vice versa) and are slower by a factor of 104. The slowest reaction (krelca. 10−6) is the cyclization 1518via a tertiary carbanion-like transition state (E: R1=R2=Me).

Three 1,4-dimethylidenecyclohexanes, bridged in the 2,6- and 3,5-positions by two ethano (4), one ethano and one propano (5), and two propano bridges (6) have been synthesized. The interaction of the two exocyclic methylidene groups has been investigated by He(I) photoelectron (PE) spectroscopy. It revealed a slightly larger energy difference (0.8 eV) for 4 and 5 as compared to the parent 1,4-dimethylidenecyclohexane (7) (0.7 eV). The interpretation of the PE spectra was based on the comparison with PE data of related systems and with the results of semiempirical calculations on 4–6.

Preparation and screening of twenty new ligands, all analogs of α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL), for the Ti-catalyzed asymmetric addition of methyltri(isopropoxy)titanium and diethylzinc to benzaldehyde are described. These ligands have the dioxolane ring of the TADDOL's replaced by cyclobutane, cyclopentane, cyclohexene, cyclohexane, bicyclo[2.2.1]heptene and -heptane and bicyclo[2.2.2]octene and -octane moieties; several have H-atoms or alkyl groups in place of the aryl groups, and nine of them have C2 symmetry. X-Ray crystallography and molecular mechanics are used to analyze the structure of the ligands, and two structural features appear to correlate with selectivity: (i) the torsion angle for the chelating O-atom and the ortho-C-atom of the axial Ph group (a small, ca. 19°, angle is optimum, Fig.8) and (ii) the “degree of perpendicularity” of the axial Ph group (Fig. 9). Competition experiments indicate that TADDOL 1a catalyzes both the methyltitanium and diethylzinc additions ≥ 50 times faster than the related dioxolane analogs 12a, 12c, and 12e (Scheme 7), indicating that both axial and equatorial aryl groups (see Footnote 6) are necessary for ligand-accelerated catalysis of these reactions. A refined mechanistic hypothesis is presented (Fig. 10) to explain the selectivities observed for these new ligands. Our analysis suggests that a combination of structural features appear necessary for good catalytic efficiency and high selectivity. These features, especially the rather subtle conformational effects, appear to be optimized (among the ligands tested) in the TADDOL's.

An enantioselective synthesis of key intermediates for the synthesis of the anti-microbially active pseudomonic acids A (1), B (2) and C (3) is described. D-Ribose (4) was used as starting material.

Rearrangements of 4,8-disubstituted 2,6-dioxa- and 2-oxa-6-aza-adamantanes to 4,10-disubstituted 2,7-dioxa- and 2-oxa-7-aza-isotwistanes as well as -twistanes. Substitutions and rearrangements involving neighboring group participation starting from 4,8-diiodo-2,6-dioxa- and 4,8-diiodo-2-oxa-6-aza-adamantanes (5 and 6, 12 and 48, resp.) were studied, yielding 4,8-disubstituted 2,6-dioxa- and 2-oxa-6-aza-adamantanes (7, 9, 39, 42 and 13, 15, 50, 52, resp.), 4,10-disubstituted 2,7-dioxa- and 2-oxa-7-aza-isotwistanes (8, 10, 41, 43 and 14, 16, 51, 53, resp.) and corresponding-twistanes (11 and 17, resp.).

The endo- and exo-alcohols 5–12 of syn-(1) and anti-tricyclo[4.2.1. 12.5]decane (2) were treated with BF3/Et3SiH (ionic hydrogenation) in order to study the behaviour of the corresponding regioselectively generated carbocations at C(3) (a (syn), b (anti)) and C(9) (c (syn), d (anti)). The anti-hydrocarbon 2 is practically the sole product obtained starting with the four 3-alcohols (viaab from 5 and 6 (syn) and viab from 9 and 10 (anti)). The four 9-alcohols in each case yield a mixture of 2-endo, 3-endo- (3) and 2-exo,3-exo-trimethylene-8,9,10-trinorbornane (4) (viac e from 7 and 8 (syn) and viad f from 11 and 12 (anti)), but no hydrocarbon 2, i.e. none of the 1,3-H shifts c a and d b is involved.

(+)-(1S, 3S, 6S, 8S)- and (−)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene. A synthesis and the determination of the sense of chirality of (+)-(1S, 3S, 6S, 8S)- and (−)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene ((+)-5 and (−)-5, respectively) is described.

Tricyclo[3.3.2.03,7]decane (9-Homo-nor-adamantane). Synthesis and Transformations A synthesis of tricyclo [3.3.2.03,7]decane (=9-homo-nor-adamantane; 1), which belongs to the adamantaneland, a family of nineteen isomeric C10H16 hydrocarbons, is described, as well as derivatives thereof. Treatment of protoadamantan-5endo-ol (11) with either thionyl chloride or phosphorus pentachloride yielded under rearrangement the chloride 18, and solvolysis of the 5endo-chloro-protoadamantane (16) led to the acetate 26, 18 and 26 having both the tricyclo [3.3.2.03,7]decane skeleton. Subsequent transformations gave the title compound 1 as well as the corresponding olefin 8.

Heterodiamantanes and Structurally Related Compounds. Part III. The Pentacyclic C11-Diethers 5, 13-Dioxapentacyclo [6.5.0.02,6.03,12.04,9]tridecane, 4, 13-Dioxapentacyclo [6.4.1.02,7.03,10.05,9]tridecane, and 3, 10-Dioxapentacyclo [7.3.1.02,7.04,12.06,11]tridecane In connection with the studies on heterodiamantanes and structurally related compounds the three novel pentacyclic diethers 3–5 were prepared starting from the cyclopentadienone dimer 6. All four compounds have as common features a central carbocyclic 6-membered ring with four axial alkyl substituents and two oxygen functions in 1, 4 position. The required eleventh C-atom was introduced by dichlorocarbene addition either to 6 ( 7) (Scheme 2) or to 29 ( 28) (Scheme 4). Diether 3 was obtained by reduction of 26(Scheme 2), a suitable precursor prepared either by intramolecular addition (24 26; Scheme 2) or substitution (30 26, 31 26; Scheme 4), as well as by direct substitution (44 3, 42 3; Scheme 5). Diether 4 was the product of a direct substitution (39 4, 36 4; Scheme 5). The synthesis of diether 5 was achieved from the addition product 51 (resulting from the alcohols 47 and 48; Scheme 6). Diether 4 is the thermodynamically least stable of the three diethers 3–5. It was easily isomerized to 5 on treatment with concentrated sulfuric acid in benzene whereas 3 and 5 remained unchanged under these conditions.

3-Azawurtzitane and 3(4 5)abeo-3-Azawurtzitane 3-Azawurtzitane (14) and 3(4 5)abeo-3-azawurtzitane (15) as well as derivatives thereof are described. The known tricyclic unsaturated ketone 1 was transformed to the properly functionalized endo-amines 3, 5 and 12. Entry to the azawurtzitane system and its corresponding abeo-compounds was achieved by three different cyclization procedures: aminomercuration with mercuric acetate in water (3 14, 5 16), olefin amination with mercuric acetate in dimethyl sulfoxide (3 18, 5 20 + 21) and intramolecular attack at an epoxide (12 24 + 25). Molecular rearrangements of 3-azawurtzitanes to 3(4 5)abeo-3-azawurtzitanes and vice versa are described involving neighbouring group participation of the N (3) atom.

Syntheses of Tricyclo [5.2.1.04,8]decane (2-Homobrendane) Three different approaches to tricyclo [5.2.1.04,8] decane (5) (and derivatives thereof), one of the 19 isomeric hydrocarbons of the ‘adamantaneland’, are described: (1) Cyclization of properly functionalized bicyclo [3.2.1]octanes as 32(cyclialkylation), 40+42 (thermocyclization) and 44+45 (photocyclization); (2) Silver-(I)-ion catalyzed rearrangement of 5,7- and 5,10-Dehydroprotoadamantane (63 and 64, respectively) yielding tricyclo[5.2.1.04,8]dec-2- (39) and -5-ene (59), respectively; (3) Thermal eliminative rearrangement of the 10endo-p-toluenesulfonate and -methanesulfonate of protoadamantane (71 and 72) and protoadamant-4-ene (76 and 77), respectively, yielding tricyclo [5.2.1.04,8]dec-2-ene (39) and -2, 5-diene (15), respectively.

An easy approach to the novel adamantane isomer 1,2endo-trimethylenenorbornane (2) is described. Starting from a mixture of pent-4-ynylcyclopentadienes 3 the tricyclic monosaturated key intermediate 5 was prepared by intramolecular cycloaddition (4) and subsequent regioselective reduction of the C(5), C(6) double bond. The title hydrocarbon 2 was obtained from 5 upon stereoselective hydrogenation by diimide. In addition specifically deuteriated analogues of 2 were prepared applying dideuteriodiimide. Compound 2 rearranged to 2endo, 6endo-trimethylenenorbornane (4-homobrendane, 10) in sulfuric acid as well as with aluminium bromide in carbon disulfide.

2-Aza-7-thia-twistanes (or 2-thia-7-aza-twistanes, respectively) The suitably substituted 9-thiabicylo[3.3.1]nonanes 7–9 and 17 were synthesized and subsequently cyclized to the 2-aza-7-thia-twistanes 21–23 and 19, respectivelly, from which several other twistane derivatives (20 and 24–29) were prepared.

The tricyclic olefinic primary amine 1 readily cyclizes to the tetracyclic secondary amine 2 at approximately 200° in protic as well as aprotic solvents although the C, C-double bond is not activated by electron-attracting groups. This unusual intramolecular addition is the consequence of the close proximity of the nucleophile and the double bond. For the synthesis of the sterically highly hindered amine 1, the tricyclic oxime 4 was reduced with TiCl3 to the remarkably stable imine 5 and the latter treated with AlH3. On the other hand, reaction of 4 with AlH3 yielded the pentacyclic aziridine 6.

Two synthetic approaches to the novel C10H16 hydrocarbon tricyclo[4.4.0.03,9]decane (1; 2-homotwistbrendane), one of the 19 members of the adamantaneland, and its Lewis-acid-catalyzed rearrangement are described. One route starts from tricyclo[4.3.0.03,8]nonan-2-one (2; 2-twistbrendanone). The missing tenth C-atom is introduced by ring enlargement (Tiffeneau-Demjanov method). Starting from methyl 8,9,10-trinorborn-5-ene-2-endo-carboxylate (8), ring enlargement by one C-atom, regio- and stereoselective introduction of a C1 unit to a 2-endo,6-endo-disubstituted bicyclo[3.2.1]octane, and ring closure by acyloin condensation are the key steps in the second approach.

A new synthesis of wurtzitane (13) is described starting from 2-oxo-protoadamant-4-ene (2). The key intermediate ketone 7 was obtained by regiospecific ring expansion of the β-amino alcohol 6. Entry to the wurtzitane system involved solvolysis of the tricyclic unsaturated mesylate 10 (11).

From treatment of D-labelled 1, 2exo-, 1, 2endo- and 2endo, 6endo-trimethylene-norbornane (1, 2 and 3, resp.) with aluminum bromide in carbon disulfide, the evidence is gained that a degenerate rearrangement is involved in the admantane rearrangement of both 1 and 2 to 3.

A synthesis of the novel C10H16 hydrocarbon 2,5-trimethylenenorbornane (tricyclo[5.3.0.03,9]decane, 1), one of the 19 members of the ‘adamantaneland’, and its Lewis-acid-catalyzed rearrangement is described.

A synthesis of twista-4,9-diene (17) from tricyclo[4.3.1.03,8]dec-4-en-10-one (2) is described.

In view of the significance of steric compression in the base-catalyzed intramolecular cyclization of polycyclic olefinic alcohols, the standard enthalpies of formation of anti9,10-10 endo-hydroxytricyclo [4.2.1.12,5]deca-3,7-dien-9-one (1) and 9-oxatetracyclo [5.4.0.03,10.04,8]undec-5-en-2-one (2) as well as the kinetics of the ether formation 1 2 were determined.

In the presence of AlBr3 in CS2 at temperatures below 0°, syn-tricyclo[4.2.1.12,5]decane (1) isomerizes exclusively to anti-tricyclo[4.2.1.12,5]decane (2) at a higher rate than the latter rearranges to 2-exo,3-exo-trimethylene-8,9,10-trinorbornane (4). However, at temperature above 0°, the anti-isomer 2 isomerizes to 4 faster than 1 to 2 and 4. As a consequence, hydride abstraction occurs at C(3) (carbocation a, which rearranges to carbocation b (anti-skeleton)) in the syn-isomer 1, and more readily at C(9) (carbocation c) than at C(3) (carbocation b) in the anti-isomer 2.

A synthesis of the two C(9) epimers 14 and 15 of 2-oxo-9-hydroxy-bicyclo[3.3.1]nonane is described starting from the two C(2) epimers 3 and 4 of 2-hydroxy-9-oxo-bicyclo[3.3.1]nonane.

(+)-(1S, 3S, 6S, 8S)-and (−)-(1R, 3R, 6R, 8R)-4, 9-Twistadiene: Synthesis and Absolute Configuration A synthesis and the determination of the absolute configuration of (+)-(1S, 3S, 6S, 8S)- and (−)-(1R, 3R, 6R, 8R)-4, 9-twistadiene ((+)- and (−)-4, respectively) is described. Their chiroptical properties are compared with those of saturated twistane ((+)- and (−)-5) as well as with those of the unsaturated and saturated 2, 7-dioxatwistane analogs (+)- and (−)-9, and (+)- and (−)-10, respectively, which also are compounds of known absolute configurations.

Acid treatment of 9exo-methyl-anti10,11-tricyclo[4.2.1.12,5]deca-3,7-diene-9endo, 10endo-diol (8) leads to the two isomeric pentacyclic ethers 7 and 9 by intramolecular nucleophilic substitution of a protonated OH-group with participation of a C,C-double bond. The higher steric compression in diol 8 on the side of the tertiary OH-group at C(9) and the C(3), C(4)-double bond, accounts for the preferred formation of 7 over 9.

Tricyclic olefinic alcohols containing an unsymmetrically alkyl-substituted C, C-double bond were cyclized intramolecularly to their corresponding ethers under basic conditions: 9 12, 10 17 + 18, and 11 12(Scheme 3, Table 1). The reactivity is mainly due to relieve of ground state strain. Alcohol 9 (endocyclic double bond) isomerized under intramolecular assistance by the hydroxyl group to 11 (exocyclic double bond) before cyclization to 12 occurred (Scheme 5). The latter step being the faster one, no isomerization 11 9 was observed.

2,6-Dioxatricyclo [3.3.2.03,7]decane, a Novel Isomer of 2,6-Dioxaadamantane Restriction among the great number of possible diheterotricyclodecanes to such with a carbocyclic 8membered ring (cyclooctane) as basic skeleton, which is crosswise bridged by two heteroatoms, and restriction to 5-, 6- and 7membered heterocyclic rings results in the isomeric diheterotricyclodecanes of the following five different structural types: 2,6-diheteroadamantane (a), 2,7-diheteroisotwistane (b), 2,7-diheterotwistance (c), 2,8-diheterohomotwistbrendane (d), and 2,6-diheterotricyclo [3.3.2.03,7]decane (e; s. Scheme 1). Starting from a suitably C (5)o(2)-functionalized 2,7-dioxaisotwistane, first representatives with the hitherto unknown skeleton of type e were prepared by molecular rearrangement involving neighboring group participation: 2,6-dioxatricyclo [3.3.2.03,7]decane (41) and the derivatives 34–40 thereof (Scheme 7).

The behaviour of the regioselectively generated carbocation centers at C(2) and C(6) in 1,2-trimethylenenorbornanes was investigated in order to study the occurrence or absence of a degenerate rearrangement E⇄M in the adamantane rearrangement of both 1,2-endo- (1) and 1,2-exo-trimethylenenorbornane (2) to 2-endo,6-endo-trimethylenenorbornane (3). A degenerate rearrangement E⇄M is inevitably involved inasmuch as a 1,2-trimethylenenorborn-2-yl cation E not only is formed directly as manifested by the conversions of the reactants 4 (C(2), C(3)-olefin) and 6 (C(2), C(3′)-olefin), but also indirectly (viaFE) if the leaving group at C(6) to be ionized occupies the endo-position (6-endo-alcohol 8). No degenerate rearrangement E⇄M is operative starting from reactants that lead directly to a 2,6-trimethylenenorborn-2-yl cation G; this is the case with both the ionization of the 6-exo-alcohol 10 having the leaving OH-group in a stereoelectronically favoured configuration to undergo simultaneous C(1), C(2)-bond migration (G) as well as the protonation of the olefin 13 which is followed by same reaction pathway.

Regioselective generation of the C(2)-carbocation a of tricyclo[4.2.2.01,5]decane (1) by treatment of both corresponding epimeric alcohols 5 and 6 with BF3 and trapping the rearranged tricyclo[5.3.0.04,8]decan-7-yl carbocation b with Et3SiH as hydride-ion donor (ionic hydrogenation) gives the corresponding hydrocarbon 3 as sole product in almost quantitative yield. The latter is a known intermediate in the Lewis-acid-catalyzed rearrangement of 1 to adamantane (4).

Photolysis of Bicyclo[3.3.1]nonan-2-one. Disproportionations to the unsaturated aldehydes 2 and 3 or the ketene 4, the secondary processes available to the acyl-alkyl biradical b[X(9) = CH2] formed from bicyclo[3.3.1]nonan-2-one (1) in a primary photochemical process by α-cleavage (Norrish type I cleavage), were studied. If the acyl-alkyl biradical b [X(9) = CH2] has a lifetime sufficient to permit rotation around one or several bonds before H-transfer occurs, considerations about the energetically most favored conformations of b allow to deduce the following preference for intramolecular H-abstraction: at C(9) (f unsaturated aldehyde 2) > at C(3) (1 ketene 4) > at C(8) (i unsaturated aldehyde 3). If H-transfer takes place very quickly, following an energetically favored small conformational change of the acyl-alkyl biradical, one expects H-abstraction at C(9) and/or C(3) to be preferred over that at C(8). These predictions were fully confirmed by the experiments. UV. irradiation of bicyclo[3.3.1]nonan-2-one (1) in n-pentane gave a complex mixture of the unsaturated aldehyde 2 and products of further photochemical reactions of 2:43 and 44, 45 and 46, 49–52, and 54–57 (see below). Photolysis of 1 in methanol, however, yielded 82% of 2 and 1,2% of ester 23, the final product from ketene 4 formed by trapping of a solvent molecule. UV. irradiation of the 9,9-dideuterio-ketone 20 confirmed the intramolecular D-abstraction at C(9) ( unsaturated aldehyde 21) and consequently the H-abstraction at C(9) in the sequence 1 2. That either of the two H-atoms at C(9) in 1 can be abstracted was demonstrated by the photolysis of the C(9)-epimeric 9-acetoxy-bicyclo[3.3.1]nonan-2-ones 24 and 25 in methanol. In both cases the unsaturated aldehyde 26 was formed, which corresponds to abstraction of H—C(9)c(7) and H—C(9)C(3)15, respectively. In separate UV. irradiation experiments it was shown that the products accompanying the unsaturated aldehyde 2 (photolysis of 1 in n-pentane) were formed in the following ways: diene 43 and acetaldehyde (44) from 2 by intramolecular γ-H abstraction followed by Norrish type II reaction; the spiro-alcohols 45 and 46 from 2 by intramolecular γ-H abstraction followed by ring closure to cyclobutanols; the oxetanes 49–52 by cycloaddition (Paterno-Buchi reaction) of acetaldehyde (44) to 3-methylidene-cyclohexene (43); the aliphatic alcohols 54–57 by addition of acetaldehyde (44) to n-pentane, i.e. H-abstraction from the hydrocarbon solvent followed by combination of the radicals thereby formed.

Proximity effects alone as well as in combination with electronic effects are responsible for the observed phenomenon of base-catalyzed ether formation initiated by nucleophilic attack on a C, C double bond of the tricyclic olefin alcohols 1–10(Scheme 1, Table 1). With compounds 1–4, bearing a keto group, formation of the ethers 11–14 proceeds through a corresponding homoenolate b(Scheme 2) as an intermediate. In one case such a species could be trapped as the methyl ether 21(Scheme 3). Special attention is given to the stereochemical course of the homoketonization. Ring opening in 21 under acidic conditions occurs regioselectively, however non-stereoselectively (Scheme 3). Full regio- and stereoselectivity (retention) is observed under basic conditions starting from the unsaturated keto alcohols 1 and 2(Scheme 4) as well as from the keto ethers 11 and 12(Scheme 5, Table 2).

A Further Approach to 2,6-Dioxatricyclo[3.3.2.03,7]decane A further synthesis of 2,6-dioxatricyclo[3.3.2.03,7]decane (10) is described by bridging the 9-oxabicyclo[4.2.1]non-7-en-3endo-ol (9). The latter compound was prepared by ring expansion starting from the known 8-oxabicyclo[3.2.1]oct-6-en-3-on (1).

A further synthetic approach to 2, 5-trimethylenenorbornane (1; tricycle [5.3.0.03,9]decane, 4-homotwistbrendane), a member of the «adamantaneland», is described starting from methyl 5-oxo-2endo-norbornanecarboxylate (5). The required C2-chain was introduced by a Wittig-Horner reaction and the ring closure of the trimethylene bridge achieved by an acyloin condensation.

The base-catalyzed intramolecular cyclization of polycyclic olefinic alcohols of type a (10-endo-hydroxy-anti9,10-tricyclo [4.2.1.12,5]dec-7-en-9-ones (type h), anti9,10-tricyclo[4.2.1.12,5] dec-3-en-9-endo-ols (type j), and anti10,11-tricyclo[4.3.1.12,5]undec-3-en-10-endo-ols (type 1)) to the ethers d and f, resp., has been studied. A mechanism for the nucleophilic addition of the corresponding alkoxide anion b to the isolated C,Cdouble bond is discussed. It is proposed that b is formed (fast acid/base equilibrium) in the first step. For the subsequent reaction sequence, there are two well distinguishable pathways: (a) Compounds with an additional carbonyl group (h) cyclize via a homoenolate-like intermediate c, which is protonated stereoselectively on the exo-side by the hydroxylic solvent. (b) Compounds without a carbonyl group (j and l) cyclize 102-104 times slower, and the reaction proceeds via a carbanion-like transition state e. The proton transfer from the hydroxylic solvent is clearly coupled with the C,Obond formation. Steric compression in the olefinic alcohols a influences the cyclization rate: (a) Alcohols with a smaller ring (h, X = CH2CH2) cyclize 70–200 times faster than the ones with a larger ring (1, X = CH2CH2CH2). (b) Replacement of the H-atom at the carbinol C-atom by a CH3 group enhances the rate of ether formation by a factor of 50–100. Due to through-bond interactions between the C,C-double bonds, olefinic alcohols with an additional endocyclic C,C-double bond (h and j, X = CHCH) cyclize 20–300 times faster than the corresponding monoolefinic ones (h and j, X = CH2CH2).

The influence of steric compression on electronic structure in polycyclic olefinic alcohols and amines is studied by PE. spectroscopy. The unsubstituted alcohol 2 and amine 7 show PE.-spectroscopic properties that can be reconciled by postulating a predominance of intramolecularly H-bonded species in the gas phase. For the alkylated derivatives 5 and 9, in which H-bonding is precluded, distinct, but only moderate lone-pair double-bond interactions are observed.

2-Thia-7-aza-isotwistanes. The access to the 2-thia-7-aza-isotwistane system was achieved by water addition to the twistene 1 yielding the isotwistanol 2, characterized also as its acetate 4. Analogous D2O/D2SO4-treatment of the twistene 1 ( 3) allowed to deduce the reaction pathway for the formation of 2. The chloride 6, obtained from 2, on treatment with lithium aluminium hydride gave a mixture of unsubstituted isotwistane 8 and twistane 9, whereas silver acetate treatment of 6 led to the isotwistyl acetate 4 and possibly only to traces of the corresponding twistyl acetate 7.

2-Aza-7-thia-isotwistanes. 2-Aza-7-thia-isotwistanes were synthesized either starting from suitable 9-thiabicyclo[3.3.1]nonenes by olefin-amination (1 4, 2 5, 3 6, 8 10 and 9 11) as well as by intramolecular substitution (25 26) or by molecular rearrangement starting from twistanes (21 19 and 22 10). From the isotwistanes thus obtained several other compounds (7, 12–18, 20, 23 and 24) were prepared, too.